Semen Discoloration Following Upadacitinib Therapy in Patients with Inflammatory Bowel Disease

Upadacitinib, a selective Janus kinase 1 inhibitor, has demonstrated efficacy in moderate-to-severe inflammatory bowel disease (IBD). Although its safety profile has been well established, genitourinary adverse events have rarely been reported. We present the first case series of semen discoloration associated with upadacitinib use in patients with ulcerative colitis and Crohn's disease. We retrospectively reviewed the medical records of six male IBD patients who developed semen discoloration during upadacitinib therapy at four referral hospitals in South Korea. Data on symptom onset, severity, and persistence were collected and analyzed. All six patients exhibited bluish or greenish semen after a median of 2 months of daily therapy with 45 mg upadacitinib. None of the patients exhibited urologic symptoms or infectious causes. Three patients reported reduced intensity and frequency of discoloration after the dose was reduced to 30 mg, while two achieved complete resolution following dose reduction to 15 mg or drug discontinuation. Urologic evaluations, including semen analysis, revealed no abnormalities. This is the first report documenting semen discoloration as a potential adverse event of upadacitinib therapy in IBD. Semen discoloration appears to be a rare, dose-related, and reversible adverse event associated with high-dose upadacitinib therapy. Further studies are needed to clarify the underlying mechanisms and long-term clinical implications.