- Fecal Incontinence
|Efficacy and Safety of Continued Treatment With Mirikizumab in a Phase 2 Trial of Patients With Ulcerative Colitis
Clin Gastroenterol Hepatol. 2022 Jan;20(1):105-115.e14.doi: 10.1016/j.cgh.2020.09.028. Epub 2020 Sep 18.
William J Sandborn 1, Marc Ferrante 2, Bal R Bhandari 3, Elina Berliba 4, Toshifumi Hibi 5, Geert R D'Haens 6, Jay L Tuttle 7, Kathryn Krueger 7, Stuart Friedrich 7, Michael Durante 7, Vipin Arora 7, April N Naegeli 7, Jochen Schmitz 7, Brian G Feagan 8
1University of California San Diego, La Jolla, California. Electronic address: email@example.com.
2Universitair Ziekenhuizen Leuven, Leuven, Belgium.
3Delta Research Partners, Bastrop, Louisiana.
4Arsenia EM, Chisinau, Moldova (the Republic of), Tokyo, Japan.
5Kitasato Institute Hospital Center for Advanced IBD Research and Treatment, Minato-ku, Tokyo, Japan.
6Amsterdam University Medical Centers, Amsterdam, the Netherlands.
7Eli Lilly and Company, Indianapolis, Indiana.
8Western University, Robarts Clinical Trials Inc, London, ON, Canada.
Background & aims: Mirikizumab is an antibody against the p19 subunit of interleukin 23 that has demonstrated clinical efficacy and was well tolerated following 12 weeks of induction treatment in a phase 2 trial of patients with moderate to severe ulcerative colitis. We present results of the open-label extended induction period in patients who did not initially respond to treatment with mirikizumab.
Methods: This study was a continuation of I6T-MC-AMAC, a double-blind trial, performed at 75 sites in 14 countries, in which patients with moderate to severe ulcerative colitis were randomly assigned to 12 weeks induction therapy with 50 mg, 200 mg, or 600 mg mirikizumab or placebo. Patients without a clinical response (a 9-point decrease in Mayo subscore of ≥2 points and ≥35% from baseline and either a decrease of rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1) at week 12 were offered the opportunity to participate in an open-label, extended induction study for another 12 weeks, in which they received either 600 mg intravenous mirikizumab (n = 20) or, following a protocol amendment, 1000 mg intravenous mirikizumab (n = 64) every 4 weeks. At week 24, patients with a clinical response continued the extension maintenance period and received 200 mg subcutaneous mirikizumab. Endpoints included clinical remission (Mayo subscores of 0 for rectal bleeding, 0 or 1 with a 1-point decrease from baseline), clinical response, endoscopic remission (Mayo endoscopic subscore of 0), or endoscopic improvement (endoscopic subscore of 0 or 1), at study weeks 24 and 52. Data were analysed for patients who received mirikizumab or placebo during the induction phase of the study.
Results: Among participants who did not respond to induction mirikizumab, 50.0% of those who received the 12-week extension of 600 mg mirikizumab and 43.8% who received the extension of 1000 mg mirikizumab achieved a clinical response; 15.0% and 9.4% achieved clinical remission, respectively. Endoscopic improvement was achieved by 20.0% of subjects in the 600 mg mirikizumab group and 15.6% subjects in the 1000 mg mirikizumab group. Among initial nonresponders to mirikizumab who had clinical response at study week 24 and continued into maintenance therapy, 65.8% maintained the clinical response, 26.3% achieved clinical remission, and 34.2% had endoscopic improvement at week 52. No new safety concerns were identified.
Conclusions: Extended doses of mirikizumab (600 mg and 1000 mg) for an additional 12 weeks produce a clinical response in up to 50% of patients who did not have a clinical response to 12 weeks of induction doses (50 mg, 200 mg, or 600 mg). Most of the responders to the extended doses maintained clinical response for up to 52 weeks. Clinicaltrials.gov no: NCT02589665.