THU0174 A Safety Analysis of Tofacitinib 5 mg Twice Daily Administered as Monotherapy or in Combination with Background Conventional Synthetic Dmards in A Phase 3 Rheumatoid Arthritis Population

BackgroundTofacitinib is an oral JAK inhibitor for the treatment of RA. In Phase 3 studies, tofacitinib demonstrated safety and efficacy at 5 and 10 mg BID when used as monotherapy or with conventional synthetic (cs) DMARDs (csDMARDs).ObjectivesTo examine the safety profile of tofacitinib 5 mg BID as monotherapy and combination therapy in the Phase 3 clinical development RA program.MethodsSafety data for tofacitinib were obtained from six double-blind Phase 3 studies of 6–24 months' duration and stratified by whether tofacitinib was administered as monotherapy (NCT00814307, ORAL Solo; NCT01039688, ORAL Start) or with csDMARDs (NCT00960440, ORAL Step; NCT00847613, ORAL Scan; NCT00856544, ORAL Sync; and NCT00853385, ORAL Standard). Patients in ORAL Start were methotrexate (MTX)-naïve while patients in all other studies had an inadequate response to cs or biologic DMARDs. Endpoints included: serious adverse events (SAEs), discontinuations due to adverse events (AEs), serious infection events (SIEs), opportunistic infections, herpes zoster (HZ), malignancies, major adverse cardiovascular events, gastrointestinal perforations, all-cause mortality and laboratory safety data.ResultsTofacitinib 5 mg BID was administered as monotherapy in 616 patients (243 from ORAL Solo and 373 from ORAL Start, mean age 51.1 years [yrs], mean RA duration 4.9 yrs, 49.8% received glucocorticoids [GC]) and combination therapy in 973 patients (mean age 53.4 yrs, mean RA duration 8.9 yrs, 57.8% received GC). Incidence rates (IRs) for SAEs, discontinuations due to AEs, SIEs and HZ were generally lower in patients receiving tofacitinib monotherapy vs combination therapy. A similar trend was observed when patients were stratified by GC use; however confidence intervals were wide and overlapping for some outcomes (Table). IRs for SIEs and HZ were greater for patients who received GC compared with those who did not, irrespective of whether tofacitinib was given as monotherapy or in combination. Similar proportions of patients in the monotherapy and combination therapy groups had confirmed laboratory decreases in haemoglobin, neutrophil and lymphocyte counts, and increases in liver enzymes and serum creatinine (Table).ConclusionsIn this analysis, IRs for SAEs, discontinuations due to AEs, SIEs and HZ were lower in the tofacitinib 5 mg BID monotherapy group vs the combination therapy group; however, IRs should be interpreted with caution as the data are from controlled studies of limited dura