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

Radiographic Joint Damage in Early Rheumatoid Arthritis Patients: Comparing Tocilizumab- and Methotrexate-based Treat-to-target Strategies

Rheumatology (Oxford) 2018; 57(2):309–17

Tocilizumab (TCZ) therapy in DMARD-naïve patients with RA, is more effective at reducing erosion progression, particularly in the feet, compared with treat-to-target methotrexate (MTX) therapy. This analysis looked at radiographic joint damage, including separate examination of erosion progression and joint space narrowing (JSN) in the hands and feet of patients enrolled in the U-Act-Early trial. Radiographic damage is a common symptom of RA, with treat-to-target strategies aimed at preventing ...

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Tapering versus Steady-state Methotrexate in Combination with Tocilizumab for Rheumatoid Arthritis: a Randomised, Double-blind Trial

Rheumatology (Oxford) 2018;57(1):84–91

Methotrexate (MTX) tapering in patients with active, severe RA receiving intravenous tocilizumab (TCZ) was non-inferior to continuing stable MTX doses in maintaining a good/moderate EULAR response. Although MTX and bDMARD combination therapy may produce better response rates than bDMARD monotherapy, one third of patients discontinue or are non-compliant with MTX due to preference or toxicity. This randomised, non-inferiority study investigated the efficacy and tolerability of MTX tapering and ma...

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

Long-term Effectiveness of Tocilizumab in Patients with Rheumatoid Arthritis, Stratified by Number of Previous Treatment Failures with Biologic Agents: Results from the German RABBIT Cohort

Rheumatol Int 2018 Apr; 38(4):579-87

In this observational study, the German RABBIT cohort was used to assess the long-term effectiveness and retention rates of tocilizumab (TCZ) in patients with prior bDMARD failures. Results of the study suggested that TCZ could be an effective treatment option for patients with difficult-to-treat RA. A total of 885 patients were involved in the study and these were categorised dependent on the number of bDMARD failures they had prior to TCZ treatment. Patient data recorded in the cohort included...

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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Successful Treatment of Arthritis Induced by Checkpoint Inhibitors with Tocilizumab: a Case Series

Ann Rheum Dis 2017;76:2061-64. doi: 10.1136/annrheumdis-2017-211560

This case series evaluated the use of tocilizumab (TCZ) as an effective treatment for patients who develop arthritis as an adverse event (AE) of immune checkpoint inhibitor (ICI) cancer treatment. Results suggested that TCZ was an effective treatment, as it reduced the arthritis disease progression.ICIs have been defined as a revolutionary treatment for metastatic melanomas; however, a common AE is the development of polyarthritis. Current arthritis treatments reduce the efficiency of ICI therap...