An Irreversible Covalent Bruton's Tyrosine Kinase Inhibitor Shows Promising Results in Rheumatoid Arthritis Patients with Methotrexate Resistance: Phase IIa Trial Findings

Written on 23 May 2023. Posted in Rheumatology News & Perspectives

A recent phase IIa trial conducted in Japan has revealed encouraging outcomes regarding the efficacy and safety of TAS5315, an irreversible covalent Bruton's tyrosine kinase (BTK) inhibitor, in patients with rheumatoid arthritis (RA) who have shown an inadequate response to methotrexate, a commonly prescribed medication for RA. The study aimed to assess the potential benefits of TAS5315 in improving RA disease activity compared to a placebo.

In the double-blind study, patients were divided into two parts. In Part A, they were randomly assigned to receive either TAS5315 at doses of 4 or 2 mg or a placebo once daily for 12 weeks. Subsequently, in Part B, all patients received TAS5315 for an additional 24 weeks. The study's primary endpoint was to determine the proportion of patients who achieved a 20% improvement according to the American College of Rheumatology criteria (ACR20) by the end of the 12-week period.

The results of the trial showcased promising outcomes for TAS5315. At week 12, a substantial number of patients in the combined TAS5315 group demonstrated a positive response, with 78.9% achieving ACR20 compared to 60.0% in the placebo group (p=0.053). Moreover, the TAS5315 group displayed higher response rates in terms of ACR50 (33.3% vs. 13.3%, p=0.072) and ACR70 (7.0% vs. 0.0%, p=0.294) when compared to the placebo group. Notably, a larger proportion of patients receiving TAS5315 achieved low disease activity or remission at week 12. Furthermore, the improvements observed in clinical and biomarker measures were sustained throughout Part B of the study, indicating the potential long-term benefits of TAS5315 treatment.

Safety considerations were also addressed in the trial. During Part A, the incidence of adverse events (AEs) associated with TAS5315 was similar to that of the placebo group. Common AEs included nasopharyngitis (10.3%), pruritus (6.9%), and cystitis (5.2%). Over the course of the 36-week study period, nine patients experienced bleeding events. Among them, four patients recovered with continued TAS5315 treatment, two patients experienced recovery after temporary interruption of the drug, and three patients recovered after discontinuation of TAS5315.

While the study did not meet its primary endpoint, the numerical differences observed in the improvement rates of all measures of RA disease activity between TAS5315 and placebo are encouraging. These findings suggest that TAS5315 may hold promise as a therapeutic option for RA patients who do not respond adequately to methotrexate. However, it is important to note that the study also highlighted the potential bleeding risks associated with TAS5315, which should be considered during treatment decisions. Further analysis and evaluation of the risk-benefit profile of TAS5315 are warranted to determine its suitability and effectiveness as a potential treatment option for RA patients.

It is essential to emphasize that TAS5315 is currently under investigation, and additional studies and evaluations are necessary to gain a comprehensive understanding of its efficacy, safety profile, and long-term effects in the management of rheumatoid arthritis.

Tags: rheumatoid arthritis, drugs, treatment, tsDMARDs

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