FDA Approval for Apremilast (Otezla) in Patients with Psoriatic Arthritis (PsA)

The FDA has approved apremilast (Otezla) to treat adult patients with active psoriatic arthritis (PsA). The currently approved DMARDs include biologics like THN-alpha-inhibitors and an IL-12/IL-23 inhibitor (ustekinumab).

The safety and effectiveness of apremilast (Otezla), a phosphodieasterase-4-inhibitor (PDE-4), were evaluated in three clinical trials involving 1,493 patients with active PsA. Patients treated with apremilast (Otezla) showed improvement in signs and symptoms of PsA compared to placebo. Link: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm390091.htm

There has been a study by Arthur Kavanaugh and colleagues (Abstract No. L13) at the 2012 ACR Meeting in Washington: “Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results of a Phase 3, Randomized, Controlled Trial”. Conclusion: “Apremilast significantly improved signs and symptoms of PsA and resulted in statistically and clinically meaningful improvements in physical function. Apremilast was generally well tolerated and no new safety or laboratory signals were detected.” Lets look at some side effects: diarrhea (placebo: 2.4%; apremilast 20 mg BID: 11.3%; and apremilast 30 mg BID, 19.0%), nausea (high dose: 18.5%), headache (10.1%, and 10.7%), and more.

At the 2013 ACR Meeting in San Diego we saw even more studies.

C.J. Edwards and colleagues presented the following study [Abstract No. 311]: “Long-Term (52-Week) Results Of a Phase 3, Randomized, Controlled Trial Of Apremilast, An Oral Phosphodiesterase 4 Inhibitor, In Patients With Psoriatic Arthritis and Current Skin Involvement (PALACE 3).” Conclusion: “Over 52 wks, APR continued to demonstrate efficacy in the treatment of PsA and associated psoriasis, including clinically meaningful improvements in signs and symptoms and physical function. APR demonstrated an acceptable safety profile with up to 52 wks of treatment and was generally well tolerated.”

M. Cutolo and colleagues presented the following study [Abstract No. 317]: “Apremilast, An Oral Phosphodiesterase 4 Inhibitor, Is Associated With Long-Term (52-Week) Improvement In Tender and Swollen Joint Counts In Patients With Psoriatic Arthritis: Results From Three Phase 3, Randomized, Controlled Trials.” Conclusion: “Over 52 wks, APR continued to demonstrate efficacy in the treatment of PsA, including clinically meaningful improvements in SJC and TJC. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks.”

G. Schett and colleagues presented the following study [Abstract No. 331]: “Apremilast, An Oral Phosphodiesterase 4 Inhibitor, Is Associated With Long-Term (52-Week) Improvement In Physical Function In Patients With Psoriatic Arthritis: Results From Three Phase 3, Randomized, Controlled Trials.” Conclusion: “Over 52 wks, APR continued to demonstrate meaningful clinical response in PsA pts, including measures of physical function. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks.”

There were some more studies shown at the  ACR 2013 Meeting in San Diego, for long-term safety look at the following study.

A. Kavanaugh and colleagues presented the following study [Abstract No. 310]: “ Long-Term Safety and Tolerability Of Apremilast, An Oral Phosphodiesterase 4 Inhibitor, In Patients With Psoriatic Arthritis: Pooled Safety Analysis Of Three Phase 3, Randomized, Controlled Trials.” Conclusion: “APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks with no new safety concerns identified with long-term exposure. These data do not indicate a need for laboratory monitoring.”

We now must look, which group of patients really benefits from the new drug. We must compare efficacy and costs in everyday life. And we still need some head to head evaluation against established biologics. How about radiographic changes erosions as well as proliferations? Still some work to be done and still a long way to go, but

Welcome Otezla!

There sure are patients waiting for you! And hopefully Otezla will get EMEA approval soon.

A New Venture into the World of Gout

Any rheumatologist having crossed Gout Creek must feel motivated to write about gout. Has anyone else?

Well I've crossed Gout Creek (New Zealand, South Island) and there have been some interesting new studies, so I feel very motivated to put a few ideas together.

We all know that alcohol isn't doing good to gout patients, but beer and liquor are tought to be more harmful than for instance a glass of wine. A new study questions this dogma.

T. Neogi and colleagues published the following study: "Alcohol quantity and type on risk of recurrent gout attacks: An internet-based case-crossover study" (Link: http://www.amjmed.com/article/S0002-9343(14)00032-1/abstract). Results: The study included 724 participants with gout (mostly men). The risk of recurrent gout attack was 1.36 for > 1-2 and 1.51 for > 2-4 alcoholic beverages higher compared with no alcohol consumption in the 24 hours prior to the gout attack. Consuming wine, beer, or liquor, all had lead to an increased risk of gout attack. The author's concluded: "Episodic alcohol consumption, regardless of type of alcoholic beverage, was associated with an increased risk of recurrent gout attacks, including potentially with moderate amounts. Persons with gout should limit alcohol intake of all types to reduce the risk of recurrent gout attacks."

I don't think that the "dogma" has been fully refuted, but it seems to be a good idea to point out to gout patients that it's better to avoid alcohol in any form. "Really, no alcohol at all?" As most people have a all or nothing attitude, allowing a teeny weeny bit of wine might ease the way to keep gout patients out of harm.

There have been some interesting papers at the EULAR 2013 Meeting in Madrid, link: http://rheumatologe.blogspot.de/2013/07/gout-at-eular-2013-meeting-in-madrid.html.

I hadn't yet written on interesting studies on gout, which had been presented at the ACR 2013 Meeting in San Diego. I'll dicuss a couple of these studies here.

J.M.A. Wijnands and colleagues presented an abstract [No. 90]: "Insufficient Evidence For An Increase In Prevalence and Incidence Of Gout: A Systematic Review and Meta-Regression Analysis." Methods: "Pubmed, Embase and Web of Science were systematically searched for primary studies on the prevalence and incidence of gout in the general population." Conclusion: "There was insufficient evidence for an increase in prevalence or incidence of gout in recent years." That's reassuring to hear, but I see more patients with more severe gout in recent years, maybe the rate of referral has changed.

Seong-Kyu Kim and collegues looked at [No. 93]: "Higher Consumption Of Sugar-Sweetened Soft Drinks Increases The Risk Of Hyperuricemia In Korean Population: The Korean Multi-Rural Communities Cohort Study." The study was superbly powered with N=9400. Conclusion: "Higher consumption of sugar-sweetened soft drinks increased the risk of hyperuricemia in the Korean population, showing a differential linear trend for hyperuricemia according to gender."

