Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate.
Yoshiya Tanaka,Makoto Suzuki,Hiroyuki Nakamura,Shigeyuki Toyoizumi,Samuel H. Zwillich,Tofacitinib Study Investigators +5 more
TLDR
To compare the efficacy, safety, and tolerability of 4 doses of oral tofacitinib with placebo in Japanese patients with active rheumatoid arthritis receiving stable background methotrexate who had an inadequate response to MTX alone.Abstract:
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.read more
Citations
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Journal ArticleDOI
2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis
Jasvinder A. Singh,Kenneth G. Saag,S. Louis Bridges,Elie A. Akl,Raveendhara R. Bannuru,Matthew C. Sullivan,Elizaveta E. Vaysbrot,Christine McNaughton,Mikala C. Osani,Robert H. Shmerling,Jeffrey R. Curtis,Daniel E. Furst,Deborah Parks,Arthur Kavanaugh,James R. O'Dell,Charles H. King,Amye Leong,Eric L. Matteson,John T. Schousboe,Barbara E. Drevlow,Seth Ginsberg,James Grober,E. William St. Clair,Elizabeth A. Tindall,Amy S. Miller,Timothy E. McAlindon +25 more
TL;DR: To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA), a large number of patients with RA are referred to a single clinic for treatment with these medications.
Journal ArticleDOI
The JAK-STAT Pathway: Impact on Human Disease and Therapeutic Intervention*
John J. O'Shea,Daniella M. Schwartz,Alejandro V. Villarino,Massimo Gadina,Iain B. McInnes,Arian Laurence +5 more
TL;DR: The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules.
Journal ArticleDOI
2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis: ACR RA Treatment Recommendations
Jasvinder A. Singh,Kenneth G. Saag,S. Louis Bridges,Elie A. Akl,Raveendhara R. Bannuru,Matthew C. Sullivan,Elizaveta E. Vaysbrot,Christine McNaughton,Mikala C. Osani,Robert H. Shmerling,Jeffrey R. Curtis,Daniel E. Furst,Deborah Parks,Arthur Kavanaugh,James R. O'Dell,Charles H. King,Amye Leong,Eric L. Matteson,John T. Schousboe,Barbara E. Drevlow,Seth Ginsberg,James Grober,E. William St. Clair,Elizabeth A. Tindall,Amy S. Miller,Timothy E. McAlindon +25 more
TL;DR: To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA), a large number of patients with RA are referred to a single clinic for treatment with these medications.
Journal ArticleDOI
JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease
TL;DR: Not only have genome-wide association studies demonstrated that this pathway is highly relevant to human autoimmunity, but targeting JAKs is now a reality in immune-mediated disease.
Journal ArticleDOI
Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis.
William J. Sandborn,Subrata Ghosh,Julián Panés,Ivana Vranic,Chinyu Su,Samantha Rousell,Wojciech Niezychowski +6 more
TL;DR: Patients with moderately to severely active ulcerative colitis treated with tofacitinib were more likely to have clinical response and remission than those receiving placebo.
References
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Frank C. Arnett,Steven M. Edworthy,Daniel A. Bloch,Dennis J. McShane,James F. Fries,Norman S. Cooper,L. A. Healey,Stephen R. Kaplan,Matthew H. Liang,Harvinder S. Luthra,Thomas A. Medsger,Donald M. Mitchell,David H. Neustadt,Robert S. Pinals,Jane G. Schaller,John T. Sharp,Ronald L. Wilder,Gene G. Hunder +17 more
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David T. Felson,David T. Felson,Jennifer J. Anderson,Jennifer J. Anderson,Maarten Boers,Claire Bombardier,Claire Bombardier,Daniel E. Furst,Daniel E. Furst,Charles H. Goldsmith,Charles H. Goldsmith,Linda M. Katz,Linda M. Katz,Robert W. Lightfoot,Robert W. Lightfoot,Harold E. Paulus,Harold E. Paulus,Vibeke Strand,Vibeke Strand,Peter Tugwell,Peter Tugwell,Michael E. Weinblatt,Michael E. Weinblatt,H. James Williams,H. James Williams,Frederick Wolfe,Stephanie Kieszak +26 more
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TL;DR: The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.
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