The 2012 ACR Meeting in Washington is over. I travelled with a large list of topics, I'm interested in. Now it's time to take a first look at results, at answers the ACR 2012 meeting is giving to questions. Detail will follow during the coming weeks and I'll use this blog post as an inventory for links.
ALX-0061
St. De Bruyn and colleagues presented: "Anti-IL-6 Receptor Nanobody (ALX-0061) Seamless "First-in-Human" Phase I/II POC Study in Patients with Active RA On Stable MTX Treatment" (No. 1307). Conclusions included: "The MAD study part will further assess early effect of ALX-0061 on disease activity with radiographic and clinical disease score evaluations."
More you can find here: http://rheumatologe.blogspot.de/2012/12/alx-0061-at-acr-annual-meeting-2012-in.html
Anakinra - IL-1Ra-Receptor antagonist
Link to the EULAR evaluation: http://rheumatologe.blogspot.de/2012/07/anakinra-and-pseudogout-calcium.html
There has been a pilot open study by P. Zufferey suggesting that IL-1_ inhibition (Anakinra) may be an interesting therapeutic approach in acute calcific periarthritis (No. 137). Other studies looked at gouty arthritis: No. 146. More studies lookes a TRAPs, FMF, and other fever syndroms as well as juvenile idiopathic arthritis. Anakinra is mentioned in a poster on relapsing polychondritis (No. 1922). Anakinra and pseudogout (calcium pyrophosphate crystal arthritis) - what has changed since the EULAR 2012? Less attention to this topic, more on other topics.
Link to the new blogpost on ACR 2012: http://rheumatologe.blogspot.de/2012/12/anakinra-at-acr-2012-in-washington.html
Ankylosing Spondylitis
New drugs? New developments? More bad news for smokers, A.B.I. Bremander and colleagues found out, that " both patients with AS and non AS axial SpA who were ever smokers reported worse clinical features compared with never smokers" (No. 95). Another study on smoking and ankylosing spondylitis by D. Poddubnyy and oclleagues (N0. 1703). J. Sieper et al. rapid improvement of ankylosing spondylitis using certolizumab (No. 558). X. Baraliakos and colleagues tested secukinumab (IL-17A inhibition) in a proof-of-concept (PoC) trial and showed via MRI, that secukinumab may reduce spinal inflammation (No. 574). R. B. M. Landewe and colleagues looked at effect of certolizumab on signs and symptoms (No. 777). Anopther study on secukinumab by D. L. Baeten (No. 2225). Two study on certolizumab by D. van der Heijde and colleagues (No. 1372 and 1705). Studies No. 591 and 592 looked at two novel inflammatory biomarkers: matrix metalloproteinase and cathepsin-derived CRP, which are associated with structural progression.
Link to the EULAR 2012 blog post: http://rheumatologe.blogspot.de/2012/07/ankylosing-spondylitis-refractory-to.html
Link to the ACR 2012 blog post on alterations in bone metabolism of HLA B27 positive healthy individuals:
http://rheumatologe.blogspot.de/2012/11/alterations-in-bone-metabolism-and-hla.html
Link to more Information: http://rheumatologe.blogspot.de/2013/01/ankylosing-spondylitis-at-acr-2012-in.html
Anti-CD20 Monoclonal Antibody (like Rituximab)
Ocrelizumab has been mentinoned together with anakinra as being of less than 1% of biologics prescribed prior to tocilizumab (No. 351). There is a new anti-CD20 agent - ocaratuzumab, which will be looked at below. "NNC0109-0012 (anti-IL-20 mAb) is a novel human monoclonal IgG4 antibody which binds to and neutralizes the activity of IL-20." See under NNC0109-0012.
More information on other agents at: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html
Anti-CD-40 Monoclonal Antibody
There´s no anti-CD40 agent, but my guess is that there will be. So I keep it on the list.
Link to preliminaries at the EULAR 2012: http://rheumatologe.blogspot.de/2012/08/targeting-cd-40-preliminaries-at-eular.html
ARRY-371797 / ARRY-797
There has been a late breaking abstract on ... osteoarthritis.