M. De Vera and colleagues presented [No. 210]: "Medication Adherence In Patients With Gout: A Systematic Review." Conclusion: "This is the first systematic review of medication adherence, with particular focus on gout patients. Adherence rates may vary according to methods used to measure adherence. Overall, synthesis of current evidence suggest that medication non-adherence is substantial in gout. Findings highlight the importance of discussing adherence with gout medications during health care professional encounters with gout patients." Among the studies included in this review, allow me to quote: Zandman 2013. N=7,644, follow up after 6 years, proportion of days covered: more than 80% - 17% of patients were still adherent!

K. Logee and colleagues presented [No. 214]: "Use Of Dual-Energy Computed Tomography In Evaluation Of Axial Gout." Nice pictures! Conclusion: "Dual-energy CT can be used to visualize the presence of axial MSU deposition. This may lead to appropriate diagnosis and management of axial gout while avoiding invasive procedures and erroneous treatment." I think, we're still far away from the second half of the authors' conclusion.

P. Sunkureddi and colleagues presented the following study [No. 1177]: "Efficacy and Safety Of Canakinumab Pre-Filled Syringe Versus Triamcinolone Acetonide In Acute Gouty Arthritis Patients." Conclusion: "CAN-PFS (Canakinumab pre-filled syringe) was superior to TA (triamcinolone acetonide) in relieving pain and reducing risk of new attacks, and had a safety profile similar to CAN-LYO (Canakinumab lyophilized powder). The safety profile was also consistent with that observed in previous CAN-LYO studies. Efficacy and safety of the two CAN (Canakinumab) formulations were comparable." I know that this study won't have much impact on daily life, but I think it's an important study for the one patient we all might see in the next years, where everything else had failed.

K.G. Saag and colleagues looked at [No. 1178]: Effect Of Febuxostat On Serum Urate Levels In Gout Subjects With Hyperuricemia and Moderate-To-Severe Renal Impairment: A Randomized Controlled Trial." Conclusion: "In subjects with moderate-to-severe renal impairment, FEB (febuxostat) urate-lowering was efficacious, with no emergent serious safety issues at 12 m (months). The sUA (serum uric acid) was significantly reduced in subjects receiving either regimen of FEB compared to PLB (placebo)." I guess, febuxostat is now fully established, though the high price might still be a problem.

S. Baumgartner and colleagues looked at [No. 1189]: "Allopurinol Dose Titration and Efficacy: A Large-Scale, 6-Month, Multicenter, Prospective Study." Conclusion: " In this large, multinational, prospective observational study of gout, optimal allopurinol dose escalation occurred infrequently. Fewer than 50% of patients overall achieved target sUA level greater than 6.0 mg/dL and the majority of those with a baseline dose of or higher than 300 mg/day did not increase their dose. These data, consistent with published literature, likely reflect real-world circumstances in which a significant proportion of patients fail to reach sUA targets with allopurinol therapy as currently used." PDCA! We have good plans (plan), we put them into practice (do), we have to check more consequently (check), and act - increase the dosage. Hopefully, patients won't leave this quality improving cycle.

F. Perez-Ruiz and colleagues presented [No. 1191]: Low-Dose Anakinra Is Effective For The Prophylaxis Of Acute Episodes Of Inflammation In Severe Tophaceous Gout." Conclusion: "This pilot study is, to our knowledge, the first to prospectively explore in pre-established doses the efficacy of low-dose anakinra for the prophylaxis of AEIs in patients with severe comorbidities and difficult to treat tophaceous gout."

R.T. Keenan and colleagues presented [No. 1193]: "Target Tophus Size and Complete Response Rates In Patients Treated With Open-Label Pegloticase For Chronic Gout Refractory To Conventional Therapy." Conclusion: "Many small and medium subcutaneous tophi resolved within the first 6 months of pegloticase therapy. These data show that substantial incremental benefit in tophus response for unresolved small to medium tophi can be gained with 9–12 months of therapy in UA responders." I have seen patients, who would benefit from pegloticase, but there are problems with getting an appoval by insurance companies as it's an off-label use.

There were lots of interesting studies on gout at both the EULAR 2013 Meeting in Madrid and the ACR 2013 Meeting in San Diego. Let's hope that we can counsel patients even better now.

Picture of tophous gout

Rituximab - to extra dose or not - and more problems

Today I’ve read an abstract concerning an extra dose of 1000 mg rituximab.

Vitall, E.M. and colleagues published the following paper: “An extra dose of rituximab improves clinical response in rheumatoid arthritis patients with initial incomplete B cell depletion: a randomised controlled trial” (Link: http://ard.bmj.com/content/early/2014/01/17/annrheumdis-2013-204544.abstract). Conclusion: “In rituximab-treated patients with incomplete B cell depletion (predictive of poor response), an extra 1000 mg infusion of rituximab at 4 weeks produced both better depletion and clinical responses than placebo with no worsening of safety. Degree of depletion is an important, but modifiable, determinant of response.”

M. Mahevas and colleagues were interested to investigate the following problem: “Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia” (Link: http://www.ncbi.nlm.nih.gov/pubmed/23798363). “The efficacy of two (RTX) regimens: standard therapy of 375 mg/m(2) weekly for 4 weeks vs. a rheumatoid arthritis (RA) regimen of 1,000 mg on days 1 and 15, to treat ITP was compared.” “Tolerance was good and comparable between the two groups. The RA regimen is an effective and safe alternative to the standard regimen to treat adults with ITP.”

And I’d like to point out to a third study, which has been presented at the ACR 2013 Meeting in San Diego [498] by M. Bredemeier and colleagues: A Systematic Review and Meta-Analysis Comparing Low- Versus High-Dose Rituximab For Rheumatoid Arthritis.” Conclusion: “Low-dose RTX has similar effectiveness and met noninferiority criteria for most primary outcomes. Considering the lower cost, it should be the standard RTX regimen for rheumatoid arthritis.”

And I nearly forgot this study, presented at the ACR 2013 Meeting in San Diego [500] by K. Chatzidionysiou and colleagues: “Fixed Versus On-Flare Retreatment With Rituximab In RA—Results From The Cererra Collaboration.” Conclusion: „A fixed retreatment strategy with RTX in RA seems to be more effective than the retreat ‘on-flare’ strategy.”

The studies show that there are still a couple of unresolved problems both in treating RA and ITP, not to mention other entities. Vitall’s study tells us to consider an extra dose, so we need to monitor B-cell depletion, which we usually don’t do in routine treatments. Reimbursement of lab tests differs in different countries. Here in Germany there might be differences in which kind of health care provider is included. Maybe there’s also the problem of an off-label use. But I think we should consider a third dose before switching to another boDMARD.

