Novel drug plus DMARDs may improve control of rheumatoid arthritis

Tofacitinib improved disease control in patients with active rheumatoid arthritis despite treatment with nonbiologic disease-modifying, anti-rheumatic drugs (DMARDs) compared to placebo, a study found.

Researchers conducted a one-year, double-blind, randomized trial at 114 centers in 19 countries among 792 patients with active rheumatoid arthritis despite taking nonbiologic DMARDs, primarily methotrexate.

Patients were randomly assigned to receive oral tofacitinib, 5 mg or 10 mg twice daily, or placebo. Patients randomly assigned to placebo advanced at month 3 to tofacitinib, 5 mg or 10 mg twice daily if they did not respond at an earlier assessment. All patients advanced to active treatment at month 6.

Results appeared in the Aug. 20 Annals of Internal Medicine.

Nearly half of patients receiving placebo (n=78, 49.1%) did not have a response at month 3 and advanced to tofacitinib, 5 mg (n=38) and 10 mg (n=40) twice daily. There were 80 (25.4%) patients assigned to 5-mg and 58 (18.2%) patients assigned to 10-mg twice-daily tofacitinib who also had no response at month 3. Forty-three patients (27%) receiving placebo met the American College of Rheumatology (ACR20) criteria at month 3.

Compared to placebo, the ACR20 response rates at month 6 were greater for the 5-mg twice-daily tofacitinib (treatment difference, 21.2%; 95% CI, 12.2% to 30.3%; P<0.001) and 10-mg twice-daily tofacitinib (25.8%; 95% CI, 16.8% to 34.8%; P<0.001) groups.

Improvements from baseline in Health Assessment Questionnaire Disability Index scores at month 3 were greater (P<0.001) for the active treatment groups compared with placebo. In addition, more patients in the active treatment groups than the placebo group had a Disease Activity Score for 28-joint counts based on an erythrocyte sedimentation rate of less than 2.6 at month 6 (P=0.005 for 5-mg twice-daily tofacitinib; P<0.001 for 10-mg twice-daily tofacitinib).

During months 0 to 12, the adverse event rate per 100 patient-years was 171.9 (95% CI, 152.5 to 193.8) in the 5-mg twice-daily tofacitinib group, 175.7 (95% CI, 155.8 to 198.2) in the 10-mg twice-daily tofacitinib group, and 342.3 (95% CI, 281.1 to 416.9) in the combined placebo group.

Serious adverse event rates were 6.9 per 100 patient-years (95% CI, 4.6 to 10.5) for the 5-mg twice-daily tofacitinib group, 7.3 (95% CI, 4.8 to 11.0) in the 10-mg twice-daily tofacitinib group, and 10.9 (95% CI, 4.9 to 24.2) in the combined placebo group.

The most common adverse events in the tofacitinib groups were upper respiratory tract infections. The exposure-adjusted event rate (new events per 100 patient-years of exposure) was 12.3 in the 5-mg group and 14.6 in the 10-mg group, compared to 12.6 in the combined placebo group. The next most common adverse event in the tofacitinib groups was nasopharyngitis, with a rate of 7.1 in the 5-mg group and 5.6 in the 10-mg groups compared to 21.6 in the combined placebo group.

The researchers concluded that when used in combination with various nonbiologic DMARDs, primarily methotrexate, 5 mg and 10 mg of tofacitinib twice daily rapidly reduced signs and symptoms of rheumatoid arthritis and improved physical function compared with placebo.