Am FriedHof vorbei zur Kapelle
Trübe LichtFlecken einer ÖlLampe
Die Schwärze der Nacht wird blau an den Rändern
Eintritt
WiderSchein der kleinen, flammenden BittKerzen
Schatten unserer Schwäche
Wieder eine Träne
Wenn unsere Zeit
Korn um Korn verronnen ist
Füllt Asche die Urne
Wer trägt die Urne
Löscht aus die Worte
Blog von Dr. med. Lothar M. Kirsch / 祁建德 // Rheumatic Diseases / Fibromyalgia / Travels / Languages / Poetry
Wednesday, November 30, 2011
Trotzdem sollen Bäume blühen
Ein KirschBaum mag geblüht haben
Bei der Hinrichtung
Eher aber hatten den Delinquenten
Wanzen gebissen
Als er auf einem JuteSack lag
Gefesselt - geschlagen - geblutet
-: geweint
Schmetterlinge mag der Wind treiben
Aber nicht in´s vergitterte Dunkel
Trotzdem sollen Bäume blühen
-: zeig´ sie mir
Bevor mir die Kapuze übergezogen wird
Palimpsest - in memoriam Hilde Domin
Bei der Hinrichtung
Eher aber hatten den Delinquenten
Wanzen gebissen
Als er auf einem JuteSack lag
Gefesselt - geschlagen - geblutet
-: geweint
Schmetterlinge mag der Wind treiben
Aber nicht in´s vergitterte Dunkel
Trotzdem sollen Bäume blühen
-: zeig´ sie mir
Bevor mir die Kapuze übergezogen wird
Palimpsest - in memoriam Hilde Domin
Worte und Sand
Ich schrieb
Unleserliche Worte in den Sand
Hoffend vielleicht
Sie würden versteinern
Einen Teil der Ewigkeit überdauern
Andere schrieben
Unleserliche Worte auf einen Stein
Den die Zeit zu Sand werden ließ
Um in den Stürmen der Zukunft zu verwehen
Vielleicht bleibt doch in all der Ewigkeit
Der AugenBlick
In dem die Worte waren
Unleserliche Worte in den Sand
Hoffend vielleicht
Sie würden versteinern
Einen Teil der Ewigkeit überdauern
Andere schrieben
Unleserliche Worte auf einen Stein
Den die Zeit zu Sand werden ließ
Um in den Stürmen der Zukunft zu verwehen
Vielleicht bleibt doch in all der Ewigkeit
Der AugenBlick
In dem die Worte waren
ACR2011 and Fibromyalgia (4)
Quite a lot of posters on fibromyalgia! I’ve taken a couple of abstracts as a couple of things might be new to one or another. It’s a very private selection. I won’t advocate some of the wonderdrugs the pharma industry is eager to promote.
Cannabinoid Use in Fibromyalgia Is Associated with Male Gender, Opioid Use and Drug Seeking Behaviour
Peter A. Ste-Marie and colleagues were interested in the use of cannabinoids in fibromyalgia. The endocannabinoid system plays a role in pain modulatory mechanisms, but little is known about the effect of administered cannabinoids in chronic pain or fibromyalgia. The authors examined the use of cannabinoids in patients with a diagnosis of fibromyalgia. Cannabinoid users were more likely to be male, be taking opioids, and demonstrate drug-seeking behaviours. A tendency for unstable current mental illness and unemployment was found for cannabinoid users. The authors caution to recommend the use of cannabinoids until a “rigorous evaluation” has been done.
[TUE] 1906
Cannabinoid Use in Fibromyalgia Is Associated with Male Gender, Opioid Use and Drug Seeking Behaviour.
Peter A. Ste-Marie1, Mary-Ann Fitzcharles2, Ann Gamsa2, Pantelis Panopalis2 and Yoram Shir2.
1University of Montreal, Montreal, QC, 2McGill University, Montreal, QCConclusion: Cannabinoids were used by 13% of all patients referred with a diagnosis of FM, and 1/3 of all males. Illicit marijuana was the most cannabinoid used. The concomitant use of opioids as well as an increased rate of drug seeking behaviour raises concerns regarding the true motive for this category of mostly self medication. Although cannabinoids may possibly offer a therapeutic effect for pain relief, caution regarding any recommendation for use should be exercised until these agents are subject to rigorous evaluation in view of concerns regarding psychological health and an association with other substance abuse.
Cannabinoid Use in Fibromyalgia Is Associated with Male Gender, Opioid Use and Drug Seeking Behaviour
Peter A. Ste-Marie and colleagues were interested in the use of cannabinoids in fibromyalgia. The endocannabinoid system plays a role in pain modulatory mechanisms, but little is known about the effect of administered cannabinoids in chronic pain or fibromyalgia. The authors examined the use of cannabinoids in patients with a diagnosis of fibromyalgia. Cannabinoid users were more likely to be male, be taking opioids, and demonstrate drug-seeking behaviours. A tendency for unstable current mental illness and unemployment was found for cannabinoid users. The authors caution to recommend the use of cannabinoids until a “rigorous evaluation” has been done.
[TUE] 1906
Cannabinoid Use in Fibromyalgia Is Associated with Male Gender, Opioid Use and Drug Seeking Behaviour.
Peter A. Ste-Marie1, Mary-Ann Fitzcharles2, Ann Gamsa2, Pantelis Panopalis2 and Yoram Shir2.
1University of Montreal, Montreal, QC, 2McGill University, Montreal, QCConclusion: Cannabinoids were used by 13% of all patients referred with a diagnosis of FM, and 1/3 of all males. Illicit marijuana was the most cannabinoid used. The concomitant use of opioids as well as an increased rate of drug seeking behaviour raises concerns regarding the true motive for this category of mostly self medication. Although cannabinoids may possibly offer a therapeutic effect for pain relief, caution regarding any recommendation for use should be exercised until these agents are subject to rigorous evaluation in view of concerns regarding psychological health and an association with other substance abuse.
Ankylosing Spondylitis – more myths
Today we’re going to discuss to further myths:
healing ankylosing spondylitis is around the corner
in ankylosing spondylitis nothing works.
Though considering before and after establishing TNF-alpha-inhibitors as an effective therapy is important, myths have a tendency to survive.
Before TNF-blockers therapeutic options for ankylosing spondylitis were limited to nonsteroidal antirheumatic drugs (NSAIDs) and physical therapy. Corticosteroids and disease-modifying antirheumatic drugs weren’t successful in ankylosing spondylitis. But even then, a high percetage of patients did well on NSAIDs and fighted ankylosis, stiffness, and deformations with physical therapy. It has been shown, that continuous NSAID-intake even delays radiographic progression. But there were patients (and there still are!) with ankylosing spondylitis not respoding to NSAID therapy! About 10-12 years ago TNF-blockers showed effectiveness in lots of patients, who were desperate while on NSAIDs. Or who couldn’t take NSAIDs because of adverse events. Today infliximab, etanercept, adalimumab, and golimumab are approved for the treatment of ankylosing spondylitis.
Diagnosis can be made earlier. We have an interest nowadays to diagnose the disease before radiographic changes appear. Therefore the New York criteria are a bit outdated. If you make the diagnosis with the help of this tool, it is already ankylosing spondylitis you see, whereas in axial spondyloarthritis you diagnose the inflammatory disease before radiographic damage begins to show. The question is: does early and more aggressive treatment with TNF-blockers show better responses? To cut the story short: early treatment with TNF-blockers in preradiographic axial Sponyloarthritis show a better clinical response and a higher rate of remission. Longer phases of sustained drugfree remission have been seen. But still you can’t call it healing ankylosing spondylitis. And please don’t forget that there are non-responders.
Even if healing ankylosing spondylitis isn’t around the corner, established therapies can improve quality of life in a large percentage of people with ankylosing spondylitis / axial spondyloarthropathies.
To be continued …
healing ankylosing spondylitis is around the corner
in ankylosing spondylitis nothing works.
Though considering before and after establishing TNF-alpha-inhibitors as an effective therapy is important, myths have a tendency to survive.
Before TNF-blockers therapeutic options for ankylosing spondylitis were limited to nonsteroidal antirheumatic drugs (NSAIDs) and physical therapy. Corticosteroids and disease-modifying antirheumatic drugs weren’t successful in ankylosing spondylitis. But even then, a high percetage of patients did well on NSAIDs and fighted ankylosis, stiffness, and deformations with physical therapy. It has been shown, that continuous NSAID-intake even delays radiographic progression. But there were patients (and there still are!) with ankylosing spondylitis not respoding to NSAID therapy! About 10-12 years ago TNF-blockers showed effectiveness in lots of patients, who were desperate while on NSAIDs. Or who couldn’t take NSAIDs because of adverse events. Today infliximab, etanercept, adalimumab, and golimumab are approved for the treatment of ankylosing spondylitis.
Diagnosis can be made earlier. We have an interest nowadays to diagnose the disease before radiographic changes appear. Therefore the New York criteria are a bit outdated. If you make the diagnosis with the help of this tool, it is already ankylosing spondylitis you see, whereas in axial spondyloarthritis you diagnose the inflammatory disease before radiographic damage begins to show. The question is: does early and more aggressive treatment with TNF-blockers show better responses? To cut the story short: early treatment with TNF-blockers in preradiographic axial Sponyloarthritis show a better clinical response and a higher rate of remission. Longer phases of sustained drugfree remission have been seen. But still you can’t call it healing ankylosing spondylitis. And please don’t forget that there are non-responders.
Even if healing ankylosing spondylitis isn’t around the corner, established therapies can improve quality of life in a large percentage of people with ankylosing spondylitis / axial spondyloarthropathies.
To be continued …
Labels:
Ankylosing spondylitis (AS),
Biologics,
M. Bechterew,
NSAIDs
Tuesday, November 29, 2011
Ich werf noch ein paar Gedichte in die Runde
RausMühle
Eines Baches klares Wasser
Das trank ich einst
Und werd´ es immer trinken
Wenn ich vorüberGeh´
Das MühlRad dreht nicht mehr
Viel Wahres haben wir verloren
Nicht FortSchritt soll Bestimmung sein
Nur Leben in Betulichkeit
Antworten auf eine nichtGestellte Frage
Kaltes Licht dreier Sterne
Wie es verwirrende Schatten wirft
In der Nekropole des Herzens
Warme Brise vom BrachLand
Wie sie betörende Erinnerungen ruft
In der Ödnis des Geistes
Gichtige Brandung des NordMeeres
Wie sie zweideutige Antworten gibt
In der Vereinsamung des Fraglosen
BackSteinRuine
Die BackSteinRuine fröstelte
Im EisKalt des NachtWindes
Der Schnee war wie ein Kleid
Das vor den Blicken schützt
Die Scham bedeckt
Im HerbstRegen
Wagte sie zu weinen
Und Moos seufzte dazu
Purple Moon
Ich kenne jetzt den blue moon
Weil er besungen wird
Aber ich zweifle
Daß jemand den purple moon kennt
Da ich ihn gerade eben erst
Erfunden habe
Eines Baches klares Wasser
Das trank ich einst
Und werd´ es immer trinken
Wenn ich vorüberGeh´
Das MühlRad dreht nicht mehr
Viel Wahres haben wir verloren
Nicht FortSchritt soll Bestimmung sein
Nur Leben in Betulichkeit
Antworten auf eine nichtGestellte Frage
Kaltes Licht dreier Sterne
Wie es verwirrende Schatten wirft
In der Nekropole des Herzens
Warme Brise vom BrachLand
Wie sie betörende Erinnerungen ruft
In der Ödnis des Geistes
Gichtige Brandung des NordMeeres
Wie sie zweideutige Antworten gibt
In der Vereinsamung des Fraglosen
BackSteinRuine
Die BackSteinRuine fröstelte
Im EisKalt des NachtWindes
Der Schnee war wie ein Kleid
Das vor den Blicken schützt
Die Scham bedeckt
Im HerbstRegen
Wagte sie zu weinen
Und Moos seufzte dazu
Purple Moon
Ich kenne jetzt den blue moon
Weil er besungen wird
Aber ich zweifle
Daß jemand den purple moon kennt
Da ich ihn gerade eben erst
Erfunden habe
Das HackBrett des Kannibalen
Auf dem HackBrett des Kannibalen
Sah ich Einschnitte
Gehackt mit großer Präzision
Weiß strahlte das harte Holz
Tief war die Wölbung in der Mitte
Reinlich
Peinlich sauber
So wirkte alles
Kein Blut
Ein heller Raum seine Küche
Und wüßt’ ich’s nicht besser
Das HackBrett des Kannibalen
Es könnte unseren Müttern gehören
Sah ich Einschnitte
Gehackt mit großer Präzision
Weiß strahlte das harte Holz
Tief war die Wölbung in der Mitte
Reinlich
Peinlich sauber
So wirkte alles
Kein Blut
Ein heller Raum seine Küche
Und wüßt’ ich’s nicht besser
Das HackBrett des Kannibalen
Es könnte unseren Müttern gehören
ACR2011 and Fibromyalgia (3)
Quite a lot of posters on fibromyalgia! I’ve taken a couple of abstracts as a couple of things might be new to one or another. It’s a very private selection. I won’t advocate some of the wonderdrugs the pharma industry is eager to promote.
Can Online Cognitive Behavioral Therapy Help in Fibromyalgia
Gwendoline Menga and colleagues conducted a 12 week randomized controlled trial in patients with fibromyalgia and mild to moderate depression and anxiety. Patients on a 6-week Internet-based CBT program were compared to a control group (usual care). “Patients in the Internet-based MoodGYM CBT program had lower FIQ and TP scores at 6 and 12 week follow-ups.” One would have wished for more robust tools in testing change of depressive mood or anxiety. And looking for effect of 6 weeks of cognitive behavioral therapy on tender points seems to be going back in time.
Don’t get me wrong, I am an advocate for cognitive behavioral therapy, not as an online-program but in a clinical setting, which I’m doing right now with a group of six patients.
[MON] 937
Fibromyalgia: Can Online Cognitive Behavioral Therapy Help?
Gwendoline Menga1, Bobby J. Dupre2, Carl Gauthier3, William E. Davis4, Tamika A. Webb-Detiege5, Eve Scopelitis3, Jerald M. Zakem4 and Robert Quinet6.
