Krznarić, Željko

Importance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No new safety risks were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel diseases (IBD), affect approximately seven million people globally. The continuous rise in IBD prevalence and the aging of populations will inevitably lead to an increasing use of health care resources. In parallel with these trends, continuing innovations in IBD therapeutics, diagnostics, and preventatives are creating more options for IBD patients seeking to reduce their disease burden. These trends pose an imminent burden on health care systems and require that we identify modifiable cost drivers in IBD care and develop strategies for delivering equitable and affordable care for all patients. Methods This Lancet Gastroenterology & Hepatology Commission, consisting of a diverse faculty of health care professionals with expertise in the field of IBD and health economists, was formed to deliver an extensive summary of the literature and discuss key topics on the costs and cost-effectiveness of treating IBD in the present, and how this is likely to look in the future. Furthermore, it offers suggestions for how to deliver affordable IBD care in the coming years. The report’s focus was on high-income countries in Europe, North America, Australia and New Zealand, and Asia. Results The Commission drew together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, as well as how to deliver affordable care for IBD in the future. The key conclusions are that (i) increases in health care costs must be evaluated against improved disease control and reductions in indirect costs, and (ii) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and cost-effectiveness of care. International collaborations should be sought in order to evaluate novel models of care (such as value-based health care, including integrated health care and participatory health care models), as well as to improve the education and training of clinicians, patients, and policymakers. Measures to reduce the costs of IBD care are summarised in Table 1. Conclusion Increases in health care costs must be evaluated against improved disease control and reductions in indirect costs. Evaluations should be systematically aligned between countries and regions. Detailed analysis of the current epidemiology and the likely effects of changing IBD management on disease course and socioeconomic outcomes is essential; and will become even more imperative in the era of precision medicine, where complex biotechnologies will require expensive analyses, highly skilled personnel, and drug development for what may sometimes be relatively small patient groups.