ARRY-371797 is a p38 inhibitor. There were some studies on the way:
• A Study of ARRY-371797 in Patients With Rheumatoid Arthritis
• A Study of ARRY-371797 in Patients With Active Ankylosing Spondylitis
• A Study of ARRY-371797 in Patients With Osteoarthritis of the Knee
All three studies have been completed by July 2012, but nothing has been published at the EULAR 2012 meeting in Berlin and I haven´t seen any results the ACR 2012 in Washington. What does it mean? My guess is that p38 inhibition isn´t working in RA and AS, but the producer (Array BioPharma) is looking desperately for an indication to put the drug on the market.
Link: http://rheumatologe.blogspot.de/2012/12/arry-797-at-acr2012-in-washington.html
ASP015K
"ASP015K is an oral Janus kinase (JAK) inhibitor with selectivity for JAK1/3 in development for treatment of rheumatoid arthritis (RA) and other autoimmune diseases." T. Zhu et al. presented: "Coadministration of ASP015K, a Novel Janus Kinase Inhibitor with Methotrexate Demonstrates Tolerability and Lack of Pharmacokinetic Interactions in Patients with Rheumatoid Arthritis" (No. 1322). Conclusions included: "Efficacy and safety of ASP015K/MTX combination therapy is being assessed in ongoing phase 2 trials in RA patients."
Here are the details:
Atacicept - to be erased
Has atacicept [works on BLys(B-lymphocyte stimulator) and APRIL (A PRoliferation Inducing Ligand)] shown new efficacy? Older information at: http://rheumatologe.blogspot.de/2012/06/atacicept.html. I haven´t seen anything on atacicept at the ACR 2012, so I´ll erase it from my list for coming meetings.
Baricitinib
Baricitinib (also known as INCB28050, LY3009104) is an oral JAK1 and JAK2 inhibitor. J. S. Smolen and colleagues looked at patient reported outcomes in patientes with rheumatoid arthritis receiving baricitinb and traditional DMARDs (No. 490). Another study be M. C. Genovese and colleagues (No. 2487). And a phase 2b study by Ch. G. Peterfy (No. 2499).
For results presented at EULAR 2012 look here: http://rheumatologe.blogspot.de/2012/06/baricitinib-ly3009104-at-eular-2012-in.html
And the ACR 2012 results are here: http://rheumatologe.blogspot.de/2012/12/baricitinib-at-acr-2012-in-washington.html
Belimumab
"Belimumab is a recombinant, human Ig-G1 monoclonal antibody that binds and antagonizes the biological activity of soluble B-lymphocyte stimulator protein, a member of the tumor necrosis factor ligand superfamily that promotes the survival of B lymphocytes." (Wendy Cai in abstract No. 616). It is used in systemic lupus erythematodes (SLE), where the producer still wonders, why the drug isn´t widely accepted among rheumatologists. Belimumab in RA? Nothing at the ACR 2012.
Biosimilars
Celltrion is still waiting for FDA approval, but is expected to launch an infliximab biosimilar in 2013; phase 3 study still going on. Expected in Europe not before 2014!
http://rheumatologe.blogspot.de/2012/06/biosimilars.html
A. da Silva and colleagues presented: "Target-Directed Development of a Proposed Biosimilar Rituximab (GP2013): Comparability of Antibody-Dependent Cellular Cytotoxicity Activity and Pre-Clinical Pharmacokinetics and Pharmacodynamics with Originator Rituximab" (No. 2153). They concluded: "This pre-clinical comparability exercise confirms that GP2013 and originator rituximab are pharmacologically similar with regard to ADCC potency, anti-tumor activity, PK exposure (AUC) and B-cell depletion."
BMS-582949 - to be erased
BMS-582949 is a dual action p38 kinase inhibitor. There is a study of G. Schieven and colleagues, which has been published at the 2010 ACR meeting (Arthritis Rheum 2010;62 Suppl 10 :1513 DOI: 10.1002/art.29279). There has been a study, http://clinicaltrials.gov/show/NCT00605735, which has been completed, but no study result have been published (updated: January 24, 2011). Nothing at the ACR 2012. So this is another dead end.
Briakinumab (ABT-874) - to be erased
Briakinumab (ABT-874) targets the interleukin-12 (IL-12) and interleukin-23 (IL-23). Briakinumab might be used to treat rheumatoid arthritis psoriasis, and other autoimmune diseases like ustekinumab. Nothing at the ACR 2012.
Brodalumab
Brodalumab targets the interleukin-17 (IL-17) and is therefore much like ixekizumab, see below.