1Ochsner Clinic Center, New Orleans, LA, 2Ochsner Health System, Baton Rouge, LA, 3Ochsner Clinic Foundation, New Orleans, LA, 4Ochsner Clinic, New Orleans, LA, 5Ochsner Medical Ctr, New Orleans, LA, 6Ochsner Medical Center - New Orleans, New Orleans, LA
Conclusion: Patients in the Internet-based MoodGYM CBT program had lower FIQ and TP scores at 6 and 12 week follow-ups. Internet-based CBT could be beneficial therapy in the treatment of mild to moderate symptoms of depression and anxiety in
Can Online Cognitive Behavioral Therapy Help in Fibromyalgia
Gwendoline Menga and colleagues conducted a 12 week randomized controlled trial in patients with fibromyalgia and mild to moderate depression and anxiety. Patients on a 6-week Internet-based CBT program were compared to a control group (usual care). “Patients in the Internet-based MoodGYM CBT program had lower FIQ and TP scores at 6 and 12 week follow-ups.” One would have wished for more robust tools in testing change of depressive mood or anxiety. And looking for effect of 6 weeks of cognitive behavioral therapy on tender points seems to be going back in time.
Don’t get me wrong, I am an advocate for cognitive behavioral therapy, not as an online-program but in a clinical setting, which I’m doing right now with a group of six patients.
[MON] 937
Fibromyalgia: Can Online Cognitive Behavioral Therapy Help?
Gwendoline Menga1, Bobby J. Dupre2, Carl Gauthier3, William E. Davis4, Tamika A. Webb-Detiege5, Eve Scopelitis3, Jerald M. Zakem4 and Robert Quinet6.
1Ochsner Clinic Center, New Orleans, LA, 2Ochsner Health System, Baton Rouge, LA, 3Ochsner Clinic Foundation, New Orleans, LA, 4Ochsner Clinic, New Orleans, LA, 5Ochsner Medical Ctr, New Orleans, LA, 6Ochsner Medical Center - New Orleans, New Orleans, LA
Conclusion: Patients in the Internet-based MoodGYM CBT program had lower FIQ and TP scores at 6 and 12 week follow-ups. Internet-based CBT could be beneficial therapy in the treatment of mild to moderate symptoms of depression and anxiety in
Ankylosing Spondylitis – overcoming myths
Yesterday we have been talking about inflammatory back pain, now we want to come to a diagnosis. Classificatory criteria may lead to the diagnosis, but these criteria weren’t put together to serve this purpose.
To come to a diagnosis you will need a couple of pieces to put together in the diagnostic puzzle. You already have inflammatory back pain and some features of spondyloarthropathies like dactylitis, enthesitis, psoriatic lesions, arthritis, Crohn’s, acute anterior uveitis, positive family history, inflammatory bowel disease, and good response to NSAIDs. Much depends now on how experienced you are making a diagnosis axial spondylitis or ankylosing spondylitis, to name two. With three features out of the ASAS set you already come to definte axial arthritis. If you are experienced, you have some options on how to continue. You don’t have MRI at hand but X-ray. X-ray changes take long to develop, but if you find typical changes of the iliosacral joints, you are very close to the diagnosis of ankylosing spondylitis, though you have been contacted too late. You need a clinical exam of the patient to make sure that function is impaired (metrology). If you come earlier into play and/or if X-ray are inconclusive or negative, you go on with HLA B27. If it’s positive you might come to the conclusion that you patient suffers from probable axial spondyloarthritis. If you didn’t find any of the features of spondyloarthropathies, but the patient tested positive for HLA B27, you need to get an MRI to reach the diagnosis of definite axial spondyloarthritis.
As you might imagine there are still lots of white areas on this map. Space , which later will be occupied by other gene predispositions and so on.
What of physicians, not being experienced in the field of spondyloarthropathies? Should we train the GPs or orthopedic colleagues to be able to make the diagnosis? If you you think that this would be feasible, well then we have created a new myth. No they don’t have to make a diagnosis, but we have to empower them to know the red flags, when to send someone to a rheumatologist. They have to screen low back pain patients for inflammatory back bain and send these patients for further diagnostic procedures. They could even leave the expensive HLA B27 test to the rheumatologist.
Read more in: M Rudwaleit, D van der Heijde, M A Khan, J Braun, J Sieper: How to diagnose axial spondyloarthritis early. Ann Rheum Dis 2004;63:535–543. doi: 10.1136/ard.2003.011247
To be continued …
To come to a diagnosis you will need a couple of pieces to put together in the diagnostic puzzle. You already have inflammatory back pain and some features of spondyloarthropathies like dactylitis, enthesitis, psoriatic lesions, arthritis, Crohn’s, acute anterior uveitis, positive family history, inflammatory bowel disease, and good response to NSAIDs. Much depends now on how experienced you are making a diagnosis axial spondylitis or ankylosing spondylitis, to name two. With three features out of the ASAS set you already come to definte axial arthritis. If you are experienced, you have some options on how to continue. You don’t have MRI at hand but X-ray. X-ray changes take long to develop, but if you find typical changes of the iliosacral joints, you are very close to the diagnosis of ankylosing spondylitis, though you have been contacted too late. You need a clinical exam of the patient to make sure that function is impaired (metrology). If you come earlier into play and/or if X-ray are inconclusive or negative, you go on with HLA B27. If it’s positive you might come to the conclusion that you patient suffers from probable axial spondyloarthritis. If you didn’t find any of the features of spondyloarthropathies, but the patient tested positive for HLA B27, you need to get an MRI to reach the diagnosis of definite axial spondyloarthritis.
As you might imagine there are still lots of white areas on this map. Space , which later will be occupied by other gene predispositions and so on.
What of physicians, not being experienced in the field of spondyloarthropathies? Should we train the GPs or orthopedic colleagues to be able to make the diagnosis? If you you think that this would be feasible, well then we have created a new myth. No they don’t have to make a diagnosis, but we have to empower them to know the red flags, when to send someone to a rheumatologist. They have to screen low back pain patients for inflammatory back bain and send these patients for further diagnostic procedures. They could even leave the expensive HLA B27 test to the rheumatologist.
Read more in: M Rudwaleit, D van der Heijde, M A Khan, J Braun, J Sieper: How to diagnose axial spondyloarthritis early. Ann Rheum Dis 2004;63:535–543. doi: 10.1136/ard.2003.011247
To be continued …
Monday, November 28, 2011
ACR2011 and Fibromyalgia (2)
Quite a lot of posters on fibromyalgia! I’ve taken a couple of abstracts as a couple of things might be new to one or another. It’s a very private selection. I won’t advocate some of the wonderdrugs the pharma industry is eager to promote.
Here is the first study.
Nocebo in Fibromyalgia drug trials
DD Mitsikostas and colleagues were interested in the question of nocebo in fibromyalgia drug trials. “In medicine, a nocebo reaction or response refers to harmful, unpleasant, or undesirable effects a subject manifests after receiving an inert dummy drug or placebo. Nocebo responses are not chemically generated and are due only to the subject's pessimistic belief and expectation that the inert drug will produce negative consequences.” [Look up the whole article on Wikipedia: http://en.wikipedia.org/wiki/Nocebo ] The background for this meta-analysis has been poor medication adherence. The hypothesis is that treatment failure and/or increased total healthcare costs may be partly related to nocebo. “Nocebo dropouts in fibromyalgia trials were 4-fold and 2-fold higher than in RCT’s for multiple
sclerosis treatment and migraine preventive treatment, respectively.” The authors see nocebo as a serious confounding factor.
I would be more concerned about the high rate of AEs in drug studies, in the 450 mg pregabalin treated fibromyalgia patients 65% complained about dizziness alone (LJ Crofford et al., Arthritis rheum. 2005; 52: 1264-1273).
[SUN] 739
Nocebo in Fibromyalgia: Meta-Analysis of Placebo-Controlled Clinical
Trials and Implications for Practice. DD Mitsikostas1, NG Chalarakis1, LI Mantonakis1, E. Delicha2 and PP Sfikakis2.
1Naval Hospital, Athens, Greece, Athens, Greece, 2First Department of Propaedeutic and Internal Medicine, Laiko, Athens University Medical School, Greece, Athens, Greece
Conclusion: Nocebo is remarkably prevalent in fibromyalgia patients participating in RCTs probably being a serious confounding factor. Since nocebo contributes to drug intolerance and treatment failure in clinical practice, identification of predisposing factors and efforts to prevent nocebo by educating these patients appropriately seems to be important for fibromyalgia outcome.
Ankylosing Spondylitis – some shattered myths?
One should thinks with all the studies and publications, myths about ankylosing spondylitis should be shattered, but in fact these myths are still around interfering with proper diagnosis, early diagnosis, and adequate therapy. Despite suffering from inflammatory back pain it still may take years for patients to have a consultation with a rheumatologist.
Most people encounter some back during their lives. So most people orthopedic physicians see have common back pain. If the pain stays, maybe HLA B27, a genetic marker ist tested – some physicians even test HLA B27 several times – well that’s sending someone multiple times to the ophthalmologist asking if the eyes are still blue. OK, it’s a genetic marker – it won’t change. One test is enough.
Myth: if you don’t test positive for HLA B27, it cant’t be ankylosing spondylitis.
Wrong! If you test negative, it still may be ankylosing spondylitis, if you test positive for inflammatory back pain and more.
Myth: if you test positive for HLA B27, it is ankylosing spondylitis.
Wrong again! If you test positive, it still may be common back pain, if you test negative for inflammatory back pain and more.
Don’t think – that’s impossible - as it is daily reality. The point is doing a very helpful lab test (HLA B27) to strengthen your hypothesis, it might be ankylosing spondylitis, when you look at someone suffering from inflammatory back pain. Or you call for the lab to do your work, coming to a diagnosis in someone suffering from persistent non-inflammatory back pain, in which HLA B27 isn’t very helpful.
Are there hints, if it is inflammatory back pain? Yes, there are. This sort of back pain starts in the younger than 40 years, mostly in adolescents or young adults. The pain starts slowly and increases over time; whereas disc hernation of fracture have an acute onset of pain. Pain lasts longer than three months. Suffering from inflammatory back pain have an impact on sleep, most people wake up during the night, especially the second half of the night. Moving around not rest alleviates pain. And there’s morning stiffness. Localization is the very low back. So you can reach very far by simply taking an accurate history. Who said it before? Ask the patients, they have all the data, but you have to ask the right questions to get the answers you need.
Having ascertained inflammatory back pain, you still are far away from a proper diagnosis, but you can increase the likelyhood by taking more facts into account. Inflammamatory back pain has a LR (likelihood ratio) of 3.1; enthesitis has a LR of 3.4; peripheral arthritis has a LR of 4.0; dactylitis has a LR of 4.5; acute anterior uveitis has a LR of 7.3; positive family history has a LR of 6.4; good pain reduction following NSAIDs has a LR of 5.1; elevated inflammatory makers like CRP od ESR have a LR of 2.5; HLA B27 has a LR of 9.0 (here you see, at the right time it’s a very valuable parameter); MRT has a LR of 9.9 [Rudwaleit M. et al. Ann Rheum Dis 2004; 63: 535 - 543; Rudwaleit M. et al. Arthritis Rheum 2005; 52: 1000 – 1008]. If you check all these, multiply the LRs, and the product is above 200, the probability is above 90% that is ankylosing spondylitis. For chronic low back pain the probability for ankylosing spondylitis is about 5%.
To be continued …
Most people encounter some back during their lives. So most people orthopedic physicians see have common back pain. If the pain stays, maybe HLA B27, a genetic marker ist tested – some physicians even test HLA B27 several times – well that’s sending someone multiple times to the ophthalmologist asking if the eyes are still blue. OK, it’s a genetic marker – it won’t change. One test is enough.
Myth: if you don’t test positive for HLA B27, it cant’t be ankylosing spondylitis.
Wrong! If you test negative, it still may be ankylosing spondylitis, if you test positive for inflammatory back pain and more.
Myth: if you test positive for HLA B27, it is ankylosing spondylitis.
Wrong again! If you test positive, it still may be common back pain, if you test negative for inflammatory back pain and more.
Don’t think – that’s impossible - as it is daily reality. The point is doing a very helpful lab test (HLA B27) to strengthen your hypothesis, it might be ankylosing spondylitis, when you look at someone suffering from inflammatory back pain. Or you call for the lab to do your work, coming to a diagnosis in someone suffering from persistent non-inflammatory back pain, in which HLA B27 isn’t very helpful.
Are there hints, if it is inflammatory back pain? Yes, there are. This sort of back pain starts in the younger than 40 years, mostly in adolescents or young adults. The pain starts slowly and increases over time; whereas disc hernation of fracture have an acute onset of pain. Pain lasts longer than three months. Suffering from inflammatory back pain have an impact on sleep, most people wake up during the night, especially the second half of the night. Moving around not rest alleviates pain. And there’s morning stiffness. Localization is the very low back. So you can reach very far by simply taking an accurate history. Who said it before? Ask the patients, they have all the data, but you have to ask the right questions to get the answers you need.
Having ascertained inflammatory back pain, you still are far away from a proper diagnosis, but you can increase the likelyhood by taking more facts into account. Inflammamatory back pain has a LR (likelihood ratio) of 3.1; enthesitis has a LR of 3.4; peripheral arthritis has a LR of 4.0; dactylitis has a LR of 4.5; acute anterior uveitis has a LR of 7.3; positive family history has a LR of 6.4; good pain reduction following NSAIDs has a LR of 5.1; elevated inflammatory makers like CRP od ESR have a LR of 2.5; HLA B27 has a LR of 9.0 (here you see, at the right time it’s a very valuable parameter); MRT has a LR of 9.9 [Rudwaleit M. et al. Ann Rheum Dis 2004; 63: 535 - 543; Rudwaleit M. et al. Arthritis Rheum 2005; 52: 1000 – 1008]. If you check all these, multiply the LRs, and the product is above 200, the probability is above 90% that is ankylosing spondylitis. For chronic low back pain the probability for ankylosing spondylitis is about 5%.
