Age-based (<65 vs ≥65 years) incidence of infections and serious infections with tofacitinib versus biological DMARDs in rheumatoid arthritis clinical trials and the US Corrona RA registry

A randomised, open-label, blinded endpoint post-authorisation safety study (Study A3921133; NCT02092467; database not locked and subject to change) evaluated the safety of tofacitinib 5 mg and 10 mg twice daily (BID) versus tumour necrosis factor inhibitors (TNFi) (adalimumab/etanercept) in rheumatoid arthritis (RA) patients aged ≥50 years with ≥1 cardiovascular risk factor. An ad hoc interim safety analysis of Study A3921133 reported incidence rates (IRs) per 100 patient-years (95% CIs) for fatal infections (within 28 days of treatment) and non-fatal serious infection events (SIEs), respectively: tofacitinib 5 mg BID, 0.18 (0.07 to 0.39) and 3.35 (2.78 to 4.01); tofacitinib 10 mg BID, 0.22 (0.09 to 0.46) and 3.51 (2.93 to 4.16); TNFi, 0.06 (0.01 to 0.22) and 2.79 (2.28 to 3.39).1 SIEs risk (fatal/non-fatal) was further increased with tofacitinib in patients aged >65 years versus younger patients; therefore, the European Medicines Agency recommended that older patients should receive tofacitinib when there is no suitable alternative treatment.2 Further to these recommendations, we sought to assess age-based (<65 vs ≥65 years) SIE risk in RA patients receiving tofacitinib in Phase 2, 3 and 3b/4 tofacitinib studies with a TNFi control/comparator arm,3–5 and in the US Corrona RA registry. The clinical data set included 2180 patients (tofacitinib 5 mg BID, n=1064 (943.4 patient-years); tofacitinib 10 mg BID, n=306 (236.6 patient-years); adalimumab, n=643 (554.3 patient-years); placebo, n=167 (108.1 patient-years)). Overall, 1841 (84.4%) patients were aged <65 years and 339 (15.6%) ≥65 years. Crude IRs (patients with events/100 patient-years) and HRs were calculated for all first infections and first SIEs, overall and by age. For all infections (online supplemental figure S1), IRs and infection risk (by HRs) were higher with active treatments versus placebo, and similar across active treatments and age groups. For SIEs (figure 1), IRs were higher in older versus younger patients for active treatments, …