August 2018

Adverse Events, Clinical Considerations and Management Recommendations in Rheumatoid Arthritis Patients Treated with JAK Inhibitors

Exp Rev Clin Immunol 2018 Nov;14(11):945-956. DOI: 10.1080/1744666X.2018.1504678

Janus kinase (JAK) inhibitors are efficacious in patients with moderate-to-severe RA and have a favourable safety profile. However adverse events (AE), in particular infections, are associated with the use of JAK inhibitors. This paper reviews the mechanism behind JAK inhibitors, the AEs associated with them, and provides consideration in the management of AEs in clinical practice. Data on two RA approved JAK inhibitors – tofacitinib (TOF) and baricitinib (BARI) – was obtained using PubMed, Medl...

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July 2018

Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a Phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT)

J Am Acad Dermatol 2018;79:266–76. doi: 10.1016/j.jaad.2018.04.013

In this phase 3 study, both 200mg and 400mg certolizumab pegol doses improved psoriasis symptoms at Week 12 measured via PASI 75. Improvement was maintained, after rerandomisation, through Week 48, with a safety profile consistent with its drug class. This Phase 3 CIMPACT trial by Lebwohl et al., assessed the safety and efficacy of certolizumab pegol for the treatment of moderate-to-severe chronic plaque psoriasis.

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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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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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January 2018

Subcutaneous Tocilizumab in Rheumatoid Arthritis: Findings from the Common-framework Phase 4 Study Programme TOZURA Conducted in 22 Countries

Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. DOI: 10.1093/rheumatology/kex443

This multi-national TOZURA study programme confirmed the efficacy and safety profile of subcutaneous tocilizumab (TC-SC) when administered as either monotherapy or in combination with csDMARDs. TOZURA was a Phase 4 study programme that evaluated open-label, TCZ-SC in patients with moderate-to-severe RA. A total of 1804 patients with active RA were enrolled in the study programme. Patients had inadequate responses to csDMARDs, anti-TNF therapies, or they were MTX-naïve. TCZ-SC was administered we...

Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis

J Rheumatol 2018 Apr; 45(4):456-464

This 2-year Phase 3 study, proved that subcutaneous tocilizumab (TC-SC) has long-term efficacy and an acceptable safety profile. Patients enrolled had been previously diagnosed with RA with an inadequate response to DMARDs. Patients were randomised 2:1 to receive doses of TCZ-SC (n=437) or PBO (n=219) every other week for 6 months. After this time, all patients received TCZ-SC. Escape therapy, defined as weekly TCZ-SC, was available to patients from Month 3. Efficacy was analysed using ACR respo...

Patient-Reported Outcomes in Newly Diagnosed Early Rheumatoid Arthritis Patients Treated to Target with a Tocilizumab- or Methotrexate-based Strategy

Rheumatology (Oxford) 2017 Dec 1;56(12):2179-2189 doi: 10.1093/rheumatology/kex319

Patient-reported outcomes (PROs) vastly improved in the first 24 weeks post-initiation of tocilizumab (TCZ) therapies compared to methotrexate (MTX) monotherapy in the U-Act-Early trial.U-Act-Early was a two-year, treat-to-target study that compared the safety and efficacy of TCZ and MTX treatment strategies in DMARD-naïve patients with early RA. Sustained remission was classed as more effective in patients given TCZ monotherapy or combination therapy with MTX compared to MTX alone. TCZ therapie...

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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JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases

Nat Rev Drug Discov 2017;16:843–62 DOI: 10.1038/nrd.2017.201

Janus kinases (JAKs) are essential mediators of downstream signaling pathways in many inflammatory and autoimmune diseases. This review summarizes current clinical data on first- and second-generation JAK inhibitors (jakinibs) and discusses their use for the treatment of immune and inflammatory conditions.First generation jakinibs such as tofacitinib, baricitinib, and ruxolitinib, non-selectively inhibit JAK-dependent pro-inflammatory cytokines, which are major contributors to immunopathology. T...

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September 2017

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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