To be continued …
Sunday, November 27, 2011
TintenFischNacht
Diese Nacht
Voller TintenFische
Die sich mit Tentakeln zwischen den Häusern festHaken
Alles Licht in ihre Münder saugen
Und wir denken an Sterne
Während wir in ihre Augen schauen
Rote Augen
Die unsere Gedanken beobachten
Die sich in uns einHaken
Nur um uns zu TintenFischen zu machen
Die den Tag zur Nacht verwandeln
Wenn alles schwarz ausgemalt sein wird
Wir werden ihn Messias nennen
Und im Schwarz der Sonne verEnden
Voller TintenFische
Die sich mit Tentakeln zwischen den Häusern festHaken
Alles Licht in ihre Münder saugen
Und wir denken an Sterne
Während wir in ihre Augen schauen
Rote Augen
Die unsere Gedanken beobachten
Die sich in uns einHaken
Nur um uns zu TintenFischen zu machen
Die den Tag zur Nacht verwandeln
Wenn alles schwarz ausgemalt sein wird
Wir werden ihn Messias nennen
Und im Schwarz der Sonne verEnden
Fallvorstellung: M. Bechterew und Therapie mit Biologikum
Ich berichte über einen Patienten mit M. Bechterew (ankylosierende Spondylitis, ICD M45.00), dem mit einem Biologikum geholfen werden konnte. Ich war selbst nach der Indikationsstellung für das Medikament skeptisch, da er bereits über 70 Jahre alt war und die Wirbelsäule und die Kreuzdarmbeingelenke schon in hohem Maße eingesteift waren.
Herr W.Z. geb. 1945
M. Bechterew (ankylosierende Spondylitis, ICD M45.00), HLA B27 positiv, seit ca. 1976 bzw. davor.
Erstvorstellung bei uns Mai 2008 mit starken Schmerzen, insbesondere beim Treppensteigen (Verkanten der Kreuzdarmbeingelenke), deutliche depressive Stimmungslage.
Aus dem damaligen Untersuchungsbefund: Halswirbelsäulen-Rotation 0° bds., Halswirbelsäulen-Seitneigung 0° bds. Schmerzen im Bereich von Halswirbelsäule und Lendenwirbelsäule. Tragus-Wand-Abstand 28,0 cm, Hinterhaupt-Wand-Abstand 21,0 cm, Kinn-Sternum-Abstand 6,0 / 7,0 cm, Atembreite 0,5 cm, Ott 30,0/30,0 cm, mod. Schober 15,0 / 17,0 cm, Domian 2,0 cm links und 2,0 cm rechts, Fingerbodenabstand 51,0 cm und Intermalleolarabstand 67,0 cm.
Der BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) betrug: 5,6.
Der BASFI (Bath Ankylosing Spondylitis Functional Index) betrug: 9,3.
Der BASMI (Bath Ankylosing Spondylitis Metrology Index) betrug: 5,0.
Therapie seither mit 300 mg Infliximab alle 8 Wochen.
Zuletzt betrugen:
der BASDAI (Bath Ankylosing Spondylitis Disease Activity Index): 0,7
der BASFI (Bath Ankylosing Spondylitis Functional Index): 3,8
der BASMI (Bath Ankylosing Spondylitis Metrology Index): 6,0
der ASDAS (Ankylosing Spondylitis Disease Activity Score): 1,39.
Aus dem neuesten Untersuchungsbefund: Halswirbelsäulen-Rotation 0-5° bds., Halswirbelsäulen-Seitneigung 0-5° bds. Tragus-Wand-Abstand 26,5 cm, Hinterhaupt-Wand-Abstand 19,0 cm, Kinn-Sternum-Abstand 6,0 / 7,0 cm, Atembreite 1,5 cm, Ott 30,0 / 30,0 cm, mod. Schober 15,0 / 19,5 cm, Domian 2,0 cm links und 2,0 cm rechts, Fingerbodenabstand 42,0 cm und Intermalleolarabstand 71,0 cm.
Das für uns Rheumatologen Faszinierende an diesem Verlauf ist das Ansprechen auch nach langer Laufzeit der Erkrankung. Auch bei einem hohen Grad an Ankylosierung kann sich der Einsatz von Biologika noch lohnen. Es wäre fatal, es diesen Patienten mit fadenscheinigen Begründungen zu verwehren. Bei dem vorgestellten Patienten hat sich eine deutliche Besserung der Lebensqualität eingestellt. Die niedergeschlagene/depressive Stimmungslage ist ohne weitere Therapiemaßnahmen nach der zweiten Infusion mit Infliximab verschwunden.
Herr W.Z. geb. 1945
M. Bechterew (ankylosierende Spondylitis, ICD M45.00), HLA B27 positiv, seit ca. 1976 bzw. davor.
Erstvorstellung bei uns Mai 2008 mit starken Schmerzen, insbesondere beim Treppensteigen (Verkanten der Kreuzdarmbeingelenke), deutliche depressive Stimmungslage.
Aus dem damaligen Untersuchungsbefund: Halswirbelsäulen-Rotation 0° bds., Halswirbelsäulen-Seitneigung 0° bds. Schmerzen im Bereich von Halswirbelsäule und Lendenwirbelsäule. Tragus-Wand-Abstand 28,0 cm, Hinterhaupt-Wand-Abstand 21,0 cm, Kinn-Sternum-Abstand 6,0 / 7,0 cm, Atembreite 0,5 cm, Ott 30,0/30,0 cm, mod. Schober 15,0 / 17,0 cm, Domian 2,0 cm links und 2,0 cm rechts, Fingerbodenabstand 51,0 cm und Intermalleolarabstand 67,0 cm.
Der BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) betrug: 5,6.
Der BASFI (Bath Ankylosing Spondylitis Functional Index) betrug: 9,3.
Der BASMI (Bath Ankylosing Spondylitis Metrology Index) betrug: 5,0.
Therapie seither mit 300 mg Infliximab alle 8 Wochen.
Zuletzt betrugen:
der BASDAI (Bath Ankylosing Spondylitis Disease Activity Index): 0,7
der BASFI (Bath Ankylosing Spondylitis Functional Index): 3,8
der BASMI (Bath Ankylosing Spondylitis Metrology Index): 6,0
der ASDAS (Ankylosing Spondylitis Disease Activity Score): 1,39.
Aus dem neuesten Untersuchungsbefund: Halswirbelsäulen-Rotation 0-5° bds., Halswirbelsäulen-Seitneigung 0-5° bds. Tragus-Wand-Abstand 26,5 cm, Hinterhaupt-Wand-Abstand 19,0 cm, Kinn-Sternum-Abstand 6,0 / 7,0 cm, Atembreite 1,5 cm, Ott 30,0 / 30,0 cm, mod. Schober 15,0 / 19,5 cm, Domian 2,0 cm links und 2,0 cm rechts, Fingerbodenabstand 42,0 cm und Intermalleolarabstand 71,0 cm.
Das für uns Rheumatologen Faszinierende an diesem Verlauf ist das Ansprechen auch nach langer Laufzeit der Erkrankung. Auch bei einem hohen Grad an Ankylosierung kann sich der Einsatz von Biologika noch lohnen. Es wäre fatal, es diesen Patienten mit fadenscheinigen Begründungen zu verwehren. Bei dem vorgestellten Patienten hat sich eine deutliche Besserung der Lebensqualität eingestellt. Die niedergeschlagene/depressive Stimmungslage ist ohne weitere Therapiemaßnahmen nach der zweiten Infusion mit Infliximab verschwunden.
Labels:
Ankylosing spondylitis (AS),
Biologics,
M. Bechterew
Friday, November 25, 2011
Des Mondes SchauerLeute
SchauerLeute hat der Mond gedungen
Sein Licht zu entladen klafterWeise
Wenn Sichel um Sichel versilbert ist
Steht Dunkelheit vor Dunkelheit
Dann ruft er wieder
SchauerLeute
Schaut her
Und sie kommen
Das nächste Viertel zu beladen
Sein Licht zu entladen klafterWeise
Wenn Sichel um Sichel versilbert ist
Steht Dunkelheit vor Dunkelheit
Dann ruft er wieder
SchauerLeute
Schaut her
Und sie kommen
Das nächste Viertel zu beladen
Drei Faltigkeit
Drei Stühle
der eine leer
der andere weggekippt
der dritte angelehnt
Drei KaffeeTassen
die eine leer
die andere umgekippt
die dritte dampft noch
Drei Faltigkeit
der eine Geist
der andere Sohn
der 3. Gott
der eine leer
der andere weggekippt
der dritte angelehnt
Drei KaffeeTassen
die eine leer
die andere umgekippt
die dritte dampft noch
Drei Faltigkeit
der eine Geist
der andere Sohn
der 3. Gott
ACR2011 and Fibromyalgia
Quite a lot of posters on fibromyalgia! I’ve taken a couple of abstracts as a couple of things might be new to one or another. It’s a very private selection. I won’t advocate some of the wonderdrugs the pharma industry is eager to promote.
Here is the first study.
Incidence and Predictors of Fibromyalgia in an Early Arthritis Cohort.
Yvonne C. Lee and colleagues analyzed data from 1198 patients in the Canadian Early Arthritis Cohort to address the question of development of fibromyalgia. Background for this have been prior findings, as the prevalence of fibromyalgia is higher in patients with rheumatoid arthritis compared to the general population (20% vs. 3%). Cumulative incidence increased from 0% at baseline to 5.9% at 12 months and 11.8% at 60 months. Female sex, depression, and poor memory were predictive of the development of fibromyalgia. Inflammatory measures were associated with a decreased risk for fibromyalgia, which may reflect physicians’ considering fibromyalgia as a diagnosis in patients with inflammatory arthritis.
[SUN] 736
Incidence and Predictors of Fibromyalgia in An Early Arthritis Cohort.
Yvonne C. Lee1, Daniel H. Solomon1, Bing Lu1, Gilles Boire2, Boulos Haraoui3, Carol A. Hitchon4, Janet E. Pope5, J. Carter Thorne6, Edward Keystone7, Diane S. Ferland8 and Vivian Bykerk9.
1Brigham and Women’s Hospital, Boston, MA, 2CHUS-Sherbrooke University, Sherbrooke, QC, 3Institut de Rhumatologie, Montreal, QC, 4University of Manitoba, Winnipeg, MB, 5St. Joseph’s Health Care, University of Western Ontario, London, ON, 6Newmarket, ON, 7Mount Sinai Hospital, Toronto, ON, 8LaSalle, QC, 9Brigham & Women’s Hospital, Boston, MA
Conclusion: The cumulative incidence of FM increased during the first 60 months after diagnosis of inflammatory arthritis, with the greatest increase occurring over the first 18 months. Although female sex, depression and poor memory were predictive of the development of FM, inflammatory measures were associated with a decreased risk for FM. These results may reflect physician decision-making processes when considering a diagnosis of FM in patients with inflammatory arthritis. Future studies are needed to better define the diagnosis of FM in patients with inflammatory arthritis and understand the role of inflammatory measures as a negative predictor of fibromyalgia.
Here is the first study.
Incidence and Predictors of Fibromyalgia in an Early Arthritis Cohort.
Yvonne C. Lee and colleagues analyzed data from 1198 patients in the Canadian Early Arthritis Cohort to address the question of development of fibromyalgia. Background for this have been prior findings, as the prevalence of fibromyalgia is higher in patients with rheumatoid arthritis compared to the general population (20% vs. 3%). Cumulative incidence increased from 0% at baseline to 5.9% at 12 months and 11.8% at 60 months. Female sex, depression, and poor memory were predictive of the development of fibromyalgia. Inflammatory measures were associated with a decreased risk for fibromyalgia, which may reflect physicians’ considering fibromyalgia as a diagnosis in patients with inflammatory arthritis.
[SUN] 736
Incidence and Predictors of Fibromyalgia in An Early Arthritis Cohort.
Yvonne C. Lee1, Daniel H. Solomon1, Bing Lu1, Gilles Boire2, Boulos Haraoui3, Carol A. Hitchon4, Janet E. Pope5, J. Carter Thorne6, Edward Keystone7, Diane S. Ferland8 and Vivian Bykerk9.
1Brigham and Women’s Hospital, Boston, MA, 2CHUS-Sherbrooke University, Sherbrooke, QC, 3Institut de Rhumatologie, Montreal, QC, 4University of Manitoba, Winnipeg, MB, 5St. Joseph’s Health Care, University of Western Ontario, London, ON, 6Newmarket, ON, 7Mount Sinai Hospital, Toronto, ON, 8LaSalle, QC, 9Brigham & Women’s Hospital, Boston, MA
Conclusion: The cumulative incidence of FM increased during the first 60 months after diagnosis of inflammatory arthritis, with the greatest increase occurring over the first 18 months. Although female sex, depression and poor memory were predictive of the development of FM, inflammatory measures were associated with a decreased risk for FM. These results may reflect physician decision-making processes when considering a diagnosis of FM in patients with inflammatory arthritis. Future studies are needed to better define the diagnosis of FM in patients with inflammatory arthritis and understand the role of inflammatory measures as a negative predictor of fibromyalgia.
Thursday, November 24, 2011
Jahre – Städte
Wie Jahre vorüberschreiten
Als Tage verkleidet
Ein jedes wie eine Stadt
Die du verläßt
Schaue noch einmal
Auf das gelbe Schild mit dem roten Streifen
Denn wisse
Du kehrst nie zurück
Wednesday, November 23, 2011
Dreimal Tod
JuteSäcke
JuteSäcke
Für die KartoffelErnte gedacht
Die ausblieb im Krieg
Wir können sie gut verwenden
Als LeichenSäcke
WiederKehr
Ich habe
Toten die Lider geschlossen
Und doch
Blickten sie mich an
Durch die Lider
Durch die Ewigkeit
Feuchte AckerFurche
Die AckerFurche war noch feucht
Vom Blut
Den Leichnam hatten sie wegGetragen
Immerhin
JuteSäcke
Für die KartoffelErnte gedacht
Die ausblieb im Krieg
Wir können sie gut verwenden
Als LeichenSäcke
WiederKehr
Ich habe
Toten die Lider geschlossen
Und doch
Blickten sie mich an
Durch die Lider
Durch die Ewigkeit
Feuchte AckerFurche
Die AckerFurche war noch feucht
Vom Blut
Den Leichnam hatten sie wegGetragen
Immerhin
In der WaldHütte
RückWärts fließt der Fluß durch die Nacht
Im Wald ruft Wind
Grau heulen Wölfe
Gedanken röten Mond
ZuckerSchnee rieselt von Tannen
Eine Spinne hängt kopfÜber
Holz knackt in kalter Luft
Die Axt hat UnGehorsam geschworen
Ich verriet sie der Wache des Tages
Mein Herz schlägt ehern
Mein Auge blickt zornLos
Der UnterGang ist spürBar
-: leise / purpurn / duftend
Im Wald ruft Wind
Grau heulen Wölfe
Gedanken röten Mond
ZuckerSchnee rieselt von Tannen
Eine Spinne hängt kopfÜber
Holz knackt in kalter Luft
Die Axt hat UnGehorsam geschworen
Ich verriet sie der Wache des Tages
Mein Herz schlägt ehern
Mein Auge blickt zornLos
Der UnterGang ist spürBar
-: leise / purpurn / duftend
Die Lusonier und ihre Sprache
Die Lusonier leben auf einer Insel, die sehr weit entfernt im Ozean liegt und sehr rund, aber nicht kreisrund ist. Es gibt Höhlen auf der Insel, in die sich die Lusonier bei Regen und in der Nacht zurückziehen. Dann tasten sie sich blind durch die Tunnels, denn Feuer oder Licht besitzen sie nicht. Die Insel ist bedeckt mit einer grünen, breitblättrigen Pflanze, die eine rote Frucht trägt. Aus den Fasern des WurzelGeflechts und der Blätter stellen sie Lusonier ihre Bekleidung her. Sie Essen die Früchte und die Blätter der Pflanze. Ansonsten tun sie nicht sehr viel. Sie spielen das Spiel, blicken auf den Ozean, der aber noch nie etwas Neues gebracht hatte, oder sie unterhalten sich.
