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P343 Efficacy of ustekinumab in Crohn’s disease at maintenance Week 56: IM-UNITI study

W. J. Sandborn*1, B. Sands2, J-F. Colombel2, C. Gasink3, R. Patel4, D. Jacobstein5, L-L. Gao5, S. Ghosh6, S. Targan7, W. De Villiers8, S. B. Hanauer9, P. Rutgeerts10, B. Feagan11

1University of California San Diego, La Jolla, USA, 2Icahn School of Medicine at Mt Sinai, New York, USA, 3Janssen Scientific Affairs, LLC, Horsham, USA, 4Janssen Pharmaceuticals, Horsham, USA, 5Janssen Research and Development, LLC, Spring House, USA, 6University of Birmingham, Birmingham, UK, 7Cedars-Sinai Medical Center, Los Angeles, USA, 8Stellenbosch University, Stellenbosch, South Africa, 9Northwestern University, Feinberg School of Medicine, Chicago, USA, 10University Hospital Gasthuisberg, Leuven, Belgium, 11Robarts Clinical Trials, Robarts Research Institute, Western University, London, Canada

Background

Ustekinumab (UST), a human IgG1κ monoclonal antibody that binds to the p40 protein subunit of IL-12 and IL-23 cytokines, is approved for moderate–severe Crohn’s disease (CD). Primary endpoint data (Wk44) from the pivotal Phase 3 study, IM-UNITI, have been previously reported. We examined efficacy of UST after 1 year of maintenance therapy (Wk56).

Methods

The Phase 3 program of UST in CD includes 2 multi-centre, double-blind, placebo (PBO) controlled 8-week induction studies, UNITI-1 (anti-TNF therapy failures) and UNITI-2 (conventional therapy failures) comprised of 1281 patients. Pts in clinical response(reduction in CDAI ≥100 points or in clinical remission) at Wk8 to IV UST induction in UNITI-1 and 2 were randomised 1:1:1 to SC UST 90 mg q8w or q12w or PBO in IM-UNITI. Pts completing Wk44 of IM UNITI qualified to participate in the IM-UNITI extension study. The study was unblinded when Wk44 analyses were completed. Due to the durable biologic effect of a single IV induction, 36% of the randomised withdrawal population on SC PBO in maintenance were in remission at Wk44. At Wk56, 84.6% of patients remained blinded; unblinded patients were conservatively assumed to have same remission status as Wk44. Wk56 remission data were assessed in this post-hoc analysis of the primary randomised population of 388 patients who initially responded to UST IV induction and were subsequently randomised to UST 90 mg q8w (n = 128), 90 mg q12w (n = 129), or PBO (n = 131) in the maintenance study. Wk56 is the first long-term extension visit 12 weeks after Wk44 of IM-UNITI.

Results

Compared with Wk44, patients on UST at Wk56 maintained remission (50.8% for UST q8w, 49.6% for UST q12w; p < 0.001), while there was a noteworthy reduction in remission rates (27.5%) in PBO patients (Table 1). The proportion of patients in clinical remission not receiving corticosteroids at Wk56 was significantly greater with UST vs. PBO (46.1% UST q8w, 43.4% UST q12w, 22.1% PBO; p < 0.001). In a subgroup analysis of conventional therapy failure patients (UNITI-2), a greater proportion of patients treated with UST achieved clinical remission that was maintained at Week 56 from Wk44 (Table 1) compared with PBO. Safety at Wk56 was similar to previous safety results reported for Wk44; no new safety events were observed.

Table 1. Efficacy at Week 44 and 56 for primary randomised population and patients who failed conventional therapy efficacy.

Conclusion

In patients with moderate–severe CD who responded to UST induction, SC UST is significantly better at maintaining clinical remission vs. PBO. Remission rates among UST patients were maintained from Wk44 to Wk56; yet, durable biologic effect from one IV induction dose seemed to diminish more rapidly from Wk44 to Wk56.