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DOP41 Efficacy and safety of extended induction treatment with upadacitinib 45 mg once daily followed by maintenance upadacitinib 15 or 30 mg once daily in patients with moderately to severely active Ulcerative Colitis

Vermeire, S.(1);Danese, S.(2);Zhou, W.(3);Klaff, J.(3);Ilo, D.(3);Yao, X.(4);Levy, G.(5);Higgins, P.D.R.(6);Loftus- Jr., E.V.(7);Panaccione, R.(8);

(1)University Hospital Leuven & KU Leuven, Gastroenterology & Hepatology, Leuven, Belgium;(2)IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy;(3)AbbVie Inc., Research and Development, North Chicago- Illinois, United States;(4)AbbVie Inc., Data & Statistical Sciences, North Chicago- Illinois, United States;(5)AbbVie Inc., Pharmacovigilance & Patient Safety, North Chicago- Illinois, United States;(6)University of Michigan, Department of Medicine- Division of Gastroenterology, Ann Arbor- Michigan, United States;(7)Mayo Clinic- College of Medicine, Division of Gastroenterology and Hepatology, Rochester- Minnesota, United States;(8)University of Calgary, Inflammatory Bowel Disease Unit- Division of Gastroenterology and Hepatology, Calgary- Alberta, Canada;

Background

Upadacitinib (UPA), a selective and reversible Janus kinase inhibitor, has been shown to be safe and effective when administered at a dose of 45 mg once daily (QD) as 8-week induction therapy in moderate-to-severe Ulcerative Colitis (UC). This analysis evaluated outcomes following extended induction (45 mg QD for 16 weeks) followed by maintenance (15 or 30 mg QD) treatment with UPA in patients with UC who did not achieve a clinical response after 8 weeks’ induction.

Methods

Patients with moderate-to-severe UC who failed to achieve a clinical response (Adapted Mayo score decrease of ≥2 points and ≥30% from baseline, plus ≥1-point decrease in rectal bleeding score [RBS] or absolute RBS ≤1) to 8 weeks’ induction treatment with UPA 45 mg QD in the U-ACHIEVE Induction (NCT02819635) or U‑ACCOMPLISH (NCT03653026) studies, continued to receive UPA 45 mg QD in an 8‑week open-label extension. Responders at the end of the open-label extension entered the U-ACHIEVE Maintenance study and were randomised 1:1 to UPA 15 mg or 30 mg QD for 52 weeks. The efficacy endpoints were evaluated at Week 16 for the induction studies and at Week 52 for the maintenance study.

Results

In total, 125 patients who failed to achieve a clinical response after 8 weeks’ induction treatment received open-label UPA 45 mg for a further 8 weeks. Of these patients, 48.3% achieved a clinical response at Week 16 and were re‑randomised to UPA 15 or 30 mg in U-ACHIEVE Maintenance. Among 16-week responders who entered the maintenance study, clinical remission, maintenance of clinical response, and endoscopic improvement, respectively, at Week 52 were achieved in 33.3% versus 19.0%, 66.7% versus 35.7%, and 37.5% versus 23.8% of those who received UPA 30 versus UPA 15 mg QD as maintenance treatment (Table 1). Adverse events of special interest were reported infrequently in the two maintenance treatment groups (Table 2).

Efficacy of extended induction treatment (16 weeks) with UPA 45 mg QD followed by maintenance treatment with UPA 15 or 30 mg QD

Summary of treatment-emergent adverse eventsa in patients who received 16 weeks’ induction treatment with UPA 45 mg followed by maintenance treatment with UPA 15 or 30 mg QDb

Conclusion

In this analysis, prolonged induction treatment for a total of 16 weeks was beneficial in almost half of UC patients who failed to achieve a clinical response after 8 weeks’ induction with UPA 45 mg. The benefit of maintenance therapy in these delayed responders was further demonstrated, with UPA 30 mg providing greater benefit than UPA 15 mg QD.