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

• Published in: International journal of rheumatic diseases Vol. 23; no. 7; pp. 882 - 897
• Main Authors: Chopra, Arvind, Shobha, Vineeta, Chandrashekara, Srikantiah, Veeravalli, Sarath C. M., Sharma, Reena, Rao, Uppuluri R., Pandya, Sapan, Wagh, Shrikant, Kadel, Jugal K., Thorat, Amit V., Adhav, Charles, Santos Estrella, Paul, Yu, Wei, Kwok, Kenneth, Wouters, Ann
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2020; John Wiley and Sons Inc
• Subjects: Adult; Aged; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - epidemiology; Body mass index; clinical aspects; Clinical Trials, Phase III as Topic; drug treatment; Enzyme inhibitors; Erythrocyte sedimentation rate; Female; Humans; India; India - epidemiology; Janus kinase; Janus Kinase Inhibitors - adverse effects; Janus Kinase Inhibitors - therapeutic use; Joint diseases; Male; Methotrexate; Middle Aged; Original; Piperidines - adverse effects; Piperidines - therapeutic use; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Randomized Controlled Trials as Topic; Remission; Remission Induction; Rheumatoid arthritis; Safety; Time Factors; tofacitinib; Treatment Outcome; Tuberculosis; India; clinical aspects; rheumatoid arthritis; India; drug treatment; tofacitinib
• ISSN: 1756-1841; 1756-185X
• DOI: 10.1111/1756-185X.13853

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 cut‐off 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 and AESIs, except that tuberculosis (TB) IR was higher in Indian (IR = 1.21; 95% CI 0.49, 2.49) vs ROW patients (IR = 0.17; 95% CI 0.11, 0.25). Conclusions Tofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD‐treated RA patients from high‐risk countries (IR = 0.00‐2.56; TB IR >0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.