Karel Pavelka and collaegues looked safety, tolerability, and efficacy of brodalumab (AMG 827) in rheumatoid arthritis and an inadequate response to Methotrexate (No. 831), but the preliminary results do not support further evaluation of brodalumab as a treatment for RA. M.A. Curchill and collaegues have done "A Phase Ib Multiple Ascending Dose Study Evaluating Safety, Pharmacokinetics, and Early Clinical Response of Brodalumab (AMG 827), a Human Anti-Interleukin 17 Receptor (IL-17R) Antibody, in Rheumatoid Arthritis" (No. 1294).
More details: http://rheumatologe.blogspot.de/2012/12/brodalumab-at-acr-2012-in-washington.html
BT061
Target CD4, “Dose-finding of Multiple Dose of BT061 in Patients With Active Rheumatoid Arthritis Incompletely Controlled on Stable Methotrexate (MTX)”, Estimated Study Completion Date: December 2013. http://clinicaltrials.gov/ct2/show/NCT01481493
Mabe we shall see some preliminary results. - No we didn´t see such results at the ACR 2012.
Canakinumab (ACZ885)
Canakinumab (ACZ885), target IL-1 beta, has been developed for the treatment of rheumatoid arthritis, but this indication has been abandoned. IL-1 beta isn’t a successful target in rheumatoid arthritis. Novartis tries desperately to find indications for its’ drug like gout as cryopyrin-associated periodic syndromes (CAPS), which are orphan diseases.
CCX354-C
CCX354-C did better than expected, when viewed from the presentation at the EULAR 2012. For EULAR 2012 look at: http://rheumatologe.blogspot.de/2012/07/ccx-354-c-at-eular-2012.html
But nothing at the ACR 2012 in Washington!
Cetrorelix
Cetrorelix is a gonadotropin-releasing hormone antagonist (GnRH antagonist). I expected some new results. Older results here: http://rheumatologe.blogspot.de/2012/07/cetrorelix-at-eular-2012.html
And there are new results! A. Kass and colleagues looked at cetrorelix in a proof-of concept study and it demonstrates efficacy in patients with active rheumatoid arthritis (No. 834). Nothing more more ! We´ll have to wait.
More details:
Clazakizumab ) - to be erased
Clazakizumab targets the interleukin-6 (IL-6). So it would be much like tocilizumab (Actemra). Nothing at the ACR 2012, so I´ll erase Clezakizumab from my list.
Clenoliximab - to be erased
Clenoliximab targets CD4. There has been a study in 1999: http://www.ncbi.nlm.nih.gov/pubmed/10511060. Another study is dated 2002 (Antibody mediated stripping of CD4 from lymphocyte cell surface in patients with rheumatoid arthritis) by T. W. Hepburn and colleagues. I think clenoliximab has been abandoned. And as nothing appeared at the ACR 2012, I´ll erase it from my list.
Co-Stimulation-Inhibition
Subcutaneous abatacept, when will it be available. It is already available.
Dekavil
Dekavil - fibronectin-A-chain connected to IL-10 http://rheumatologe.blogspot.de/2012/07/dekavil-at-eular-2012.html
The poster says it´s dekavil, but the name isn´t mentioned in the abstract! M. Galeazzi and colleagues presented: "A Phase Ib Clinical Trial with F8-IL10, an Anti-Inflammatory Immunocytokine for the Treatment of Rheumatoid Arthritis (RA), Used in Combination with Methotrexate (MTX)" (No.1291). Cohort of 3-6 patients are far too small. Maybe we have to wait for a couple of years to eveluate dekavil.
More details are here:
Fezakinumab - to be erased
Fezakinumab targets IL-13 an has been designed for the treatment of inflammatory diseases, but my guess is that it’s more against asthma. Nothing at the EULAR 2012 meeting in Berlin. Nothing at the ACR 2012, so I´ll erase fezakinumab from my list.
Fibromyalgia
Fibromyalgia has been an important issue for me at the ACR 2012 in Washington.
