AbbVie announced the European Commission (EC) approved RINVOQ® (upadacitinib 45 mg [induction dose] and 15 mg and 30 mg [maintenance doses]) for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. The EC approval is supported by data from two induction studies, U-ACHIEVE induction and U-ACCOMPLISH, and one maintenance study, U-ACHIEVE maintenance. Statistical significance was achieved for the primary endpoint and all secondary endpoints with RINVOQ 45 mg in the two induction studies and both RINVOQ 15 mg and 30 mg in the maintenance study.

Clinical Remission: During the U-ACHIEVE and U-ACCOMPLISH induction trials, 26% and 33% of patients treated with RINVOQ 45 mg achieved clinical remission at week 8, the primary endpoint, compared to 5% and 4% of patients who received placebo. During the U-ACHIEVE maintenance trial, 42% and 52% of patients treated with RINVOQ 15 mg or 30 mg, respectively, achieved clinical remission at week 52, the primary endpoint, compared to 12% of patients who received placebo. Additionally, 57% and 68% of patients receiving RINVOQ 15 mg or 30 mg, respectively, achieved corticosteroid-free remission, defined as clinical remission (per Adapted Mayo Score) and corticosteroid free for =90 days immediately preceding week 52 among patients who achieved clinical remission at the end of the induction treatment, compared to 22% of patients on placebo.

Clinical Response & Mucosal Healing: Seventy-three and 74% of patients treated with RINVOQ 45 mg achieved clinical response (per Adapted Mayo Score) at week 8 compared to 27 and 25% of patients receiving placebo during the U-ACHIEVE and U-ACCOMPLISH induction trials, respectively. In both trials, a significantly greater proportion of patients experienced clinical response per partial Adapted Mayo Score (symptomatic response) as early as week 2 (U-ACHIEVE: 60% vs 27% and U-ACCOMPLISH: 63% vs 26%). Mucosal healing was observed in 36% and 44% of patients treated with RINVOQ 45 mg in U-ACHIEVE and U- ACCOMPLISH, respectively, at week 8, compared to 7% and 8% of patients, respectively, who received placebo.

In the maintenance study at week 52, mucosal healing was observed in 49% and 62% of patients treated with RINVOQ 15 mg and 30 mg, respectively, compared to 14% who received placebo. In the placebo-controlled ulcerative colitis induction and maintenance clinical trials, the overall safety findings were generally consistent with the known safety profile of upadacitinib; no new important safety risks were observed.1 The rates of overall adverse events (AE), serious AEs, and AEs resulting in treatment discontinuation were lower with upadacitinib compared to placebo.1 The most commonly reported adverse reactions (=5% of patients) with RINVOQ 45 mg, 30 mg or 15 mg were upper respiratory tract infection, blood CPK increased, acne, neutropaenia, and rash.1 In the overall clinical program, major cardiovascular events, thrombotic events, malignancy excluding non-melanoma skin cancer, and gastrointestinal perforation were reported infrequently (all <1.0 cases per 100 patient-years in patients who received at least one RINVOQ dose). The three Phase 3 studies are multicenter, randomized, double-blind, placebo-controlled studies to evaluate the efficacy and safety of RINVOQ 45 mg once daily as induction therapy, and RINVOQ 15 mg and 30 mg once daily as maintenance therapy in subjects with moderate to severe ulcerative colitis.

Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.1,2,3-6,17,18 In human cellular assays, RINVOQ preferentially inhibits signalling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing. Indications: Ulcerative colitis - RINVOQ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent.

Rheumatoid arthritis - RINVOQ is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Psoriatic arthritis - RINVOQ is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs.

RINVOQ may be used as monotherapy or in combination with methotrexate. Ankylosing spondylitis - RINVOQ is indicated for the treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. Atopic dermatitis - RINVOQ is indicated for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy.

Contraindications: RINVOQ is contraindicated in patients hypersensitive to the active substance or to any of the excipients, in patients with active tuberculosis (TB) or active serious infections, in patients with severe hepatic impairment, and during pregnancy.