TY - JOUR
T1 - Tofacitinib or Adalimumab versus Placebo in Rheumatoid Arthritis
AU - van Vollenhoven, Ronald F.
AU - Fleischmann, Roy
AU - Cohen, Stanley
AU - Lee, Eun Bong
AU - Garcia Meijide, Juan A.
AU - Wagner, Sylke
AU - Forejtova, Sarka
AU - Zwillich, Samuel H.
AU - Gruben, David
AU - Koncz, Tamas
AU - Wallenstein, Gene V.
AU - Krishnaswami, Sriram
AU - Bradley, John D.
AU - Wilkinson, Bethanie
AU - AUTHOR GROUP
AU - Bossingham, David H.
AU - Hall, Stephen
AU - Nash, Peter T.
AU - Schrieber, Leslie
AU - Sokolovic, Sekib
AU - Oparanov, Boycho
AU - Yablanski, Kiril
AU - Batalov, Anastas
AU - Bichovska, Daniela
AU - Goranov, Ivan
AU - Nikolov, Nikolay G.
AU - Chow, Andrew
AU - Klinkhoff, Alice V.
AU - Beaulieu, Andre Damien
AU - Pope, Janet
AU - Tremblay, Jean-Luc
AU - Nair, Bindu
AU - Wilson, Diane B.
AU - Aliste, Marta
AU - Ballesteros, Francisco
AU - Holuigue, Gloria
AU - Flores, Ana Maria
AU - Alpizar, Raul
AU - Brenes-Silesky, Francisco
AU - Alfaro-Vargas, Daniel
AU - Kaliterna, Dusanka Martinovic
AU - Cikes, Nada
AU - Prus, Visnja
AU - Rosa, Jan
AU - Nemec, Petr
AU - Vitek, Petr
AU - Dvorak, Zdenek
AU - Novosad, Libor
AU - Urbanova, Zuzana
AU - Mosterova, Zdenka
AU - Danneskiold-Samsoe, Bente
PY - 2012
Y1 - 2012
N2 - BACKGROUND Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis. METHODS In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity). RESULTS At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P <0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts. CONCLUSIONS In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.govnumber, NCT00853385.)
AB - BACKGROUND Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis. METHODS In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire-Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity). RESULTS At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P <0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts. CONCLUSIONS In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.govnumber, NCT00853385.)
U2 - https://doi.org/10.1056/NEJMoa1112072
DO - https://doi.org/10.1056/NEJMoa1112072
M3 - Article
C2 - 22873531
SN - 0028-4793
VL - 367
SP - 508
EP - 519
JO - New England journal of medicine
JF - New England journal of medicine
IS - 6
ER -