September 2018

Structural Damage Progression in Patients with Early Rheumatoid Arthritis Treated with Methotrexate, Baricitinib, or Baricitinib plus Methotrexate Based on Clinical Response in the Phase 3 RA-BEGIN Study

Clinical Rheumatology 2018;37:2381–90 DOI 10.1007/s10067-018-4221-0

Patients with active RA and little or no prior DMARD treatment, who achieved sustained clinical responses, were less likely to show structural damage progression, irrespective of treatment.RA-BEGIN was a 52-week double-blind, multicentre Phase 3 trial, which assessed the safety and efficacy of BARI as monotherapy or in combination with MTX versus MTX monotherapy, in RA patients with no or limited prior DMARDs use.1-4 This post-hoc analysis evaluated the structural damage progression in patients ...

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July 2018

Thromboembolism with Janus Kinase (JAK) Inhibitor for Rheumatoid Arthritis: How Real is the Risk?

Drug Safety 2018 Jul;41(7):645–53

Current data suggests that JAK inhibitors may increase the risk of thromboembolism and pulmonary thrombosis (PT) in RA.Two JAK inhibitors – baricitinib (BARI) and tofacitinib (TOF) – are considered effective treatments for RA, however, there are concerns about the thromboembolic risks associated with them. In August 2017, the summary of product characteristics for BARI was revised to include a warning of developing DVT and pulmonary embolism (PE), with recommendations that BARI should be used wi...

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Safety and Efficacy of Upadacitinib in Patients with Active Rheumatoid Arthritis Refractory To Biologic Disease-Modifying Anti-Rheumatic Drugs (SELECT-BEYOND): a Double-Blind, Randomised Controlled Phase 3 Trial

Lancet 2018;391:2513–24

Upadacitinib (UPA) extended release formulation was effective in treating patients with moderate-to-severe RA with an inadequate response to bDMARDs.Phase 2 study data has shown that UPA is an efficacious and safe treatment for active RA.1,2 SELECT-BEYOND was a double-blind, long-term extension, Phase 3 study to assess the efficacy of UPA in patients with RA who were bDMARD-IR. The first 12-weeks of SELECT-BEYOND were placebo-controlled, with a double-blind period followed by an ongoing double-b...

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March 2018

Worldwide, 3-year, Post-Marketing Surveillance Experience with Tofacitinib in Rheumatoid Arthritis

Rheumatol Ther 2018 Jun; 5(1):283–91

This real-world analysis of tofacitinib (TOF) revealed that AEs reported by patients with RA from 2012 to 2015 were consistent with the known safety profile of TOF – no new safety risks were identified.As of August 2017, it is estimated that more than 102 000 patients worldwide have received TOF, but TOF safety has not been evaluated in patients with real-world experience. This analysis addressed this – by evaluating the safety of TOF from post-marketing surveillance (PMS) reports from patients ...

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Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis

Rheumatol Ther 2018 Jun; 5(1):203–14. DOI: 10.1007/s40744-018-0093-7

Methotrexate (MTX) or Glucocorticoid (GC) discontinuation has little effect on CDAI response in patients given tofacitinib (TOF) for up to 3 years. Patients receiving TOF who showed initial improvements benefitted from initiation of MTX or GCs. Concomitant treatments such as MTX or GC are commonly used in combination with RA therapies to improve or accelerate clinical responses. However, their use is associated with many adverse events so clinicians aim to use them for a minimal duration.This po...

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February 2018

Professor Iain McInnes Reviews the Most Important Papers from 2017

Please click the links below to go to the CSF review of each paper.

2017 was a successful year for rheumatoid arthritis research, with some key advances in JAK inhibitors and IL-6 inhibitors, as outlined below. - Tofacitinib was suggested as a potential treatment for psoriatic arthritis, and NICE recommended tofacitinib as a treatment for moderate to severe rheumatoid arthritis - Baricitinib studies supported the potential use of baricitinib as a treatment for rheumatoid arthritis - Filgotinib Phase 2 studies suggested that filgotinib could be effective a...

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December 2017

Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III studies

J Rheumatol 2018 Feb; 45(2):177-87

In this post hoc analysis, six Phase 3 studies were used to analyse the effect of glucocorticoids (GC) on the efficacy of tofacitinib (TOF) in patients with RA. Concomitant use of GC did not affect the clinical or radiographic outcomes of patients treated with TOF. Data from all six clinical trials were evaluated, with four studies (ORAL Scan, ORAL Standard, ORAL Sync and ORAL Step) being pooled for analysis. In these studies, MTX was used as a comparison and patients were required to maintain a...

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November 2017

Safety and Efficacy of Baricitinib in Elderly Patients with Rheumatoid Arthritis

RMD Open. 2017; 3(2): e000546. doi: 10.1136/rmdopen-2017-000546

In this post hoc analysis of pooled data from two randomised controlled trials, RA-BUILD and RA-BEAM, age was shown not to be a contraindication for use of baricitinib. Patients in RA-BUILD were csDMARD-inadequate responder(IR) patients who received an oral placebo or 2 mg or 4 mg baricitinib once daily. Patients in RA-BEAM were MTX-IR patients and received an oral placebo, 4 mg baricitinib once daily or subcutaneous adalimumab every 2 weeks. Efficacy and safety of baricitinib in elderly patient...

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October 2017

Patient-reported Outcomes of Baricitinib in Patients with Rheumatoid Arthritis and No or Limited Prior Disease-modifying Antirheumatic Drug Treatment

Arthritis Res Ther. 2017 Sep 18;19(1):208

RA-BEGIN was a Phase 3, double-blind randomised active comparator-controlled study to evaluate baricitinib as monotherapy or in combination with MTX in patients with active RA who were naïve to csDMARDS and bDMARDS. In this analysis of the RA-BEGIN study, baricitinib alone or with MTX when used as initial therapy resulted in significant improvements in most patient-reported outcome measures compared with MTX. At baseline, study participants had active RA, impaired physical function, moderate le...

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July 2017

Efficacy and Safety of Tofacitinib Monotherapy, Tofacitinib with Methotrexate, and Adalimumab with Methotrexate in Patients with Rheumatoid Arthritis (ORAL Strategy): A Phase 3b/4, Double-Blind, Head-To-Head, Randomised Controlled Trial

Lancet. 2017 Jul 29;390(10093):457-468. doi: 10.1016/S0140-6736(17)31618-5

In this first head-to-head non-inferiority trial assessing a JAKi ± MTX directly compared with a TNFi + MTX in patients with RA, tofacitinib (TOF) + MTX showed non-inferiority to adalimumab (ADA) + MTX. Non-inferiority was not shown for TOF monotherapy versus TOF + MTX, or versus ADA + MTX.In this 52-week study, MTX-inadequate responder (IR) patients were randomised 1:1:1 to receive TOF 5 mg BID monotherapy, TOF 5 mg BID + MTX or ADA 40 mg every other week + MTX. The primary endpoint, ACR50 resp...

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