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 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.

Keywords: India; clinical aspects; drug treatment; rheumatoid arthritis; tofacitinib.

FIGURE 1

The proportion of Indian patients achieving (A) ACR20, (B) ACR50, and (C) ACR70 responses at months 3 and 6; and the proportion of ROW patients achieving (D) ACR20, (E) ACR50, and (F) ACR70 responses at months 3 and 6. Patients receiving placebo in ORAL Solo and ORAL Step advanced in a blinded manner to tofacitinib 5 or 10 mg b.i.d. at month 3; placebo‐treated non‐responders (defined as patients not achieving ≥20% reduction from baseline in swollen and tender joint counts) in ORAL Scan, ORAL Sync, and ORAL Standard advanced in a blinded manner to tofacitinib 5 or 10 mg b.i.d. at month 3; remaining placebo‐treated patients advanced at month 6; efficacy analyses were based on observed cases without imputation for missing data; all endpoints are reported by descriptive statistics with no formal hypothesis testing. ACR, American College of Rheumatology; b.i.d., twice daily; CI, confidence interval; ROW, rest of the world

FIGURE 2

The proportion of Indian patients achieving (A) DAS28‐4(ESR) <2.6, (B) DAS28‐4(ESR) ≤3.2, and (C) change from baseline in HAQ‐DI, at months 3 and 6; and the proportion of ROW patients achieving (D) DAS28‐4(ESR) <2.6, (E) DAS28‐4(ESR) ≤3.2, and (F) change from baseline in HAQ‐DI, at months 3 and 6. Patients receiving placebo in ORAL Solo and ORAL Step advanced in a blinded manner to tofacitinib 5 or 10 mg b.i.d. at month 3; placebo‐treated non‐responders (defined as patients not achieving ≥20% reduction from baseline in swollen and tender joint counts) in ORAL Scan, ORAL Sync, and ORAL Standard advanced in a blinded manner to tofacitinib 5 or 10 mg b.i.d. at month 3; remaining placebo‐treated patients advanced at month 6; efficacy analyses were based on observed cases without imputation for missing data. b.i.d., twice daily; CI confidence interval; DAS28‐4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; ROW, rest of the world; SE, standard error