TY - JOUR
T1 - Tofacitinib versus Methotrexate in Rheumatoid Arthritis
AU - Lee, Eun Bong
AU - Fleischmann, Roy
AU - Hall, Stephen
AU - Wilkinson, Bethanie
AU - Bradley, John D.
AU - Gruben, David
AU - Koncz, Tamas
AU - Krishnaswami, Sriram
AU - Wallenstein, Gene V.
AU - Zang, Chuanbo
AU - Zwillich, Samuel H.
AU - van Vollenhoven, Ronald F.
AU - AUTHOR GROUP
AU - Lue, Cummins
AU - Schnitz, William Martin
AU - Baraf, Herbert Stuart Block
AU - Bolster, Marcy Behar
AU - Kivitz, Alan Jan
AU - Kimmel, Steven Charles
AU - Fudman, Edward Joel
AU - Quaidoo, Emmanuel Adolphus
AU - Churchill, Melvin Albert
AU - Birbara, Charles Allen
AU - Longley, Selden
AU - Stohl, William
AU - Niemer, Mark William
AU - Payne, Dayton Dennis
AU - Kaine, Jeffrey Louis
AU - Kafka, Shelly Pearl
AU - Fleischmann, Roy Mitchell
AU - Charles-Schoeman, Christina Marie
AU - Kavanaugh, Arthur Francis
AU - Kremer, Joel Marc
AU - Ritter, Jeffrey Sanders
AU - Stack, Michael Thomas
AU - Barron, Melanie Creech
AU - Aelion, Jacob Asher
AU - Griffin, Robert Michael
AU - Peng, Stanford Lee-Yu
AU - Walsh, Bridget Tyrell
AU - Silverfield, Joel Charles
AU - Ghirlanda, Mariano Ricardo
AU - Tate, Guillermo A.
AU - Citera, Gustavo
AU - Ximenes, Antonio Carlos
AU - Radominski, Sebastiao Cezar
AU - Keiserman, Mauro W.
AU - Zerbini, Cristiano Augusto de Freitas
AU - Calabresse, Renato Jimenez
AU - Cabezas, Pedro Claudio Miranda
AU - Ponce, Lucia
PY - 2014
Y1 - 2014
N2 - Background Methotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate. Methods We randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (>= 70% reduction in the number of both tender and swollen joints and >= 70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician). Results Mean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [ P <0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P <0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels. Conclusions In patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events
AB - Background Methotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate. Methods We randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (>= 70% reduction in the number of both tender and swollen joints and >= 70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician). Results Mean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [ P <0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P <0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels. Conclusions In patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events
U2 - https://doi.org/10.1056/NEJMoa1310476
DO - https://doi.org/10.1056/NEJMoa1310476
M3 - Article
C2 - 24941177
SN - 0028-4793
VL - 370
SP - 2377
EP - 2386
JO - New England journal of medicine
JF - New England journal of medicine
IS - 25
ER -