The use of tofacitinib in combination with conventional background disease-modifying antirheumatic drugs is associated with rapid, significant, and clinically meaningful reductions in signs and symptoms of rheumatoid arthritis, as well as with improvement in physical function, according to findings from a phase III study.
The data were presented by Dr. Joel M. Kremer at a press briefing during the annual meeting of the European Congress of Rheumatology.
"The very rapid responses were sustained beyond 6 months to 12 months," Dr. Kremer noted.
The findings from the 12-month, placebo-controlled study are consistent with those from phase II studies and a phase III monotherapy study of the novel oral JAK inhibitor, and no new safety signals were detected, said Dr. Kremer, a rheumatologist and the Pfaff Family Professor of Medicine at Albany (N.Y.) Medical College.
In 792 patients with inadequate response to nonbiologic background DMARDs – most often methotrexate – who were randomized to receive either 5 mg or 10 mg of tofacitinib or placebo twice daily, tofacitinib was statistically superior to placebo for all primary efficacy end points, including an ACR 20 response (that is, an American College of Rheumatology score based on a 20% improvement in specified parameters), a DAS28-4(ESR) response (that is, a disease activity score based on a 28-joint count and the erythrocyte sedimentation rate) of less than 2.6 at month 6, and a change in HAQ-DI (Health and Quality of Life–Disability Index) at month 3.
In the 5-mg, 10-mg, and placebo groups, respectively, ACR 20 responses at 6 months were 52.7%, 58.3%, and 31.2%; DAS28-4(ESR) responses of less than 2.6 at 6 months were 11.0%, 14.8% and 2.7%; and changes in HAQ-DI at 3 months were –0.46, –0.56, and –0.21.
Significant differences between the treatment and placebo groups were seen by week 2, Dr. Kremer noted.
The most common adverse events included infections and infestations, which were generally mild. However, four deaths and four opportunistic infections occurred. Deaths included one from acute heart failure and one from respiratory failure in the 10-mg treatment group, and one from traumatic brain injury and one from RA in the 5-mg treatment group, both following discontinuation of treatment (at 22 and 42 days, respectively). Serious infectious events (including opportunistic infections, such as TB, Cryptococcus, and herpes zoster) occurred in two patients in the 5-mg group and in four patients in the 10-mg group during months 0-4, and in one patient in each group during months 3-6. Other adverse events included decreases in neutrophils, increases in LDL and HDL cholesterol levels, small increases in serum creatinine, and anemia.
Patients in the study were mostly women (81.4%) with a mean age in the treatment and placebo groups, respectively, of 50.8 and 53.3 years at baseline, and a mean disease duration of 8.1 and 10.2 years. Nonresponders in the placebo group at month 3 were advanced to tofacitinib, and all remaining patients in the placebo group were advanced at 6 months.
"This large, phase III trial adds to the body of evidence on the efficacy of tofacitinib," Dr. Kremer concluded.
There were four deaths but only one was thought to be treatment related, Dr. Kremer noted. The patient’s spouse refused to grant permission for an autopsy, he added.
Dr. Kremer reported receiving grant and/or research support from Pfizer Inc. and serving as a consultant for Pfizer. Other study authors disclosed having similar relationships with Pfizer, as well as serving on the speakers bureau and/or being a shareholder or employee of Pfizer.