Tofacitinib monotherapy more effective than methotrexate in treating RA patients

WASHINGTON — Patients with rheumatoid arthritis who were methotrexate-naive displayed inhibited structural damage and improvement in symptoms and physical functioning with tofacitinib monotherapy compared with methotrexate, according to data presented at the American College of Rheumatology Annual Meeting.

In a phase 3, 24-month, double-masked study, researchers evaluated 952 patients with active rheumatoid arthritis (RA). Patients were treated with 5 mg tofacitinib twice daily (n=371) or 10 mg twice daily (n=395) or 10 mg methotrexate (MTX; n=186) weekly with 5 mg per week increments to 20 mg per week. At month 6, primary endpoints compared tofacitinib with methotrexate for mean changes from baseline (BL) in van der Heijde-modified Total Sharp Score (mTSS) and ACR70 response.

Roy M. Fleischmann

All patients displayed similar demographic and disease characteristics at BL, including radiographic scores (mTSS: 20.30, 18.85 and 16.51 for 5 mg tofacitinib, 10 mg tofacitinib and MTX, respectively). At month 6, both doses of tofacitinib produced statistically superior mean changes in mTSS and ACR70 compared with MTX. By month 1, patients receiving both dosages of tofacitinib showed statistically significant differences in ACR70 response compared with MTX, and efficacy increased during the study. In secondary radiographic endpoints at month 6, a significant difference also was shown in tofacitinib compared with MTX, regarding smaller changes in joint space narrowing scores and greater proportion of points with no progression from BL (in TSS change ≤0.5). Throughout the study, tofacitinib produced better results compared with MTX for other secondary endpoints, including ACR20 and ACR50 responses, mean change in DAS28-4(ESR), DAS28-4(ESR) <2.6 rates and mean change in Health Assessment Questionnaire Disability Index.

Safety of tofacitinib was similar to what was reported in previous phase 3 trials, the researchers noted. Most reported adverse events (infections) were mild or moderate. Herpes zoster was reported in 2.2% of 5-mg tofacitinib patients, 2.5% of 10-mg tofacitinib patients and 1.1% of MTX patients. One patient in the 10-mg tofacitinib group had bone tuberculosis and another MTX patient developed cytomegalovirus infection. Two patients receiving tofacitinib died during the trial. Tofacitinib-treated patients displayed increases in LDL- and HDL-cholesterol levels. There was a low incidence of asparate and alanine aminotransferase elevations of at least three times high normal.

“Both [tofacitinib at 5 mg and 10 mg] are statistically superior to methotrexate monotherapy,” researcher Roy M. Fleischmann, MD, clinical professor in the internal medicine department at the University of Texas Southwestern Medical School, said during his presentation. “[Tofacitinib] significantly inhibits progression of structural damage.”

Disclosures: Dr. Fleischmann and other researchers reported numerous financial disclosures.

For more information:

Lee EB. P2486: Radiographic, Clinical and Functional Comparison of Tofacitinib Monotherapy Versus Methotrexate in Methotrexate-Naive Patients with Rheumatoid Arthritis. Presented at: American College of Rheumatology 2012 Annual Meeting; Nov. 10-14, Washington.