A102 TOLERABILITY OF USTEKINUMAB IN INDUCTION AND MAINTENANCE FOR THE TREATMENT OF CROHN’S DISEASE

Abstract

Background: Tolerance to therapy is critical for patients to receive the maximal treatment beneft. In Phase 3 clinical trials for ustekinumab (UST) for moderate to severe Crohn's disease (CD), UNITI-1 enrolled anti-TNF failures and UNITI-2 enrolled conventional therapy failures. In UNITI-1, 36.4% had previous intolerance (infusion-related reactions [IRR], delayed hypersensitivity reactions, or injection site reactions [ISR]) that led to discontinuation of the anti-TNF. UNITI-2 enrolled patients that were not intolerant to anti-TNFs, but some were intolerant to immunomodulators (39%) or corticosteroids (15%). Here we assess tolerability as measured by IRR, delayed hypersensitivity, or ISR to UST in the Phase 3 CD trials. METHOD(S): All enrolled patients in UNITI-1 and UNITI-2 were given an intravenous (IV) induction infusion of UST 130mg, UST ~6 mg/kg, or placebo (PBO). Te IM-UNITI maintenance study began 8 weeks afer IV induction; UST IV responders were randomized to UST 90mg SC Q8W, UST 90mg SC Q12W, or PBO. Non-randomized patients, included non-responders to placebo who received 130mg IV UST, then continued to UST 90mg SC Q12W maintenance therapy; non-responders to IV UST who received UST 90 mg SC, then continued UST 90 mg SC Q8W in maintenance; and IV placebo responders who received placebo SC in maintenance. RESULT(S): Overall, IRR were infrequent: 4.0% and 1.9% of all patients in UNITI 1 &2, respectively, experienced infusion reactions to the single IV dose. Tere were no differences in IRR between PBO &UST, or between UST doses (UNITI 1 IRRs in 2.0%, PBO and 4.5% UST 130mg and 3.6%, UST ~6 mg/kg; UNITI 2 IRRs in 2.9%, PBO and 2.4% UST 130mg and 1.4%, UST ~6 mg/kg). During IM-UNITI, in non-randomized patients who were non-responders to placebo induction and received a 130mg IV injection, IRR to PBO and UST were similar and infrequent (2.5% and 1.8%, respectively). Tere were no anaphylactic or delayed hypersensitivity reactions to any IV dose. Afer SC administration, ISRs were infrequent and not different across groups. In the combined (randomized and non-randomized) population, ISRs were 1.7% with PBO, and 3.0% with UST. No serious ISRs were reported. Te most common ISR was erythema, reported in 1.1% of PBO, and 1.7% of UST. Tere were no anaphylactic or delayed hypersensitivity reactions to any SC dose. Amongst randomized patients, ISRs were infrequent and consistent between groups. ISRs occurred in 3/418 (0.7%) of all UST 90mg Q12W injections and in 12/599 (2.0%) of all UST 90mg Q8W injections. One patient in the entire phase 3 program discontinued therapy due to ISR. CONCLUSION(S): In a broad population of patients with Crohn's disease, many of whom were intolerant to previous therapies, UST had a tolerable profle. Rates of IRR and ISR were minimal, and were not different between groups, nor populations.