SAN FRANCISCO, CA—Clinical efficacy of the oral Janus kinase inhibitor tofacitinib at Month 6 was greater than placebo and “appeared similar regardless of methotrexate dose” in patients with rheumatoid arthritis (RA) a post-hoc analysis presented at the 2015 ACR/ARHP Annual Meeting has found.
To examine the effect of methotrexate dose on tofacitinib efficacy, Roy Fleischmann, MD, clinical professor in the Department of Internal Medicine at the University of Texas Southwestern Medical School and Medical Director, Metroplex Clinical Research Center, Dallas, TX, and colleagues conducted a post-hoc analysis of data from ORAL Scan, a Phase 3, two-year randomized clinical trial that evaluated tofacitinib therapy in patients with RA and an inadequate response to methotrexate.
The ORAL Scan study randomly assigned 797 patients with RA to tofacitinib 5mg twice daily (n=321), tofacitinib 10mg twice daily (n=316), or placebo (n=160) with advancement to 5mg twice daily or to 10mg twice daily at Month 3 or Month 6, in combination with background methotrexate.
The dose of methotrexate was stable throughout the study and was categorized as Low (≤12.5mg/week; n=242), Medium (>12.5 to <17.5mg/week; n=333), or High (≥17.5mg/week; n=222). At Month 6, the following end points were evaluated: ACR response rates, proportion of patients achieving low disease activity measured by the Clinical Disease Activity Index (CDAI ≤10), CDAI defined remission rate (CDAI ≤2.8), proportion of patients achieving an improvement ≥0.5 in the Health Assessment Questionnaire-Disability Index (HAQ-DI), and least squares mean change from baseline in HAQ-DI, Disease Activity Score (DAS28-4[ESR]), and CDAI.
“At Month 6, greater efficacy was seen with tofacitinib compared to placebo for all endpoints across the three methotrexate dose groups,” Dr. Fleischmann reported.
He cautioned that “further analysis is needed to address the question of whether there is a dose response for starting methotrexate in combination with tofacitinib, as tofacitinib was added to patients who were methotrexate-inadequate responders in this study. To examine the effect of methotrexate dose on tofacitinib efficacy, a randomized clinical trial would be needed in which different doses of methotrexate are added to tofacitinib in methotrexate-naive patients.”