Comparative Effectiveness of Common Immunomodulator Agents over 5 Year Clinical Outcomes in Crohnʼs Disease Patients

Abstract

Introduction: Studies comparing the therapeutic impact of immunomodulators in Crohn's disease (CD) are limited. Lémann Index (LI) quantifies bowel damage in CD and change in LI or Delta Lémann Index (DLI) may be used to track damage trajectory. We compared the clinical course and damage trajectories of CD patients on different immunomodulators.Table 1: Comparison of Crohn's disease related characteristics, healthcare utilization and bowel damage trajectories in subgroups stratified based on the use of immunomodulator agentsMethods: Using a registry maintained at a tertiary center, CD patients with yearly clinical encounters and on treatment with any single immunomodulator for ≥3 years(y) during a 5y follow-up, were included. Analysis was limited to the commonly utilized agents at our center: azathioprine (AZA), 6-mercaptopurine (6MP) and methotrexate (MTX). LI was calculated from the first (LI1) and last (LI2) clinical encounters and DLI was calculated as LI2-LI1. Comparative analysis was done amongst groups created based on immunomodulator used. Results: A total of 145 CD patients formed the study cohort [median age 44y (IQR: 33-56); 53.8% female; median disease duration 9y (IQR: 6-19), overall surgical exposure 65.5%]. AZA, 6MP and MTX were used by 54.5%, 26.2% and 19.3% of the cohort respectively. In the MTX group, 12 (42.9%) patients had prior AZA/6MP exposure and were switched to MTX due to ineffectiveness (n=8/12) or adverse reactions (n=4/12). Also, 19 (67.9%) patients had prior anti-TNF agent exposure and MTX was used instead or added on due to ineffectiveness (n=10/19) or adverse reactions (n=6/19). The 3 groups showed no significant differences in age, age at onset, disease duration, location or behavior. The MTX group had significantly higher CD related surgical exposure, more frequent biochemical markers' elevation, higher 5y healthcare utilization and was more often on steroids and anti-TNF agents. Trajectory of deterioration (DLI>0) was more frequent in MTX group. On univariate analysis, deterioration showed significant positive correlation with use of MTX (r=0.199; p=0.017) and negative correlation with use of 6MP (r=-0.191; p=0.021); however, no significant association was noted on multivariate analysis. Conclusion: CD patients treated with MTX have worse 5y clinical outcomes, compared to AZA and 6MP users. This could reflect a patient subset with more refractory disease for which we usually reserve MTX, or a group that loses access to more effective therapies due to intolerance. Further studies to better characterize outcomes in MTX users with intention to limit less effective therapies are warranted.