Long‐term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy

Abstract

SummaryBackgroundIn Phase 3 studies of ustekinumab, a fully human monoclonal IL‐12/23p40 antibody approved for moderate‐to‐severe Crohn's disease, patients entered a long‐term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM‐UNITI maintenance are reported.Methods UNITI‐1 (TNF‐antagonist failures) and UNITI‐2 (conventional therapy failures) patients (N = 1281) entered IM‐UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose‐adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8–32). All Week 44 completers could enter the long‐term extension without further dose adjustment. Placebo patients discontinued following study unblinding.ResultsA total of 718 patients (all treated) entered the long‐term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient‐years) were similar among all placebo and ustekinumab patients (Week 0‐96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed.ConclusionsSubcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.

Real‐world short‐term effectiveness of ustekinumab in 305 patients with Crohn’s disease: results from the ENEIDA registry

“…These studies enabled a dosing schedule to be stablished and determined the most efficacious way to administer the drug in CD. They also proved its usefulness for inducing and maintaining clinical and endoscopic remission in patients with moderate to severe CD …”

“…Nonstenosing/nonpenetrating 173 (50) Stenosing 102 (30) Penetrating 62 (20) Extra-intestinal manifestations 120 (39) Smoking 84 (28) Previous surgery 171 (56) Previous anti-TNFα therapy (%) 0 11 (4) 1 98 (32) 2 151 (49) ≥3 45 (15) Previous anti-TNFα experience (%) 294 (96) Primary failure 79 (27) Secondary failure 153 (52) Adverse event or intolerance 62 (21) Previous therapy with vedolizumab (%) 87 (29) Primary failure 29 (33) Secondary failure 34 (39) Adverse event or intolerance 24 (28) Severity at baseline (%) 200 (66) Mild 30 (15) Moderate 106 (53) Severe 64 (32) HBI score at baseline 7 (4.1); 6 (4,9) CRP (mg/L) at baseline 8.5 (2.3, 25) FC ( (Figure 3).…”

“…They also proved its usefulness for inducing and maintaining clinical and endoscopic remission in patients with moderate to severe CD. [8][9][10] Studies from clinical practice to date were performed before the drug came onto the market, when it was only indicated for psoriasis, was requested for compassionate use, and was administered subcutaneously (SC) and at various doses. [11][12][13][14][15] Khorrami et al 13 studied 116 patients treated with ustekinumab SC in several Spanish hospitals.…”

Editorial: ustekinumab and Crohn's disease—what can we learn from long‐term extension studies?

“…Ustekinumab, a fully humanised monoclonal antibody to the p40 subunit of both IL 12 and IL 23, is indicated for the treatments of moderate to severe Crohn's disease. Sandborn et al now report long‐term (92 weeks) efficacy data from the ustekinumab registration trials . The participants represent two groups of patients typically seen in clinical practice, specifically those who had failed or were intolerant to one or more anti‐TNF drugs (UNITI‐1), and those who had failed or were intolerant to conventional immunomodulators (IMUNITI‐2).…”

“…Sandborn et al now report long-term (92 weeks) efficacy data from the ustekinumab registration trials. 8 The participants represent two groups of patients typically seen in clinical practice, specifically those who had failed or were intolerant to one or more anti-TNF drugs (UNITI-1), and those who had failed or were intolerant to conventional immunomodulators (IMUNITI-2). Those included were those who responded to induction and then maintained their response through the subsequent 44 weeks of the randomised IM-UNITI maintenance study.…”