Gastroenterology · Medical Literature
Mirikizumab is associated with rapid and sustained improvements in novel measures of bowel urgency in moderately-to-severely active ulcerative colitis: 28-week results from the LUCENT-URGE trial.
Abstract
LUCENT-URGE (NCT05767021) was a Phase 3b, multicenter, open-label, single-arm study investigating bowel urgency (BU) in patients with moderately-to-severely active ulcerative colitis (UC) and BU at baseline, treated with mirikizumab. Patients without prior mirikizumab exposure received intravenous mirikizumab 300 mg at weeks (W)0, 4, and 8, followed by subcutaneous mirikizumab 200 mg at W12, 16, 20, and 24. The primary objective was improvement in the validated BU severity measure (Urgency Numeric Rating Scale [UNRS]) at W12. Secondary objectives included improvement in BU at W28, novel measures of stool deferral time (SDT), bowel urgency frequency (BUF), and associations between BU measures. UNRS, BUF, and SDT were collected using a daily diary; the shortest weekly SDT was used for analysis. Baseline observation carried forward was used as the response for the corresponding visit for all missing observations. Missing continuous data were treated as having no change from baseline. All three BU measures at W12 were sustained or improved through W28. With mirikizumab treatment, 52.2% improved BU severity, 55.1% improved BUF, and 40.7% improved shortest weekly SDT. Patients with shortest weekly SDT ≥ 15 min or no urgency increased from 4.1% at baseline to 29.7% at W28. At W12, 36 (20.9%) achieved clinical remission and 54 (31.4%) achieved endoscopic remission, improving to 62 (36.1%) and 76 (44.2%) at W28, respectively. The safety profile was generally consistent with the known profile. In the first comprehensive approach assessing complex BU symptoms in UC, mirikizumab was associated with improvements in several BU and clinically related measures through W28. ClinicalTrials.gov, NCT05767021.
Clinical relevance
In patients with moderately-to-severely active ulcerative colitis and confirmed bowel urgency at baseline, does treatment with mirikizumab produce rapid and sustained improvements across multiple validated and novel measures of bowel urgency—including urgency severity (UNRS), urgency frequency (BUF), and stool deferral time (SDT)—over 28 weeks? __SNAPSHOT__ {"studyDesign":"Phase 3b, multicenter, open-label, single-arm interventional study (LUCENT-URGE; NCT05767021)","setting":"Multicenter; international (specific countries not reported in abstract); academic and community gastroenterology centers","sampleSize":"n=172 enrolled (full analysis set); intervention arm only (single-arm design)","population":"Adults with moderately-to-severely active ulcerative colitis and bowel urgency present at baseline; prior mirikizumab exposure excluded. Mean age 41.1 years; 58.7% male; 93.2% White; mean disease duration 8.0 years; 64.0% severely active UC; 45.3% extensive UC or pancolitis; baseline mean UNRS 6.9; baseline mean BUF 6.9 episodes/day; 51.7% on concomitant corticosteroids (mean prednisone-equivalent 15.5 mg); 36.6% with prior failure of one or more advanced therapies.","intervention":"Mirikizumab 300 mg IV at Weeks 0, 4, and 8 (induction), followed by mirikizumab 200 mg SC every 4 weeks at Weeks 12, 16, 20, and 24 (maintenance phase, treat-through design to Week 28)","comparator":"Not applicable (single-arm, open-label study; no placebo or active comparator)","primaryOutcome":"Improvement in bowel urgency severity as measured by the Urgency Numeric Rating Scale (UNRS) at Week 12","followUp":"28 weeks","fundingSource":"Industry (Eli Lilly and Company, manufacturer of mirikizumab)"}
Key findings
All three bowel urgency (BU) measures assessed at Week 12 were sustained or further improved through Week 28 with continuous mirikizumab treatment. At Week 28: 52.2% of patients achieved improvement in BU severity (UNRS); 55.1% achieved improvement in BU frequency (BUF), representing a 55% reduction in daily urgency episodes from baseline by Week 12; and 40.7% achieved improvement in shortest weekly stool deferral time (SDT). At baseline, only 4% of patients could delay restroom use for at least 15 minutes after feeling urgency; by Week 28, approximately one-third of patients reached this threshold. Severity was reduced by more than half by Week 28. The study also reported directional alignment between BU measure improvements and improvements in clinical response, clinical remission, and endoscopic outcomes, consistent with data from the prior LUCENT-1 and LUCENT-2 trials. No specific p-values, confidence intervals, or NNT/NNH are reported in the available abstract for LUCENT-URGE. Comparative adverse event data specific to this trial are not reported in the abstract.
