Researchers from the Netherlands have determined—in a 24-month Phase 3 clinical trial—that tofacitinib improves disease activity and inhibits progression of joint damage in rheumatoid arthritis (RA) patients who did not respond to methotrexate (MTX). Results of the 12-month interim analysis of the efficacy of tofacitinib appear in Arthritis & Rheumatism.
“Tofacitinib inhibits Janus kinase (JAK) enzymes that are found in white blood cells, and which help to regulate the immune system, ” explains lead investigator Dr. Désirée van der Heijde from Leiden University Medical Center in The Netherlands in the January 24, 2013 news release. “We are examining the oral JAK inhibitor, tofacitinib, as a disease-modifying anti-inflammatory drug (DMARD) and for its ability to modulate the immune system in those with RA.”
In this double-blind, placebo-controlled study, 797 participants were randomized to receive 5 mg of tofacitinib twice daily (BID); 10 mg of tofacitinib BID; placebo to tofacitinib 5 mg BID; or placebo to tofacitinib10 mg BID. Participants had a mean age of 53 years, 85% were female, 54% were non-Caucasian, and the mean duration of RA was nine years. Patients who did not respond to placebo were advanced to tofacitinib at three months and the remaining placebo participants at six months.
Results from a 12-month interim analysis show that tofacitinib is effective in preserving joint structure in patients with moderate to severe RA who had an inadequate response to MTX therapy. The difference from placebo in mean change from baseline in the van der Heijde modified total Sharp score was statistically significant for tofacitinib at 10 mg BID but not at 5 mg BID at month 6 (co-primary endpoint) and month 12.
Patients treated with tofacitinib at both 5 and 10 mg BID doses displayed less progression of joint erosion and joint space narrowing compared to placebo at 6 and 12 months. Change in the joint space narrowing score was statistically significant at month 12 for the tofacitinib groups versus placebo. Researchers also reported that the proportion of patients with no radiographic progression in the tofacitinib groups was significantly greater compared to placebo.
Dr. van der Heijde told OTW, “Tofacitinib will be tested in other RA populations: both early disease before the use of MTX and late disease after the use of TNF-blockers. Moreover, in combination with MTX as well as monotherapy. With the knowledge of efficacy in various patient populations, it will be possible to decide when the drug can be used in the management of patients with RA. This is another drug that is efficacious in the treatment of patients with RA, so it is important that patients see a rheumatologist early to get the appropriate treatment.”
