Lipid Changes After Induction Therapy in Patients with Inflammatory Bowel Disease: Effect of Different Drug Classes and Inflammation

Lay Summary Prednisone and tofacitinib induction therapy increase lipid levels, whereas no changes are observed for immunomodulators and newer biologics. The observations seem drug-specific on top of control of inflammation. Studies on long-term consequences of IBD drug-induced lipid changes are required. Background Dyslipidemia may be an important modifiable risk factor contributing to the increased cardiovascular risk in inflammatory bowel disease (IBD). The lipid metabolism is subject to both systemic inflammation and drug therapy; however, it is unclear if this effect is drug-class dependent. Our aim was to assess lipid changes after IBD induction therapy and evaluate associated factors with a particular focus on drug class and disease activity. Methods In this prospective study, consecutive IBD patients starting systemic therapy (eg, corticosteroids, thiopurines, methotrexate, anti-TNF-alpha agents, vedolizumab, ustekinumab, and tofacitinib) were included. Primary outcomes were changes in total cholesterol, high density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides at week 10. Results One hundred ninety-eight IBD patients (107 women [54%], median age 36 years; interquartile range [IQR], 27-47) were included: 137 Crohn's disease (67%), 61 ulcerative colitis (29%), and 8 IBD-unclassified (4%). Median C-reactive protein and fecal calprotectin at baseline were 5.1 mg/L (IQR, 1.6-12.0) and 1040 ug/g (IQR, 383-1800), respectively. Relative increases in total cholesterol, HDL-c, and LDL-c were significant after prednisone (+26%, +31%, +12%) and tofacitinib therapy (+20%, +25%, +26%), respectively. Results remained after adjusting for concomitant corticosteroids, cholestyramine, and PSC diagnosis. Changes in clinical scores were inversely correlated with total cholesterol changes (R -186, P = .014), as was CRP with total cholesterol and LDL-c (R -0.292 and R -0.259, P < .001). No correlation was found with FCP. Lipid changes remained after adjusting for age and CRP. Conclusions Prednisone and tofacitinib induction therapy significantly increase serum lipid levels, whereas no changes were observed in other drug classes. The observations seem drug-specific inasmuch as adjustment for systemic inflammation did not alter the results.