Practice implications
LUCENT-URGE establishes that mirikizumab produces clinically meaningful, multi-dimensional improvements in bowel urgency—spanning severity, frequency, and stool deferral capacity—sustained over 28 weeks in a population enriched for this symptom at baseline. The finding that stool deferral time improved (from ~4% able to defer ≥15 minutes at baseline to ~one-third by Week 28) is particularly noteworthy given the functional and quality-of-life burden of urgency incontinence in UC. However, critical limitations constrain interpretation: (1) the open-label, single-arm design precludes causal attribution or estimation of a placebo-subtracted treatment effect; (2) no comparator arm exists, so the magnitude of true drug effect on BU beyond spontaneous disease fluctuation or regression to the mean cannot be determined; (3) the study population was predominantly White males treated at academic or specialized centers, limiting generalizability to more diverse populations; (4) the 36.6% prior advanced-therapy failure rate suggests a moderately refractory cohort, but subgroup-specific response rates are not reported in the abstract; (5) results apply only to patients with active BU at baseline, not to all UC patients initiating mirikizumab; and (6) only an abstract and press release data are available for some endpoints—the full peer-reviewed publication should be consulted for complete statistical analyses. Practice should not change solely on the basis of this single-arm study, but these data support the clinical relevance of BU as a treatment target and reinforce the multi-dimensional symptomatic benefit of mirikizumab seen in LUCENT-1/-2. __LIMITATIONS__ Open-label, single-arm design: absence of a placebo or active comparator makes it impossible to isolate the drug effect from natural disease course, regression to the mean, or placebo response,No blinding: patient-reported diary outcomes (UNRS, BUF, SDT) are especially susceptible to open-label bias and expectation effects,Industry sponsorship by Eli Lilly (manufacturer of mirikizumab) introduces potential for selective outcome reporting and framing bias,Baseline observation carried forward (BOCF) used for missing data, which may underestimate treatment benefit but does not account for differential dropout patterns in a single-arm trial,Population is 93.2% White, limiting generalizability to non-White patients,BUF and SDT are novel, unvalidated measures without established minimal clinically important difference (MCID) thresholds; their psychometric properties in UC are not yet fully established,No safety data reported in the available abstract; adverse events and tolerability across 28 weeks cannot be assessed from this summary,No subgroup analyses reported in the abstract (e.g., by prior biologic failure, disease extent, or corticosteroid use), limiting precision of applicability,Relatively small sample size (n=172) for a Phase 3b study, with no statistical power calculation reported in the abstract,Results are available only from the abstract and a press release as of the publication date; the full peer-reviewed manuscript may contain additional data, including confidence intervals and p-values not yet extractable __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ LUCENT-URGE demonstrates that mirikizumab produces rapid (by Week 12) and sustained (through Week 28) improvements across three measures of bowel urgency—severity, frequency, and stool deferral time—in patients with moderately-to-severely active UC who have confirmed urgency at baseline. However, the open-label, single-arm design without a comparator arm prevents estimation of the true placebo-adjusted treatment effect, and results should be interpreted as supportive evidence for mirikizumab's multi-dimensional symptomatic impact rather than as definitive, practice-changing data. Clinicians may use these findings to counsel patients about the likelihood of urgency-specific improvement with mirikizumab, particularly those for whom BU is a dominant symptom burden.