Mahévas’ study shows us, that even in ITP a less aggressive strategy might also work. And this leads to the study of M. Bredemeier and colleagues. They describe another possible group of patients, who need less rituximab. And the last quoted study favours a fixed strategy instead of an “on-flare” strategy, but doesn’t answer, if a strategy shortly before a flare would succeed. I know the difficulty lies in determinating “shortly before a flare”; but that’s where we rheumatologists come into play.

To sum it up, in treating RA patients with rituximab we might encounter a group that needs a higher dose, a group that needs a standard dose, another one that needs a lower dose, and these groups might be further divided to fixed or variable infusion intervals. No easy task and more studies are needed. 

Iguratimod at the ACR 2013 Meeting in San Diego

Iguratimod (T-614) is a novel disease modifying anti-rheumatic drug (DMARD). Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation. As I have already written this before, please look for the links below. 2012 there had been three studies, 2013 one study at the EULAR Meeting in Madrid (a study by a Chinese group).

There has only been on study at the ACR 2013 Meeting. Daisuke Kobayashi and colleagues published the following study [#1422]: “Efficacy and Safety Of a Novel Disease-Modifying Antirheumatic Drug, Iguratimod, As Add-On Therapy For Patients With Rheumatoid Arthritis.” The study has been small (N=26). Conclusion: “Iguratimod is effective as add-on therapy in RA patients who have shown inadequate responses to previous therapy, although caution is necessary regarding hemorrhagic tendency in patients receiving warfarin, which was cautioned by Ministry of Health, Labour and Welfare of Japan.”

I think iguratimod is indeed a promising candidate for treatment of active rheumatoid arthritis and might become a needed alternative in the conventional (traditional) DMARD class. I wished the sponsor would press more for results, also for studies, which would result in an appearance on the world market.

Link:

Iguratimod at the EULAR Meeting 2012 http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

Iguratimod at the EULAR Meeting 2013 http://rheumatologe.blogspot.de/2013/06/iguratimod-at-eular-2013.html

Biosimilars at the 2013 ACR Meeting in San Diego

I’ve already written a longer text after the 2013 EULAR in Madrid last year, please use the link below. At this time EMEA's Committee for Medicinal Products for Human Use (CMHP) had recommended biosimilars of infliximab by Celltrion and Hospira to be granted the same indications as Remicade®. I haven’t seen any news on when biosimilars will be available in Europe so far. So, the meetings are extremely important to look at the progress of biosimilars.

At the ACR meeting there were only four publications concerning biosimilars.

Rituximab Biosimilar (CT-P10) by Celltrion:

Dae-Hyun Yoo and colleagues, most working for Celltrion, presented the following study [#1736]: “A Randomized, Controlled, Multicenter, 2-Arm, Parallel-Group, Double-Blind Study To Demonstrate The Equivalence Of CT-P10 To Innovator Rituximab With Respect To Pharmacokinetic Profile In Patients With Rheumatoid Arthritis.” Conclusion: „CT-P10 and RTX were equivalent in terms of AUC0–last and Cmax in patients with active RA. Clinical efficacy for ACR20/50/70 and EULAR response rates and PD for B-cell kinetics were comparable between the two treatment groups. CT-P10 was well tolerated with a safety profile comparable to that of RTX up to week 24.“

Etanercept Biosimilar (GP2015) by Novartis:

A. da Silva and colleagues, most working for Novartis, presented this study [#1862]: “Target-Directed Development Of a Proposed Biosimilar Etanercept, GP2015: Comparability Of In Vitro Target Binding and Pre-Clinical Efficacy and Pharmacokinetics.” Conclusion: “This non-clinical similarity exercise confirms that GP2015 and the reference medicinal product are pharmacologically highly-similar with regard to target binding, anti-TNF_ biological activity and PK exposure. Future clinical trial(s) are needed to provide evidence of similar efficacy and safety of GP2015 to that of the originator product.”

Rituximab Biosimilar (PF-05280586) by Pfizer:

D. Thomas and colleagues of Pfizer presented the following study [#2372]: “Comparison Of Proposed Biosimilar PF-05280586 With Rituximab: Nonclinical and Phase I Clinical Assessments.” Conclusion: “PF-05280586 showed in vitro structural and functional similarity to rituximab-EU. PF-05280586 and rituximab appear to be well tolerated in nonclinical and clinical studies. These results support the development of PF-05280586 as a proposed biosimilar to rituximab.”

Infliximab Biosimilar (CT-P13) by Celltrion:

Dae-Hyun Yoo and colleagues, most working for Celltrion, presented the following study [#2392]: “Impact Of CT-P13 and Originator Infliximab Treatment On Quality Of Life Derived From The Health Assessment Questionnaire (HAQ) and Short-Form 36 (SF-36) From a Randomized, Double-Blind Trial In Patients With Active RA.” Conclusion: “Treatment with infliximab improved physical function as assessed by HAQ in patients with moderate to severe physical disability which was sustained over a one year interval. These data support the comparability with respect to improvement in physical function of CT-P13 and INX in patients with active RA.”

Most advanced candidates are the infliximab and rituximab biosimilars by Celltrion. Quite strange that Pfizer is also working on a biosimilar of rituximab, but is still far behind, which also applies to the etanercept biosimilar of Novartis.

I’ve just checked my notebook, no further information.

So we have to wait for EMEA and FDA to move.

PS. If you hear something about biosimilars being introduced to the market elsewhere, please let us know.

Links:

Biosimilars at the 2013 EULAR Meeting in Madrid http://rheumatologe.blogspot.de/2013/07/biosimilars-after-eular-2013.html

Newer Biologics at the ACR 2013 Meeting in San Diego

I've listed the newer biologics. Already I've marked some red as there haven't been new studies or an old study had been presented. I have already gone into detail concerning Mavrilimumab, SAN-300, and Tregalizumab. I'll have a look at other compounds soon.

Links:

Mavrilimumab http://rheumatologe.blogspot.de/2013/11/mavrilimumab-at-acr-2013-meeting-in-san.html

SAN-300 http://rheumatologe.blogspot.de/2014/01/san-300-at-2013-acr-meeting-in-san-diego.html

Tregalizumab http://rheumatologe.blogspot.de/2014/01/tregalizumab-at-acr-2013-meeting-in-san.html

SAN-300 at the 2013 ACR Meeting in San Diego

SAN-300 is an anti Very late antigen-1 (VLA-1) MAB. It already has been used in ophthalmology to promote survival of corneal allografts. Or in 2002 it reduced glomerular and tubulointerstitial scarring in a rat model of (crescentic) glomerulonephritis. And now it’s being tested in healthy subjects and patients with active RA, as VLA-1 facilitates migration, proliferation, and retention of lymphocytes and monocytes/macrophages.

