Background Previous studies1–2 suggest the structural benefit of IV abatacept in patients with RA who have previously failed MTX, TNF therapy or combination of both. Objectives This study evaluates the structural effect of SC abatacept in a cohort of patients with RA, comparing the structural findings with clinical outcomes and measuring any difference between 1 or 2 TNF failure cohorts on stable MTX. average 17 mg/wk. Methods Thirty four (34) patients were enrolled over 18-months into an open-label 1-year trial. Patients received SC abatacept 125 mg/week on background MTX. Patients on prednisone remained on a stable dose ≤10 mg. daily. MRIs of the hands/wrists were performed on a 0.3T Esaote S-Scan and scored blinded using a modified OMERACT/RAMRIS scoring system at Baseline, Wks. 12, 24 and 48. A global response of progression, regression, or no change was calculated for each time point. Clinical outcomes were measured by a DAS28(ESR) at similar time points. Results 27 patients completed; 7 patients discontinued including 3 treatment failures. Of the 27 patients who completed the trial, 15 patients had prior exposure to 1 TNF and 12 patients had prior exposure to 2 TNFs. The clinical and structural findings of each group were analyzed independently since individual clinical responses did not directly correlate with the structural response due to disease duration, disease activity at the time of trial entry, and prior drug exposure. Structurally, there were patients in both groups who showed improvement in synovitis and osteitis by MRI, however, the patients who had only 1 prior TNF exposure had a more robust response overall for both synovitis and osteitis. Of the 27 completed patients, 25 were positive DAS28 responders. 2 patients were non-responders. Clinical remission was achieved in 4 patients, low disease activity in 6 patients, moderate disease activity in 8 patients, and high disease activity remained in 7 patients. Clinically, there was no clear trend to distinguish any difference between the two groups. Both clinical and structural responses occurred within 6-months. 2 patients who had a clinical response at 6 months failed to sustain a response at 12 months. No adverse events were noted. Conclusions Overall, this small cohort of patients suggests that SC abatacept has clinical and structural benefit in patients who have had treatment with either 1 or 2 TNFs and is a viable choice of therapy. The structural findings were comparable to the benefits of IV abatacept which have been previously published.1 The group that had 1 TNF exposure showed a greater improvement with respect to synovitis and osteitis than the population with 2 TNF exposure. It is possible that the structural benefit may be more robust when a switch from TNF therapy to an alternative mechanism of action such as abatacept is made after only 1 TNF failure. Further analysis is needed to determine if 6 months can be used as a cut-off point that prognosticates the value of continuing further therapy in the face of a lack of clinica...

BackgroundTofacitinib 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.ObjectivesThis 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.Methods20 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.ResultsOf 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.ConclusionsOur 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 ...