• Rheumatology Clinical Trials
• Rheumatoid Arthritis

Treatment with the oral Janus kinase (JAK) inhibitor tofacitinib was associated with an improvement in the signs and symptoms of rheumatoid arthritis (RA), physical function, and patient reported outcomes in RA patients with an inadequate response to tumor necrosis factor inhibitors (TNFi). The improved response was maintained over 24 months. Data from 11 studies [Monotherapy: NCT00550446, NCT00687193, NCT00814307; background DMARD: NCT00413660, NCT00603512, NCT00960440, NCT00847613, NCT00856544, NCT00853385; LTE: NCT00413699, NCT00661661] were pooled and Gerd R. Burmester, MD, Charité University Hospital, Berlin, Germany, presented the results.

In a prior study, tofacitinib improved the signs and symptoms of RA in 399 TNFi treatment refractory patients over 6 months [Burmester G-R et al. Arthritis Rheum 2011]. The purpose of this analysis was to provide additional short-and long-term data concerning the effect of tofacitinib on the signs and symptoms of RA, physical function, pain, and fatigue compared with placebo in this patient population and to further characterize the activity of tofacitinib by number of failed TNFi, by reason for failure (adverse event vs lack of efficacy). In the newer study, data from 9 randomized Phase 2 and 3 studies (n=614) and 2 open-label long-term extension studies (n=510) were analyzed. Patients were treated with tofacitinib (5 or 10 mg BID) either as monotherapy or on a background of nonbiologic disease-modifying antirheumatic drugs (DMARDs), or, in Phase 2 and 3 studies, with placebo.

Efficacy in reducing the signs and symptoms of RA was assessed by changes in American College of Rheumatology improvement response criteria (ACR20/50/70) and 28-joint Disease Activity Score (DAS28)-4 erythrocyte sedimentation rate (ESR) scores. Physical function was assessed by mean change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI). Pain and fatigue were assessed using change from baseline on the Short Form-36 Bodily Pain item and the Functional Assessment of Chronic Illness Therapy-Fatigue item. More than 60% of the patients had failed at least one TNFi in all groups.

At Month 3, significantly greater ACR20/50/70 responder rates were seen with tofacitinib compared with placebo (p<0.0001, p<0.0001, p<0.05, respectively). This pattern was consistent regardless of 1 or 2 prior TNFi failures. Tofacitinib also improved mean DAS28–4 ESR scores, values for HAQ-DI, and body pain and fatigue at 3 months and over 24 months. No new safety signals were detected in the previously presented randomized controlled trial in TNFi inadequate response patients treated with tofacitinib [Burmester GR et al. Arthritis Rheum 2011].

The investigators concluded that tofacitinib may offer a benefit in difficult-to-treat patients resistant to standard DMARDs.

• © 2012 MD Conference Express®