R. S. Katz and colleagues looked at "Misperceptions of FMS Patients about Their Disease " (No. 1564) And R. S. Katz and colleagues looked at "How FMS Patients Become Workaholics" (No. 1565). The list would be too long, but one interesting paper had been done by W. K. Pang and colleagues: "Financial Conflicts of Interest and Industry Sponsorship Are Associated with Positive Outcomes in Fibromyalgia Randomized Controlled Trials" (No. 1870) "Industry sponsorship and FCOIs are common in published fibromyalgia drug therapy RCTs and are more likely to be associated with positive outcomes."
Fostamatinib
Concerning fostamatinib (a SYK inhibitor), how far have we come during the the time since EULAR 2012? Any date for launching the drug? http://rheumatologe.blogspot.de/2012/07/fostamatinib-at-eular-2012.html
I was surprised seeing a rat CIA study on fostamatinib (P. Pine et al. No. 329). Nothing more! Perhaps asking for a date when fostamatinib is to be launched was a bit premature. But is there any drug in sight?
More details are here:
GLPG0634
F. Namour and colleagues presented: "Once Daily High Dose Regimens of GLPG0634 in Healthy Volunteers Are Safe and Provide Continuous Inhibition of JAK1 but Not JAK2." (No. 1331).
F. Vanhoutte and colleagues presented: "Selective JAK1 Inhibition in the Treatment of Rheumatoid Arthritis: Proof of Concept with GLPG0634" (No. 2489). Conclusions included: "These early clinical results are the first to demonstrate that selective inhibition of JAK1 is efficacious and safe for the treatment of RA. Consistent with the lack of inhibition of JAK2, no anemia was observed. ..."
Let´s see if this compound from Galapagos is going to make it. Good luck!
For more details look here:
Iguratimod
Iguratimod, a new DMARD, is under way from Japan. A new DMARD is of interest as some patients have contraindications for biologics. Result presented at EULAR 2012 are here: http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html
But nothing at the ACR 2012.Maybe this drug is to be launched in Japan first, then in Europe, and much later in the US. I still hope that this drug is going to come.
Ixekizumab
Ixekizumab targets the interleukin-17 (IL-17) and is also known as LY2439821. It has been introduced at the ACR 2011 in Chicago: http://rheumatologe.blogspot.de/2011/11/ly2439821-anti-il-17-monoclonal.html. There hasn’t been any new study at the EULAR 2012 meeting in Berlin. M. Genovese et al. showed the results already presented at the ACR 2011 meeting in Chicago. But also at the ACR 2012 in Washington wasn´t the place to present new results. Let´s wait and see!
KB-003 - to be erased
Target GM-CSF, “The study was terminated upon completion of safety run-in due to program refocus.” http://clinicaltrials.gov/ct2/show/results/NCT00995449. I haven´t seen anything at the ACR 2012, so I´ll erase KB-003 from my list.
Mavrilimumab
Mavrilimumab is a human MAB for the treatment of rheumatoid arthritis. It targets the GMCSF receptor and alpha-chain. http://rheumatologe.blogspot.de/2012/07/mavrilimumab-at-eular-2012.html But nothing at the ACR 2012. I had thought to hear more from mavrilimumab but instead MOR103 came up with some data.
MDX-1100 - to be erased
Target CXCL10, but doesn’t seem to be very effective: “The ACR50 and ACR70 response rates on day 85 did not differ between the groups.” http://www.ncbi.nlm.nih.gov/pubmed/22147649. The ACR20 response rate, however, was significantly higher among MDX-1100-treated patients. No further results at the ACR 2012!
Modified release prednisone
On modified release prednisone: http://rheumatologe.blogspot.de/2012/06/modified-release-prednisone.html. I had been very skeptical about this product from the very beginning. The studies presented at the EULAR 2012 nurtured this skepticism.
R. Alten et al. presented: "Improved Fatigue-Related Quality of Life in CAPRA-2, a 12 Week Study of 5-Mg Modified (Delayed) Release Prednisone in Rheumatoid Arthritis" (No. 367). Surprise, surprise prednisone is better than placebo. Frank Buttgereit et al.: "Relationship Between Morning Stiffness Duration and Severity, Pain Intensity, and Measures of Disease Activity in a 12 Week Efficacy Study of a Modified (Delayed-Release) Prednisone Plus Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis" (No. 1274). What the poster showed, but is omitted in the abstract: patientes had to be "on stable DMRADs" - fine, but the DAS28 had been at 5.2 and morning stiffness lasted more than 2 1/2 hours! Who leaves pats. on stable DMARDs at a DAS28 of 5.2 and morning stiffness longer than 2 1/2 hours? That´s the perfect study design to make sure that prednisone MR is effective. What the two studies don´t show is the need for this drug. The idea that prednisone MR is chronotherapy is marketing hype. The drug counteracts the chronicity of cytokine release. The reason to avoid evening or night doses of glucocorticoids is not to overule the body´s own clock. My colleague here at the Rheinisches Rheuma Zentrum is working on this topic - as soon as he has published his ideas, I´ll put on a link to his page. More to follow on my blog, too.
