Introduction

Mirikizumab (miri), an anti-IL-23p19 antibody, has demonstrated efficacy and safety in moderately to severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092) among patients who had an inadequate response, loss of response, or intolerance to conventional or advanced therapy. At the LUCENT-1 induction baseline, 41% of the population had experienced a biologic/tofacitinib failure, and 36.3% experienced at least one anti-TNF failure. Among patients with one prior anti-TNF failure only, this analysis evaluated the clinical efficacy of miri compared to placebo (PBO) in induction and maintenance therapy and the efficacy of miri in extended induction.

Aims & Methods

In LUCENT-1, UC patients were randomized to receive 3 intravenous (IV) doses of 300mg miri or PBO every four weeks (Q4W) at W0, W4, and W8 (induction population). In LUCENT 2, responders to miri induction at W12 were re-randomized to subcutaneous (SC) 200mg miri or PBO Q4W through W52 of continuous therapy (maintenance population). Patients not achieving clinical response with miri 300mg IV at W12 received extended induction treatment with open-label 300mg miri IV at W12, W16, and W20 (extended induction population). Patients responding to extended induction at W24 entered open-label maintenance and received 200mg miri Q4W SC until W52 (extended induction responders). Endpoints evaluated were clinical response, clinical remission, symptomatic remission, endoscopic remission, corticosteroid (CS)-free remission, and histologic-endoscopic mucosal remission (HEMR). Efficacy in the subgroup of patients with failure of one anti-TNF only was assessed using Cochran-Mantel-Haenszel tests at W12 (induction population) and W52 (maintenance population).

Results

At LUCENT-1 baseline, of patients who experienced anti-TNF failure, 45% of patients (n=190) had one prior anti-TNF failure only. The one anti-TNF failure subgroup had a longer disease duration, higher rate of pancolitis, similar disease severity (MMS and ES) and slightly higher baseline CS and IMM use, compared to the overall LUCENT population. In the induction and maintenance population, a significantly greater proportion of miri-treated patients achieved the following efficacy endpoints compared with PBO [miri vs. PBO, p-value]: clinical response (W12: [64.4% vs. 34.1%, p=0.001]; W52: [67.2% vs. 44.8%, p=.03]), clinical remission (W52: [44.3% vs. 17.2%, p=.017]), symptomatic remission (W52: [63.9% vs. 34.5%, p=.005]) (Table). Among the extended induction population, 45.7% achieved clinical response at W24; 75% achieved clinical response, 30% achieved clinical remission and CS-free remission at W52 (Table).
Table: Efficacy of miri vs PBO for subjects with Only One Prior anti-TNF Failure^a

Conclusion

Mirikizumab is efficacious for induction and maintenance therapy in patients with moderately to severely active UC who have failed one prior anti-TNF.

Disclosure

• A. Hart has served as a speaker, consultant, and advisory board member for: AbbVie, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Genentech, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Pfizer, Pharmacosmos, Takeda, and Roche
• M. D. Martín-Arranz has served as a speaker or has received research or educational funding or advisory fees from: AbbVie, Eli Lilly and Company, Faes Farma, Ferring Pharmaceuticals, Janssen, Merck Sharp & Dohme, Pfizer, Shire Pharmaceuticals, Takeda, and Tillots Pharma
• D. Laharie has received consulting, boards, transports, or fees from: AbbVie, Amgen, Biogaran, Biogen, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Janssen, Merck Sharp & Dohme, Pfizer, Prometheus, Roche, Takeda, and Theradiag
• K. Matsuoka has received fees for grants and/or contracts from: AbbVie, EA Pharma, JIMRO, Kissei, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, and Zeria Pharmaceutical; lecture fees from: AbbVie, EA Pharma, Eli Lilly and Company, Gilead Sciences, Janssen, JIMRO, Kissei, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, and Zeria Pharmaceutical; and manuscript preparation fees from: Eli Lilly and Company
• E. Dhesi, I. Redondo, S. Baygani, and K. Samaan are employees and shareholders of: Eli Lilly and Company
• L. Zaremba-Pechmann is a contractor for: Eli Lilly and Company through HaaPACS
• S. Navabi has served as an advisor for: Eli Lilly and Company
• Medical writing assistance was provided by Estelle Sontag, PhD, and Alice Carruthers, PhD, of ProScribe – Envision Pharma Group, and was funded by Eli Lilly and Company
• Previously presented at the European Crohn's and Colitis Organisation - 2024 Congress

Introduction

The Inflammatory Bowel Disease (IBD) disk is patient-led symptom scoring system for use during clinic visits to give physicians an overview of quality-of-life status in areas such as Emotion, Body Image, Sleep, Energy, Interpersonal Relations, Abdominal Pain, Education and Work, Sexual Function, Joint Pain, and Regulating Defecation.
The disk can be used to assess the need for psychological intervention in those with chronic diseases that exhibit high Emotion scores.