Die lusonische Sprache, auch Lusonisch genannt, setzte sich ursprünglich nur aus fünf Wörtern zusammen.
Byörr –: ja oder nein. Zumeist „ja“, da die Lusonier ein lebensBejahendes Volk sind. ByörrByörr ist die Verstärkung, als ein kräftiges „ja“, aber auch ein „nein“, wenn ein „ja“ erwartet wird.
Kallalala –: eher weiblich, die Kunst, das Runde, Mond, das Wasser,
Shukav –: eher männlich, die Technik, das Eckige, Sonne, die Erde,
Eggening -: Tätigkeiten
Murbo -: Glaube, Liebe, Hoffnung.
Ein lusonisches Paar sitzt zusammen und blickt der untergehenden Sonne nach.
Er: Shukav Eggening Kallalala.
Sie: Byörr.
Er: Murbo Kallalala Eggening Shukav.
Sie: ByörrByörr. Murbo.
Er: Byörr.
Sie: Shukav Murbo Eggening Kallalala Shukav.
Er: Byörr. Murbo Eggening.
Sie: ByörrByörr. Murbo Shukav Eggening Murbo Kallalala.
Er: Byörr. ByörrByörr. Murbo Eggening Murbo Kallalala.
Sie: ByörrByörr. Murbo Murbo Eggening.
Er: Byörr, Murbo.
Sie: Byörr.
Kanns schon jemand übersetzen?
Tuesday, November 22, 2011
The Anti-IL17A Monoclonal Antibody Secukinumab in the Treatment of Active Ankylosing Spondylitis
At the ACR Late-breaking Poster Session Dominique Baeten and colleagues reported about the Anti-IL17A Monoclonal Antibody Secukinumab (AIN457, showed sood safety and efficacy in the treatment of active ankylosing spondylitis. 30 patients fulfilling the 1984 modified New York criteria for active AS were enrolled into this double-blind, placebo-controlled, multicenter proof-of-concept study. Secukinumab met the primary endpoint of this study with reaching higher ASAS20 responses than placebo at week 6. No early safety signal has been noticed.
[L7]
The Anti-IL17A Monoclonal Antibody Secukinumab (AIN457) Showed Good Safety and Efficacy in the Treatment of Active Ankylosing Spondylitis.
Dominique Baeten1,Joachim Sieper2,Paul Emery3,Jürgen Braun4,Désirée v.d. Heijde5,Iain McInnes6,Jacob M. van Laar7,Robert Landewé8,Paul Wordsworth9,Jürgen Wollenhaupt10,Herbert Kellner11,Jacky Paramarta1,Arthur P Bertolino12,Andrew M Wright13,Wolfgang Hueber12. 1Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands,2Medicine/Rheumatology Department, Charite Campus Benjamin Franklin, Berlin,Germany,3Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom,4Rheumazentrum Ruhrgebiet, Herne, Germany,5Rheumatology Department, Leiden University Medical Center, Leiden, The Netherlands,6Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom,7Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom,8Maastricht University Medical Center, Department of Internal Medicine/Rheumatology, Maastricht, The Netherlands,9Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford, United Kingdom,10Division of Rheumatology, Eilbeck Hospital, Hamburg, Germany,11Division of Rheumatology, Centre for Inflammatory Joint Diseases, Munich, Germany,12Novartis Institutes for BioMedical Research, Basel, Switzerland,13Novartis Pharma AG, Basel, Switzerland.
Conclusion: The primary endpoint of this study was met, as secukinumab induced significantly higher ASAS20 responses than placebo at week 6. No early safety signal was noted in this study population. Interim data presented here suggest that secukinumab may be useful for the treatment of moderate to severe active ankylosing spondylitis and thereby warrant larger long-term studies on safety and efficacy.
Labels:
ACR2011,
Ankylosing spondylitis (AS),
Secukinumab
Impact of Different Biologic Agents on the Improvement of Fatigue
Anja Strangfeld and colleagues looked into the improvement of fatigue in patients under therapy as repeorted to the German biologics register RABBIT. Fatigue significantly affects physical health and limits social live of patients with rheumatoid arthritis. TNF leads to prolonged brain activity upon nociceptive stimulation. TNF-inhibition rapidly reverses this effect without being linked primarily to anti-inflammatory effects of the drugs. Biologic agents improved fatigue significantly more frequently than conventional DMARDs.
[SUN] 461
Impact of Different Biologic Agents on the Improvement of Fatigue.
Anja Strangfeld1, Matthias Schneider2, Jörg Kaufmann3, Andreas Krause4, Angela Zink5 and Joachim Listing6.
1Deutsches Rheumaforschungszentrum, Berlin, Germany, 2Heinrich-Heine-University, Duesseldorf, Germany,
3Rheumatologist, Ludwigsfelde, Germany, 4Immanuel Krankenhaus Berlin-Buch, Berlin, Germany, 5Deutsches Rheumaforschungszentrum and Charité University Medicine, Berlin, Germany, 6German Rheumatism Research Centre, Berlin, Germany
Conclusion: Treatment with a biologic agent improved fatigue significantly more frequently than with a conventional DMARD. This finding is supported by experimental research in which Hess et al. observed that blocking TNF does not only have anti-inflammatory effects but also an impact on processes in the CNS.
[SUN] 461
Impact of Different Biologic Agents on the Improvement of Fatigue.
Anja Strangfeld1, Matthias Schneider2, Jörg Kaufmann3, Andreas Krause4, Angela Zink5 and Joachim Listing6.
1Deutsches Rheumaforschungszentrum, Berlin, Germany, 2Heinrich-Heine-University, Duesseldorf, Germany,
3Rheumatologist, Ludwigsfelde, Germany, 4Immanuel Krankenhaus Berlin-Buch, Berlin, Germany, 5Deutsches Rheumaforschungszentrum and Charité University Medicine, Berlin, Germany, 6German Rheumatism Research Centre, Berlin, Germany
Conclusion: Treatment with a biologic agent improved fatigue significantly more frequently than with a conventional DMARD. This finding is supported by experimental research in which Hess et al. observed that blocking TNF does not only have anti-inflammatory effects but also an impact on processes in the CNS.
Proof of Concept Study of ATN-103 (ozoralizumab) in Rheumatoid Arthritis
Roy Fleischmann and colleagues assessed in this multiple ascending dose / proof of concept study the safety and efficacy in subjects with active rheumatoid arthritis compared to placebo. ATN-103 (ozoralizumab), a novel TNF inhibitor, is a humanized, trivalent, bispecific Nanobody that contains 2 human TNF-binding domains linked to a human serum albumin-binding domain. Statistical significance compared to placebo for the primary endpoint was achieved by the 80 mg Q4 dose regimen only. Statistically significant improvements over placebo in secondary endpoints were achieved for 80 mg Q4 dose regimen in DAS28, ACR50, and more. The author’s didn’t see dose dependent increase in either AEs or SAEs or dose limiting toxicities.
[WED] 2630
A Multiple Ascending Dose/Proof of Concept Study of ATN-103 (ozoralizumab) in Rheumatoid Arthritis Subjects on a Background of Methotrexate.
Roy Fleischmann1, Savithree Nayiager2, Ingrid Louw3, Bernadette Rojkovich4, Caifeng Fu5, Chandrasekhar Udata6, Parvin Fardipour7, Bonnie Marshall7, Michelle Hinz7, Amarnath Sharma7, Kathy Shields7 and Gail Comer7.
1Metroplex Clinical Research Center, Dallas, TX, 2St. Augustine Hospital, Berea, KwaZulu-Natal, South Africa, 3Panorama Medical Centre, Panorama, Western Cape, South Africa, 4Polyclinic of the Hospitaller Brothers of St John of God, Budapest, Hungary, 5Pfizer, Cambridge, MA, 6Pfizer, La Jolla, CA, 7Pfizer, Collegeville, PA
Conclusion: The 80 mg Q4wk group was significantly better than PBO at week 16 in ACR20, ACR50, DAS28, HAQ-DI and other secondary endpoints. There was no dose dependent increase in either Aes or SAEs or dose limiting toxicities. Exposure to ATN-103 increased in a dose-proportional manner.
Fostamatinib
New data from the EULAR 2013 at: http://rheumatologe.blogspot.de/2013/06/fostamatinib-at-eular-2013.html
Fostamatinib is an oral spleen tyrosine kinase inhibitor, but there hadn’t been as much new data as there had been on Tofacitinib during the 2011 ACR Meeting in Chicago. There are ongoing phase 3 studies, but we have to wait for next year’s EULAR and ACR meetings for results that might lead to marketing and availability.
Effects Fostamatinib on Health-Related Quality of Life in Active Rheumatoid Arthritis
Michael E. Weinblatt and colleagues looked into effects of the oral SYK inhibitor, Fostamatinib, in patients with rheumatoid arthritis, who failed to respond to methotrexate The analysis of this phase II study assessed the impact of fostamatinib on health-related quality of life. Fostamatinib significantly improved health-related quality of life outcomes including physical function, pain, fatigue, and overall physical health status.
[SUN] 420
Effects of the Oral SYK Inhibitor, Fostamatinib (R788), on Health-Related Quality of Life in a Phase II Study of Active Rheumatoid Arthritis.
Michael E. Weinblatt1, Arthur Kavanaugh2, Mark C. Genovese3, David A. Jones4, Theresa K. Musser5, Elliott B. Grossbard5 and Daniel B. Magilavy5.
1Brigham and Women’s Hospital, Boston, MA, 2University of California San Diego, San Diego, CA, 3Stanford University, Palo Alto, CA, 4AstraZeneca, Macclesfield, United Kingdom, 5Rigel Pharmaceuticals, South San Francisco, CAConclusion: In this phase II study, 100 mg bid fostamatinib significantly improved HRQL outcomes including physical function, pain, fatigue, and overall physical health status. Phase III clinical trials of fostamatinib in RA are in progress.
Safety of Fostamatinib (R788) in Patients with Rheumatoid Arthritis From up to 2 Years of Exposure
Arthur Kavanaugh and colleagues presented data on longer-term safety and tolerability for fostamatinib. Data came from randomized, placebo-controlled, fostamatinib phase II trials (TASKi1, 2, and 3), the TASKi1 extension study and from an ongoing open-label study (C-935788-012). Thie analysis included 803 patients with 1,038 patien-years of fostamatinib exposure (mean exposure 1.3 years).
[WED] 2594
Longer-Term Safety of Fostamatinib (R788) in Patients with Rheumatoid Arthritis—Analysis of Clinical Trial Data From up to 2 Years of Exposure.
Arthur Kavanaugh1, Michael E. Weinblatt2, Mark C. Genovese3, Theresa K. Musser4, Elliott B. Grossbard4, Daniel B. Magilavy4, Sally Hollis5, Eveline Wesby van-Sway5 and David Millson5.
1University of California San Diego, San Diego, CA, 2Brigham and Women’s Hospital, Boston, MA, 3Stanford University, Palo Alto, CA, 4Rigel Pharmaceuticals, South San Francisco, CA, 5AstraZeneca, Macclesfield, United KingdomConclusion: No new significant safety signals were identified with longer-term dosing of fostamatinib. Biologic refractory patients on a background of mixed DMARDs had a higher incidence rate of AEs, SAEs, and SIEs compared to MTX inadequate responders on background MTX; further confounding factors may play a role. This will be explored in ongoing phase III studies.
Sunday, November 20, 2011
Graves of the Kings
You will be shown some graves of former kings. While the grave and surroundings of King Tongmyong, founder of the Koguryo dynasty, in Ryongsanri, together with the Jongnung Temple produce an atmosphere of serenity and tranquillity, the stilted, pyramid construction of King Tangun’s Mausoleum does the opposite. It is very clear that history is constructed here. Everything is new. Well, lets face it, most of the graves are recent constructions on old graves. On every site you are told, that the “Japanese aggressors” robbed the corpses.
Korean Art Gallery
Most probably you will be shown the Central History Museum (left side of the picture) and not the Korean Art Gallery (right side of the picture). In the history museum one tries to prove the long Korean history from primitive society to modern age. So the art gallery is little bit more normal, if you compare it with museums elsewhere in the world. There are interesting paintings and calligraphy among other exhibits. Sorry, no photography inside.
An Oral S1P Lyase Inhibitor [LX3305 (LX2931)] has been studied in a Phase 2 Trial in Patients with Active Rheumatoid Arthritis
Roy M. Fleischmann and colleagues studied LX3305 (LX2931), an oral S1P lyase inhibitor in patients with active rheumatoid arthritis on stable methotrexate therapy. Sphingosine-1-phosphate (S1P) is a lipid metabolite affecting lymphocyte trafficking and signal transduction pathways. Preclinical studies already showed that the inflammatory response in models of rheumatoid arthritis could be reduced by S1PL activity reduction. The safety, tolerability, and efficacy of LX3305 were evaluated in a multicenter, multinational, randomized, double-blind, placebo-controlled phase 2 trial in patients with active rheumatoid arthritis and an inadequate response to stable doses of methotrexate. LX3305, at 150 mg po QD for 12 weeks, showed a potential clinical benefit in patients with active rheumatoid despite stable-dose methotrexate therapy; but this was only shown n a post-hoc analysis. The results of this study suggest that inhibition of S1PL by LX3305 represents a new mechanism for immune modulation.