To sum it up: I'm even more sceptic about modified release prednisone after the ACR 2012!
MOR103
Target GMCSF, there had been some interesting data, but only published by MorphoSys: http://www.morphosys.com/pressrelease/morphosyss-mor103-antibody-demonstrates-excellent-safety-and-efficacy-rheumatoid-arthritis-patients.
There has been a late breaking poster on MOR103. People at MorphoSys seems to be happy with their new child. The German review “Rheuma Management” speaks of promising data. Unless there’s data from a larger study I refrain from taking the same line. Link: http://rheumatologe.blogspot.de/2012/12/mor103-at-acr-2012-in-washington.html
Nerelimomab - to be erasedNerelimomab targets TNF-alpha and therefore might not be investigated further (enough TNF-alpha-inhibitors already on the market). I'll have to erase this one, too, as nothing has been presented at the ACR 2012.
NKG2a
NKG2A / NNC141-0100 at the EULAR 2012 Link: http://rheumatologe.blogspot.de/2012/07/nkg2a-nnc141-0100-at-eular-2012.html
J. Wahle and colleagues presented an in vitro study with the title "Effect of Anti-NKG2A Antibody Treatment On NK Cell Receptor Expression in Rheumatoid Arthritis Patients" (No. 1080). So there`s some more time to wait!
Here's the link to more information:
NNC0114-0005
NNC0114-0005 is a recombinant anti-IL-21 monoclonal antibody. St. Ignatenko and collaegues presented: "First in Human Study with Recombinant Anti-IL-21 Monoclonal Antibody in Healthy Subjects and Patients with Rheumatoid Arthritis" (No. 1279). Conclusions included: "The improvements in DAS28-CRP for patients with RA at the highest dose level may suggest biologic and clinical activity of NNC0114-0005."
Link:
NNC0109-0012
"NNC0109-0012 (anti-IL-20 mAb) is a novel human monoclonal IgG4 antibody which binds to and neutralizes the activity of IL-20." L. SEnolt and olleagues presented: "Clinical Responses and Patient Reported Outcomes to NNC0109-0012 (anti-IL-20 mAb) in Rheumatoid Arthritis (RA) Patients Following 12-Weeks Dosing and 13 Weeks Follow up: Results From a Phase 2a Trial" (no. 836). Conclusion consisted: "The data from this trial support further clinical development of NNC0109-0012 (anti-IL-20 mAb) in RA."
Link to more information:
Ocaratuzumab
Ocaratuzumab is a Fc- and Fab engineered anti-CD20 antibody, which showed rapid and sustained depletion of circulating B-cells in rheumatoid arthritis patients (No. 835). A. O'Reilly and colleagues also discussed the possibility of using ocaratuzumab subcutaneously.
Link to more information:
Olokizumab
Olokizumab targets interleukin-6 (IL-6). So it would be much like tocilizumab (Actemra). I haven’t seen any study at the EULAR 2012 meeting in Berlin. But I have seen some results on olokizumab at the ACR 2012.
R. Fleischmann and colleagues presented: "A Pilot Study Investigating the Tolerability and Pharmacodynamic Effect of Single Intravenous/Subcutaneous Doses of Olokizumab, an Anti-Interleukin-6 Monoclonal Antibody, in Patients with Rheumatoid Arthritis (No. 1339). They conluded: "These results provided the rationale for a further study to investigate the clinical efficacy of olokizumab in RA." No second study!
Link to more information:
Ozoralizumab (ATN-103)
R. M. Fleischmann and colleagues presented: "A Novel Individualized Treatment Approach in Open-Label Extension Study of Ozoralizumab (ATN-103) in Subjects with Rheumatoid Arthritis On a Background of Methotrexate" (No. 1311). "Ozoralizumab (ATN-103), a novel TNF_ inhibitor, is a trivalent, bispecific Nanobody (R) that potently neutralises TNF ..." Results: " ... EULAR good/moderate response rate was 97% ...". Conclusions: " ... This treatment approach could prove beneficial to patients an minimize treatment costs."
