S1712 Infertility Risk of Upadacitinib, Methotrexate, and Sulfasalazine for Males and Females With Inflammatory Bowel Disease

Introduction: Inflammatory Bowel Disease (IBD) is an autoimmune condition that includes ulcerative colitis and Crohn's disease, primarily. The recommended treatment involves medications that suppress and modulate the immune system, such as methotrexate (MTX), Upadacitinib, and sulfasalazine. Given the nature of the disease, its management, and the demographics of the affected population, fertility is an important consideration for this patient group. Previous studies have shown that fertility in patients with IBD is comparable to that of the general population, and most drugs used to treat the condition have not demonstrated significant effects on fertility. However, sulfasalazine has been associated with alterations in semen composition. This study aims to evaluate the risk of infertility in males and females with IBD who are treated with Upadacitinib, MTX, or sulfasalazine. Methods: This retrospective study was conducted through TriNetX, a nationwide database, comprising 36,757 patients across 69 healthcare organizations. The cohort group consisted of females aged 18 to 45 years and males aged 18 to 60 years, identified through International Classification of Diseases codes associated with IBD and infertility, including the use of the medications under study. An analysis of outcomes tool was utilized to evaluate the outcomes of interest. Results: This study evaluated the risk of infertility associated with upadacitinib, MTX, and sulfasalazine in both females and males. In females, upadacitinib was associated with a low infertility risk of 0.7% (mean follow-up: 343 days), while in males, the risk was slightly lower at 0.5% (mean follow-up: 319 days). Both findings suggest minimal risk of infertility with upadacitinib. For MTX, the risk was 4.6% in females (mean follow-up: 1500 days) and 1.0% in males (mean follow-up: 1576 days), indicating a low but slightly higher risk of infertility compared to upadacitinib. Sulfasalazine showed a similar pattern, with a 3.7% risk in females (mean follow-up: 1665 days) and 0.8% in males (mean follow-up: 1758 days). Conclusion: This study demonstrates that upadacitinib, MTX, and sulfasalazine, are associated with low infertility risks in both males and females. Although methotrexate and sulfasalazine showed slightly higher risks of infertility, these risks remained low overall, with no significant impact observed in the general patient population. Notably, sulfasalazine was associated with alterations in semen composition, but this did not translate into a significant infertility risk.