[WED] 2593
The Oral S1P Lyase Inhibitor LX3305 (LX2931) Demonstrates Favorable Safety and Potential Clinical Benefit at 12-Weeks in a Phase 2 Proof-of-Concept Trial in Patients with Active Rheumatoid Arthritis on Stable Methotrexate Therapy.
Roy M. Fleischmann1, Jeffrey E. Poiley2, Rumen Stoilov3, Vibeke Strand4, Joel Freiman5, Tamas Oravecz5, Arthur Sands5, Brian Zambrowicz5 and Lexicon Pharmaceuticals RA Clinical Development6.
1University of Texas Southwestern Medical Center and Metroplex Clinical Research Center, Dallas, TX, 2Arthritis Associates, Orlando, FL, 3University Multiprofile Hospital for Active Treatment (UMHAT) St. Ivan Rilski EAD, Sofia, Bulgaria, 4Stanford University, Palo Alto, CA, 5Lexicon Pharmaceuticals, Inc., The Woodlands, TX, 6The +Woodlands, TX
Conclusion: LX3305, at 150 mg po QD for 12 weeks, produced a favorable safety profile and a potential clinical benefit in patients with active RA despite stable-dose methotrexate therapy. These results suggest that inhibition of S1PL by LX3305 represents a new mechanism for immune modulation, and supports further clinical development of LX3305 as a small molecule therapy for rheumatoid arthritis.
[WED] 2593
The Oral S1P Lyase Inhibitor LX3305 (LX2931) Demonstrates Favorable Safety and Potential Clinical Benefit at 12-Weeks in a Phase 2 Proof-of-Concept Trial in Patients with Active Rheumatoid Arthritis on Stable Methotrexate Therapy.
Roy M. Fleischmann1, Jeffrey E. Poiley2, Rumen Stoilov3, Vibeke Strand4, Joel Freiman5, Tamas Oravecz5, Arthur Sands5, Brian Zambrowicz5 and Lexicon Pharmaceuticals RA Clinical Development6.
1University of Texas Southwestern Medical Center and Metroplex Clinical Research Center, Dallas, TX, 2Arthritis Associates, Orlando, FL, 3University Multiprofile Hospital for Active Treatment (UMHAT) St. Ivan Rilski EAD, Sofia, Bulgaria, 4Stanford University, Palo Alto, CA, 5Lexicon Pharmaceuticals, Inc., The Woodlands, TX, 6The +Woodlands, TX
Conclusion: LX3305, at 150 mg po QD for 12 weeks, produced a favorable safety profile and a potential clinical benefit in patients with active RA despite stable-dose methotrexate therapy. These results suggest that inhibition of S1PL by LX3305 represents a new mechanism for immune modulation, and supports further clinical development of LX3305 as a small molecule therapy for rheumatoid arthritis.
LY2439821, An Anti-IL-17 Monoclonal Antibody, has been studied in Patients with Rheumatoid Arthritis in A Phase 2 Study
Mark C. Genovese and colleagues compared multiple subcutaneous doses of LY2439821 (3, 10, 30, 80, or 180 mg), an anti-IL-17 monoclonal antibody, in patients with rheumatoid arthritis in two populations: naȉve to biologic therapy or inadequate responders to tumor necrosis factor alpha inhibitors for the improvement of signs and symptoms of rheumatoid arthritis. The DAS28-CRP LSMEAN change from baseline showed a significant change even at the lowest level of LY2439821 tested (3 mg). The author saw an improvement of signs and symptoms of rheumatoid arthritis compared to placebo with a rapid onset of action.
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A Phase 2 Study of Multiple Subcutaneous Doses of LY2439821, An Anti-IL-17 Monoclonal Antibody, in Patients with Rheumatoid Arthritis in Two Populations: Naȉve to Biologic Therapy or Inadequate Responders to Tumor Necrosis Factor Alpha Inhibitors.
Mark C. Genovese1, Maria W. Greenwald2, Chul Soo Cho3, Alberto Berman4, Ling Jin5, Gregory Cameron6, Li Xie5, Daniel Braun5, Subhashis Banerjee5 and Laura Warner7.
1Stanford University, Palo Alto, CA, 2Desert Medical Advances, Palm Desert, CA, 3St Marys Hospital, Seoul, 4Hospital Padilla, Tucuman, Argentina, 5Eli Lilly and Company, Indianapolis, IN, 6Eli Lily and Company, Indianapolis, IN, 7i3 Statprobe, Indianapolis, INConclusion: LY significantly improved signs and symptoms of RA compared to PB with a rapid onset of action and a safety profile comparable to other biologic therapies with no unexpected safety concerns.
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A Phase 2 Study of Multiple Subcutaneous Doses of LY2439821, An Anti-IL-17 Monoclonal Antibody, in Patients with Rheumatoid Arthritis in Two Populations: Naȉve to Biologic Therapy or Inadequate Responders to Tumor Necrosis Factor Alpha Inhibitors.
Mark C. Genovese1, Maria W. Greenwald2, Chul Soo Cho3, Alberto Berman4, Ling Jin5, Gregory Cameron6, Li Xie5, Daniel Braun5, Subhashis Banerjee5 and Laura Warner7.
1Stanford University, Palo Alto, CA, 2Desert Medical Advances, Palm Desert, CA, 3St Marys Hospital, Seoul, 4Hospital Padilla, Tucuman, Argentina, 5Eli Lilly and Company, Indianapolis, IN, 6Eli Lily and Company, Indianapolis, IN, 7i3 Statprobe, Indianapolis, INConclusion: LY significantly improved signs and symptoms of RA compared to PB with a rapid onset of action and a safety profile comparable to other biologic therapies with no unexpected safety concerns.
Tofacitinib - An Oral Janus Kinase Inhibitor
Tofacitinib (CP-690,550) is an oral Janus Kinase Inhibitor. While biologics interfere with intercellular communication, the new small molecules interfere with intracellular communication.
Tofacitinib in Patients with Active Rheumatoid Arthritis: A 12-Week Phase 2b Study
Y. Tanaka and colleagues compared efficacy, safety, and tolerability of 5 doses of tofacitinib monotherapy vs placebo for treatment of rheumatoid arthritis in Japanese pts with inadequate response to DMARDs. The primary endpoint, however, has been ACR20 response rate at week 12 . All tofacitinib doses were superior compared with placebo and a clear dose-response has been observed. ACR50 and ACR70 response rates also showed a dose-response at Wk 12. The most common adverse events were nasopharyngitis, hyperlipidemia, and increased LDL; these were reported to be mild in severity.
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Tofacitinib (CP-690,550), An Oral Janus Kinase Inhibitor, As Monotherapy in Japanese Patients with Active Rheumatoid Arthritis: A 12-Week Phase 2b Study.
Y. Tanaka1, T. Takeuchi2, H. Yamanaka3, M. Suzuki4, H. Nakamura4, S. Toyoizumi4, J. D. Bradley5 and S. H. Zwillich5. 1University of Occupational & Environmental Health, Kitakyushu, Fukuoka, Japan, 2Keio University School of Medicine, Tokyo, Japan, 3Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan, 4Pfizer Inc., Tokyo, Japan, 5Pfizer Inc., Groton, CT
Conclusion: When used as monotherapy, tofacitinib dosed 1 mg BID demonstrated superior ACR20 response rates compared with placebo at week 12. Doses of tofacitinib 5, 10, and 15 mg BID demonstrated superiority to placebo in DAS28-4(ESR) 2.6. The safety profile of tofacitinib monotherapy was manageable in Japanese patients with longstanding active rheumatoid arthritis.
Tofacitinib in Combination with Methotrexate Reduced the Progression of Structural Damage in Patients with Rheumatoid Arthritis: a 24-Month Phase 3 Study
Désirée van der Heijde and colleagues compared efficacy, reduction of structural damage progression, and safety of tofacitinib vs placebo in pts with active rheumatoid arthtitis with inadequate response to methotrexate (MTX). Tofacitinib significantly reduced progression of structural damage vs placebo in patients with active rheumatoid arthtitis on methotrexate.
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Tofacitinib (CP-690,550), An Oral Janus Kinase Inhibitor, in Combination with Methotrexate Reduced the Progression of Structural Damage in Patients with Rheumatoid Arthritis: a 24-Month Phase 3 Study.
Désirée van der Heijde1, Y. Tanaka2, Roy Fleischmann3, Edward C. Keystone4, et al.
1Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 2University of Occupational & Environmental Health, Kitakyushu, Fukuoka, Japan, 3University of Texas Southwestern Medical Center, etc.
Conclusion: In this P3 study, tofacitinib significantly reduced progression of structural damage vs PBO in pts with active RA on MTX. Consistent with other studies, tofacitinib demonstrated significant and clinically meaningful reductions in signs and symptoms of RA and physical function. No new safety signals were detected.
Tofacitinib in Combination with Traditional Disease-Modifying Anti-Rheumatic Drugs: Phase 3 Study
V. Strand and colleagues compared efficacy and safety of tofacitinib vs placebo in pts with active rheumatoid arthritis with an inadequate response to one DMARD (traditional or biologic). The study showed statistically significant and clinically meaningful improvements in multiple patient-reported outcomes vs placebo at month 3.
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Tofacitinib (CP-690,550) in Combination with Traditional Disease-Modifying Anti-Rheumatic Drugs: Phase 3 Study Patient-Reported Outcomes in Patients with Active Rheumatoid Arthritis and An Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs.
V. Strand1, J. M. Kremer2, Z. G. Li3, S. Hall4, Roy M. Fleischmann5, M. C. Genovese6, et al.
1Stanford University, Palo Alto, CA, 2Albany Medical College and The Center for Rheumatology, Albany, NY, 3Peking University People’s Hospital, etc.
Conclusion: In this Phase 3 study of tofacitinib in combination with traditional DMARDs, treatment with 5 and 10 mg BID resulted in consistent statistically significant and clinically meaningful improvements in multiple patient-reported outcomes vs placebo at month 3.
Tofacitinib in the Treatment of Rheumatoid Arthritis: Open-Label, Long-Term Extension Studies up to 36 Months
J. Wollenhaupt and colleagues reported the safety and tolerability of tofacitinib and the durability of clinical response up to 36 months in long-term extension studies in patients with active rheumatoid arthritis. A total of 3227 patients were treated for a total duration of 3118 patient-years. Tofacitinib demonstrated a well-tolerated safety profile and sustained long-term efficacy over a period of 36 months.
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Tofacitinib (CP-690,550), An Oral Janus Kinase Inhibitor, in the Treatment of Rheumatoid Arthritis: Open-Label, Long-Term Extension Studies up to 36 Months.
J. Wollenhaupt1, J. C Silverfield2, E. B. Lee3, S. Wood4, K. Soma5, L. Wang5, H. Nakamura6, Y. Komuro6, C. I. Nduaka5, D. Gruben5, S. H. Zwillich5 and J. D. Bradley5.
1Teaching Hospital of the University of Hamburg, Hamburg, Germany, 2Tampa Medical Group, P.A., Tampa, FL, 3Hanyang University Hospital, Seoul, 4Pfizer Inc., Groton, NJ, 5Pfizer Inc., Groton, CT, 6Pfizer Inc., Tokyo, Japan
Conclusion: Treatment with tofacitinib at doses of 5 or 10 mg BID in pts with RA demonstrated a well-tolerated safety profile and sustained long-term efficacy over a 36-mo period.
Tofacitinib (CP-690,550), An Oral Janus Kinase Inhibitor, or Adalimumab Versus Placebo in Patients with Rheumatoid Arthritis on Background Methotrexate: A Phase 3 Study
R.F. van Vollenhoven and colleagues compared the efficacy and safety of tofacitinib and an active comparator, adalimumab, vs placebo in patients with active rheumatoid arthritis with inadequate response to methotrexate. Efficacy of tofacitinib and Adalimumab were similar, when given on methotreaxate background.
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Tofacitinib (CP-690,550), An Oral Janus Kinase Inhibitor, or Adalimumab Versus Placebo in Patients with Rheumatoid Arthritis on Background Methotrexate: A Phase 3 Study.
R.F. van Vollenhoven1, R. M. Fleischmann2, S. B. Cohen3, E. B. Lee4, G. Meijide5, S. Wagner6, S. Forejtova7, S. H. Zwillich8, D. Gruben8, T. Koncz9, G. Wallenstein8, S. Krishnaswami8, J. D. Bradley8, B. Wilkinson8 and the ORAL Standard investigators10.
1Karolinska Institute, Stockholm, Sweden, 2Metroplex Clinical Research Center, Dallas, TX, 3Metroplex Clinical Research
Conclusion: Tofacitinib demonstrated rapid, significant, and clinically meaningful reductions in signs and symptoms of RA and physical function. No new tofacitinib safety signals were detected. Efficacy results with tofacitinib and ADA, when both were given on MTX background, were similar.
Tofacitinib: Analysis of Infections and All-Cause Mortality Across Phase 3 and Long-Term Extension Studies in Patients with Rheumatoid Arthritis
S. Cohen and colleagues showed data on infection and mortality for patients with rheumatoid arthritis, pooled from P3 and long-term extension studies. The safety profile of tofacitinib was consistent with the previous experience and no new safety signals were observed.
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Tofacitinib (CP-690,550), An Oral Janus Kinase Inhibitor: Analysis of Infections and All-Cause Mortality Across Phase 3 and Long-Term Extension Studies in Patients with Rheumatoid Arthritis.
S. Cohen1, S. C. Radominski2, P. Asavatanabodee3, S. P. Wood4, K. Soma4, C. I. Nduaka4, L. Wang4, D. Gruben4, H. Valdez5, S. H. Zwillich4 and J. Bradley4.
1Metroplex Clinical Research Centre, Dallas, TX, 2Universidade Federal do Paraná, Curitiba, Brazil, 3Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand, 4Pfizer Inc., Groton, CT, 5Pfizer Inc., New York, NY
Conclusion: In P3 and LTE studies, mortality rates were consistent with the expected rate in pts with active RA, including those receiving therapy with other DMARDs. The safety profile of tofacitinib with regard to infection AEs was consistent with the previously reported P2 experience and no new safety signals were observed.
Saturday, November 19, 2011
Learned Helplessness as a Predictor of Change in Functional Disability in
An interesting study on functional disability has been conducted by Elizabeth M. Camacho and colleagues. Learned helplessness may manifest in patients with inflammatory polyarthritis, when they feel to out of control, and as a result they may stop helping themselves, be non-compliant with their medication for instance. And this may have an impact on outcome like functional disability. The authors show that learned helplessness predicted change in disability. Therefore it is worth while to work on this risk factor in patients with inflammatory polyarthritis for a better disease outcome.
