Background Tofacitinib has been shown to reduce the clinical signs and symptoms of some RA patients at an approved dose of 5 mg bid. Studies report that 10 mg bid is an effective dose. This is the first community practice trial to measure the clinical and structural benefits of stepping up the initial dose of 5 mg bid in non-responders to 10 mg bid in order to achieve a clinical response using a treat to target approach.
Objectives This study evaluates the optimal dose of tofacitinib (5 mg bid VS 10 mg bid) needed to reach treatment target in a cohort of patients with active RA while comparing the corresponding structural findings measured by low field MRI.
Methods 20 RA patients who were unresponsive to either methotrexate (10–25 mg weekly) or MTX plus up to 2 prior biologics with synovitis, osteitis or erosions on Baseline MRI (Esaote 0.3T) were treated with 5 mg bid tofacitinib with a treat to target goal of Low Disease Activity (LDA) or remission depending on the Clinical Activity Index (CDAI) score at Baseline. If the target was not met and sustained for 3 months, the dose of tofacitinib was increased to 10 mg bid in an attempt to reach target. MRIs of the hand/wrist were blindly read by a musculoskeletal radiologist using a rheumatoid arthritis MRI scoring system (RAMRIS). A CDAI score of >10 was needed at study entry.
Results Of the 20 enrolled patients, 6 remained at 5 mg bid and 14 were dose escalated to 10 mg bid most at the 12 week period. Of the 5 mg bid group, 3 completed the trial at target and 3 early termed (ET) for lack of efficacy, relocation and AE. Structurally, there was no change in erosions in all 3 patients; 2 showed regression of synovitis and 1 showed no change; 2 showed regression in osteitis and 1 no change. Of the 14 patients escalated to 10 mg bid, 11 completed the trial with 7 remissions, 2 at LDA, and 1 at MDA. 3 patients ET due to lack of efficacy. In the 10 mg bid group, 9 patients showed no change in erosions, 1 regression and 1 progression. 5 patients showed no change in synovitis and 6 showed regression, and 7 showed no change in osteitis, 3 showed regression and 1 showed progression. The CRP values correlated with the improvement of the clinical and structural results, in particular, the levels improved after the dose was increased to 10 mg bid.
Conclusions Our results suggest that a significant number of patients treated with the standard dose of 5 mg bid may potentially have improved outcomes including LDA or remission when treated at a higher dose (10 mg bid). As is evidenced by the results in this study, 11 of the 14 patients had significant improved response after treatment with the step up dose. It would appear that this improved result occurs by 3 months of therapy. Furthermore, the structural findings correlate in large part to the clinical findings showing stabilization or improvement in the majority of patients. A larger study is needed to validate these clinical and structural responses as well as to evaluate the safety outcomes using 10 mg bid for intervals of more than 12 months.
Disclosure of Interest None declared