Link: http://rheumatologe.blogspot.de/2012/12/ozoralizumab-atn-103-at-acr-2012-in.html
Pamapimod - to be erased
R. Alten and colleagues presented a study on “Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy” in April 2009. Sorry to say, but “pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.” Actually, patients on pamapimod achieved poorer results than those on methotrexate. Some people already think that rheumatoid arthritis might be the wrong indication for this kind of drugs. As there hasn´t been anything new at the ACR 2012, I´ll erase this one, too.
Pateclizumab
Pateclizumab is an anti-Lymphotoxin-alpha Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/pateclizumab-anti-lymphotoxin-alpha.html
Nothing at the ACR 2012, but I´ll wait until the EULAR 2013 before I´ll erase pateclizumab from my list of interests.
Pioglitazone
Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, used in diabetes usually, has been tested in rheumatoid arthritis: "A Proof-of-Concept Randomized Controlled Trial" by M. J. Ormseth and colleagues (No. 832). Pioglitazone "modestly reduces RA disease activity measured by DAS28 CRP and CRP levels".
If you want more, then here's the link: http://rheumatologe.blogspot.de/2012/12/pioglitazone-at-acr-2012-in-washington.html
Placulumab - to be erased
Placulumab targets TNF-alpha and therefore might not be investigated further (enough TNF-alpha-inhibitors already on the market). Nothing on Placulumab at the EULAR 2012 meeting in Berlin. As there hasn´t been anything new at the ACR 2012, I´ll erase this one, too.
PRTX-100 (Staphylococcal Protein A)
E. Bernton et al. presented: "A Phase 1, Randomized, Double-Blind, Placebo-Controlled Multiple-Dose Study of Intravenous Staphylococcal Protein A in Patients with Active Rheumatoid Arthritis On Methotrexate: Safety, Pharmacokinetics and Efficacy" No. 833). "Results of this pilot study support further clinical trials of PRTX-100 at doses of 1.5 _g/kg and higher." As I had been part in testing immoniadsorption, I´m not too confident in PRTX-100. But it´s still too early for skepticism.
You find more here:
http://rheumatologe.blogspot.de/2012/12/prtx-100-staphylococcal-protein-a.html
Psoriatic Arthritis
Non-anti-TNF Biologics in Psoriatic Arthritis at EULAR 2011. http://rheumatologe.blogspot.de/2012/07/non-anti-tnf-biologics-in-psoriatic.html. I hope for new results on new drugs as therapy for psoriatic arthritis still lags behind.
There´s another study of Bremander on smoking. B. I. Bremander and colleagues presented: "Smoking Is Associated with Worse and More Widespread Pain, Worse Fatigue, General Health and Quality of Life in a Swedish Population Based Cohort of Patients with Psoriatic Arthritis" (No. 1828).
Studies on ustekinumab are discussed below.
I've found some data on apremilast in psoriatic arthritis:
http://rheumatologe.blogspot.de/2012/12/psoriatic-arthritis-at-acr-2012-in.html
Ruxolitinib
Ruxolitinib is a JAK1/JAK2 inhibitor, which could be useful to treat rheumatoid arthritis. There has been a study being presented at the 2008 ACR meeting, here’s an article referring to this study. http://www.istockanalyst.com/article/viewiStockNews/articleid/2739159. Nothing new at the EULAR 2012 meeting in Berlin. Ruxolitinib hasn´t been a hot topic at the ACR 2012. But there has been a study mentioning the drug (No. 1807).
But here I discuss the topic further: http://rheumatologe.blogspot.de/2012/12/ruxolitinib-at-acr-2012-in-washington.html
Sarilumab
Sarilumab, another anti-IL-6 monoclonal antibody, has already been in a phase 2 study in 2011, what’s new? More than presented at the EULAR 2012? http://rheumatologe.blogspot.de/2012/06/sarilumab-news-from-eular-2012.html
M. C. Genovese and colleagues presented a study on sarilumab in mederate to severe rheumatoid arthritis and looked at improvements of emoglobin levels (No. 1320). Pavel Belomestnov and colleagues found a substantial reductions in acute phase reactants (No. 1337). And that´s all! Oops! I´m inclined to give advice to share holders, but I´m a total dummie concerning stock markets. Where are the final results of the phase 2 study? Isn´t there any phase 3 study? OK, let´s wait for the 2013 meetings!