Ch. Inderjeeth and colleagues presented the following study [1439]: “Safety, Pharmacokinetics, and Pharmacodynamics Of SAN-300, a Novel Monoclonal Antibody Against Very Late Antigen-1: Results Of a Phase 1 Study In Healthy Volunteers and Patients With Active Rheumatoid Arthritis.” In “Results” we read: “[…] The single patient with active RA who received SAN-300 2.0 mg/kg IV met ACR50 at Days 15 and 29 and achieved a good response per EULAR criteria based on DAS28-CRP at Day 15 (_1.66; absolute score 2.31), and a moderate response at Day 29 (_0.92; 3.05). The placebo patient did not meet criteria for ACR20 or DAS28-CRP response at any time point. Conclusion: “In this first-in-human study, SAN-300, an antibody against novel therapeutic target VLA-1, showed nonlinear pharmacokinetics. […] Given favorable tolerability, encouraging RO [receptor occupancy], and ease of administration, the SC route of administration warrants investigation in future multiple-dose studies in patients with active RA.”

When I read the background I thought that the producer of SAN-300 looks for a new field to yield fruit. But the results of this phase 1 study warrant further investigation. Who know, if we’re not going to get another useful drug to fight RA.

ABT-122 at the 2013 ACR Meeting in San Diego

ABT-122 is a dual variable domain immunoglobulin targeting both TNF-alpha and IL-17. Mouse studies showed the combination more efficacious than treatment with either antibody.

Chung-Ming Hsieh and collegues presented the following study [1427]: “Discovery and Characterization Of ABT-122, An Anti-TNF/IL-17 DVDIg ™ Molecule As a Potential Therapeutic Candidate For Rheumatoid Arthritis.” Results: “In acute mouse models in vivo, these DVD-Ig™ molecules also demonstrated potent inhibition of human TNF and IL-17 activity. The DVD-Ig™ molecule with the best affinity and potency, as well as the longest half-life in rat was designated ABT-122 for further development.” Conclusion: “Based on the combined efficacy in a preclinical mouse arthritis model, the demonstrated efficacy of TNF-targeted therapy in RA patients, and encouraging response to IL-17 antibodies in RA clinical trials, we will be evaluating the efficacy and safety profile of the anti-TNF/IL-17 DVD-Ig™ molecule in human RA clinical trials.”

The crucial point will be: does better efficacy also mean more side effects. Perhaps we have been too restrictive in combining biologics in the past. Maybe strategies using more than one biologic agent, maybe in a certain sequence, will yield a therapeutic approach with less side effects and more efficacy. But I’m dreaming …

ABT-122 is in preclinical evaluation, and let’s hope that we see clinical data soon. The approach is interesting.

Tregalizumab at the ACR 2013 Meeting in San Diego

You might not have heard about tregalizumab before! Tregalizumab has been developed as a biomarker to monitor response to biologics. Wikipedia is quite taciturn on tregalizumab: “Tregalizumab is an immunomodulator. It binds to CD4.” http://en.wikipedia.org/wiki/Tregalizumab The abstract at the ACR meeting puts it this way: “Tregalizumab is a humanized, agonistic monoclonal antibody which binds to a unique epitope of CD4, and induces Treg-specific activation and suppresses CD4 and CD8 effector cell proliferation and activity in vitro.”

E. Dokoupilova and colleagues presented the following study [1412]: “Use Of a Biologic Marker For An Integrated Pharmacodynamic and Clinical Analysis To Inform Further Clinical Development, Including Dose Selection For The Phase 2b Trial - Treat 2b - Of Tregalizumab In Rheumatoid Arthritis.” Conclusion: “Interim efficacy and safety data from the Phase 2b Study 979, combined with data from previous RCTs, indicated the feasibility and tolerability of this therapeutic approach. […] The available data support further development of tregalizumab.”

The abstract informs us of very early data, so I think we have to wait for more, stressable data. We would be lucky to have another mode of action. 

Protein kinase inhibitors - where do we stand after the 2013 ACR Meeting

As we've seen quite a lot of compounts being studied during the past two or three years, I think it's to look how much hype or hope there is.

This list remains incomplete, I know, but it shows that our hopes are mixed with lots of hype. And this list is my personal interpretation; someone might disagree and should do so in the commentary part. Red stands for problems or that I don't think it will develop into a drug on the market. Yellow stands for might develop into a drug, still to early. Though I still have my doubts in fostamatinib (lake of showing effect on reducing radiographic progression), I have put fosta on yellow again as new results have been shown.

I think that too many pharmaceutical companies tried to run for a small molecule, which is easier to produce, but might be sold at a high price.

I hope that we'll get these drugs in the future, though well tested, safe, and not at the top pricing drug companies expect.

Xeljanz right now stands alone on the U.S. market (green). EMEA hasn't approved yet and the European market will have to wait for another while as studies on radiographic progression take time. Even if there is much hype, I hope for Xeljanz at least to make it to the European market.

But maybe the future isn't as dim as my list seems to predict. Concerning rheumatology we're living in exciting times.

For an older text you might look here: http://rheumatologe.blogspot.de/2013/06/protein-kinase-inhibitors-hype-or-hope.html

Influence of Weather on Rheumatoid Arthritis Disease Activity

It's still a big question, but we're getting closer to an answer. People with rheumatoid arthritis often complain about the influence of weather an disease activity. There were two studies at the ACR 2013 Meeting in San Diego addressing the issue.

T. Sawada and colleagues presented the following study [Abstract #1356]: "Disease Activity Of Rheumatoid Arthritis Is Influenced By Seasonal Change, As Analyzed Based On a Nationwide Japanese Cohort Database." This study looked more at seasonal variations than weather and found, that "RA disease activity, as assessed both subjectively and objectively, was lowest in fall." Sorry, that won't get us any further, though one would have to take this account, when doing studies in Japan.

E. Savage and colleagues presented the second study [Abstract #1359]: "Does Rheumatoid Arthritis Disease Activity Correlate With Weather Conditions?" The authors come mostly from Belfast, Northern Ireland, but one also from St. Vincent’s Hospital, Melbourne, Australia, where I had the pleasure to do some research on DRGs. I guess that the data has been collected in Belfast. 133 patients either on stable etanercept or adalimumab were recruited for this study. The authors lokked at "three weather components from the seven quantitative variables (maximum temperature, minimum temperature, hours of sunshine, mm rainfall, relative humidity, wind-speed and pressure)." Conclusion: "This study demonstrates statistically significant lower DAS-28 scores in sunny and dry conditions. A non-significant trend to higher DAS-28 scores in times of low temperature, and dull, wet and windy weather was also noted." I'm surprised to hear about sunny and dry weather in Belfast, but now we have statistically significant results that prove patients complaints.

