July 2019

Clinical Outcomes in Patients Switched from Adalimumab to Baricitinib Due to Non-Response and/or Study Design: Phase III Data in Patients with Rheumatoid Arthritis

Ann Rheum Dis. 2019 Jul;78(7):890-898.

Switching from ADA to BARI without a lengthy washout period can be executed with acceptable safety and tolerability and was associated with maintained disease control. Switching therapies in RA is commonplace in myriad scenarios including inadequate responses, intolerances and patient preference. Assessing the safety and efficacy of new treatments such as BARI, in the context of use as a replacement therapy, is beneficial. A previous study (RA-BEACON) has demonstrated that safely switching from ...

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June 2019

Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models

J Immunol 2019;202:2888–2906. DOI: 10.4049/jimmunol.1800583

BTK is involved in both adaptive and innate immune responses and mediates signalling of several immune receptors of relevance to RA and SLE pathogenesis. Targeting BTK is a promising approach therefore for autoimmune disorders with aberrant B cell responses. Evobrutinib is a novel, highly specific, and irreversible BTK inhibitor. In vivo and animal models showed that evobrutinib modulated B cell and innate immune cell activation, was efficacious, and prevented joint damage. The potency of evobru...

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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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Evaluation of Pneumococcal and Tetanus Vaccine Responses in Patients with Rheumatoid Arthritis Receiving Baricitinib: Results from a Long-Term Extension Trial Substudy

Arthritis Res Ther. 2019 Apr 18;21(1):102

Approximately two thirds of long-term BARI treated patients achieved satisfactory humoral and functional responses to 13-serotype pneumococcal conjugate vaccine (PCV-13), whereas tetanus toxoid vaccine (TTV) responses were less robust. Both RA management guidelines and recommendations suggest vaccinating patients with RA against pneumococcal disease with PCV-13 and PPSV-23. The inhibition of the JAK mediated signal transduction pathways in RA treatment could diminish vaccine responses. Given the...

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April 2019

Tuberculosis, Hepatitis B and Herpes Zoster in Tofacitinib-Treated Patients with Rheumatoid Arthritis

Immunotherapy. 2019 Mar;11(4):321-333.

The risk of TB and hepatitis B virus (HBV) appears to be no greater with TOF than with bDMARDs. Most cases of TB during TOF studies occurred in regions with high background rate of TB, including east Asian countries. TOF is also associated with a higher rate of herpes zoster (HZ) compared with bDMARDs. DMARDs used to treat RA can increase the risk of infections by causing a degree of immunosuppression. A range of bacterial and viral infections have been observed in association with DMARD therapy...

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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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Tofacitinib in Combination with Methotrexate in Patients with Rheumatoid Arthritis: Clinical Efficacy, Radiographic and Safety Outcomes from the 24-Month Phase 3 ORAL Scan Study

Arthritis Rheumatol. 2019 Jun;71(6):878-891

RA patients receiving TOF 5 or 10 mg BID plus MTX showed sustained clinical and radiographic treatment effects through months 12-24. The safety profile was consistent with previous TOF studies. The 12-month data from the ORAL Scan study have been previously reported. This report assesses durability of responses, including structural damage progression, and safety with TOF through 24 months. Patients were randomized 4:4:1:1 to receive TOF 5 or 10 mg BID, or PBO advanced to TOF with stable, backgr...

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January 2019

Characterization and Changes of Lymphocyte Subsets in Baricitinib-Treated Patients With Rheumatoid Arthritis: An Integrated Analysis.

Arthritis Rheumatol. 2018 Dec;70(12):1923-1932. doi: 10.1002/art.40680

This review shows that changes in lymphocyte subsets were largely within normal reference ranges and were not associated with efficacy or safety end points. BARI is a selective JAK1/JAK2 inhibitor, approved for the treatment of moderate to severe RA. BARI treatment is associated with changes to circulating lymphocyte and lymphocyte subsets, however detailed analyses of these effects, and their relevance to efficacy and safety is lacking. This study investigated the changes in lymphocyte cell sub...

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