August 2019

Efficacy and Safety of Peficitinib (ASP015K) in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III Randomised, Double-Blind, Placebo-Controlled Trial (RAJ4) in Japan

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215164

Peficitinib (PEF) 100 and 150 mg demonstrated robust clinical and structural efficacy in patients with RA who have an inadequate response to MTX. In Japan, two JAK inhibitors, TOF and BARI are currently available for RA patients with an inadequate response to conventional therapies. This randomized phase 3 study (RAJ4), assessed the efficacy and safety of two PEF doses in combination with MTX compared to PBO, in Japanese MTX-IR. Patients were randomized 1:1:1 to PBO, PEF 100 mg and 150 mg with M...

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Safety and Effectiveness of Upadacitinib or Adalimumab Plus Methotrexate in Patients with Rheumatoid Arthritis Over 48 Weeks with Switch to Alternate Therapy in Patients with Insufficient Response

Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215764

Consistent with Wk26 data, significantly more UPA patients achieved LDA and remission versus ADA and PBO over 48 weeks. RA patients often change therapy due to inadequate response and intolerance. The SELECT COMPARE study was designed to explore switching to JAK inhibitors from TNF inhibitors without a wash-out period (and vice versa). The long-term safety and efficacy of UPA was compared to ADA and PBO in MTX-IR.1629 patients were blindly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W and PBO, wi...

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June 2019

Impact of Janus Kinase Inhibitors on Risk of Cardiovascular Events in Patients with Rheumatoid Arthritis: Systematic Review and Meta-Analysis of Randomised Controlled Trials

Ann Rheum Dis. 2019 Aug;78(8):1048-1054.

Existing evidence from RCTs indicated no significant change in CV risk for JAK inhibitor (JAKinib) treated RA patients in a short-term perspective compared to placebo.Patients with RA have an elevated risk of CV morbidity and mortality, which cannot be fully explained by traditional CV risk factors. Reaching remission or LDA in order to reduce CV events (CVE) is encouraged in the current EULAR recommendations. JAKinibs and their roles in the modulation of CV risk remain undetermined. This study ...

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May 2019

A Systematic Review and Meta-Analysis of Infection Risk with Small Molecule JAK Inhibitors in Rheumatoid Arthritis

Rheumatology (Oxford). DOI: 10.1093/rheumatology/kez087

How JAKinibs increase the risk of HZ reactivation is unclear. Roles of different JAKs in the immune response may suggest differences in safety profiles between drugs, underpinned by their differential JAK selectivity profiles. The authors undertook a systematic review and meta-analysis to evaluate SI and opportunistic indicator infections including HZ in RA Phase II/III clinic trials with JAKinibs. A literature review of RCT of TOF (5 mg BID), BARI (4 mg OD) and UPA (15 mg OD) was conducted. A p...

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Safety and Efficacy of Tofacitinib For Up to 9.5 Years in The Treatment of Rheumatoid Arthritis: Final Results of a Global, Open-Label, Long-Term Extension Study

Arthritis Res Ther. 2019 Apr 5;21(1):89.

TOF 5 mg and 10mg BID demonstrated a consistent safety profile and sustained efficacy for up to 9.5 years in this open-label LTE ORAL Sequel study.TOF 5 mg and 10 mg BID demonstrated consistent safety (as monotherapy and combination therapy) and efficacy within this open-label LTE study of RA patients. As RA requires long-term treatment, it’s important to assess the long-term efficacy and safety of RA therapies to understand the potential lifelong impact on patient health and quality of life. Th...

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March 2019

Baricitinib Induces LDL-C and HDL-C Increases in Rheumatoid Arthritis: A Meta-Analysis of Randomized Controlled Trials

Lipids Health Dis. 2019 Feb 18;18(1):54.

This study confirmed that BARI induced a stable dose-dependent increase in LDL-C and HDL-C levels. There was no significant difference of CV risk between BARI and placebo groups.High risk of CV events is strongly associated with RA. Mechanisms underlying the excess risk of CV events in RA remains unclear. This study aims to provide additional insight into the clinical safety of BARI, focusing on the effects of BARI on LDL-C and HDL-C levels and CV risk. A Cochrane analysis was performed on studi...

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Network Meta‐Analysis of Tofacitinib versus Biologic Treatments in Moderate‐to‐Severe Rheumatoid Arthritis Patients

J Clin Pharm Ther. 2019 Jun;44(3):384-396.

This study suggests that many bDMARDs and tsDMARDs can be considered equivalent therapeutic alternatives in bDMARD-naïve RA patients, with inadequate response to csDMARDs.In the absence of randomised controlled trials comparing drugs, indirect comparisons and network meta-analysis may provide information to help select an optimal treatment alternative. In this network meta-analysis, 27 randomized controlled trials were analysed to assess the possibility that some drugs on the market may be consi...

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February 2019

Risk of Serious Infection in Patients with Rheumatoid Arthritis in Routine Care with Abatacept, Rituximab and Tocilizumab in Denmark and Sweden

Ann Rheum Dis. 2019 Mar;78(3):320-327. DOI: 10.1136/annrheumdis-2018-214326

Differences in baseline characteristics and numerical differences in IR of SI between ABA, RRTX and TOZ were observed. The relative risk (RR) of SIs seemed to vary modestly with drug.TNFi treated RA patients in large observational studies have suggested an initial twofold increased risk of SIs compared with biologic-naïve patients. Long-term observational studies on the risk of SIs in patients treated with non-TNFi bDMARDs are sparse.This study aimed to estimate crude as well as age and gender-a...

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Comparisons of Hepatitis C Viral Replication in Patients with Rheumatoid Arthritis Receiving Tocilizumab, Abatacept and Tofacitinib Therapy

Ann Rheum Dis. 2019 Jun;78(6):849-850.

Tocilizumab (TCZ), abatacept (ABA) and tofacitinib (TOF) appear to have no major safety concerns for treatment of RA patients with hepatitis C virus (HCV) infections.HCV is an infectious disease which continues to present a major therapeutic challenge for clinicians in treating patients with RA. Previous reports demonstrate that the use of TNF targeted therapies in RA patients with HCV infections appear to have no major safety concerns. During short-term therapy with TCZ and ABA, data has shown ...

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January 2019

A Pooled analysis of the Safety of Tofacitinib as Monotherapy or in Combination with Background Conventional Synthetic Disease-Modifying Antirheumatic Drugs in a Phase 3 Rheumatoid Arthritis Population

Semin Arthritis Rheum. 2018 Dec;48(3):406-415. doi: 10.1016/j.semarthrit.2018.07.006.

In this pooled analysis of Phase 3 Tofacitinib (TOF) trials, safety profiles were generally similar between patients receiving monotherapy and combination therapy. Although selected adverse events of interest showed lower incidence rates (IRs) for TOF monotherapy patients.TOF has been studied as monotherapy and in combination with csDMARDs. In this post-hoc analysis, data were pooled from six Phase 3 TOF studies in RA patients to further examine the safety profile when used as monotherapy or in ...

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