July 2017

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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June 2017

Biologics or Tofacitinib for People with Rheumatoid Arthritis Naïve to Methotrexate: a Systematic Review and Network Meta-analysis

Cochrane Database Syst Rev. 2017 May 8;5:CD012657. doi: 10.1002/14651858.CD012657

This Cochrane systemic review and network meta-analysis looked at the benefits and harms of biologics or tofacitinib in patients with RA not previously treated with MTX.Using data from 19 RCTs including 6,485 participants, the review found that biologics (abatacept, adalimumab, etanercept, golimumab, infliximab, rituximab) in combination with MTX improved signs and symptoms of RA (ACR50) and increased the chances of remission (DAS <1.6 or DAS28 <2.6). There was also some evidence of an improveme...

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Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)

Ann Rheum Dis 2017;76:1009–19

In these two Phase 2b studies, filgotinib (a selective JAK-1 inhibitor) was shown to improve the signs and symptoms of RA (compared with placebo), either as monotherapy or when added to MTX.DARWIN 1 included 594 patients with moderate to severe RA on a stable dose of MTX, while DARWIN 2 included 283 patients who stopped taking MTX before the start of the study. After 12 weeks’ treatment, significantly more patients who were receiving filgotinib 100 mg or 200 mg daily in DARWIN 1 or any filgotini...

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Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1)

Ann Rheum Dis 2017;76:998–100

In these two Phase 2b studies, filgotinib (a selective JAK-1 inhibitor) was shown to improve the signs and symptoms of RA (compared with placebo), either as monotherapy or when added to MTX.DARWIN 1 included 594 patients with moderate to severe RA on a stable dose of MTX, while DARWIN 2 included 283 patients who stopped taking MTX before the start of the study. After 12 weeks’ treatment, significantly more patients who were receiving filgotinib 100 mg or 200 mg daily in DARWIN 1 or any filgotini...

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Outcomes of Tumor Necrosis Factor Inhibitor Cycling versus Switching to a Disease-modifying Anti-rheumatic Drug with a New Mechanism of Action Among Patients with Rheumatoid Arthritis

J Med Econ 2017;20:464–73

This retrospective study looked at claims-based datasets to establish whether it is preferable to switch to another TNF inhibitor (TNFi) or to a therapy with a different mechanism of action (MOA) when RA treatment failure occurs with an initial TNFi, due to inadequate response or lack of tolerability.Administrative claims data from a large US database were used to compare treatment patterns, treatment effectiveness (based on fulfillment of six criteria) and costs in in the 12 months after RA pat...

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May 2017

Discontinuation of Tofacitinib after achieving Low Disease Activity in Patients with Rheumatoid Arthritis: a Multicentere, Observational Study

Rheumatology. Doi 10.1093/rheumatology/kex068

This study showed that in patients who achieved low disease activity (LDA), it is possible to discontinue tofacitinib without flare in approximately one-third of patients. Patients from the tofacitinib Phase 3 programme and long-term extension study were enroled. Discontinuation was based on physician-patient decision making with informed consent. The primary endpoint was the proportion of patients who remained tofacitinib free at post-treatment Week 52. Of 64 patients treated with tofacitinib w...

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Tocilizumab Combination Therapy or Monotherapy or Methotrexate Monotherapy in Methotrexate-naïve Patients with Early Rheumatoid Arthritis: 2-year Clinical and Radiographic Results from the Randomized, Placebo-controlled FUNCTION Trial

Ann Rheum Dis Published Online First: 7 April 2017. Doi 10.1136/annrheumdis-20160210561

Burmester et al. present data showing that 52-week efficacy and safety of intravenous tocilizumab plus methotrexate, or tocilizumab monotherapy are maintained through to Week 104 in patients with early rheumatoid arthritis. Patients were assigned to four treatment groups: 4 mg/kg TCZ + MTX, 8 mg/kg TCZ + MTX, 8 mg/kg TCZ + placebo or placebo + MTX. Patients not achieving DAS28 ≤3.2 at Week 52 and who were not receiving 8 mg/kg TCZ were rescued to 8 mg/kg TCZ + MTX. Of the 1162 randomly assigned ...

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April 2017

EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-modifying Antirheumatic Drugs: 2016 Update

Ann Rheum Dis Published Online First: 06March2017. doi:10.1136/annrheumdis-2016-210715

The EULAR 2016 recommendations update, based on three systematic literature reviews (SLRs) and expert opinion, comprises four overarching principles and 12 recommendations compared with 14, respectively, in 2013. These recommendations intend to inform regarding EULAR’s most recent consensus on the management of RA, with the aim of attaining the best outcomes with current therapies.All DMARD types: csDMARDs, bDMARDs, tsDMARD and bsDMARD are addressed, and cost aspects are taken into consideration...

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The Emerging Safety Profile of JAK Inhibitors in Rheumatic Disease

Nature Reviews Rheumatology 2017;13:234–43

This review discusses the current understanding of the safety of JAK inhibitors, including providing an overview of the changes in laboratory parameters, infection and malignancy risks associated with each JAK inhibitor compound.The review discusses the adverse event profiles and cellular changes characteristically seen with each JAK inhibitor, as well as the overlap or differences between the various compounds. The relative specificities for different JAKs between each compound do not always p...

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March 2017

Cardiovascular Safety of Tocilizumab versus Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis – a Multi-database Cohort Study

Arthritis Rheumatol 2017 Feb 28. doi: 10.1002/art.40084

This multi-database population-based US cohort study found no evidence of an increased cardiovascular (CV) risk among RA patients who switched from a different biologic drug or tofacitinib to tocilizumab (TCZ) versus to a TNF inhibitor (TNFi).The study used claims data in patients with RA newly starting treatment with TCZ or a TNFi from three large databases: Medicare (n=7397), PharMetrics (n=8119) and MarketScan (n=12512). Included within the analysis were 9218 TCZ initiators propensity-score m...

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