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

Transaminase Levels and Hepatic Events During Tocilizumab Treatment: Pooled Analysis of Long-Term Clinical Trial Safety Data in Rheumatoid Arthritis

Arthritis Rheumatol. 2017 Sep;69(9):1751-1761. doi: 10.1002/art.40176

In this pooled analysis investigating liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab (TCZ) treatment for RA in clinical trials, although transaminase elevations were frequent, rates of hepatic serious AEs remained low. Data were pooled from patients who received ≥1 dose of IV TCZ with or without DMARDs in Phase 3 or 4 clinical trials, long-term extensions, and a pharmacology study.A total of 4171 patients were included in the all-exposure population with...

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September 2017

The Safety and Immunogenicity of Live Zoster Vaccination in Rheumatoid Arthritis Patients Before Starting Tofacitinib: A Randomized Phase II Trial

Arthritis Rheumatol. 2017 Oct;69(10):1969-1977. doi: 10.1002/art.40187

Patients with RA who started treatment with tofacitinib 2–3 weeks after being vaccinated against herpes zoster had similar varicella zoster virus (VZV)-specific humoral and cell-mediated responses to the live vaccine compared to patients who received placebo.In this Phase 2 study, humoral and cell-mediated immune responses were evaluated before receipt of live zoster vaccine (LZV) and at 2, 6 and 14 weeks after vaccination, having been randomised to tofacitinib 5 mg BID or placebo, 2–3 weeks aft...

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Herpes Zoster and Tofacitinib Therapy in Patients with Rheumatoid Arthritis

Arthritis Rheumatol 2014;66:2675–84

Patients who were treated with tofacitinib in the RA clinical development programme were more likely to develop herpes zoster than were those who received placebo.Cases of herpes zoster reported by investigators in the Phase 2, Phase 3 and long-term extension studies of tofacitinib were evaluated. Herpes zoster was noted in 5% of tofacitinib-treated patients; only 7% of these cases were serious, no patients with herpes zoster died and only 10% permanently discontinued tofacitinib treatment.The o...

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Safety and Efficacy of Baricitinib through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis

J Rheumatol. 2018 Jan;45(1):14-21. doi: 10.3899/jrheum.161161

This open-label extension (OLE) of a Phase 2b randomised controlled trial (RCT) found that safety data collected over 2 years of treatment were generally consistent with previous findings for baricitinib in RA.In the RCT, baricitinib demonstrated significant improvement in disease activity compared with placebo and an acceptable safety profile in patients with RA and an inadequate response to MTX. Patients who completed the 24-week double-blind period of the study were eligible for the OLE. Rate...

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August 2017

Analysis of Non-melanoma Skin Cancer across the Tofacitinib Rheumatoid Arthritis Clinical Programme

Clin Exp Rheumatol 2017;35:614–22

Because non-melanoma skin cancer (NMSC) is one of the most common malignancies associated with RA immunomodulatory therapies, this analysis looked to determine the rate of NMSC incidence per 100 patient-years in patients with RA receiving TOF in the clinical trial programme. The Phase 1, 2, and 3 IRs (combined) for both TOF 5- and 10 mg were low and comparable to those of adalimumab, MTX and placebo, IRs remained stable over time. TOF doses used in the 2 Phase 1; 8 Phase 2; and 6 Phase 3 studies...

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July 2017

Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

Ann Rheum Dis 2017;76:1253-1262. DOI 10.1136/annrheumdis-2016-210457

This analysis of exposure to tofacitinib, an oral JAKi for the treatment of RA, for up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. Adverse events were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.Data were collated into an integrated safety summary of tofacitinib in adult patients with active RA, and included data spanning the tofacitinib clinical programme: from 2 Pha...

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Treatment of Rheumatoid Arthritis with Anti-Tumor Necrosis Factor or Tocilizumab Therapy as First Biologic in a Global Comparative observational Study

Arthritis Care Res (Hoboken). 2017 Oct;69(10):1484-1494. doi: 10.1002/acr.23303

To date, the comparative efficacy of tocilizumab and TNFi for patients with RA has only been investigated in a single head-to-head trial and network meta-analyses. This study, ACT-iON, is the first prospective, large-scale, global, multicentre, comparative effectiveness study comparing initiation of intravenous tocilizumab with initiation of a TNFi in patients with RA as the first-line biologic treatment after inadequate response to csDMARDs. Patients were observed in a real-world, clinical pra...

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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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Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective Janus kinase 1 Inhibitor, after Short-term Treatment of Rheumatoid Arthritis: Results of Two randomized Phase IIA Trials

Arthritis Rheumatol. 2017 Oct;69(10):1949-1959. doi: 10.1002/art.40186

In two 4-week exploratory Phase 2a trials in MTX-inadequate responder (IR) patients with RA, the highly selective JAK1 inhibitor filgotinib met the primary endpoint of ACR20 at Week 4, showing greater response than placebo.Study 1, a proof-of-concept study, included 127 patients randomised to placebo, filgotinib 100 mg BID or filgotinib 200 mg QD. Study 2, was a dose-ranging study and included 91 patients randomised to placebo, filgotinib 30 mg QD, filgotinib 75 mg QD, filgotinib 150 mg QD or fi...

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