Mavrilimumab at the ACR 2013 Meeting in San Diego

Mavrilimumab is a human MAB for the treatment of rheumatoid arthritis. It targets the GM-CSF receptor-alpha. More at: http://en.wikipedia.org/wiki/Mavrilimumab

Usually we are talking about T and B cells in rheumatoid arthritis or maybe dendritic cells, but now neutrophils and macrophages come into focus. GM-CSF controls activation, differentiation, and survival of macrophages and neutrophils.

I've just been to an ACR review/update course here in Germany and the colleagues were very much in favour of this new drug.

There have been three studies on mavrilimumab at the ACR 2013 Meeting in San Diego.

G.-R. Burmester and colleagues presented the following study [Abstract #1733]: "Early and Sustained Improvement In Pain and Physical Function As Measured By Visual Analog Scale and Short Form-36 Physical Component Summary Score In Rheumatoid Arthritis Patients Treated With Mavrilimumab, An Investigational Anti-GM-CSFR-Alpha Monoclonal Antibody, In a Phase 2a Study." Conclusion: "Treatment with mavrilimumab 100mg resulted in an early onset and sustained improvement in pain relief and physical functioning as measured by VAS and SF-36 PCS, respectively, in moderate-severe RA patients. These findings are consistent with improvement in the disease activity (DAS28-CRP) and support further investigation of the blockade of the GM-CSF receptor with mavrilimumab in Phase 2b studies conducted in both DMARD-IR and TNF-IR patients."

W. White and colleagues presented the second study [Abstract #2377]: "Biomarkers Associated With Rheumatoid Arthritis Disease Activity Including Joint Damage Correlate With Changes In Clinical Response In Subjects Treated With Mavrilimumab At Doses Above 10 Mg." Conclusion: "Promising clinical safety and efficacy results of mavrilimumab support further clinical development at doses greater than 10 mg. Mechanistically, the drug suppressed both acute phase and inflammatory blood markers. Tracking of disease activity by MBDA showed a clear biomarker-based dose-response relationship. The association of MBSD decline with radiographic damage will be assessed in an on-going phase 2b study."

But there hasn't been any data on radiographic changes up to now.

P.C. Ryan and colleagues resented a study on monkeys [Abstract #2378]: "Safety Of Mavrilimumab In Cynomolgus Monkeys: Relevance Of Nonclinical Findings In Lung To Human Safety." Conclusion: "These results suggest that suppressing macrophage activity by targeting GM-CSF receptor alpha may be a novel approach with an acceptable safety profile for the treatment of RA."

Interestingly in "results" the results of a study published at the EULAR 2012 Meeting in Berlin has been quoted: "In EARTH,

mavrilimumab demonstrated good clinical activity with no clinically significant or persistent changes in the lung function tests performed. Likewise, the serum biomarkers of lung damage, SP-D and KL-6, showed no clinically significant changes following mavrilimumab treatment." The study at the EULAR 2012 had been by S. Spitz and colleagues [Abstract AB0576]; "Evaluation Of Surfactant Protein-D And Kl-6 As Potential Pulmonary Safety Biomarkers During Mavrilimumab Treatment".

It is like in a detective story - the inspector frowns if someone gives an alibi without being asked for it. Though as macrophages are involved the side effects on the lung should be monitored.

The recent data looks much better than what has been presented last year, but still we lack a study of longer duration with data on radiographic progression. And as the studies EARTH explorer 1 and 2 look at other dosages (also 150 mg) and test against golimumab for 24 weeks, results on radiographic progression still have a long way to come.

Summing it up: it looks better for mavrilimumab than a year ago, but still we don't know if there's going to be a new drug.

Links:

http://rheumatologe.blogspot.de/2013/06/mavrilimumab-at-eular-2013-meeting.html 

http://rheumatologe.blogspot.de/2013/03/mavrilimumab.html 

http://rheumatologe.blogspot.de/2012/07/mavrilimumab-at-eular-2012.html 

Lodotra (modified or delayed release prednisone) at the ACR 2013 Meeting in San Diego

Let me talk again about modified or delayed release prednisone (Lodotra) as two studies have been presented at the ACR 2013 Meeting in San Diego.

F. Buttgereit and colleagues presented this study [Abstract # 2255]: "Threshold Analysis of Patient Reported Morning Stiffness Where Delayed-Release (DR) Prednisone Was Compared to, and Replaced, Immediate Release Prednisone in Rheumatoid Arthritis (RA) Patients Receiving Conventional Disease-Modifying Antirheumatic Drugs (DMARDs) Over 1 Year." IR-prednisone, taken in the morning, is compared to DR-prednisone, taken once daily at bedtime (e.g. 10pm). Conclusion: DR prednisone, as compared to IR prednisone, produces significantly higher MS response rates as defined by 25/50/75% improvement thresholds.  [...]."

The same patients were analysed in this study, which had been presented by R. Alten and colleagues [Abstract # 2265]: "Switching From Immediate Release (IR) Prednisone To Delayed Release (DR) Prednisone Improves Patient Reported Outcomes In Rheumatoid Arthritis (RA) Patients On Conventional Disease-Modifying Antirheumatic Drugs (DMARDs)." Conclusion: "This analysis demonstrates that RA patients on stable DMARD therapy, who have not adequately responded to IR-prednisone with respect to morning stiffness, showed statistically significant and clinically meaningful improvement in this symptom when switched to DR prednisone [...]."

Where's the catch? There's more than one. First: would you call a patient, who suffers two hours of morning stiffness, stable? Second: the advocates of Lodotra claim chronotherapy for their therapy, but we're already doing chronotherapy. We give immediate release prednisone in the morning to optimize (reduce) side effects. Lodotra is given in the evening to be released during the night to optimize (increase) therapeutic effects. In any study designed as this study DR prednisone will be better than IR prednisone. This is due to the time, when the drug is given. So the study shows that prednisone given at different times has different effects on morning stiffness. If you really want to test, if the DR mechanism has any advantage over IR prednisone, you would have to give both at the same time in the evening. My guess is that significance dwindles to a trend. Unless I see such a designed study, I won't prescribe DR prednisone.

