P0680 Upadacitanib in Inflammatory Bowel Disease: Evaluating the risk of neutropenia and impact of thiopurine exposure
Authors: Sharpe M , Khose S , Fletcher J , Samanta S 
Published: January 2025

Abstract

Background
Upadacitanib is becoming more prevalent in treatment for inflammatory bowel disease (IBD)1. Upadicinitnib selectively inhibits januse kinase 1 (JAK1), modulating immune and hematopoietic processes, such as neutrophil production. JAK1 inhibition lowers neutrophil count, increasing the risk of neutropenia2. While beneficial for immune control, upadacitinib poses haematological risks3,4. The impact of prior immunomodulator use on upadacitinib’s haematological safety profile remains an area of concern. The aim of the study was to identify the incidence and outcomes of neutropenia during upadacitanib therapy and the impact of prior thiopurine exposure.

Methods
Data was retrospectively collected using the hospital electronic database, including inpatients and outpatients with IBD initiated on upadacitinib from June 2023-May 2024. Patient demographic and clinical data was collected. Absolute neutrophil count x 109 (ANC) was recorded pre and post upadacinitnib initiation. 57 patients were identified, and of these, 15 were excluded due to inadequate blood tests monitoring. Age adjusted logistic regression assessed the link between thiopurine exposure within one year of upadacitinib and ANC &lt;2 during monitoring post initiation with odds ratios (OR) and 95% confidence intervals (CIs) charted on forest plot.

Results
Of 42 total patients, demographic data showed 22 males vs 20 females and a mean age 45.95 years (SD=15.14). Ethnicities included 23 white, 16 asian, 3 from other ethnic groups. None had ANC &lt;2 at initiation of upadacitinib. During upadacitinib therapy, 31 patients had ANC which remained &gt;2 (74%) and 11 patients developed ANC &lt;2 (26%), which showed no significance. None of the 11 patients with ANC &lt;2 during upadacitinib therapy were found to develop severe infections or required discontinuation. 3 patients had historical thiopurine induced neutropenia, of these only 1 developed ANC &lt;2, showing no significance. Age adjusted logistic regression showed, prior thiopurine use within the past year increases the odds of developing upadacitinib associated neutropenia ANC &lt;1.5 by 3.833 times (95% CI 0.70-20.97, p = 0.12), neutropenia 1.5-2 by 24.9 times (95% CI 1.20-512.57) p = 0.037), and neutropenia &lt;2 by 7.69 times (95%CI 1.62-36.18, p = 0.01) as compared to the patients with ANC &gt;2.

Conclusion
Upadacitinib did not significantly increase the risk of neutropenia or present factors limiting its use. Thiopurine exposure within the past year significantly increased the risk of neutropenia &lt;2 whilst on upadacitinib. This heightened risk emphasizes the need for close monitoring of neutrophil counts in thiopurine-exposed patients. Larger cohorts and longer follow-ups are needed to confirm these findings.

References
1.NICE Guidance. Upadacitinib for treating moderately to severely active ulcerative colitis. Technology appraisal guidance.4 January 2023: TA856.
2.O’Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36(4):542-550.
3.Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of upadacitinib in rheumatoid arthritis: Integrated analysis from the SELECT phase 3 clinical program. Arthritis Res Ther. 2019;21(1):282.
4.Burmester GR, Cohen SB, Winthrop KL, et al. Safety profile of upadacitinib over 15,000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. RMD Open. 2023;9