Safety Profile of Upadacitinib in Rheumatoid Arthritis: Integrated Analysis from the SELECT Phase III Clinical Programme

Ann Rheum Dis 2020 DOI:10.1136/annrheumdis-2020-218510

This integrated Phase III safety analysis of UPA showed that UPA had a similar profile to ADA and MTX for serious infections, malignancies, and thromboembolic events. Patients receiving UPA had increased risk of HZ and creatine phosphokinase elevation versus ADA.This integrated Phase III safety analysis of UPA examined >3500 RA patients and 4000 patient-years of exposure. Data were pooled from 3834 patients in SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY studies. Patients received extended-release UPA 15 or 30 mg QD, placebo, MTX, or ADA monotherapy, dependent on the study enrolled in. Exposure-adjusted event rates were calculated for each therapy, with treatment-emergent adverse events and laboratory data were analysed. The most common treatment-emergent adverse event associated with UPA, were URTIs, nasopharyngitis, and UTIs. Exposure-adjusted event rates of serious treatment-emergent adverse events with UPA 15 mg, were comparable with ADA but higher than MTX. Serious infection rates were similar between UPA 15 mg and ADA and did not increase over time. UPA was associated with a higher HZ risk than comparator groups, but most cases were non-serious. Rates of adjudicated MACE and VTE were comparable across treatment groups, and CPK elevations were more frequent with UPA versus placebo, MTX or ADA; these were typically asymptomatic, and few led to discontinuation.The results of this integrated safety analysis suggest that UPA has a similar safety profile to other JAK inhibitors as demonstrated in their clinical development programmes.