Links to other blogposts on Lodotra on this blog:
http://rheumatologe.blogspot.de/2013/06/modified-release-prednisone-at-eular.html

http://rheumatologe.blogspot.de/2012/11/lodotra-auf-dem-kongress-der.html (Text in German)
http://rheumatologe.blogspot.de/2012/06/modified-release-prednisone.html 
http://rheumatologe.blogspot.de/2010/06/lodotra-my-problems-with-new-miracle.html

Osteoarthritis Satellite Symposium at the ACR 2013 Meeting in San Diego

Very near to the end of the ACR 2013 Meeting in San Diego I went to a Satellite Symposium with the full title of "Prognosis and Treatment of Knee Osteoarthritis Update 2013". Let's have a closer look at some of the data presented at this event.

V. Byers Kraus presented a cell study that concluded: "Chondroitin sulfate ... suggesting that it may inhibit an inflammasome component, assembly, or action" and "this mechanism may also play a role in Osteoarthritis ...“ Too much suggesting and may!

J. Martel-Pelletier presented: "Effects of Glucosamine and Chondroitin Sulfate on Knee Osteoarthritis Structural Changes over Time: Data from the OAI Cohort". It isn't a blinded trial but retrospective data was used. Out of 1300 patients 600 were selected. The presentation showed charts with an extreme amount of numbers. Comparing joint space width (JSW) in patients not taking analgesics two parameters showed a significant difference, but ... 13 other parameters didn't show a significant difference! If you looked at MRI changes and JSW you also had some effects, but these were different, when examined at 12 and at 24 months! Conclusion: "Data from this study provide support for the structure-modifying effects of Glu/CS combination in knee osteoarthritis subjects. [...]". Please no; these effects are more likely to be due to chance. Besides, how can you tell if people taking glucosamine and chondroitin sulfate aren't more health orientated and do more exercises, change diet, and so on?

C.W. Wu presented a study on oral hyaluronic acid for the treatment of osteoarthritis knee pain. The study was small sized and of 51 patients only 40 completed the study. The WOMAC has been non significant or even identical at month 2 and conveniently made a big leap in the next four months to show a significant difference; now explanation for this inconsistent data. A comparison between hyaluronic acid turnover in placebo and verum group has been made, but only in nine placebo patients and ten verum patients. I'd be more careful with conclusions on this set of data. A test on 12 cytokines and chemokines has been done, placebo had an increase and verum a decrease in ALL parameters, but no values were given. Role of each in osteoarthritis? Significant changes or not?

There were other studies, but only on comorbidities, drug utilization, and a DNA-based test.

I don't think that the studies, which I've outlined above, prove anything that warrant the use of glucosamine and/or chondroitin sulfate in knee osteoarthritis. Or maybe they prove indirectly how in vain the drug companies try to find something to base their advertisements on.

ACR Meeting 2013 in San Diego the scientific part

These are some of my interests in the ACR meeting 2013 in San Diego. It's a kind of overview. I'll use it to comment directly and/or to show the links to further information on this blog (at most times). So it's a work in progress. I'll date all the the entries, because otherwise I wouldn't know myself, when I'd written which entry. I've kept the colour coding. Black entries are past the meeting. The original text is at the end in small letters.

01.11.2013

AC0025

Poster #2353: A dual target inhibitor - BTK and JAK3 (AC0025). Preliminary rat study.

29.10.2013

Adalimumab and smoking

Poster #2439: Smoking not associated with reponse to adalimumab in axial SpA. The smoker's choice?

29.10.2013

Alginate-Chitosan beads

I'm very skeptical, but I'll have my time to see how this develops as the study is on rabbits (#76).

27.10.2013

Apremilast

There are a few posters on apremilast (PDE4) in psoriatic arthritis.

27.10.2013

B cell differentiation inhibition

There's a new approach. The cereblon E3 ubiquitin ligase complex is modulated by CC-220, which results in an inhibition of B cell differentiation. I must admit, that I hear of this for the first time. Two abstracts: #41 and #42.

27.10.2013

Brodalumab

Phase 2 study, 24 weeks physical function in psoriatic arthritis. #318

27.10.2013

CC-220

See: B cell differentiation inhibition

27.10.2013

CD40

Poster #40 on blockade of CD40 - CD40L pathway, which "dampens multiple immune responses". Preclinical characterization.

27.10.2013

Clazakizumab

Poster #2385: Anti-IL-6 MAB clazakizumab shows higher potency than tocilizumab. Will this be an advantage? Maybe tocilizumab should be available before clazakinumab comes to the market (which might take a while!)

29.10.2013

Delayed release prednisone

Poster #2265: Delayed release prednisone. I question the study, because I don't consider two hours of morning stiffness as stable disease and would change therapy. The authors compare prednisone given in the evening with a delay mechanism with prednisone given in the morning. They should have compared the delayed release prednisone with common prednisone, given in the evening, at the time. If someone present a study done this way ... , but I guess no one will, at least the drug company can't be interested.

29.10.2013

Methods, as in the abstract: “CAPRA-1, a 12-week, double-blind, controlled study, randomized patients to IR-prednisone taken in the morning or DR-prednisone taken once daily at bedtime (eg, 10pm) in addition to standard DMARD treatment. …”

01.11.2013

http://rheumatologe.blogspot.de/2013/11/lodotra-modified-or-delayed-release.html
04.11.2013

Fibrofog and Alzheimer's

This is good news! the data by Katz et al. don't support a transition from fibrofog to Alzheimer's disease.

27.10.2013

Fibromyalgia

Poster #1108 on methylphenidate in Fibromyalgia - conclusions with too many hypothesis.

Dianne Whiting presented an interdisciplinary program for Fibromyalgia. Exercises, Yoga, education, CBT, more.
Poster #1092 on low dose naltrexone in Fibromyalgia - luckily it ended: may be effective, further trial needed. My 2 ct.: dead end street.

28.10.2013

Fish oil and knee OA

Poster #2147: Fish oil doesn't have an effect on structural progression of knee OA. They used 9 g, which would be 18 cps. in Germany.

29.10.2013

Fostamatinib

OSKIRA-2, a phase 3 study. I'll have to check the to posters with earlier publications. #455 and #456.

27.10.2013

Poster #1295 talks about mechanisms for fostamatinib induced blood pressure elevation. And, how about data on radiographic progression?

28.10.2013

Free fatty acids

Poster #1842: Free fatty acids affect arthritic cell. Exact nature not known yet.

29.10.2013

GLPG0634 (JAK1 inhibitor)

#478 Study on dogs and monkeys.

