Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.

Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout.

Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population.

Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population.

Clinical trial identifier: NCT00856544 and NCT00413699.

Keywords: Clinical Efficacy; Patient-Reported Outcomes; Rheumatoid Arthritis; Safety; Tofacitinib.

Conflict of interest statement

An Y, Bao CD, Chen ZW, Gu JR, Li ZG, Liu Y, Xu HJ, and Zhao DB have nothing to disclose. Kremer J has served as a consultant for, and has received research support from, AbbVie, Amgen, BMS, Genentech, Pfizer Inc, and UCB; he has also received payment for lectures, including service on speakers’ bureaus, from AbbVie. Hwang LJ was an employee and shareholder of Pfizer Inc at the time of analysis. Wang L and Wu QZ are employees and shareholders of Pfizer Inc.

Figures

Figure 1

ACR20/50 response rates in Chinese patients through: (a) Month 12 in ORAL Sync by treatment sequence (FAS, NRINAP); and (b) Month 48 in ORAL Sequel (OC). ACR: American College of Rheumatology; BID: Twice daily; FAS: Full analysis set; NRINAP: Nonresponder imputation, no advancement penalty; OC: Observed cases; SE: Standard error.

Figure 2

LS mean change from baseline in DAS28-4 (ESR) through: (a) Month 6 in ORAL Sync (FAS, longitudinal model); (b) Month 12 in ORAL Sync by treatment sequence (FAS, longitudinal model); and (c) Month 48 in ORAL Sequel (FAS, no imputation). *P < 0.05; †P < 0.001; ‡P < 0.0001. BID: Twice daily; DAS28-4 (ESR): Disease Activity Score in 28 joints using erythrocyte sedimentation rate; FAS: Full analysis set; LS: Least squares; SE: Standard error.

Figure 3

LS mean change from baseline in HAQ-DI through: (a) Month 6 in ORAL Sync (FAS, longitudinal model); and (b) Month 48 in ORAL Sequel (FAS, no imputation). *P < 0.05; †P < 0.001; horizontal dashed line represents MCID, 0.22. BID: Twice daily; FAS: Full analysis set; HAQ-DI: Health Assessment Questionnaire-Disability Index; LS: Least squares; MCID: Minimal clinically important difference; SE: Standard error.