And here are the details:
SBI-087
SBI-087 is a SMIP (= small molecule immune pharmaceutical) binding to CD-20 http://rheumatologe.blogspot.de/2012/07/sbi-087-at-eular-2012.html
Nothing at the ACR 2012. If there isn´t anything at the EULAR2013, I´ll erase this one, too.
Secukinumab
Secukinumab is an Anti-Il17a Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/secukinumab-anti-il17a-monoclonal.html
X. Baraliakos and colleagues tested secukinumab (IL-17A inhibition) in a proof-of-concept (PoC) trial and showed via MRI, that secukinumab may reduce spinal inflammation (No. 574). Another study on secukinumab in ankylosing spondylitis by D. L. Baeten (No. 2225).
Link to more information:
Sirukumab MAB against IL-6 - to be erased
Sirukumab (formerly known as CNTO 136) is a human MAB that binds to the cytokine IL-6, designed for the treatment of rheumatoid arthritis. So sirukumab will be competiting with tocilizumab. Link: http://rheumatologe.blogspot.de/2012/07/sirukumab-at-eular-2012.html
As there hasn´t been anything new at the ACR 2012, I´ll erase this one, too.
Small molecules / protein kinase inhibitors
Safety of different small molecules / protein kinase inhibitors http://rheumatologe.blogspot.de/2012/06/safety-of-different-small-molecules.html
Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, used in diabetes usually, has been tested -see above.
ALX-0061 is an Anti-IL-6 Receptor Nanobody - see above.
Ozoralizumab (ATN-103) - see above. "
ASP015K is an oral Janus kinase (JAK) inhibitor with selectivity for JAK1/3 in development for treatment of rheumatoid arthritis (RA) and other autoimmune diseases." For ASP015K see above.
An interesting study by Y. Zhao: and colleagues: "Atsttrin-aˆ, an Engineered Protein Derived From Progranulin Growth Factor, Binds to TNF Receptors and Exhibits Potent Anti-Inflammatory Activity in Mice" (No. 2449). Theay concluded that Atsttrin-a "... may represent a promising alternative in treatment of rheumatoid arthritis".
GLPG0634 inhibts JAK1 but not JAK2, which could be a useful concept concerning adverse events - see above.
Synavive
Synavive, a combination of 2 mgs of prednisolone and 200 mgs of dipyramidole: http://rheumatologe.blogspot.de/2012/07/synavive-crx-102-at-eular-2012.html.
A new idea, what how much benefit for our patients? Still unclear as there hasn´t been anything presented at the ACR 2012.
Tabalumab
Tabalumab is an anti-BAFF Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/tabalumab-ly2127399-anti-baff.html. I´m very skeptical about benefit in RA.
M. W. Greenwald et al. presented: "Long-Term Safety and Efficacy of Tabalumab, an Anti-B-Cell Activating Factor Monoclonal Antibody, in Patients with Rheumatoid Arthritis: A 52-Week, Open-Label Extension Study" (No. 447). Another study by the same authors: No. 1276. W. J. Komocsar and colleagues presented: "Gene Expression Profiling and Pathway Changes Associated with Clinical Response to Tabalumab Blockade of Membrane Bound and Soluble B Cell Activating Factor in Rheumatoid Arthritis" (No. 1315).
Here are the details:
Tocilizumab
In a head to head study tocilizumab monotherapy has been studied against humira monotherapy. http://rheumatologe.blogspot.de/2012/06/tocilizumab-monotherapy-vs-humira.html
Concerning Tocilizumab, my most important question to solve at the EULAR and ACR 2012 has been: How about subcutaneous tocilizumab? http://rheumatologe.blogspot.de/2012/06/tocilizumab-at-eular-2012.html.
The answer has been 2014. I had hoped for better news, but didn´t get some. There have been some intereseting studies, which I`ll have to look at later.
Tofacitinib
The oral jak inhibitor tofacitinib (CP-690,550) had already attracted most attention at the EULAR 2012. See here: http://rheumatologe.blogspot.de/2012/07/tofacitinib-oral-jak-inhibitor-at-eular.html.
