Abstract Background Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, is effective in moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD). Although its safety profile is well characterised, genitourinary adverse events have rarely been reported. This study aimed to describe the clinical characteristics of patients who developed semen discolouration during upadacitinib therapy. Methods We retrospectively reviewed medical records of six male patients with inflammatory bowel disease (IBD) who developed bluish or greenish semen discolouration during upadacitinib treatment at four referral hospitals in South Korea. Data regarding symptom onset, intensity (visual analogue scale VAS; Figure 1), persistence, and change following dose adjustment were collected. Urological and laboratory evaluations, including urinalysis and semen analysis, were performed where available. Results All six patients developed bluish or greenish semen discolouration after a median of 2 months (range 1–4) of daily upadacitinib 45 mg therapy (Table 1). None exhibited urological symptoms or infectious causes. Three patients reported reduced intensity and frequency of discolouration after dose reduction to 30 mg, while two achieved complete resolution following dose reduction to 15 mg or drug discontinuation. In cases where photographs were submitted, patient-provided images illustrated the range of colour changes observed (Figure 2A-C). Urological evaluations, including semen analyses, revealed no abnormalities. All patients maintained clinical response or remission. The phenomenon appeared dose-dependent and reversible, with no evidence of impaired reproductive function. Clinical characteristics of all six cases were summarised (Table 1). Conclusion Semen discolouration appears to be a rare, dose-related, and reversible adverse event associated with high-dose upadacitinib therapy in IBD. Although clinically benign, it may cause patient anxiety and affect adherence. Clinicians should recognise and counsel patients regarding this phenomenon. Further studies are warranted to elucidate its mechanisms, pharmacogenetic factors, and long-term implications. References: 1. Friedberg S, Choi D, Hunold T, et al. Upadacitinib is effective and safe in both ulcerative colitis and Crohn’s disease: prospective real-world experience. Clin Gastroenterol Hepatol. 2023;21:1913–23.e2. 2. Gilmore R, Fernandes R, Hartley I, et al. Upadacitinib induction is effective and safe in ulcerative colitis patients including those with prior exposure to tofacitinib: a multicentre real-world cohort study. Intest Res. 2025;23:347–57. Wang S, Wang X, Ding J, et al. 3. Disproportionality analysis of upadacitinib-related adverse events in inflammatory bowel disease using the FDA Adverse Event Reporting System. Front Pharmacol. 2025;16:1436183. Hayashi N, Ikeda M, Liu J, et al. 4. Acne among Japanese patients with atopic dermatitis receiving upadacitinib in the phase 3 RISING UP study. Dermatol Ther (Heidelb). 2023;13:1817–30. Conflict of interest: Dr. Lee, Jeong Hwa: No conflict of interest Hwang, Sung Wook: no conflicts Kim, Eun Soo: Personal Fees: I have served as a speaker or an advisory board member for AbbVie, Eli Lilly, J & J, Takeda Pharmaceutical, Bristol-Myers Squibb, Samsung Bioepis, Pfizer, Celltrion and Ferring Pharmaceuticals.
Lee et al. (Thu,) studied this question.