Abstract Background People with inflammatory bowel disease (IBD) are not immune to the obesity pandemic, with an estimated 25% of patients being affected by obesity, and 30% being overweight.1 Obesity is associated with poorer outcomes and inferior response to biological therapy in patients with IBD.2 Janus kinase inhibitors (JAKi) such as Upadacitinib and Tofacitinib are effective IBD therapies and demonstrate pharmacokinetics that are unaffected by body weight.3 This study aimed to assess whether obesity, determined by body mass index (BMI), can impact treatment outcomes in patients with IBD on JAKi therapy. Methods Retrospective multi-centre study, including adult IBD patients who were commenced on Upadacitinib or Tofacitinib from May 2021 to October 2025. Obesity was defined as BMI 30kg/m2. Demographic and clinical data was collected from initiation through to discontinuation or persistence of JAKi. The primary outcome was treatment persistence during the follow up period. Results Over the study period 122 patients were commenced on JAKi with 50% female, 42% Crohn’s disease and median age 41 years (SD 15.1). The cohort was predominately biologic experienced, with only 15% biologic naive and 55% having had exposure to at least two biologics. The cohort mean BMI was 27.7kg/m2 (SD 6.9) and mean weight was 80.51kg (SD 19.7). Over a median follow up period of 10.5 months, 12.4% of patients stopped JAKi treatment, and 87.6% persisted on JAKi treatment. Those who had an obese BMI at initiation of JAKi treatment were more likely to discontinue JAKi treatment over the follow up period (obese 26.7% compared with non-obese 5.7%, log-rank χ² = 5.55, p = 0.018, see Figure 1). Conclusion An obese BMI at commencement of JAKi was associated with lower persistence. This may be attributed to more severe disease phenotypes, suboptimal adherence related to lower health awareness, and the impact of obesity-associated factors such as poor sleep and mental health. The persistent of JAKi over the follow up period was high. Further prospective studies are needed to validate our findings. Given published reports of JAK inhibitor–associated weight gain, obesity in IBD warrants a proactive and integrated weight management approach.4 References: 1. Kaazan P, Seow W, Yong S, Heilbronn LK, Segal JP. The Impact of Obesity on Inflammatory Bowel Disease. Biomedicines. 2023;11(12):3256. doi:https://doi.org/10.3390/biomedicines11123256 2. Yarur AJ, Bruss A, Moosreiner A, et al. Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study. Gastroenterology. 2023;165(4):963-975.e5. doi:https://doi.org/10.1053/j.gastro.2023.06.036 3. Singh S, Picardo S, Seow CH. Management of Inflammatory Bowel Diseases in Special Populations: Obese, Old, or Obstetric. 2020;18(6):1367-1380. doi:https://doi.org/10.1016/j.cgh.2019.11.009 4. Xiong G, Yu E, Heung M, Yang J, Lowe M, Abu-Hilal M. Weight gain secondary to the use of oral Janus kinase inhibitors: A systematic review and meta-analysis. JAAD international. 2024;19:1-9. doi:https://doi.org/10.1016/j.jdin.2024.11.009 Conflict of interest: Tan, Zoe: No conflict of interest Barnes, Alex: No conflict of interest Jeong, Minwoo: No conflict of interest Smith, Lorelle: No conflict of interest Mountifield, Reme: No conflict of interest Spizzo, Paul: No conflict of interest Bampton, Peter: No conflict of interest Kaazan, Patricia: No conflict of interest
Tan et al. (Thu,) studied this question.