27.10.2013

Poster #2381: GLPG0634 effects on DAS28 and ACRxx, but only in a four week study. Good respose rates though.

29.10.2013

HAQ and consequences of physical activity

Poster #2273: Patient Survey on HAQ reveals an unrecognized aspect of disease activity in RA: consequences of physical activity.

29.10.2013

HM-0523

A novel Syk inhibitor. Abstract #474 tells us that HM-0523 significantly ameliorates the severity of arthritis in rodents.

27.10.2013

Iguratimod

There's a study on iguratimod, which has received Japanese approval in Sept. 2012. Too bad, only N=23! So they should present a larger overview. I don't know, why the company isn't pressing to get an approval by FDA or EMEA.

28.10.2013

Ixekizumab

#343 shows a phase 2 study.

27.10.2013

Knee osteoarthritis
A look at a satellite symposium on glucosamine, chrondroitin sulfate, and hyaluronic acid in knee osteoarthritis.
http://rheumatologe.blogspot.de/2013/11/osteoarthritis-satellite-symposium-at.html
04.11.2013

Life events and developing RA

Poster #2402: Association between life events and an increased risk of developing RA.

29.10.2013

Mavrilimumab

Poster #2378: Mavrilimumab shows a study on lung AE in cynomolgus monkeys. Not very reassuring.

29.10.2013
But there's more, I've found all in all studies, which are worth discussing.

http://rheumatologe.blogspot.de/2013/11/mavrilimumab-at-acr-2013-meeting-in-san.html
05.11.2013

Methotreate

Study #1362 claims: iSyMind reduces MTX induced nausea. A pilot trial of N=4. These people have chuzpe! Perhaps they think of a change of paradigm?

28.10.2013

Poster #1977: Pain related anxiety as a barrier to use methotrexate (MTX) - needle, autoinjector etc. tested on healthy volunteers.

29.10.2013

NI-0101

Poster #????: Novel anti-human TLR4 MAB (NI-0101). Cell study!

29.10.2013

Omega-3 fatty acids and SLE

Poster #2538: SLE patients benefit from omega-3 fatty acids.

29.10.2013

Opiods in Osteoarthritis

EA Wright and colleagues looked at the development of opioid prescriptions in patients with knee osteoarthritis. The authors found a steady increase. The public impact of higher opioid use should be carefully monitored.

27.10.2013

Psoriatic Arthritis - conventional DMARDs

A study be E Lie and colleagues (#343) looked at conventional DMARDs in psoriatic arthritis. The drug survival rate of SSZ after two years is about 30%, LEF is at 41%, and MTX lies at 62%. And MTX achieves higher rates of ACR20, ACR50 and ACR70 at 6 months.

27.10.2013

Sleep disturbances in rheumatic conditions

Poster #1930 i s on sleep disturbances (SD) in different rheumatic conditions. SD leads to higher disease activity.

Authors stress to look also at SD and not only at joint swelling and pain. I'd like to add fatigue.

29.10.2013

Strontium ranelate

A study of strontium ranelate in long bone fractures with delayed union. Single arm study though. Not convincing.

28.10.2013

It seems that the drug company of strontium ranelate is desperately seeking a new field. How about comparing strontium ranelate to a bisphosphonate in the same indication?

01.11.2013

Tender Point Measurement at home (FMS)

There's a study suggesting that self measurement of tender points will have a positive effect. I see in it a method to promote pain sensitization. And: don't physicians and patients have better topics than tender points to talk about?

27.10.2013

Tocilizumab

SC equal to IV. I hope, we"ll soon see an approval to be able to use it.

27.10.2013

Poster #1207: Efficacy of tocilizumab in pats. with AA amyloidosis. But not all responding.

alhkim @alhkim thinks of dz heterogeneity.

I'm surprised that it should work at all in AA amyloidosis. I was waiting for some study, as Prof. Kishimoto mentioned it earlier this year.

28.10.2013

Tofacitinib

There have been eight posters on tofacitinib today. #438 to #445. Most were circling around the question of side effects.

ORAL Sequel had a higher rate of SAE than ORAL Standard (#438).

Tofacitinb has the same rate of gastrointestinal events as TNFi (3439).

Cardiovascular events are not increased (#440).

Tofacitinib has a higher rate of herpes zoster (#441).

Tolerability with and without DMARDs are equal (#442).

US and rest of the world pats. are equal in respect of efficacy and side effects (#443).

Dosing every two weeks has less side effects (#444).

Tofacitinib is an independent risk factor in multi morbid elderly patients (#445).

27.10.2013

Effects of smoking in pats. receiving tofacitinib. Need for longer observation #1418

28.10.2013

Poster #1977: After a plethora of posters on tofacitinib, just one with data on radiographic progression.

29.10.2013

Triple therapy

There's a study on discontinuation rates of triple therapy in RA, result: high rate, but further work is needed.

28.10.2013

Unique self joint examination tool

Poster #2242: Despite a unique self joint examination tool, pat. and physicians joints counts differ significantly.

29.10.2013

Ustekinumab

Poster #????: Actually more than one poster on ustekinumab in psoriatic arthritis. It's approved in Europe, now.

29.10.2013

VX-509

Poster #2350: New data by VX-509 (JAK3i). Pain, HAQ-DI etc. are better, but DAS28 or ACR20 aren’t shown.

29.10.2013

Weather and RA

Poster #1359 addresses the question: Does RA disease activity correlate with weather conditions? DAS28 is lower under sunny and dry weather conditions.

28.10.2013

There have been two posters/abstracts addressing the issue, look here: http://rheumatologe.blogspot.de/2013/11/influence-of-weather-on-rheumatoid.html
06.11.2013

This is the scientific part of my ideas on the 2013 ACR meeting in San Diego. I plan it to write part of it, while I'm still at the meeting and not afterwards. So it's a work in progress. I'll keep topics in alphabetical order per day and rearrange the text at home. I'll go into details to some of the topics, when I'm back home.

Alginate-Chitosan beads
I'm very skeptical, but I'll have my time to see how this develops as the study is on rabbits (#76).

Apremilast
There are a few posters on apremilast (PDE4) in psoriatic arthritis.

B cell differentiation inhibition
There's a new approach. The cereblon E3 ubiquitin ligase complex is modulated by CC-220, which results in an inhibition of B cell differentiation. I must admit, that I here of this for the first time. Two abstracts: #41 and #42.

Brodalumab
Phase 2 study, 24 weeks physical function in psoriatic arthritis. #318

CC-220
See: B cell differentiation inhibition

CD40
Poster #40 on blockade of CD40 - CD40L pathway, which "dampens multiple immune responses". Preclinical characterization.