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Learned Helplessness Predicts 2-Year Change in Functional Disability in
Patients with Inflammatory Polyarthritis.
Elizabeth M. Camacho1, Suzanne Verstappen1, Diane K. Bunn2 and Deborah DPM Symmons1.
1University of Manchester, Manchester, United Kingdom, 2University of East
Anglia, Norwich, United Kingdom
Conclusion: Learned helplessness predicted change in disability. For the majority of people learned helplessness changed over 2 years, and hence it should be regarded as a modifiable risk factor for disease outcome in inflammatory polyarthritis.
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Learned Helplessness Predicts 2-Year Change in Functional Disability in
Patients with Inflammatory Polyarthritis.
Elizabeth M. Camacho1, Suzanne Verstappen1, Diane K. Bunn2 and Deborah DPM Symmons1.
1University of Manchester, Manchester, United Kingdom, 2University of East
Anglia, Norwich, United Kingdom
Conclusion: Learned helplessness predicted change in disability. For the majority of people learned helplessness changed over 2 years, and hence it should be regarded as a modifiable risk factor for disease outcome in inflammatory polyarthritis.
The RADAI (Rheumatoid Arthritis Disease Activity Index) Can Be Informative in Patients with Rheumatic Diseases Other Than Rheumatoid Arthritis
Self-reports of patients’ complaints are a useful tool, but you need lots of different paper and in clinical practice soon the set of instruments is too large to handle. So this study is very interesting as it shows, that you can get useful data with just one tool in patients with very different diseases including systemic lupus erythematosus, gout, psoriatic arthritis, and osteoarthritis as well as rheumatoid arthritis, of course. The instrument is easy to use and is independent of ESR or CRP, so one can use it, if these parameters aren’t available; e.g. patient calls from a vacation trip.
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A Self-Report RADAI (Rheumatoid Arthritis Disease Activity Index) Count of Painful Joints Can Be Informative in Patients with Rheumatic Diseases Other Than Rheumatoid Arthritis.
Isabel Castrejo´n1, Yusuf Yazici2 and Theodore Pincus1. 1NYU Hospital for Joint Diseases, New York, NY, 2Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, NY
Conclusion: A self-report joint count derived from the RADAI can be informative in patients with many rheumatic diagnoses, including SLE, gout, psoriatic arthritis and OA, in addition to RA.
[TUE] 2053
A Self-Report RADAI (Rheumatoid Arthritis Disease Activity Index) Count of Painful Joints Can Be Informative in Patients with Rheumatic Diseases Other Than Rheumatoid Arthritis.
Isabel Castrejo´n1, Yusuf Yazici2 and Theodore Pincus1. 1NYU Hospital for Joint Diseases, New York, NY, 2Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, NY
Conclusion: A self-report joint count derived from the RADAI can be informative in patients with many rheumatic diagnoses, including SLE, gout, psoriatic arthritis and OA, in addition to RA.
Duloxetine 30 mg once daily not effective in Patients with Fibromyalgia
Lesley M. Arnold and colleagues were interested in the question, whether duloxetine 30 mg QD dose in adult patients with fibromyalgia with or without major depressive disorder was effective in statistically significant pain reduction. The background lies in previous fibromyalgia trials, which showed a reduction of pain in one week trials at a dosage of 30 mg daily. 30 mg duloxetine daily did not reduce pain significantly compared to placebo. Though there “were no new safety issues identified”, which wasn’t to be expected as other studies with higher a dosage had been done already, but verum-treated patients had at least twice the incidence of nausea, dry mouth, somnolence, and insomnia.
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A Randomized, Double-Blind Comparison of Duloxetine 30 Mg Once Daily (QD) and Placebo in Adult Patients with Fibromyalgia.
Lesley M. Arnold1, Shuyu Zhang2 and Beth Pangallo3. 1University of Cincinnati College of Medicine, Cincinnati, OH, 2Eli Lilly and Company, Indianapolis, IN, 3ELi Lilly and Company, Indianapolis, IN
Conclusion: The primary result of the study did not demonstrate the
analgesic effect of the duloxetine 30 mg QD in the treatment of fibromyalgia with or without MDD. Duloxetine 30 mg QD was generally well tolerated, and there were no new safety issues identified.
[TUE] 1916
A Randomized, Double-Blind Comparison of Duloxetine 30 Mg Once Daily (QD) and Placebo in Adult Patients with Fibromyalgia.
Lesley M. Arnold1, Shuyu Zhang2 and Beth Pangallo3. 1University of Cincinnati College of Medicine, Cincinnati, OH, 2Eli Lilly and Company, Indianapolis, IN, 3ELi Lilly and Company, Indianapolis, IN
Conclusion: The primary result of the study did not demonstrate the
analgesic effect of the duloxetine 30 mg QD in the treatment of fibromyalgia with or without MDD. Duloxetine 30 mg QD was generally well tolerated, and there were no new safety issues identified.
Friday, November 18, 2011
Secukinumab to treat Rheumatoid Arthritis –A Phase II Trial
Secukinumab is an Anti-Interleukin 17A Monoclonal Antibody.
A phase II trial on efficacy and safety of secukinumab reported by Marc C. Genovese et al. didn’t achieve the primary efficacy endpoint after one year. Still too early to quit secukinumab, as this is due to an increase in ACR20 response in the placebo group between weeks 12 and 16; ACR20 in the secukinumab 75mg group was achieved in 47%, in the 150 mg group also in 47%, and in the 300 mg group in 54%, with placebo achieving ACR20 response in 36%, so the verum groups achieved higher precentages of ACR20 but did not reach statistical significance. We’ll have to wait a little while longer to have this worked out and will probably see more during the next meetings either at #EULAR12 in Berlin or at #ACR2012 in Washington.
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One Year Efficacy and Safety Results of a Phase II Trial of Secukinumab in Patients with Rheumatoid Arthritis.
Mark C. Genovese1, Patrick Durez2, Hanno B. Richards3, Jerzy Supronik4, Eva Dokoupilova5, Jacob A. Aelion6, Sang-Heon Lee7, Christine E. Codding8, Herbert Kellner9, Takashi Ikawa10, Sophie Hugot3, Gregory Ligozio11 and Shephard Mpofu3.
1Stanford University, Palo Alto, CA, 2Cliniques Universitaires Saint-Luc, Universite´ Catholique de Louvain, Brussels, Belgium, 3Novartis Pharma AG, Basel, Switzerland, 4NZOZ Centrum Medyczne Artur Racewicz, Bialystok, Poland, 5Medical Plus s.r.o, Uherske Hradiste, Czech Republic, 6Arthritis Clinic, Jackson, TN, 7Konkuk University Medical Center, Seoul, South Korea, 8Health Research of Oklahoma, Oklahoma City, OK, 9Centre for Inflammatory Joint Diseases, Munich, Germany, 10Kobe–Konan Yamate Clinic, Kobe, Japan, 11Novartis Pharmaceuticals Corporation, East Hanover, NJ
Conclusion: The primary efficacy endpoint was not achieved in this trial possibly due to an unexplained increase in ACR20 in the placebo group between weeks 12 (24%) and 16 (36%). However, ACR20-responders at Week 16 experienced maintenance or improvement of efficacy through Week 52 with highest efficacy in patients who remained on 150mg throughout the trial. Patients on secukinumab who were non-responders at Week 16 did not gain much additional efficacy benefit after dose escalation. Secukinumab was well tolerated and the rate and frequency of AEs remained stable over time without unexpected safety findings.
Fibromyalgia and Depression
There’s a nice study by Robert S. Katz et al. from 1Rush University Medical Center addressing the question whether depression or alcoholism in parents is associated with an increased risk to develop fibromyalgia (FMS) in offspring. And the answer is no for alcoholism, and yes for paternal and maternal depression. Interesting is that FMS patients were significantly more likely than control patients to report fibromyalgia (diagnosis or symptoms) in their mothers, but not in their fathers.
[TUE] 1900
Fibromyalgia and Parental Medical Histories of Depression and Alcoholism.
Robert S. Katz1, Ben J. Small2, Sharon M. Ferbert3, Patricia Kuenzi1 and Susan Shott1. 1Rush University Medical Center, Chicago, IL, 2Rush University Medical School, Chicago, IL, 3Advocates for Funding Fibromyalgia Treatment, Education and Research(AFFTER), Libertyville, IL
Conclusion: FMS patients were significantly more likely than control patients to report that their parents had a diagnosis or symptoms of depression, and significantly more likely to report that their mothers had a FMS diagnosis or symptoms. No statistically significant differences were found with respect to paternal FMS or maternal or paternal alcoholism.
[TUE] 1900
Fibromyalgia and Parental Medical Histories of Depression and Alcoholism.
Robert S. Katz1, Ben J. Small2, Sharon M. Ferbert3, Patricia Kuenzi1 and Susan Shott1. 1Rush University Medical Center, Chicago, IL, 2Rush University Medical School, Chicago, IL, 3Advocates for Funding Fibromyalgia Treatment, Education and Research(AFFTER), Libertyville, IL
Conclusion: FMS patients were significantly more likely than control patients to report that their parents had a diagnosis or symptoms of depression, and significantly more likely to report that their mothers had a FMS diagnosis or symptoms. No statistically significant differences were found with respect to paternal FMS or maternal or paternal alcoholism.
Wednesday, November 16, 2011
Fibromyalgia and Smoking
Concerning fibromyalgia and smoking there has been an interesting poster at the 2011 ACR Meeting in Chicago. The poster has been on display on Tuesday, the 8th of November. Jenna Goesling and colleagues looked into smoking and fibromyalgia. They found higher rates of smoking in patients with fibromyalgia than in patients not suffering from fibromyalgia. My interpretation is that smoking is used by patients to alleviate pain but leads to the opposite; same as for stress, which serves patients not to think of pain on a short term basis, but which enhance pain in the long run. And smoking was “associated with greater pain, more interference, anxiety, and depression.” We are already used to tell our patients to stop smoking, but now we have a sound scientific basis to do so.
Here is a part of the abstract of the mentioned poster shown at the 2011 ACR Meeting in Chicago:
1912
Smoking and Fibromyalgia: The Need for a Multidisciplinary Approach to Treatment.
Jenna Goesling1, Chad M. Brummett1, Kevin Rakovitis1, Daniel J. Clauw2 and Afton L. Hassett3. 1University of Michigan Health System, Ann Arbor, MI, 2University of Michigan, Ann Arbor, MI, 3University of Michigan Medical School, Ann Arbor, MI
Conclusion: Smoking rates were higher among patients who met survey criteria for FM compared to patient’s who did not meet FM criteria. When comparing only patients who met FM criteria, smoking was associated with greater pain, more interference, anxiety, and depression. These results suggest that smokers who met survey criteria for FM have several comorbid factors that likely interfere with functioning. In conclusion, a multidisciplinary approach to treatment of chronic pain among current smokers, especially in patients who meet FM criteria, should include both cessation advice and treatment for co-occurring mood disorders. It follows that further consideration of the complex relation between smoking, mood and pain may help inform treatment decisions and interventions among patients who meet survey criteria for FM. Future studies will focus on differences in post-treatment outcomes between smokers and non-smokers who meet FM criteria.
Here is a part of the abstract of the mentioned poster shown at the 2011 ACR Meeting in Chicago:
1912
Smoking and Fibromyalgia: The Need for a Multidisciplinary Approach to Treatment.
Jenna Goesling1, Chad M. Brummett1, Kevin Rakovitis1, Daniel J. Clauw2 and Afton L. Hassett3. 1University of Michigan Health System, Ann Arbor, MI, 2University of Michigan, Ann Arbor, MI, 3University of Michigan Medical School, Ann Arbor, MI
Conclusion: Smoking rates were higher among patients who met survey criteria for FM compared to patient’s who did not meet FM criteria. When comparing only patients who met FM criteria, smoking was associated with greater pain, more interference, anxiety, and depression. These results suggest that smokers who met survey criteria for FM have several comorbid factors that likely interfere with functioning. In conclusion, a multidisciplinary approach to treatment of chronic pain among current smokers, especially in patients who meet FM criteria, should include both cessation advice and treatment for co-occurring mood disorders. It follows that further consideration of the complex relation between smoking, mood and pain may help inform treatment decisions and interventions among patients who meet survey criteria for FM. Future studies will focus on differences in post-treatment outcomes between smokers and non-smokers who meet FM criteria.
Monday, November 14, 2011
Eminent family members of the Kim
The reverence to members of the Kim family and the Juche ideology have traits of a religion. The personal cult around President Kim Il Sung has been extended also to his son, his grandson, his wife, and other memmers of the family Kim.
Kim Il Sung is spoken of as the Great Leader. His son Kim Jong Il bears the honorific title of Dear Leader. Kim Jong Un has left the titles Brilliant Comrade and Young Dear Generalbehind and is addressed nowadays as the Great Successor.
Places, where Kim Il Sung stayed become something like pilgrimage locations. He is the Eternal President of the DPRK. His birthplace is visited daily by thousands. You will be able to see, where he sat on a certain train or the chair on which he sat is part of an exhibition. Preservation of things connected with Kim Il Song are “for the eternal life of President Kim”. Any place you visit, you will be told when or how often the Great or the Dear Leader have visited it.
Reverence to Kim Jong Suk (mother of Kim Jong Il) takes its route towards Virgin Mary worship. It is located on top of the Revolutionary Martyrs’ Cemetary.
People in North Korea know far less about the Kim family and sheer selfpreservation might lead to not asking questions. You might end up in an education/forced labour camp. “The North Korean elite is also obsessed with secrecy” (Lonely Planet). Who knows about the stroke of Kim Jong Il, who of the death of his wife (cancer)?
People wear a batch with a picture of the Great Leader on the left breast (above the heart). And … there are no jokes about the Kims.
Kim Il Sung is spoken of as the Great Leader. His son Kim Jong Il bears the honorific title of Dear Leader. Kim Jong Un has left the titles Brilliant Comrade and Young Dear Generalbehind and is addressed nowadays as the Great Successor.
Places, where Kim Il Sung stayed become something like pilgrimage locations. He is the Eternal President of the DPRK. His birthplace is visited daily by thousands. You will be able to see, where he sat on a certain train or the chair on which he sat is part of an exhibition. Preservation of things connected with Kim Il Song are “for the eternal life of President Kim”. Any place you visit, you will be told when or how often the Great or the Dear Leader have visited it.
