Development and validation of a novel patient-reported outcome for microscopic colitis—Microscopic Colitis Score (MCS)

Background & Aims: Despite debilitating symptoms, no standardized disease severity index exists for microscopic colitis (MC). This gap hinders alignment with U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) standards, which emphasize the importance of patient-reported outcome measures (PROMs) in new therapy approval. This study aimed to validate the Microscopic Colitis Symptom Questionnaire (MCSQ) and develop the Microscopic Colitis Score (MCS), a novel disease severity index. Method: This prospective, multicenter study included 131 patients with biopsy-confirmed MC (67 remission, 64 active disease). Patients completed MCSQ and health-related quality of life (HRQoL) assessments [IBDQ-32, Short Health Scale (SHS)] at baseline and follow-up. Clustering analysis systematically identified distinct disease severity groups. MCS was developed as a composite score derived from MCSQ. Results: Factor analysis revealed a three-factor MCSQ model with good internal consistency (Cronbach’s alpha=0.88). Test–retest reliability (intraclass correlation coefficient=0.88) and responsiveness to treatment (P< .01) of all MCSQ items were high. MCS, ranging from 0 (asymptomatic) to 15 (maximum symptoms), correlated strongly with HRQoL measures such as IBDQ-32 total score (rp=−0.78), IBDQ-32 bowel symptoms (rp=−0.80), and SHS bowel symptoms (rp=0.69). Receiver–operating characteristic curves indicated that MCS could accurately identify patients in remission [as per Hjortswang criteria; area under the curve (AUC)=0.85], as well as mild (AUC=0.97), moderate (AUC=0.93), or severe disease (AUC=0.96). Conclusions: MCSQ and MCS are valid, reliable, and responsive tools that meet FDA and EMA standards. Both accurately reflect the diverse symptoms of MC. Compared to the binary Hjortswang criteria, MCS provides a nuanced evaluation of disease activity and holds promise for assessing therapeutic efficacy in future trials.