Safety of Ustekinumab With and Without Concomitant Corticosteroids or Immunosuppressants in Patients With Moderately to Severely Active Crohnʼs Disease

Abstract

Introduction: Ustekinumab (UST), a monoclonal antibody to IL-12 and 23, was recently approved for the treatment of moderate-severe CD. Herewe report safety data with and without concomitant use of Immunomodulators (IMM) and corticosteroids (CS) in induction and maintenance in patients pooled from the Phase 2 and 3 CD studies. Methods: Percentages of patients experiencing safety events (AEs, SAEs, infections, and deaths) were assessed with and without concomitant IMM or CS use at baseline after IV ustekinumab (UST) or placebo (PBO) induction (8 weeks) and were then also compared with SC UST or PBO maintenance (up to 44 weeks) from the Phase 2 and 3 CD clinical studies. Patients who received IV ustekinumab (doses included: 130mg flat dose and 1, 3, 4.5, & 6 mg/kg) during the placebo-controlled induction period (Week 0-8) were pooled from 2 Phase 2 (C0379T07 & CERTIFI) and 2 Phase 3 (UNITI-1 and 2) clinical studies (total n= 1,986). For maintenance, SC UST (combining 90mg q8w and q12w) and PBO were pooled and compared in the randomized responder populations (ie responders to IV ustekinumab induction) from the maintenance phase of the Phase 2 CERTIFI (Week 8 to Week 22) and Phase 3 IM-UNITI (Week 0 to Week 44) studies (total n= 541). Results: No deaths occurred in either the induction or maintenance phases in any groups. Through 8 weeks of induction, the percentages of patients with AEs, SAEs, and infections were similar between UST and PBO both on and off IMM and CS (Table). In maintenance, proportions of patients experiencing AEs, SAEs, and infections were also similar between UST and PBO groups regardless of concomitant medication, although proportions of patients on CS in both the UST and PBO groups experienced slightly higher rates of AEs compared with those not on CS. Additionally, in maintenance, PBO patients on CS also experienced slightly higher rates of SAEs and infections than the other groups.Table: Table. Safety Events with and without concomitant immunosuppressants through up to 52 weeks (8 weeks induction and 44 weeks maintenance) from the Crohn's clinical trial programConclusion: No differences were identified based on the use of concomitant IMMs or CSs in UST-treated patients with either IV induction or with SC maintenance compared to PBO. The concomitant use of IMM or CS during either IV induction or SC maintenance treatment with UST did not adversely impact the previously reported favorable safety profile of UST in moderate to severe CD patients, although concomitant CS did result in slightly higher rates of events during maintenance, particularly in the PBO group.