创作:爱的抉择 审核:szx 2019年09月11日
  • 纳入249名中重度溃疡性结肠炎患者,在第0、4、8周分别静脉注射不同剂量(50mg、200mg、600mg)的靶向IL23 p19亚基的单抗mirikizumab或安慰剂;
  • 第12周时,200mg组患者有22.6%获得临床缓解,显著高于安慰剂组的4.8%;
  • 50mg、200mg、60mg组分别有41.3%、59.7%、49.2%患者产生临床应答,均显著高于安慰剂组的20.6%;
  • 在第12周时的临床应答患者分为2组,每4周或每12周皮下注射200mgmirikizumab,第52周时的临床缓解率分别为46.8%及37.0%。
Gastroenterology [IF:17.373]

Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis



2019-09-04, Article

Abstract & Authors:展开

Background & Aims: Interleukin 23 (IL23) contributes to pathogenesis of ulcerative colitis (UC). We investigated the effects of mirikizumab, a monoclonal antibody against the p19 subunit of IL23, in a phase 2 study of patients with UC.
Methods: We performed a trial of the efficacy and safety of mirikizumab in patients with moderate to severely active UC, enrolling patients from 14 countries from January 2016 through September 2017. Patients were randomly assigned to groups given intravenous placebo (n=63), mirikizumab 50 mg (n=63) or 200 mg (n=62) with exposure-based dosing, or mirikizumab 60 mg with fixed dosing (n=61), at weeks 0, 4, and 8. Of assigned patients, 63% had prior exposure to a biologic agent. Clinical responders (decrease in 9-point Mayo score, including ≥2 points and ≥35% from baseline with either a decrease of rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1) at week 12 who had received mirikizumab were randomly assigned to groups that received maintenance treatment with mirikizumab 200 mg subcutaneously every 4 weeks (n=47) or every 12 weeks (n=46). The primary endpoint was clinical remission (Mayo subscores of 0 for rectal bleeding, with 1-point decrease from baseline for stool frequency, and 0 or 1 for endoscopy) at week 12. A multiple testing procedure was used that began with the 600-mg dose group, and any non-significant comparison result ended the formal statistical testing procedure.
Results: At week 12, 15.9% (P=.066), 22.6% (P=.004), and 11.5% (P=.142) of patients in the 50-mg, 200-mg, and 600-mg groups achieved clinical remission, respectively, compared with 4.8% of patients given placebo. The primary endpoint was not significant (comparison to 600 mg, P>.05). Clinical responses occurred in 41.3% (P=.014), 59.7% (P<.001), and 49.2% (P=.001) of patients in the 50-mg, 200-mg, and 600-mg groups, respectively, compared to 20.6% of patients given placebo. At week 52, 46.8% of patients given subcutaneous mirikizumab 200 mg every 4 weeks and 37.0% given subcutaneous mirikizumab 200 mg every 12 weeks were in clinical remission.
Conclusions: In a randomized trial of patients with UC, mirikizumab was effective in inducing a clinical response after 12 weeks. Additional studies are required to determine the optimal dose for induction of remission. Mirikizumab demonstrated durable efficacy throughout the maintenance period. no: NCT02589665

First Authors:
William J Sandborn

Correspondence Authors:
William J Sandborn

All Authors:
William J Sandborn,Marc Ferrante,Bal R Bhandari,Elina Berliba,Brian G Feagan,Toshifumi Hibi,Jay L Tuttle,Paul Klekotka,Stuart Friedrich,Michael Durante,MaryAnn Morgan-Cox,Janelle Laskowski,Jochen Schmitz,Geert R D'Haens