Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Tasocitinib (CP-690,550) Appears To Be Effective and Tolerated When Administered Either as Long-Term Monotherapy or on Background Methotrexate in Patients with Rheumatoid Arthritis.
Connell1, Carol A., Riese2, Richard, Wood2, Susan, Bradley2, John, Zwillich2, Samuel H.
Tasocitinib (CP-690,550) is an oral, selective Janus kinase inhibitor that has previously demonstrated efficacy in treating rheumatoid arthritis (RA) and a manageable safety profile in randomized studies. Patients were enrolled in this long-term follow-up study upon completion of participation in a prior randomized study of tasocitinib (PRST). Here safety and efficacy is compared between patients who received tasocitinib monotherapy and those on background methotrexate (MTX).
In this Phase 2/3 open label study of 1070 patients who had participated in a PRST, treatment was initiated with either 5 or 10 mg tasocitinib twice daily. Key outcome measures included safety and ACR20 response rates. Results are presented for all patients (ALL, n=1070), patients who completed Month 12 (M12, n=648), and patients who completed Month 24 (M24, n=207) visits. The baseline is that of the PRST for patients who enrolled within 14 days of PRST participation; if enrollment was >14 days after PRST participation, baseline was the start of this study. Some PRSTs required background MTX; others were conducted as monotherapy.
Background MTX use was reported in 422/1070 (39.4%, ALL MTX), 332/648 (51.2%, M12 MTX), and 162/207 (78.3%, M24 MTX). Treatment-related adverse events (TRAEs) were generally manageable and infrequently led to discontinuation (70/1070). The most frequently reported TRAEs were infections and infestations for both MTX and non-MTX treatment groups. The most common TRAEs reported by MTX patients were urinary tract infection (4.7%), bronchitis (4.0%), and sinusitis (3.6%); in non-MTX patients, the most common TRAEs were upper respiratory tract infection (2.5%), bronchitis (2.3%), and herpes zoster (2.2%). These TRAEs and TRAEs of abnormal liver laboratory tests are presented by treatment group in the table below.
|Tasocitinib monotherapy (n=639)||Tasocitinib + MTX (n=422)|
|Treatment-related AEs, n||Mild||Mod||Severe||Mild||Mod||Severe|
|Infections and Infestations, n (%)||49(7.7%)||38(6.0%)||4(0.6%)||47(11.1%)||45(10.7%)||14(3.3%)|
|Upper respiratory tract infection||13||3||0||8||5||0|
|Urinary tract infection||4||3||1||10||8||2|
|Liver Laboratory Test AEs, n (%)||3(0.5%)||5(0.8%)||0||15(3.6%)||11(2.6%)||0|
|Alanine aminotransferase increased||0||1||0||6||3||0|
|Aspartate aminotransferase increased||0||1||0||5||2||0|
|Gamma-glutamyl transferase increased||0||0||0||1||2||0|
|Hepatic enzyme increased||3||2||0||1||3||0|
|Liver function test abnormal||0||1||0||2||1||0|
ACR20 response rates demonstrated similar efficacy of tasocitinib between ALL MTX and non-MTX patients, as well as M12 and M24 patients (Figure 1). ACR20 response rates at Month 24 were 81.8% and 77.8% for M24 MTX and non-MTX patients, respectively.
Figure 1.% responders for ACR20a by MTX use for pts initially treated with tasocitinib 5 or 10 mg BID.
The safety profile of tasocitinib, regardless of background MTX use, was generally tolerable and manageable. Tasocitinib demonstrated sustained efficacy over 24 months in the treatment of RA. ACR response rates were similar in patients receiving tasocitinib monotherapy compared with patients on background MTX therapy.
To cite this abstract, please use the following information:
Connell, Carol A., Riese, Richard, Wood, Susan, Bradley, John, Zwillich, Samuel H.; Tasocitinib (CP-690,550) Appears To Be Effective and Tolerated When Administered Either as Long-Term Monotherapy or on Background Methotrexate in Patients with Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2171