Abstract | BACKGROUND: 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: 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. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.).
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Authors | Eun Bong Lee, Roy Fleischmann, Stephen Hall, Bethanie Wilkinson, John D Bradley, David Gruben, Tamas Koncz, Sriram Krishnaswami, Gene V Wallenstein, Chuanbo Zang, Samuel H Zwillich, Ronald F van Vollenhoven, ORAL Start Investigators |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 370
Issue 25
Pg. 2377-86
(Jun 19 2014)
ISSN: 1533-4406 [Electronic] United States |
PMID | 24941177
(Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antirheumatic Agents
- Piperidines
- Protein Kinase Inhibitors
- Pyrimidines
- Pyrroles
- tofacitinib
- Cholesterol
- Creatinine
- Janus Kinase 3
- Methotrexate
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Topics |
- Administration, Oral
- Adult
- Antirheumatic Agents
(administration & dosage, adverse effects)
- Arthritis, Rheumatoid
(blood, complications, drug therapy)
- Cholesterol
(blood)
- Creatinine
(blood)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Herpes Zoster
(etiology)
- Humans
- Janus Kinase 3
(antagonists & inhibitors)
- Male
- Methotrexate
(administration & dosage, adverse effects)
- Middle Aged
- Piperidines
(administration & dosage, adverse effects)
- Protein Kinase Inhibitors
(administration & dosage, adverse effects)
- Pyrimidines
(administration & dosage, adverse effects)
- Pyrroles
(administration & dosage, adverse effects)
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