At the ACR 2012 the real hit has been: tofacitinib has been approved by the FDA, with a black box warning on opportunistic infections, tuberculosis, cancers, lymphoma, and is available on the US market as Xeljanz. EMEA approval still pending. More on the scientific data presented will come later.
Ustekinumab
Ustekinumab and other options in psoriatic arthritis. http://rheumatologe.blogspot.de/2012/07/ustekinumab-and-other-options-in.html.
In a first part I restrict the blogpost to Ustekinuimab.
A. Kavanaugh and colleagues presented: "Ustekinumab Improves Arthritis-Related and Skin-Related Quality of Life in Patients with Active Psoriatic Arthritis: Patient Reported Outcomes From Randomized and Double Blinded Phase III Psummit I Trial" (No. 569). Conclusion: "Ustekinumab improves general as well as arthritis and skin-related quality of life, and reduces the impact of disease on work productivity in patients with active PsA."
Ch. T. Ritchlin and colleagues presented: "Ustekinumab in Active Psoriatic Arthritis Including Patients Previously Treated with Anti-TNF Agents: Results of a Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study" (No. 2557). The conclusion looked like this: "UST reduced signs & symptoms, improved physical fxn, enthesitis & improved plaque PsO. Safety profiles were similar between UST & PBO." - Welcome to twitter!
Another study (actually all are the same) by A. Kavanaugh and colleagues (No. 2562).
Quite lot discussion you'll find here: http://rheumatologe.blogspot.de/2012/12/ustekinumab-at-acr-2012-in-washington.html
Veltuzumab
Target CD20, VELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis – the study is ongoing. Please check: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html
If you wait for results you have to join me. Nothing new elucidated at the ACR 2012 in Washington. If there isn´t some development until EULAR 2013, I´ll erase this one.
VX-702
About VX-702, a novel p38 MAPK inhibitor, isn´t much better to be said than of most of p38 MAPK inhibitors. N. Damjanov and colleagues of Belgrade University School of Medicine published two studies: “Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies” and concluded: “The modest clinical efficacy plus the transient suppression of biomarkers of inflammation observed in this study suggest that p38 MAPK inhibition may not provide meaningful, sustained suppression of the chronic inflammation seen in RA.”
And nothing new at the ACR 2012. If there isn´t some development until EULAR 2013, I´ll erase this one, too.
Zanolimumab - to be erased
Zanolimumab targets CD4 and has an expected trade name (HuMax-CD4). It should be used to treat rheumatoid arthritis, psoriasis, and more. Wikipedia: “The drug is currently undergoing Phase II trials[5].” When I looked further I’ve found a study: “Trial With HuMax-CD4 in Patients With Rheumatoid Arthritis Failing Treatment With Methotrexate and a TNF-Alpha Blocker”, which had been completed in 2005, but: “No publications provided”. So I guess, this drug also has been abandoned in the treatment of rheumatoid arthritis.
Nothing at the ACR 2012 meeting in Washington, so I´ll erase zanolimumab from this list.
There are more studies I might comment on like these abstracts:
No. 234 central pain sensitization in OA
No. 258 failure of Hou lou xiao ling Dan in OA
No. 453 fish oil
No. 485 IFX withdrawal better may be better than prolonging intervals
No. 562 on MTX and liver fibrosis in PsA and RA
No. 594 on bone metabolism in HLA B27 positive healthy subjects
No. 605 and 627 on Zostavax and SLE
No. 884 PDE-4 inhibition
No. 952 phone based CBT in fibromyalgia
No. 1135 glucosamin, chondroitin, and combo in OA
No. 1187 smoking and inflammatory cytokine profile
No. 1202 and 1204 on porphyromonas gingivum
No. 1761 Suppression of RA B cells by XmAb5871, an Anti-CD19 MAB
No. 1799 ONO-4059, a Bruton´s tyrosine kinase (Btk) inhibitor
No. 1821 clinical predictors of MTX liver enzymes elevation
No. 1862 Canada FMS guidelines
No. 1863 Ritalin and FMS
No. 2073 green tea epigallocatechin-gallates and mouse arthritis
No. 2327 CGEN-15001 (complicated name) and CIA
No. 2430 E-patient and early RA
You are doing a lot of erasing. So many things that do not work.
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