Reverence to Kim Jong Suk (mother of Kim Jong Il) takes its route towards Virgin Mary worship. It is located on top of the Revolutionary Martyrs’ Cemetary.
People in North Korea know far less about the Kim family and sheer selfpreservation might lead to not asking questions. You might end up in an education/forced labour camp. “The North Korean elite is also obsessed with secrecy” (Lonely Planet). Who knows about the stroke of Kim Jong Il, who of the death of his wife (cancer)?
People wear a batch with a picture of the Great Leader on the left breast (above the heart). And … there are no jokes about the Kims.
Pyongyang Metro
The Pyongyang Metro has two lines. Traffic isn’t as busy as one might expect. The Metro runs 150 m below surface, which makes it one of the deepest undergrounds. The reason is clear, the depth makes it a good nuclear shelter. Going down and up takes considerable time, so people ofter sit on the stairs of the escalators. The stations below resemble the Moscow Metro.
Skyscrapers in North Korea and Chicago
As I have recently been to Chicago, where the first skyscrapers had been build, I am now able to compare these. There are some buildings that resemble the West, like the Pyongyang Koryo Hotel or the Yanggakdo Hotel; and there you see one essential point, these have been build to be used by foreigners. An ambitious project has been the Ryugyong Hotel, a pyramid shaped construction, butworks began in the n80ies, had been stopped during the 90ies as the economy collapsed, and might open in 2012. It dominates the skyline, for sure, even if it isn’t finished or won’t be finished after all. There are lots of pictures in the booklet “DPR Korea Tour” issued by the National Tourist Administration, but you won’t find a hint at the Ryugyong Hotel. The rest of the huge buildings bear lots of concrete. While the elevators might just cover the needs of the passengers, they might be unoperational elsewhere in Pyongyang. I heard about people going up to the 20th floor using the stairs. Lack of electricity?
Hyperuricemia and Gout
Gout follows hyperuricemia, which follows overindulging in food and drinks. On twitter you would block and report such fellows! The incidence of gout has risen during the last decades (Arromdee et al. have shown the incidence to double from the 70ies to the 90ies; Zhu et al. have shown an increase of up to 114% in certain subgroups in the US).
Marc Pillinger, MD, who is Associate Professor of Medicine and Pharmacology at the NYU Langone Medical Center, gave an interesting talk on gout at the 2011 ACR Scientific Meeting in Chicago. He asked about the factors, why gou and hyperuricemia are increasing in the population. People live longer, there are more people with kidney disease, diuretics are used more often, diet patterns have changed, and obesityhas become epidemic. Gout is expensive and gout patients habour lots of co-morbidities as hypertension, hyperlipidemia, chronic kidney disease, diabetes, coronary artery disease. Studies indicate, that lowering uric acid in these patients might reverse these co-morbidities (hypertension, hyperlipidemia, chronic kidney disease, diabetes, coronary artery disease) – lots of research work still to be done though! Some studies found an increased prevalence and severity of osteoarthritis.
Old treatment options are reducing inflammation by NSAIDs, colchicine, corticosteroids, and lowering uric acid by allopurinol, benzbromarone, probenecid. New treatment options are reducing inflammation by anakinra (Il-1 receptor antagonist), rilonacept (Il-1 trap), canakimumab (Anti-Il-1 Ig), and lowering uric acid by febuxostat, pegloticase (pegylated uricase), lesinurad. Pegloticase is highly effective to reduce urid acid, and reduces tophi.
Some foods promote gout as purines in meat and seafood, but also alcoholic beverages, fructose, and more.
Beer is the worst alcoholic beverage to promote hyperuricemia and gout. A really large study (more than 47,000 men) conducted at the Massachusetts General Hospital by Dr. Hyon Choi and her colleagues showed, that consumers of two to four beers a week had a risk increase of 25%, consuming at least 2 beers a day results in a risk increase of 200% of developing gout. Though alcohol itself increases the risk, it is the amount of purines found in beer, that make it worse than the other alcoholic beverages. High-fructose corn syrup (HFCS) results in high uric acid formation, and should therefore be avoided (there are other serious health concerns such as cardiovascular disease, diabetes, and fatty liver disease).
Let’s have a look at some excerpts from abstracts from the 2011 ACR Scientific Meeting in Chicago:
[223] Gout Vs Hyperuricemia As Risk Factors for Coronary Artery Disease – A Pilot Study.
Victoria Furer, Rennie N. G. Howard, Jonathan Samuels and Michael H. Pillinger.
NYU Hospital for Joint Diseases, New York, NY
Conclusion: This well-characterized, prospectively-enrolled cohort study suggests that the presence of gout conveys an additional level of CAD risk beyond that of hyperuricemia. Although larger studies are needed, our pilot study demonstrates the feasibility of using a prospective enrollment strategy to distinguish between hyperuricemia and gout comorbidity.
[1013] Rilonacept for Gout Flare Prevention in Patients on Uric Acid-Lowering Therapy: Results of a Double-Blind, Placebo-Controlled, Phase 3, International Safety Study.
John S. Sundy1, H. Ralph Schumacher2, Judith Kirstein3, Essack Mitha4, Steven P. Weinstein5, Jian Wang5, Shirletta King-Davis5 and Robert R. Evans5.
1Duke University Medical Center, Durham, NC, 2VA Medical Center and University of Pennsylvania, Philadelphia, PA, 3Advanced Clinical Research, West Jordan, UT, 4Newtown Clinical Research, Johannesburg, Gauteng, South Africa, 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Conclusion: Rilonacept demonstrated an acceptable safety and tolerability profile in gout patients with typical comorbid conditions. The rate of serious infections was low. Rilonacept resulted in a substantial reduction in gout flares in patients at high risk of flaring.
[1014] Rilonacept Efficacy for Gout Flare Prevention in Patients with Tophi and/or Polyarticular Disease Who Initiate Uric Acid-Lowering Therapy.
Robert Terkeltaub1, H. Ralph Schumacher2, A. Kivitz3, Steven P. Weinstein4, Richard Wu4, Rebecca Gall4 and Robert R. Evans4.
1VA Medical Ctr, San Diego, CA, 2VA Medical Center and University of Pennsylvania, Philadelphia, PA, 3Altoona Center for Clinical Research, Duncansville, PA, 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Conclusion: The presence of tophi and/or polyarticular disease represents a risk factor for gout flares in patients initiating uric acid-lowering therapy. Among patients with these risk factors, rilonacept demonstrated efficacy for gout flare prevention that was generally similar to that observed for the overall population.
[1016] Long-Term Efficacy and Safety of Canakinumab Versus Triamcinolone Acetonide in Acute Gouty Arthritis Patients.
J.P. Brown1, A. So2, A. Dikranian3, R. Alten4, T. Bardin5, H. R. Schumacher6, A. Gimona7, G. Krammer7, A. Karpov7 and N. Schlesinger8.
1CHUQ-CHUL Research Centre, Laval University, Quebec City, QC, 2CHUV, Lausanne, Switzerland, 3San Diego Arthritis Medical Clinic, San Diego, CA, 4Charite´ Teaching Hospital–Schlosspark-Klinik, Berlin, Germany, 5Hoˆpital Lariboisie`re, Paris, France, 6University of Pennsylvania and VA Medical Center, Philadelphia, PA, 7Novartis Pharma AG, Basel, Switzerland, 8UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ
Conclusion: In frequently flaring patients with limited treatment options, canakinumab demonstrated superior 24 week efficacy against TA with comparable safety and tolerability to 12-week data.
[1021] Efficacy and Safety of Lesinurad (RDEA594), A Novel Uricosuric Agent, Given In Combination with Allopurinol in Allopurinol-Refractory Gout Patients: Preliminary Results from the Randomized, Double-Blind, Placebo-Controlled, Phase 2B Extension Study.
John Sundy1, Fernando Perez-Ruiz2, Eswar Krishnan3, Vijay Hingorani4, Jody Welp4, Matt Suster4, Kimberly Manhard4, Matt Cravets4, David Hagerty4 and Barry Quart4.
1Duke University Medical Center, Durham, NC, 2Hospital De Cruces, Baracaldo, Spain, 3Stanford University, Stanford, CA, 4Ardea Biosciences, Inc., San Diego, CA
Conclusion: Addition of lesinurad produced consistent, sustained reductions in sUA levels in patients not adequately responding to standard doses of ALLO. Most subjects achieved target sUA levels of _6 mg/dL on either the 200 or 400mg lesinurad dose. Lesinurad was well-tolerated and no dose-related side effects were observed with combination treatment. Lesinurad is a promising investigational drug for the treatment of hyperuricemia in gout
patients.
[1022] Febuxostat (vs. Allopurinol) In Treating the Hyperuricemia of Gout In Diabetic Patients.
Michael A. Becker1, Patricia A. MacDonald2, Barbara Hunt2 and Robert L. Jackson2.
1University of Chicago Medical Center, Chicago, IL, 2Takeda Global Research & Development Center, Inc., Deerfield, IL
Conclusion: Despite very high rates of CV, renal, and additional metabolic co-morbidities, diabetic gouty subjects tolerated UL therapy with either FEB or ALLO, but FEB 80mg treatment achieved sUA _6.0 mg/dL more often than ALLO treatment at commonly prescribed doses.
[1023] Rilonacept for Gout Flare Prevention: Subgroup Analysis of Patients Initiating or Continuing Uric Acid-Lowering Therapy in a Randomized, Placebo-Controlled Trial.
John S. Sundy1, H. Ralph Schumacher2, Roy M. Fleischmann3, Johannes M. Engelbrecht4, Steven P. Weinstein5, Jian Wang5, Shirletta King-Davis5 and Robert R. Evans5.
1Duke University Medical Center, Durham, NC, 2VA Medical Center and University of Pennsylvania, Philadelphia, PA, 3MCRC, University of Texas, Dallas, TX, 4Vergelegan Medi-Clinic, West Cape, South Africa, 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Conclusion: Weekly treatment with rilonacept 160mg resulted in similar efficacy in patients initiating or continuing uric acid-lowering therapy who were at risk of gout flares. Pre-filled syringes demonstrated efficacy similar to lyophilized drug in vials. Efficacy was also consistent in patients meeting the additional inclusion criteria from previous phase 3 studies. No new safety signals were observed.
[1025] Pharmacological Treatment of Acute Gout: A Systematic Review.
Puja Khanna1, Manjit K. Singh2, John D. FitzGerald3, Sangmee Bae2, Shraddha Prakash3, Marian Kaldas3, Maneesh Gogia3, Paul Maranian4, Robert Terkeltaub5 and Dinesh Khanna6.
1University of Michigan, Ann Harbor, MI, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, 3UCLA, Los Angeles, CA, 4UCLA Medical School, Los Angeles, CA, 5VA Medical Ctr, San Diego, CA, 6University of Michigan, Ann Arbor, MI
Conclusion: NSAIDs and colchicine are effective in treating acute gout attack. Corticosteroid, ACTH, and canakinumamb can be used in patients who have contraindications to NSAIDs and colchicine.
[1027] Efficacy of Combined Treatment with Allopurinol and Benzbromarone in Gout Patients with Chronic Renal Impairment.
Ji Seon Oh1, Seung Won Choi1, Bon San Koo2, Min Wook So2, Yong-Gil Kim2, Chang-Keun Lee2 and Bin Yoo2.
1University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea, 2University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
Conclusion: This study results suggest that combined treatment with allopurinol and benzbromarone may be an effective strategy for achieving the goal of uric acid levels in gout patients with moderate to severe renal impairment.
[1032] Uncontrolled Serum Uric Acid Is Associated with An Increased Risk of Developing Renal Disease In Veterans with Gout.
Eswar Krishnan1, Hari Sharma2, Bhavik J. Pandya3, Maryna Marynchenko2, Andrew Yu2, Eric Wu2, Jinan Liu4 and Lizheng Shi4.
1Stanford University, Stanford, CA, 2Analysis Group, Inc., Boston, MA, 3Takeda Pharmaceuticals International, Inc., Deerfield, IL, 4Tulane University, New Orleans, LA
Conclusion: Compared to controlled sUA levels, uncontrolled sUA levels are associated with increased risk of a new diagnosis of renal disease among veterans with gout.
[1033] Clinical Characteristics of Difficult-to-Treat Gout Patients: a Principal Components Analysis.
Elizaveta Vaysbrot1, Yoojin Lee1, Sarah McLaughlin1, Neetu Agashivala2, Anthony Yadao3, Timothy E. McAlindon1 and William F. Harvey1.
1Tufts Medical Center, Boston, MA, 2Novartis Pharmaceutical Corporation, East Hanover, NJ, 3Novartis Pharmaceuticals Corporation, East Hanover, NJ
Conclusion: The four out of five factors had components with clinical relationships: cardiovascular diseases, gastrointestinal disorders, metabolic syndrome and features of advanced gout. The components in factor 4 did not have a clear clinical relationship. The study was limited by its retrospective nature, small sample size, and an inexact, exploratory nature of PCA method. Characteristics of this population may vary if using different definitions of difficult-to-treat. Despite the limitations, our results confirm the clinical intuition that the above conditions are linked to difficult-to-treat gout and may help design future research.
[1083] Presence of Gout Is Associated with Increased Osteoarthritis Prevalence and Severity.
Rennie N. G. Howard1, Jonathan Samuels1, Soterios Gyftopoulos1, Svetlana Krasnokutsky2, Joseph Leung3, Christopher Swearingen4 and Michael H. Pillinger1.
1NYU Langone Medical Center/NYU Hospital for Joint Diseases, New York, NY, 2NYU Hospital for Joint Disease, New York, NY, 3New York, NY, 4University of Arkansas for Medical Sciences, Little Rock, AR
Conclusion: Our data suggest that presence of gout puts subjects at significantly higher risk for increased knee OA prevalence and severity. AH may independently convey knee OA risk but our sample size was inadequate
for statistical confirmation. MSU crystal deposition as detected by US was also significantly higher in subjects with knee OA. Presence of gout or AH, as well as MSU crystal deposition on US, could potentially serve as useful biomarkers for knee OA risk, severity and progression. The possibility that gout and/or AH might contribute to OA risk suggests that UA management should be assessed as a potential intervention in OA patients.
[1599] Allopurinol Initiation and the Risk of Death in the General Population.
Yanyan Zhu1, Yuqing Zhang2, John D. Seeger3, Young Hee Rho4, Christine Peloquin1 and Hyon K. Choi1.