Fibrofog and Alzheimer's
This is good news! the data ba Katz et al. don't support a transition from fibrofog to Alzheimer's disease.

Fostamatinib
OSKIRA-2, a phase 3 study. I'll have to check the to posters with earlier publications. #455 and #456.

GLPG0634 (JAK1 inhibitor)
#478 Study on dogs and monkeys.

HM-0523
A novel Syk inhibitor. Abstract #474 tells us that HM-0523 signicifantly ameliorates the severity of arthritis in rodents.

Ixekizumab
#343 shows a phase 2 study.

Opiods in Osteoarthritis
EA Wright and colleagues looked at the development of opioid prescriptions in patients with knee osteoarthritis. The authors found a steady increase. The public impact of higher opioid use should be carefully monitored.

Psoriatic Arthritis - conventional DMARDs
A study be E Lie and colleagues (#343) looked at conventional DMARDs in psoriatic arthritis. The drug survival rate of SSZ after two years is about 30%, LEF is at 41%, and MTX lies at 62%. And MTX achieves higher rates of ACR20, ACR50 and ACR70 at 6 months.

Tender Point Measurement at home (FMS)
There's a study suggesting that self measurement of tender points will have a positive effect. I see in it a method to promote pain sensitization. And: don't physicians and patients have better topics than tender points to talk about?

Tocilizumab
SC equal to IV. I hope, we"ll soon see an approval to be able to use it.

Tofacitinib
There have been eight posters on tofacitinib today. #438 to #445. Most were circling around the question of side effects.
ORAL Sequel had a higher rate of SAE than ORAL Standard (#438).
Tofacitinb has the same rate of gastrointestinal events as TNFi (3439).
Cardiovascular events are not increased (#440).
Tofacitinib has a higher rate of herpes zoster (#441).
Tolerability with and without DMARDs are equal (#442).
US and rest of the world pats. are equal in respect of efficacy and side effects (#443).
Dosing every two weeks has less side effects (#444).
Tofacitinib is an independent risk factor in multi morbid elderly patients (#445).

Sunday, 27th of October.


Fibromyalgia 

Poster #1108 on methylphenidate in Fibromyalgia - conclusions with too many hypothesis.      

Dianne Whiting presented an interdisciplinary program for Fibromyalgia. Exercises, Yoga, education, CBT, more.
Poster #1092 on low dose naltrexone in Fibromyalgia - luckily it ended: may be effective, further trial needed. My 2 ct.: dead end street.

Fostamatinib
Poster #1295 talks about mechanisms for fostamatinib induced blood pressure elevation. And, how about data on radiographic progression?

Iguratimod
There's a study on iguatimod, which has received Japanese approval in Sept. 2012. Too bad, only N=23! So they should present a larger overview. I don't know, why the company isn't pressing to get an approval by FDA or EMEA.

Methotreate
Study #1362 claims:  iSyMind reduces MTX induced nausea. A pilot trial of N=4. These people have chuzpe! Perhaps they think of a cange of paradigm?

Strontium ranelate
A study of strontium ranelate in long bone fractures with delayed union. Single arm study though. Not convincing.

Tocilizumab
Poster #1207:  Efficacy of tocilizumab in pats. with AA amyloidosis. But not all responding.
alhkim @alhkim thinks of  dz heterogeneity.
I'm surprised that it should work at all in AA amyloidosis. I was waiting for some study, as Prof. Kishimoto mentioned it earlier this year.

Tofacitinib
Effects of smoking in pats. receiving tofacitinib. Need for longer observation #1418

Triple therapy
There's a study on discontinuation rates of triple therapy in RA, result: high rate, but further work is needed.

Weather and RA
Poster #1359 addresses the question: Does RA disease activity correlate with weather conditions? DAS28 is lower under sunny and dry weather conditions.

Monday, 28th of October

AC0025
Poster #2353: A dual target inhibitor - BTK and JAK3 (AC0025). Preliminary rat study.

Adalimumab and smoking Poster #2439: Smoking not associated with reponse to adalimumab in axial SpA. The smoker's choice?

Clazakizumab
Poster #2385: Anti-IL-6 MAB clazakizumab shows higher potency than tocilizumab. Will this be an advantage? Maybe tocilizumab should be available before clazakinumab comes to the market (which might take a while!)

Delayed release prednisone Poster #2265: Delayed release prednisone. I question the study, because I don't consider two hours of morning stiffness as stable disease and would change therapy. The authors compare prednisone given in the evening with a delay mechanism with prednisone given in the morning. They should have compared the delayed release prednisone with common prednisone, given in the evening, at the time. If someone present a study done this way ... , but I guess no one will, at least the drug company can't be interested.

Fish oil and knee OA
Poster #2142: Fish oil doesn't have an effect on structural progression of knee OA. They used 9 g, which would be 18 cps. in Germany
      
Free fatty acids
Poster #1842: Free fatty acids affect arthritic cell. Exact nature not known yet.

GLPG0634
Poster #2381: GLPG0634 effects on DAS28 and ACRxx, but only in a four week study. Good respose rates though.

HAQ and consequences of physical activityPoster #2273: Patient Survey on HAQ reveals an unrecognized aspect of disease activity in RA: consequences of physical activity.

Life events and developing RA Poster #2402: Association between life events and an increased risk of developing RA.

Mavrilimumab
Poster #2378: Mavrilimumab shows a study on lung AE in cynomolgus monkeys. Not very reassuring.

Methotrexate and anxiety Poster #1977: Pain related anxiety as a barrier to use methotrexate (MTX) - needle, autoinjector etc. tested on healthy volunteers.

NI-0101
Poster #????: Novel anti-human TLR4 MAB (NI-0101). Cell study!


Omega-3 fatty acids and SLE
Poster #2538: SLE patients benefit from omega-3 fatty acids. 

Sleep disturbances in rheumatic conditions
Poster #1930 i s on sleep disturbances (SD) in different rheumatic conditions. SD leads to higher disease activity.
Authors stress to look also at SD and not only at joint swelling and pain. I'd like to add fatigue.
 Tofacitinib Poster #1977: After a plethora of posters on tofacitinib, just one with data on radiographic progression.

Unique self joint examination toolPoster #2242: Despite a unique self joint examination tool, pat. and physicians joints counts differ significantly.

UstekinumabPoster #????: Actually more than one poster on ustekinumab in psoriatic arthritis. It's approved in Europe, now.

VX-509 Poster #2350: New data by VX-509 (JAK3i). Pain, HAQ-DI etc. are better, but no DAS26 or ACR20 is shown.
 
Tuesday, 29th of October