Patients with moderate-to-severe active RA had significant improvements in clinical signs and symptoms with upadacitinib (UPA) compared with placebo.In Phase 2 studies, UPA showed favourable efficacy when administered twice daily as an immediate-release formulation at doses of 6–12 mg in patients with active RA who had TNFi-IR.1,2 An extended-release formulation allowing once-daily (QD) administration was developed for Phase 3 studies. SELECT-NEXT was a double-blind, multicentre, Phase 3 study t...
July 2018
March 2018
Response to Baricitinib based on Prior Biologic Use in Patients with Refractory Arthritis
Rheumatology (Oxford) 2018 May; 57(5):900-908
Baricitinib (BARI) 2 or 4 mg had a beneficial treatment effect on patients with moderate to severe RA compared with placebo (PBO), irrespective of the number or nature of prior patient bDMARD use. The current therapeutic target for patients with established RA is low disease activity, but many patients fail to achieve this due to inadequate responses to DMARD therapies. With this patient population growing, therapies for these patients are considered one of the greatest unmet needs in RA. This s...
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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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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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March 2017
A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti–Tumor Necrosis Factor Therapy
Arthritis Rheumatol 2016;68:2867–77
The summary and accompanying slide deck have been developed in conjunction with the Genovese et al. study (Study 1) which examined ABT-494 in MTX-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor.Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intolerant of...
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January 2017
Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase 2b Study in Patients with Active Rheumatoid Arthritis
Arthritis Rheumatol 2017. DOI 10.1002/art.40036.
In this analysis of the effect of baricitinib on changes in lipid profile, lipoprotein particle size and apolipoprotein content, increases in serum lipids were observed with HDL-C increases correlating with improved clinical outcomes.Eligible patients (N=301) met the inclusion criteria for the Phase 2b randomised, double-blind, placebo-controlled study.1 Patients were assigned in a 2:1:1:1:1 ratio to once-daily doses of placebo or baricitinib 1, 2, 4, or 8 mg, respectively. Those receiving 2 mg,...
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October 2016
Tofacitinib in Combination with Conventional DMARDs in Patients with Active Rheumatoid Arthritis: PROs from a Phase 3 Randomised Controlled Trial
Arthritis Care Res 2016; Accepted article. DOI 10.1002/acr.23004
Further evidence is presented that treatment with tofacitinib improves patient-reported outcomes (PROs), in addition to improving underlying disease activity.Data were analysed from the Phase 3 ORAL Sync 12-month randomised controlled trial in adult patients with active RA and previous inadequate response to ≥1 conventional or biologic DMARD(s). Patients received (4:4:1:1) TOF 5mg or 10mg BID or Placebo advanced to 5 mg or10 mg BID plus conventional DMARD(s).PROs assessed at Month 3 were: Patien...
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December 2015
Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs
Arthritis Research & Therapy (2015) 17:307 DOI: 10.1186/s13075-015-0825-9 [Epub ahead of print]
RA presents a significant health and socioeconomic burden particularly in physical functioning, fatigue, and emotional roles. A phase III 6-month study of tofacitinib in patients with active RA, who had prior inadequate responses to cDMARDs or bDMARDs, uses patient-reported outcomes (PROs) to assess the impact on quality of life. Patients were randomized 4:4:1:1 to receive tofacitinib 5 or 10 mg BID, or placebo for 3 months followed by tofacitinib 5 or 10 mg BID. At month 3, tofacitinib 5 and 10...
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May 2015
Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial
Arthritis Res Ther. 2015 Apr 6;17(1):95.
Mean increases from baseline in patient serum creatinine (SCr) levels have been observed in the clinical development programme for the JAK inhibitor tofacitinib. These increases predominantly occurred within the first three months, and reversed with tofacitinib withdrawal.
This phase 1, randomised, placebo-controlled, parallel-group, 2-period study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib, relative to placebo, in 148 patients with active RA. Result...
This phase 1, randomised, placebo-controlled, parallel-group, 2-period study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib, relative to placebo, in 148 patients with active RA. Result...
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October 2013
Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis
Ann Intern Med. 2013;159;253-261
Many patients with active RA have an inadequate response to biologic and nonbiologic DMARDs. Kremer et al carried out a one year, randomized trial studying the efficacy of tofacitinib in conjunction with background nonbiologic DMARDs (primarily methotrexate) in these patients. The results showed that using tofacitinib in combination with nonbiologic DMARDs rapidly improved physical function and reduced signs and symptoms of RA versus placebo, measured by ACR20 rates, DAS28 and HAQ-DI. The data f...