Experience with upadacitinib using in treatment of ulcerative colitis in real clinical practice (pooled data)

AIM : to evaluate the efficacy and safety of Upadacitinib (UPA) — an oral selective janus-kinase 1 (JAK1) inhibitor in real clinical practice for the treatment of ulcerative colitis. PATIENTS AND METHODS : in 2021-2023, as part of a multicenter, prospective, open, uncontrolled study, fortysix patients with mild-to-moderate ulcerative colitis (UC) were included (male: female ratio = 16:30, mean age 34 ± 3.1 years). Extraintestimal manifestation (EIM) initially was diagnosed in 7 patients (jonts and skin). Indications for UPA administration were: resistance to corticosteroids, ineffectiveness of basic and previously biologics treatment. The effectiveness was evaluated using the Mayo score, the Schroeder endoscopic index, as well as dynamic of hemoglobin, CRP and ESR. UPA was prescribed in accordance with the instructions for use: 45 mg for induction and 15/30 mg for maintenance therapy. The evaluation criteria were: the frequency of early primary clinical response within 1 week, the rate of clinical response/remission and endoscopic response/remission, the changes of EIM and the rate of adverse events (AE) in 8 weeks of induction and in 48 weeks of maintenance treatment. RESULTS: all patients completed the induction course of UPA for 8 weeks. Early clinical response within 1 week with reduction of stool movements to 3 or less per day, absence of blood in stool was achieved in 25 (54.3%) patients. Clinical remission developed in 34 (73.9%) and clinical response in 3 (6.5%) of patients at the end of induction. Normal CRP and ESR levels and endoscopic remission was detected in 24 (52.2%) of patients in 8 weeks. The severity of EIM at the end of induction decreased in 4/7 (57.1%). One case of herpes zoster was registered as serious AE with drug withdrawal within the induction. The results of UPA maintenance therapy at week 48 were assessed in 16 patients. Clinical remission was maintained in 14/16 (87.5%) patients, with 11/16 (68.7%) of them receiving UPA at a maintenance dose of 30 mg per day, and 3/16 (31.3%) patients receiving 15 mg per day. In 2/16 cases (12.5%), clinical activity was maintained. Endoscopic remission developed in 10/16 (62.5%) patients, which was expressed in a decrease in the endoscopic Schroeder index decreases to ≤ 1 points, with 8 patients receiving a maintenance dose of 30 mg per day, and 2 patients receiving 15 mg per day. In the remaining patients, 4/16 (25%) (3 — UPA 30 mg, 1 — UPA 15 mg) cases had mild inflammation, and 2/16 (12.5%) (UPA 15 mg) had moderate activity. CONCLUSIONS: in real practice, UPA allows to achieve an early clinical response, clinical and endoscopic remission after induction with good tolerability and safety in UC patients who refractory to corticosteroids and biologics.