Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs.
Roy Fleischmann,Maurizio Cutolo,Mark C. Genovese,Eun Bong Lee,Keith S. Kanik,Seth Sadis,Carol A. Connell,David Gruben,Sriram Krishnaswami,Gene V. Wallenstein,Bethanie Wilkinson,Samuel H. Zwillich +11 more
Reads0
Chats0
TLDR
Tofacitinib monotherapy at a dose of ≥3 mg twice a day was efficacious in the treatment of patients with active RA over 24 weeks and demonstrated a manageable safety profile.Abstract:
Objective
To compare the efficacy, safety, and tolerability of 5 doses of oral tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response to disease-modifying antirheumatic drugs.
Methods
In this 24-week, double-blind, phase IIb study, patients with RA (n = 384) were randomized to receive placebo, tofacitinib at 1, 3, 5, 10, or 15 mg administered orally twice a day, or adalimumab at 40 mg injected subcutaneously every 2 weeks (total of 6 injections) followed by oral tofacitinib at 5 mg twice a day for 12 weeks. The primary end point was the responder rate according to the American College of Rheumatology 20% improvement criteria (ACR20) at week 12.
Results
Treatment with tofacitinib at a dose of ≥3 mg twice a day resulted in a rapid response with significant efficacy when compared to placebo, as indicated by the primary end point (ACR20 response at week 12), achieved in 39.2% (3 mg; P ≤ 0.05), 59.2% (5 mg; P < 0.0001), 70.5% (10 mg; P < 0.0001), and 71.9% (15 mg; P < 0.0001) in the tofacitinib group and 35.9% of patients in the adalimumab group (P = 0.105), compared with 22.0% of patients receiving placebo. Improvements were sustained at week 24, according to the ACR20, ACR50, and ACR70 response rates as well as classifications of remission according to the 3-variable Disease Activity Score in 28 joints (DAS28) using C-reactive protein and the 4-variable DAS28 using the erythrocyte sedimentation rate. The most common treatment-emergent adverse events (AEs) in patients across all tofacitinib treatment arms (n = 272) were urinary tract infection (7.7%), diarrhea (4.8%), headache (4.8%), and bronchitis (4.8%).
Conclusion
Tofacitinib monotherapy at ≥3 mg twice a day was efficacious in the treatment of patients with active RA over 24 weeks and demonstrated a manageable safety profile.read more
Citations
More filters
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
Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis
Roy Fleischmann,Joel M. Kremer,John J. Cush,Hendrik Schulze-Koops,Carol A. Connell,John D. Bradley,David Gruben,Gene V. Wallenstein,Samuel H. Zwillich,Keith S. Kanik +9 more
TL;DR: In patients with active rheumatoid arthritis, tofacitinib monotherapy was associated with reductions in signs and symptoms of rheumatism and improvement in physical function and tofacit inib treatment wasassociated with elevations in low-density lipoprotein cholesterol levels and reductions in neutrophil counts.
References
More filters
Journal ArticleDOI
The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
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
TL;DR: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA).
Book
SF-36 health survey: Manual and interpretation guide
TL;DR: TheSF-36 is a generic health status measure which has gained popularity as a measure of outcome in a wide variety of patient groups and social and the contribution of baseline health, sociodemographic and work-related factors to the SF-36 Health Survey: manual and interpretation guide is tested.
Journal Article
Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date, and these new revised classified criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatism.
Journal ArticleDOI
Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for rheumatic diseases to date as mentioned in this paper, and these new revised classification criteria are very important as they should provide understanding of the possibly changing face of rheumatoid arthritis.
Journal ArticleDOI
Modified disease activity scores that include twenty-eight-joint counts : development and validation in a prospective longitudinal study of patients with rheumatoid arthritis
M.L.L. Prevoo,M.A. van 't Hof,H.H. Kuper,M.A. van Leeuwen,L. B. A. Van De Putte,P.L.C.M. van Riel +5 more
TL;DR: The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists) and are as valid as disease activity scores that include more comprehensive joint counts.
Related Papers (5)
EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
Josef S Smolen,Robert Landewé,Ferdinand C. Breedveld,Maya H Buch,Maya H Buch,Gerd R Burmester,Maxime Dougados,Paul Emery,Paul Emery,Cécile Gaujoux-Viala,Laure Gossec,Jackie L Nam,Jackie L Nam,Sofia Ramiro,Kevin L. Winthrop,Maarten de Wit,Daniel Aletaha,Neil Betteridge,Johannes W. J. Bijlsma,Maarten Boers,Frank Buttgereit,Bernard Combe,Maurizio Cutolo,Nemanja Damjanov,Johanna M. W. Hazes,Marios Kouloumas,Tore K Kvien,Xavier Mariette,Karel Pavelka,Piet L. C. M. van Riel,Andrea Rubbert-Roth,Marieke Scholte-Voshaar,David Scott,T. Sokka-Isler,John B. Wong,Désirée van der Heijde +35 more