1Boston University School of Medicine, Boston, MA, 2Boston University Clinical Edpidemiology Reserach and Training Unit, Boston, MA, 3Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, 4Vanderbilt Medical Center, Nashville, TN
Conclusion: In this general population study, allopurinol initiation was associated with a modestly reduced risk of death. The overall benefits of allopurinol may outweigh its impact of rare, potentially serious adverse effects at a population level
[1602] Uncontrolled Serum Uric Acid In Veteran Gout Patients Is Associated with a Higher Risk of Diabetes.
Bhavik J. Pandya1, Maryna Marynchenko2, Hari Sharma2, Andrew Yu2, Eric Wu2, Lizheng Shi3, Jinan Liu3 and Eswar Krishnan4.
1Takeda Pharmaceuticals International, Inc., Deerfield, IL, 2Analysis Group, Inc., Boston, MA, 3Tulane University, New Orleans, LA, 4Stanford University, Stanford, CA
Conclusion: Among VISN 16 pts with gout, uncontrolled sUA was associated with a higher risk of a new diagnosis of diabetes when compared with controlled sUA.
Marc Pillinger, MD, who is Associate Professor of Medicine and Pharmacology at the NYU Langone Medical Center, gave an interesting talk on gout at the 2011 ACR Scientific Meeting in Chicago. He asked about the factors, why gou and hyperuricemia are increasing in the population. People live longer, there are more people with kidney disease, diuretics are used more often, diet patterns have changed, and obesityhas become epidemic. Gout is expensive and gout patients habour lots of co-morbidities as hypertension, hyperlipidemia, chronic kidney disease, diabetes, coronary artery disease. Studies indicate, that lowering uric acid in these patients might reverse these co-morbidities (hypertension, hyperlipidemia, chronic kidney disease, diabetes, coronary artery disease) – lots of research work still to be done though! Some studies found an increased prevalence and severity of osteoarthritis.
Old treatment options are reducing inflammation by NSAIDs, colchicine, corticosteroids, and lowering uric acid by allopurinol, benzbromarone, probenecid. New treatment options are reducing inflammation by anakinra (Il-1 receptor antagonist), rilonacept (Il-1 trap), canakimumab (Anti-Il-1 Ig), and lowering uric acid by febuxostat, pegloticase (pegylated uricase), lesinurad. Pegloticase is highly effective to reduce urid acid, and reduces tophi.
Some foods promote gout as purines in meat and seafood, but also alcoholic beverages, fructose, and more.
Beer is the worst alcoholic beverage to promote hyperuricemia and gout. A really large study (more than 47,000 men) conducted at the Massachusetts General Hospital by Dr. Hyon Choi and her colleagues showed, that consumers of two to four beers a week had a risk increase of 25%, consuming at least 2 beers a day results in a risk increase of 200% of developing gout. Though alcohol itself increases the risk, it is the amount of purines found in beer, that make it worse than the other alcoholic beverages. High-fructose corn syrup (HFCS) results in high uric acid formation, and should therefore be avoided (there are other serious health concerns such as cardiovascular disease, diabetes, and fatty liver disease).
Let’s have a look at some excerpts from abstracts from the 2011 ACR Scientific Meeting in Chicago:
[223] Gout Vs Hyperuricemia As Risk Factors for Coronary Artery Disease – A Pilot Study.
Victoria Furer, Rennie N. G. Howard, Jonathan Samuels and Michael H. Pillinger.
NYU Hospital for Joint Diseases, New York, NY
Conclusion: This well-characterized, prospectively-enrolled cohort study suggests that the presence of gout conveys an additional level of CAD risk beyond that of hyperuricemia. Although larger studies are needed, our pilot study demonstrates the feasibility of using a prospective enrollment strategy to distinguish between hyperuricemia and gout comorbidity.
[1013] Rilonacept for Gout Flare Prevention in Patients on Uric Acid-Lowering Therapy: Results of a Double-Blind, Placebo-Controlled, Phase 3, International Safety Study.
John S. Sundy1, H. Ralph Schumacher2, Judith Kirstein3, Essack Mitha4, Steven P. Weinstein5, Jian Wang5, Shirletta King-Davis5 and Robert R. Evans5.
1Duke University Medical Center, Durham, NC, 2VA Medical Center and University of Pennsylvania, Philadelphia, PA, 3Advanced Clinical Research, West Jordan, UT, 4Newtown Clinical Research, Johannesburg, Gauteng, South Africa, 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Conclusion: Rilonacept demonstrated an acceptable safety and tolerability profile in gout patients with typical comorbid conditions. The rate of serious infections was low. Rilonacept resulted in a substantial reduction in gout flares in patients at high risk of flaring.
[1014] Rilonacept Efficacy for Gout Flare Prevention in Patients with Tophi and/or Polyarticular Disease Who Initiate Uric Acid-Lowering Therapy.
Robert Terkeltaub1, H. Ralph Schumacher2, A. Kivitz3, Steven P. Weinstein4, Richard Wu4, Rebecca Gall4 and Robert R. Evans4.
1VA Medical Ctr, San Diego, CA, 2VA Medical Center and University of Pennsylvania, Philadelphia, PA, 3Altoona Center for Clinical Research, Duncansville, PA, 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Conclusion: The presence of tophi and/or polyarticular disease represents a risk factor for gout flares in patients initiating uric acid-lowering therapy. Among patients with these risk factors, rilonacept demonstrated efficacy for gout flare prevention that was generally similar to that observed for the overall population.
[1016] Long-Term Efficacy and Safety of Canakinumab Versus Triamcinolone Acetonide in Acute Gouty Arthritis Patients.
J.P. Brown1, A. So2, A. Dikranian3, R. Alten4, T. Bardin5, H. R. Schumacher6, A. Gimona7, G. Krammer7, A. Karpov7 and N. Schlesinger8.
1CHUQ-CHUL Research Centre, Laval University, Quebec City, QC, 2CHUV, Lausanne, Switzerland, 3San Diego Arthritis Medical Clinic, San Diego, CA, 4Charite´ Teaching Hospital–Schlosspark-Klinik, Berlin, Germany, 5Hoˆpital Lariboisie`re, Paris, France, 6University of Pennsylvania and VA Medical Center, Philadelphia, PA, 7Novartis Pharma AG, Basel, Switzerland, 8UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ
Conclusion: In frequently flaring patients with limited treatment options, canakinumab demonstrated superior 24 week efficacy against TA with comparable safety and tolerability to 12-week data.
[1021] Efficacy and Safety of Lesinurad (RDEA594), A Novel Uricosuric Agent, Given In Combination with Allopurinol in Allopurinol-Refractory Gout Patients: Preliminary Results from the Randomized, Double-Blind, Placebo-Controlled, Phase 2B Extension Study.
John Sundy1, Fernando Perez-Ruiz2, Eswar Krishnan3, Vijay Hingorani4, Jody Welp4, Matt Suster4, Kimberly Manhard4, Matt Cravets4, David Hagerty4 and Barry Quart4.
1Duke University Medical Center, Durham, NC, 2Hospital De Cruces, Baracaldo, Spain, 3Stanford University, Stanford, CA, 4Ardea Biosciences, Inc., San Diego, CA
Conclusion: Addition of lesinurad produced consistent, sustained reductions in sUA levels in patients not adequately responding to standard doses of ALLO. Most subjects achieved target sUA levels of _6 mg/dL on either the 200 or 400mg lesinurad dose. Lesinurad was well-tolerated and no dose-related side effects were observed with combination treatment. Lesinurad is a promising investigational drug for the treatment of hyperuricemia in gout
patients.
[1022] Febuxostat (vs. Allopurinol) In Treating the Hyperuricemia of Gout In Diabetic Patients.
Michael A. Becker1, Patricia A. MacDonald2, Barbara Hunt2 and Robert L. Jackson2.
1University of Chicago Medical Center, Chicago, IL, 2Takeda Global Research & Development Center, Inc., Deerfield, IL
Conclusion: Despite very high rates of CV, renal, and additional metabolic co-morbidities, diabetic gouty subjects tolerated UL therapy with either FEB or ALLO, but FEB 80mg treatment achieved sUA _6.0 mg/dL more often than ALLO treatment at commonly prescribed doses.
[1023] Rilonacept for Gout Flare Prevention: Subgroup Analysis of Patients Initiating or Continuing Uric Acid-Lowering Therapy in a Randomized, Placebo-Controlled Trial.
John S. Sundy1, H. Ralph Schumacher2, Roy M. Fleischmann3, Johannes M. Engelbrecht4, Steven P. Weinstein5, Jian Wang5, Shirletta King-Davis5 and Robert R. Evans5.
1Duke University Medical Center, Durham, NC, 2VA Medical Center and University of Pennsylvania, Philadelphia, PA, 3MCRC, University of Texas, Dallas, TX, 4Vergelegan Medi-Clinic, West Cape, South Africa, 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Conclusion: Weekly treatment with rilonacept 160mg resulted in similar efficacy in patients initiating or continuing uric acid-lowering therapy who were at risk of gout flares. Pre-filled syringes demonstrated efficacy similar to lyophilized drug in vials. Efficacy was also consistent in patients meeting the additional inclusion criteria from previous phase 3 studies. No new safety signals were observed.
[1025] Pharmacological Treatment of Acute Gout: A Systematic Review.
Puja Khanna1, Manjit K. Singh2, John D. FitzGerald3, Sangmee Bae2, Shraddha Prakash3, Marian Kaldas3, Maneesh Gogia3, Paul Maranian4, Robert Terkeltaub5 and Dinesh Khanna6.
1University of Michigan, Ann Harbor, MI, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, 3UCLA, Los Angeles, CA, 4UCLA Medical School, Los Angeles, CA, 5VA Medical Ctr, San Diego, CA, 6University of Michigan, Ann Arbor, MI
Conclusion: NSAIDs and colchicine are effective in treating acute gout attack. Corticosteroid, ACTH, and canakinumamb can be used in patients who have contraindications to NSAIDs and colchicine.
[1027] Efficacy of Combined Treatment with Allopurinol and Benzbromarone in Gout Patients with Chronic Renal Impairment.
Ji Seon Oh1, Seung Won Choi1, Bon San Koo2, Min Wook So2, Yong-Gil Kim2, Chang-Keun Lee2 and Bin Yoo2.
1University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea, 2University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
Conclusion: This study results suggest that combined treatment with allopurinol and benzbromarone may be an effective strategy for achieving the goal of uric acid levels in gout patients with moderate to severe renal impairment.
[1032] Uncontrolled Serum Uric Acid Is Associated with An Increased Risk of Developing Renal Disease In Veterans with Gout.
Eswar Krishnan1, Hari Sharma2, Bhavik J. Pandya3, Maryna Marynchenko2, Andrew Yu2, Eric Wu2, Jinan Liu4 and Lizheng Shi4.
1Stanford University, Stanford, CA, 2Analysis Group, Inc., Boston, MA, 3Takeda Pharmaceuticals International, Inc., Deerfield, IL, 4Tulane University, New Orleans, LA
Conclusion: Compared to controlled sUA levels, uncontrolled sUA levels are associated with increased risk of a new diagnosis of renal disease among veterans with gout.
[1033] Clinical Characteristics of Difficult-to-Treat Gout Patients: a Principal Components Analysis.
Elizaveta Vaysbrot1, Yoojin Lee1, Sarah McLaughlin1, Neetu Agashivala2, Anthony Yadao3, Timothy E. McAlindon1 and William F. Harvey1.
1Tufts Medical Center, Boston, MA, 2Novartis Pharmaceutical Corporation, East Hanover, NJ, 3Novartis Pharmaceuticals Corporation, East Hanover, NJ
Conclusion: The four out of five factors had components with clinical relationships: cardiovascular diseases, gastrointestinal disorders, metabolic syndrome and features of advanced gout. The components in factor 4 did not have a clear clinical relationship. The study was limited by its retrospective nature, small sample size, and an inexact, exploratory nature of PCA method. Characteristics of this population may vary if using different definitions of difficult-to-treat. Despite the limitations, our results confirm the clinical intuition that the above conditions are linked to difficult-to-treat gout and may help design future research.
[1083] Presence of Gout Is Associated with Increased Osteoarthritis Prevalence and Severity.
Rennie N. G. Howard1, Jonathan Samuels1, Soterios Gyftopoulos1, Svetlana Krasnokutsky2, Joseph Leung3, Christopher Swearingen4 and Michael H. Pillinger1.
1NYU Langone Medical Center/NYU Hospital for Joint Diseases, New York, NY, 2NYU Hospital for Joint Disease, New York, NY, 3New York, NY, 4University of Arkansas for Medical Sciences, Little Rock, AR
Conclusion: Our data suggest that presence of gout puts subjects at significantly higher risk for increased knee OA prevalence and severity. AH may independently convey knee OA risk but our sample size was inadequate
for statistical confirmation. MSU crystal deposition as detected by US was also significantly higher in subjects with knee OA. Presence of gout or AH, as well as MSU crystal deposition on US, could potentially serve as useful biomarkers for knee OA risk, severity and progression. The possibility that gout and/or AH might contribute to OA risk suggests that UA management should be assessed as a potential intervention in OA patients.
[1599] Allopurinol Initiation and the Risk of Death in the General Population.
Yanyan Zhu1, Yuqing Zhang2, John D. Seeger3, Young Hee Rho4, Christine Peloquin1 and Hyon K. Choi1.
1Boston University School of Medicine, Boston, MA, 2Boston University Clinical Edpidemiology Reserach and Training Unit, Boston, MA, 3Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, 4Vanderbilt Medical Center, Nashville, TN
Conclusion: In this general population study, allopurinol initiation was associated with a modestly reduced risk of death. The overall benefits of allopurinol may outweigh its impact of rare, potentially serious adverse effects at a population level
[1602] Uncontrolled Serum Uric Acid In Veteran Gout Patients Is Associated with a Higher Risk of Diabetes.
Bhavik J. Pandya1, Maryna Marynchenko2, Hari Sharma2, Andrew Yu2, Eric Wu2, Lizheng Shi3, Jinan Liu3 and Eswar Krishnan4.
1Takeda Pharmaceuticals International, Inc., Deerfield, IL, 2Analysis Group, Inc., Boston, MA, 3Tulane University, New Orleans, LA, 4Stanford University, Stanford, CA
Conclusion: Among VISN 16 pts with gout, uncontrolled sUA was associated with a higher risk of a new diagnosis of diabetes when compared with controlled sUA.
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