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Phase II study of tofacitinib (CP‐690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate
Author(s) -
Tanaka Yoshiya,
Suzuki Makoto,
Nakamura Hiroyuki,
Toyoizumi Shigeyuki,
Zwillich Samuel H.
Publication year - 2011
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.20494
Subject(s) - tofacitinib , medicine , rheumatoid arthritis , tolerability , methotrexate , adverse effect , placebo , rheumatology , gastroenterology , pharmacology , alternative medicine , pathology
Objective To compare the efficacy, safety, and tolerability of 4 doses of oral tofacitinib (CP‐690,550) with placebo in Japanese patients with active rheumatoid arthritis (RA) receiving stable background methotrexate (MTX) who had an inadequate response to MTX alone. Methods A total of 140 patients were randomized to receive tofacitinib 1, 3, 5, and 10 mg twice a day or placebo in this 12‐week, phase II, double‐blind study. All patients remained on background MTX. Efficacy and safety were assessed at weeks 1, 2, 4, 8, and 12. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Results ACR20 response rates at week 12 were significant ( P < 0.0001) for all tofacitinib treatment groups: 1 mg twice a day, 64.3%; 3 mg twice a day, 77.8%; 5 mg twice a day, 96.3%; and 10 mg twice a day, 80.8% versus placebo, 14.3%. A significant dose‐response relationship for the ACR20 was observed ( P < 0.0001). Low disease activity was achieved by 72.7% of patients with high baseline disease activity for tofacitinib 10 mg twice a day at week 12 ( P < 0.0001). Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index, and Disease Activity Score 28‐3 (C‐reactive protein) were also reported. The most commonly reported adverse events (AEs) were nasopharyngitis (n = 13) and increased alanine aminotransferase (n = 12) and aspartate aminotransferase (n = 9) levels. These AEs were mild or moderate in severity. Serious AEs were reported by 5 patients. No deaths occurred. Conclusion In Japanese patients with active RA with an inadequate response to MTX, tofacitinib in combination with MTX over 12 weeks was efficacious and had a manageable safety profile.