July 2016

Risk for Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologics

Arthritis Rheumatol. 2016 May 17. DOI 10.1002/art.39761 [Epub ahead of print]

Historically, patients with RA have suffered with upper tract gastrointestinal perforation (GIPs), associated with NSAID use. More recently, the IL-6 receptor antagonist tocilizumab (TCZ) has been associated with lower tract GIPs. Janus kinase (JAK) inhibitors, including tofacitinib (TOF), with some downstream effects on IL-6 signalling, also have potential for an increased risk of GIPs.There is limited real-world evidence and almost no comparative evidence on the risk for GIP associated with TC...

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Two-year Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis in Clinical Practice

Reumatol Clin. 2016; May 10 doi: 10.1016/j.reuma.2016.03.014 [Epub ahead of print]

The efficacy and safety of tocilizumab has been studied in several randomized clinical trials (RCTs) but due to the strict inclusion and exclusion criteria of RCTs, real-life observational studies are needed to supplement the findings from these trials. This small longitudinal, open-label study from an outpatient clinic in Spain evaluated the effectiveness, survival rate and reasons for treatment discontinuations in 85 patients treated with tocilizumab over a 24-month period. The study also ass...

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study

J Rheumatol. 2016;43(3):504–511.

Clinical trials have shown baricitinib once daily to be effective in patients with RA. However, this Janus kinase (JAK) 1/JAK2 inhibitor has not been evaluated in a Japanese population. In this 12-week, placebo-controlled study, 145 Japanese patients were enrolled and received placebo, 1 mg, 2 mg, 4 mg or 8 mg oral baricitinib daily. Efficacy results were encouraging and consistent with earlier trials. Significantly more baricitinib patients achieved ACR20 response at Week 12 of treatment compar...

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May 2016

The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase 2b Study of Adults with Active Psoriatic Arthritis

Arthritis Rheumatol. 2016 Mar 24. DOI 10.1002/art.39700 [Epub ahead of print]

Encouraging results have been seen with clazakizumab in RA, but the results of anti-IL6 therapy in patients with psoriatic arthritis (PsA) have so far been unclear. This Phase 2b dose-ranging study examined the efficacy and safety of clazakizumab given subcutaneously q4w, with or without MTX, in 165 patients with PsA who had inadequate response to NSAIDs.ACR20 response at Week 16, the primary endpoint, was significantly higher in patients receiving clazakizumab 100 mg compared with placebo (52.4...

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Real-world Comparative Risks of Herpes Virus Infections in Tofacitinib and Biologic-treated Patients with Rheumatoid Arthritis

Ann Rheum Dis. 2016 Apr 25;0:1–5 doi: 10.1136/annrheumdis-2016-209131

Herpes Zoster (HZ) complications can cause considerable morbidity including debilitating pain syndromes. Clinical trials of tofacitinib have suggested it may increase the risk of HZ. Although unclear, the mechanism may involve reduced CD4 T-cell function and interference of interferon signalling. Following approval of tofacitinib in the US in 2012, real-world data from Medicare (2006–2013) and from the US longitudinal database, Marketscan, (2010–2014) were analysed. A total of 2526 patients who...

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March 2016

Comparative effects of biologics on cardiovascular risk among older patients with rheumatoid arthritis

Ann Rheum Dis 2016;0:1–6 doi:10.1136/ annrheumdis-2015-207870 [Epub ahead of print]

Since RA patients are at an increased risk of a CV event, there have been several studies to determine if RA treatments alter this risk. In a retrospective study, Zhang and colleagues assess the risk of CV events in patients initiating bDMARDs.Using Medicare medical and pharmacy claims data, the incidence rate (IR) of acute myocardial infarction (AMI) and of a composite CHD* was calculated across RA patients initiating 8 different biologics: ABA, ADA, CER, ETA, GOL, INF, RIT, and TOC. There were...

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Pregnancy outcome after tocilizumab therapy in early pregnancy – a case series from the German Embryotox Pharmacovigilance Center

Reproductive Toxicology doi:10.1016/j.reprotox.2016.01.002

MTX users have an increased incidence of spontaneous abortions (SABs) compared to baseline risk (42.5%1 vs. 13-17%2). Tocilizumab (TCZ) has been shown to have similar efficacy with or without MTX. There is currently limited data on the effect of TCZ on pregnancy, but with more safety data, TCZ could be an alternative for RA patients of reproductive age. The patients were enrolled at Embryotox Berlin, a pharmacovigilance center providing risk assessment during pregnancy, between 2011 and 2014 dur...

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Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study)

Ann Rheum Dis 2016 Jan 5 DOI: 10.1136/annrheumdis-2015-208426 [Epub ahead of print

MTX is the primary drug in RA management because of its long-term effectiveness and safety profile; however, in patients who have insufficient response (IR) to MTX, treatment adjustments are needed – either to combine a bDMARD with MTX or to switch to a bDMARD from MTX. In the SURPRISE study, the efficacy and safety of adding TCZ to MTX (ADD-ON) or switching MTX to TCZ (SWITCH) was evaluated in 233 patients with moderate to highly active RA who were randomised 1:1. Both treatment groups were adm...

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January 2016

Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials

Arthritis Res Ther. 2015 Dec 15;17(1):362

Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. By modulating the signalling of cytokines that are integral to lymphocyte activation, proliferation, and function, tofacitinib may suppress multiple elements of immune response. A systematic literature search including all biologics and tofacitinib procured 66 RCTs and 22 LTEs that were included in a meta-analysis to provide estimated incidence rates, risk ratios, and risk differences of serious infection for each therapy. Es...

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December 2015

Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis

Ann Rheum Dis. 2015;0:1-7. doi:10.1136/annrheumdis-2015-207872 [Epub ahead of print]

RA patients have increased risk of CVD compared with the general population that is not fully explained by traditional risk factors. This is a post-hoc analysis of data from a clinical trial that compared IL-6 and TNF-α signaling inhibition to compare changes in lipids and lipid-associated CV risk markers in 324 patients treated with TCZ IV q4w or ADA SC q2w for 24 weeks. HDL-SAA and sPLA2 IIA is also measured in an additional subpopulation of 87 and 97 TCZ and ADA patients, respectively.Greater...

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