July 2016

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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Baricitinib in Patients with Refractory Rheumatoid Arthritis

N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247

For patients who have an inadequate response or unacceptable side effects associated with biologic DMARDs, the options for treatment beyond conventional DMARDs are limited. This phase 3 trial of the JAK 1/2 inhibitor, baricitinib, studied its efficacy in bDMARD-IR patients. 527 patients were randomized to either baricitinib 2mg, 4mg or placebo for up to 24 weeks. At week 12 the primary endpoints were tested hierarchically to control type 1 error; these endpoints were ACR20, HAQ-DI score, DAS28-C...

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Effects of Tofacitinib and other DMARDs on Lipid Profiles in Rheumatoid Arthritis: Implications for the Rheumatologist

Semin Arthritis Rheum 2016;46:71–80

Increased inflammation and CV disease have been associated with lower total cholesterol (TC) and low density lipoprotein (LDL-C) levels in RA patients – an apparent paradox to what is observed in the general population. Previously, reduced high-density lipoprotein (HDL-C) levels have been associated with increased risk of CV, and an inverse relationship observed with levels of HDL-C level and C-reactive protein (CRP).This analysis of the literature with regard to studies using DMARDs in RA patie...

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March 2016

Tofacitinib or adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis

Strand et al. Rheumatology (Oxford). 2016 Feb 29. doi:pii: kev442. [Epub ahead of print]

RA not only affects the physical aspects of a patient’s health but also has an impact on the psychological well-being causing a significant disease burden. This paper reports on the patient-reported outcomes (PROs) from the ORAL Standard study. This study investigated tofacitinib 5mg BID, 10mg BID, adalimumab vs. placebo over 12 months with a primary endpoint at month 3. All treatment groups showed significant improvements over placebo in HAQ-DI, PtGA and Pain with LSM changes in baseline sustai...

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Clinical Relevance of VPAC1 Receptor Expression in Early Arthritis: Association with IL-6 and Disease Activity

 PLoS ONE 11(2): e0149141. doi:10.1371/journal. pone.0149141

VPAC1 and VPAC2 both mediate anti-inflammatory and immunoregulatory responses in RA. Both these are receptors of vasoactive intestinal peptide (VIP), a broadly distributed peptide found in neural, endocrine and immune cells, which triggers biological response when interacting with the aforementioned receptors. It has recently been described in Martinez et al. that those patients with low levels of VIP have worse disease outcome.1This study analyzed 250 blood samples from the Princesa early Arthr...

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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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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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Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study

Arthritis Research & Therapy (2016) 18:13 DOI: 10.1186/s13075-015-0913-x

One of the major challenges of RA treatment is choosing the correct treatment and dose for the individual patient, as treatment response can be heterogeneous. To help select the appropriate treatment, there is a need for effective and non-invasive ways to monitor disease activity and progression. In the LITHE study, Bay-Jensen et al. investigate whether early biomarker measurements could predict early joint protection response to TCZ. The biomarkers (CRPM, VICM, C1M, C2M, C3M, and CTX-I/OC [bone...

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