AuthorCandice Jade McCaughey
Cameron Hennenberg, Candice McCaughey, Xialing A. Chen, Karen Anne O'Laco, Karen Kwaning, Gala Brewer,Jenny S. Sauk, Alyssa Parian, Berkeley N. Limketkai
Mechanisms of Weight Change After Initiation of Biologic Therapy for Inflammatory Bowel Disease
Introduction: In recent years, biologic therapies have played an increasing role in the suppression of inflammatory activity and slowed progression of disease in inflammatory bowel disease (IBD). Emerging data suggest that rapid weight gain occurs among patients starting biologic therapies, although the mechanisms driving these observations are unclear. We hypothesize that biologic therapy-associated weight gain results from a correction of inflammation-related malnutrition rather than from an intrinsic medication effect.
Methods: This retrospective study included patients at two tertiary-care academic centers who initiated biologic therapy for the first time and had at least 52 weeks of follow-up data. Patient demographics, IBD characteristics, disease activity, anthropometric data, and laboratory data were collected over the study period. Longitudinal changes in weight were evaluated over the 52 weeks of follow-up, stratified according to the presence of unmitigated inflammation (flare status, identified by inflammatory markers and endoscopic evidence) at weeks8 and 52. Multivariable linear regression was further used to evaluate weight change according to flare status, while adjusting for IBD type, age, sex, disease duration, and smoking status.
Results: The study included 202 patients with IBD (101 Crohn’s disease, 97 ulcerative colitis, 4 indeterminate colitis), whose average age was 37.8 and whose average IBD duration was 7.6 years. The majority of patients were started on infliximab (53%), followed by adalimumab (37%), vedolizumab (7%), and ustekinumab (2%). When evaluating absolute weight change from time of biologic therapy initiation, patients overall had a steady increase in weight at 0.9, 1.5, 2.5, and 3.8 kg at weeks 4, 8, 26, and 52, respectively. Stratified by flare status, those experiencing a persistent flare did not observe a weight increase until week 26, while those without a flare had continued unabated weight increase. Adjusted for potential confounders, a persistent flare was associated with an early reduction in weight at week 8 (-2.2 kg; 95% CI -3.9 to -0.5), but not at subsequent time points. When evaluating weight change from normal baseline weight, patients overall experienced a weight increase regardless of flare status.
Conclusion: The study findings suggest that correction of inflammation and its malabsorptive/catabolic effects is a mechanism of weight gain after initiation of biologic therapy. However, contrary to our original hypothesis, there appears to be an additional medication-related weight gain that occurs regardless of flare status. The weight gain also leads to excess weight above the patient’s reported normal baseline.