Tofacitinib in the treatment of Indian patients with rheumatoid arthritis: A post hoc analysis of efficacy and safety in Phase 3 and long‐term extension studies over 7 years

Abstract

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized tofacitinib efficacy/safety in Indian vs rest of the world (ROW; excluding India) RA patients. Methods: Efficacy data were pooled for disease-modified antirheumatic drug (DMARD) inadequate responders from Phase (P)3 studies. For Indian patients, ORAL Solo and ORAL Scan; ROW (excluding India), these studies plus ORAL Step, ORAL Sync, and ORAL Standard. Safety data also included ORAL Start (P3; methotrexate-naïve) and ORAL Sequel (long-term extension [LTE] study; data cutoff March 2017) for Indian patients, and these studies plus A3921041 (LTE study; Japanese study) for ROW. Efficacy outcomes at months 3/6: American College of Rheumatology (ACR)20/50/70; Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission/low disease activity; change from baseline in Health Assessment Questionnaire-Disability Index. Incidence rates (IRs; patients with events/100 patient-years) for adverse events of special interest (AESIs) were assessed throughout. Descriptive data underwent no formal comparison. Results: One-hundred-and-ninety-seven Indian and 3879 ROW patients were included. Compared with ROW patients, Indian patients were younger, had lower body mass index, shorter RA duration, and higher baseline disease activity; most Indian patients were non-smokers and all were biologic DMARD (bDMARD)-naïve. Month 3 ACR20 rates with tofacitinib 5 mg twice daily/10 mg twice daily/placebo were 67.4%/82.1%/40.9% (India) and 59.0%/66.1%/28.2% (ROW), and month 6 rates were 76.2%/92.1%/88.9% (India) and 69.0%/74.2%/66.5% (ROW). Month 3/6 improvements in other outcomes were generally numerically greater with tofacitinib vs placebo, and similar in both populations. Compared with ROW, Indian patients had numerically fewer AEs/serious AEs, and similar IRs for discontinuations due to AEs This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Tubercular Pleural Effusion in a Patient of Ulcerative Colitis Treated With Tofacitinib

“…This is more marked in high TB incidence regions, including India. 4 However, an increase in tuberculosis in patients with underlying inflammatory bowel disease has not been reported. In wake of reported risk of TB in rheumatoid arthritis, screening for latent tuberculosis should be done in patients planned for tofacitinib therapy for ulcerative colitis.…”

Real-World Evidence of the Effectiveness and Safety of Generic Tofacitinib in Rheumatoid Arthritis Patients: A Retrospective, Single-Centre Analysis from Western India

“…All our patients received monotherapy; the effectiveness of tofacitinib monotherapy has been reported in the ORAL-START trial. The patients in this study represent a homogenous ethnicity with a wide age range, including 12 patients older than 70 years, unlike the younger Indians in the ORAL studies (9) but similar the US-based CORRONA registry, in which patients on tofacitinib had a disease duration of >10 years. (12) Additionally, the Indian patients in the clinical trials were bDMARD naïve; our patients therefore represent a more severe disease cohort like is seen in real-world studies.…”

“…(18) TB incidence was 1.21 per 100 per year in Indian patients from clinical trials; interestingly, all those who developed TB were not amongst the 23 patients who had LTBI on screening. (9) Given our substantive number of TB, screening for LTBI may be prudent in this population.…”

“…Indian patients included in the clinical trials of the innovator tofacitinib were found to have similar efficacy but a different infection profile, (primarily TB) in a post-hoc analysis. (9) While randomised controlled trials [RCTs] provide high-quality data that show evidence of causality, they are artificial environments with strict inclusion criteria, close follow-up and monitoring, and fewer comorbidities. (10) Consequently, the interpretability of the results to real-world patients is compromised; a gap bridged by observational studies and registries.…”

Real-world evidence of the effectiveness and safety of generic tofacitinib in rheumatoid arthritis patients: a retrospective, single-centre analysis from Western India

“…Indian patients included in the clinical trials of the innovator tofacitinib were found to have similar efficacy but a different infection profile, (primarily TB) in a post hoc analysis. [9] While randomised controlled trials (RCTs) provide high-quality data that show evidence of causality, they are artificial environments with strict inclusion criteria, close follow-up and monitoring, and fewer comorbidities. [10] Consequently, the interpretability of the results to realworld patients is compromised, a gap bridged by observational studies and registries.…”