July 2017

Pathogenetic Insights from the Treatment of Rheumatoid Arthritis

Lancet 2017;389:2328–37 DOI 10.1016/S0140-6736(17)31472-1

This review paper examines the understanding gained from looking at the effects of specific immune interventions in the treatment of RA.The introduction of novel IL-6 agents has provided the ideal opportunity to explore the distinct effect of cytokine inhibition, as opposed to receptor inhibition, at the molecular level. Mechanistic insights into TNF could also be obtained in the future with advanced molecular and informatics approaches, and future biopsy studies will be important to explore the...

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May 2017

Estimated Medical Expenditure and Risk of Job Loss among Rheumatoid Arthritis Patients undergoing Tofacitinib Treatment: Post Hoc Analyses of Two Randomized Clinical Trials

Rheumatology doi: 10.1093/rheumatology/kex087

The results of this post hoc analysis of two Phase 3 studies of tofacitinib (TOF) show that improvements in health-related quality of life related to TOF treatment are likely to translate into significant reductions in estimated medical expenditure and likelihood of current and future job loss. Data from 399 MTX inadequate responder (IR) patients from ORAL Step, and 716 TNF inhibitor (TNFi)-IR patients from ORAL Standard were included in this analysis. Patients were receiving 5 mg or 10 mg TOF B...

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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

Sarilumab improves Patient-reported Outcomes in Rheumatoid Arthritis Patients with Inadequate Response/Intolerance to Tumour Necrosis Factor Inhibitors

RMD Open 2017;3:e000416. DOI:10.1136/rmdopen-2016-000416

Evidence is presented that treatment with sarilumab demonstrates patient-reported benefits in TNF-IR patients with moderate to severe RA. These improvements complement the clinical efficacy previously reported for sarilumab, and are consistent with those seen in the MOBILITY trial (MTX-IR patients)1, yet in a more difficult-to-treat population.Data were analysed from the 24-week Phase 3 TARGET randomised controlled trial in adult patients with active RA and previous inadequate response or intole...

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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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Efficacy and Safety of Sirukumab in Patients with Active Rheumatoid Arthritis Refractory to Anti-TNF Therapy (SIRROUND-T): A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multinational, Phase 3 Study

Lancet 2017;pii:S0140-6736(17)30401-4

In this Phase 3 multicentre, randomised controlled trial in patients with active RA who were refractory or intolerant to previous biological treatment with at least one TNF inhibitor, sirukumab 50 mg every four weeks (Q4W) or 100 mg every two weeks (Q2W) was well tolerated and significantly improved signs and symptoms of disease.Patients were randomised 1:1:1 to placebo (n=294), sirukumab 50 mg Q4W (n=292) or sirukumab 100 mg Q2W (n=292), while continuing any concomitant DMARDs. Of the 878 rando...

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February 2017

Tocilizumab Use in Pregnancy: Analysis of a Global Safety Database Including Data from Clinical Trials and Post-marketing Data

Semin Arthritis Rheum 2016;46:238–45. DOI 10.1016/j.seminarthrit.2016.05.004.

This dataset is the largest series of tocilizumab (TCZ)-exposed pregnancies to date; considering the limitations of global safety databases, the data presented provide information to assist physicians and patients in making informed decisions.At present, published experience on TCZ use during pregnancy is very limited. In the current analysis, all pregnancy-related reports in the Roche Global Safety Database until December 31, 2014 were analysed. Outcomes assessed included: spontaneous abortion,...

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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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December 2016

Biologic or Tofacitinib Monotherapy for Rheumatoid Arthritis in People with Traditional Disease-modifying Anti-rheumatic Drug (DMARD) Failure: a Cochrane Systematic Review and Network meta-analysis (NMA)

Cochrane Database Syst Rev 2016;11:CD012437.

Treatment options for RA patients who are MTX/DMARD incomplete responders (IR) include other DMARDs, biologics or tofacitinib (TOF). However, there is a lack of direct head-to-head comparator trials of biologics in people with RA. This review provides an update of the 2009 Cochrane overview, ‘Biologics for rheumatoid arthritis’,1 and provides comparisons and estimates for biologic or TOF monotherapy in MTX/DMARD-IR people with RA.The benefits and harms of biologic monotherapy (TNFis: adalimumab,...

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