Aims & Methods

Assessing the performance of the IBD disk as a screening tool in a clinic setting for referrals to the IBD Psychology service.
A prospective initiative was introduced in which all patients were given an IBD disk at their clinic visit. Those with Emotion scores ≥ 7 were offered a referral to the IBD Psychology service.
Retrospective review was performed on all referrals to the IBD Psychology service over eight clinical weeks. Baseline demographics were collected such as age, sex, disease sub-type, surgical history, and disease activity at the time of clinic visit. Outcomes that were analysed included the number of patients who were willing to engage in the psychology service, reasoning for declining the service, and overall Emotion scores as reported on the disk.

Results

Over eight clinics, all patients were invited to fill out an IBD disk (n=234) and 29% of these patients (n=69) were offered a referral to the IBD Psychology service. The median age of referred patients was 43 years, 59% were female (n=41), 57% had Crohn’s Disease (n=39), and 75% had no history of surgery (n=52). Of the referrals, 88% of patients were offered a psychology referral on the basis of high Emotion score on their IBD disk (n=61/69). The remaining patients (n=8/69) were referred following consultation with their physician.
46% of patients that were offered a referral, accepted it (n=32), with 75% (n=24/32) in the IBD disk cohort and 25% (n=8/32) in the other referral cohort. The patients that declined referral did so due to already engaging with external psychological support (n=12), personal reasons (n=12), or unknown reasons (n=13). The patients in the other referral cohort were offered referrals due to them enquiring about the psychology service (n=2) or from further prompting about their emotions from their physicians (n=6).
The median age of both IBD disk and non IBD disk cohorts was 43. The IBD disk cohort was 62% female (n=38/61) versus 38% female (n=3/8) in the other referral cohort. 54% of patients had a diagnosis of Crohn’s Disease (n=33/61), 38% Ulcerative Colitis (n=23/61), and 8% IBD-Undiagnosed (n=5/61) versus 75% Crohn’s Disease (n=6/8), 13% Ulcerative Colitis (n=1/8), and 13% IBD-U (1/8) in the IBD disk cohort and other referral cohort respectively.
Only 25% (n=17/69) patients that were referred had a history of IBD related surgery and 54% (n=37/69) of those referred were experiencing active disease during their clinic appointments.

Conclusion

The IBD disk is a helpful tool identifying patients for referrals to the IBD Psychology service for high emotional needs. Additional prompting from the treating physician during clinic appointments may identify more patients who would benefit from a psychology referral.

References

IBD Disk from AbbVie SA/NV - BE-IMM-210029 (v2.0) - August 2022

Clinical Case Summary

Celiac disease (CD) is one of the most common autoimmune disorders, affecting up to 1% of the population. The overlap of CD with other benign and malignant pathologies can make the diagnostic course complex.

We present the case of a 51-year-old man with no known medical history, who developed generalized edema. In this context, and after etiological investigation, CD was diagnosed with modified Marsh classification 3c. In the following 6 months, despite gluten avoidance, decreased anti-transglutaminase antibody titers and weekly albumin replacement, the patient developed progressive anasarca. Laboratory findings suggested nephrotic syndrome with proteinuria of 30g/24h. Renal biopsy confirmed membranous nephropathy (MN). At this point, the diagnosis of secondary MN due to CD was made, following the exclusion of other potential etiologies. The patient showed only partial remission of proteinuria which led to new studies revealing a surprising de novo positivity of anti-PLA2R. Immunosuppressive therapy was started, with full remission. After 3 months of stopping this therapy the patient again presented with generalized edema associated with inguinal, cervical, and axillary lymphadenopathy and lymphocytosis. Excisional lymph node biopsy revealed classical mantle cell lymphoma. Endoscopic studies showed diffusely infiltrative pseudonodules in the stomach, duodenum, ileum, and colon. Histological evaluation confirmed gastrointestinal involvement of the lymphoma. The patient is currently under R-CHOP chemotherapy. It is now believed that MN was a paraneoplastic glomerular presentation of an indolent neoplasm masked by immunosuppressants rather than a causal relationship with CD.

We highlight a case where the systemic presentation of CD made the diagnosis of refractory disease versus mimicking pathologies challenging, necessitating extensive etiological study. Despite the association of CD with T-cell lymphomas, other unrelated malignancies should be considered.