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In two phase 3 trials, mirikizumab, a p19-directed anti–interleukin-23 antibody, was superior to placebo with regard to clinical remission of ulcerative colitis at 12 weeks (induction) and 40 weeks (maintenance).

BackgroundHere we report the efficacy and safety of the Phase (Ph)3 LUCENT-2 study, a double-blind, randomized withdrawal maintenance study, in patients who responded to mirikizumab (miri) induction therapy.MethodsMiri induction clinical responders (primary efficacy population N=544) were re-randomized in a 2:1 ratio to receive blinded miri 200 mg or PBO subcutaneously (SC) every four weeks (Q4W) for 40 weeks. Randomization was stratified by biologic-failed status, induction remission status, baseline (BL) corticosteroid (CS) use, and geographic region (North America/Europe/other). The primary objective was to determine if miri was superior to PBO in achieving clinical remission at Week 40. Key secondary objectives were multiplicity controlled and included CS-free remission, endoscopic remission, histologic-endoscopic mucosal remission (HEMR), improvement in bowel urgency, bowel urgency remission, and maintenance of clinical remission.ResultsBaseline demographic and disease characteristics were balanced across the two treatment groups, including BL corticosteroid use (miri 37.0%, PBO 38.0%) and biologic failure status (miri 35.1%, PBO 35.8%). A significantly greater proportion of patients treated with miri achieved clinical remission at Week 40 (miri 49.9%, PBO 25.1%; Δ=23.2 [95%CI 15.2, 31.2]; p<0.001). Among miri treated patients who achieved clinical remission at Week 40, approximately 90% were in CS-free remission. All key secondary endpoints were achieved (each: p<0.001), including a significantly greater proportion of patients who maintained clinical remission, and who achieved bowel urgency remission and HEMR compared to PBO. The frequency of treatment-emergent adverse events (TEAEs) in miri patients was similar to PBO. There were fewer serious adverse events and discontinuations due to adverse events in miri patients compared to PBO. The most common TEAEs were nasopharyngitis and arthralgia with miri and ulcerative colitis with PBO.ConclusionsIn patients responding to miri induction therapy, the miri 200 mg SC Q4W maintenance regimen demonstrated an acceptable safety profile and clinically meaningful and statistically significant improvements across clinical, symptomatic, endoscopic, and histologic endpoints. The safety profile was consistent with previous miri studies in UC. These results confirm miri’s Ph2 efficacy and build on the Ph3 induction efficacy demonstrated in LUCENT-1.

Abstract Introduction The efficacy and safety of mirikizumab (miri), an IL-23p19 antibody, has been evaluated in moderate-to-severe ulcerative colitis (UC) in a phase 2, randomized, double-blind, placebo (pbo)-controlled trial (AMAC, NCT02589665; presented at DDW 2018). Miri demonstrated efficacy on multiple measures in the 12-week induction treatment. Aims and Methods This analysis evaluated the effects of miri on health-related quality of life (HRQoL) in patients with UC. Patients with moderate-to-severe UC (Mayo score 6-12; Endoscopic subscore ≥2) were randomised 1:1:1:1 to receive intravenous miri 50 mg (N=63) or 200 mg (N=62), both with possible exposure-based increase (2-12 fold or 1.5-3 fold, respectively, to a maximum 600 mg dose), or fixed dose miri 600 mg (N=61), or pbo (N=63) at Weeks 0, 4, and 8. Patients could receive oral 5-aminosalicylic acid (ASA), corticosteroids (≤20 mg/d prednisone equivalent), or thiopurines; must have failed ≥1 conventional UC therapy; and were either naïve to or had prior exposure to biologics. HRQoL was measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) and evaluated using a mixed model repeated measures (MMRM) analysis. The percentage of patients at Week 12 with clinical response,1endoscopic healing,2 IBDQ total score ≥170, and IBDQ improvement ≥16 were also assessed. Results As early as Week 4, and continuing through Week 12, IBDQ total scores improved versus baseline and versus pbo across all miri groups except miri 50 mg versus pbo at Week 12 (Table). At Week 12, the proportions of patients with IBDQ total score ≥170 were higher with miri 50 mg, 200 mg, and 600 mg than pbo (44%, 56%, 54% vs. 30%, respectively) and higher proportions of miri- than pbo-treated patients had improvements ≥16 points from baseline in IBDQ total score. At Week 12, clinical response and endoscopic healing rates were greater for miri 50 mg and 200 mg versus pbo (Table). Conclusion Induction treatment with miri was associated with HRQoL improvement in patients with UC. These are the first data evaluating the effects of an IL-23p19 antibody on the HRQoL of patients with UC.