Vladea, Ramona

Abstract Background and aims This post hoc analysis evaluated the corticosteroid-sparing effects of risankizumab (RZB) therapy in patients with moderate-to-severe ulcerative colitis in the phase 3 induction and maintenance studies, INSPIRE and COMMAND. Methods Patients were randomized (2:1) to 12 weeks of intravenous RZB or placebo (PBO) induction therapy; responders to intravenous RZB were randomized (1:1:1) to receive subcutaneous RZB 180 mg, 360 mg, or PBO (RZB withdrawal) maintenance therapy. Baseline corticosteroid doses were maintained during induction, with a mandatory taper beginning at maintenance week 0. Efficacy outcomes were evaluated by baseline corticosteroid use at induction week 12, while corticosteroid-free clinical and endoscopic outcomes were assessed at maintenance week 52 among the overall population and among patients on corticosteroids at baseline. Safety was also assessed. Results At baseline, 35.7% (348/975) of patients were taking corticosteroids. At induction week 12, greater rates were observed for clinical, endoscopic, and patient-reported outcomes in RZB 1200 mg-treated patients compared with PBO, regardless of baseline corticosteroid use. RZB 180 mg and 360 mg treatment resulted in higher corticosteroid discontinuation rates (RZB 180 mg 64.9% [48/74]; RZB 360 mg 54.2% [32/59]; PBO [withdrawal] 36.8% [25/68], P ≤ .01) and corticosteroid-free clinical, endoscopic, and patient-reported outcomes at week 52, compared with PBO (withdrawal). The rates of treatment-emergent adverse events were similar regardless of baseline corticosteroid use during induction and maintenance. Conclusions The efficacy of RZB induction therapy was independent of corticosteroid use, with high rates of corticosteroid-free outcomes observed in the overall population and among patients with baseline corticosteroid use, reaffirming the potential of RZB to serve as a corticosteroid-sparing therapy for patients with ulcerative colitis. Clinicaltrial.gov numbers NCT03398148 and NCT03398135

Abstract Background and Aims This post hoc analysis assessed the efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis stratified by corticosteroid use from the ulcerative colitis Phase 3 clinical trial programme. Methods Patients were randomised [1:2] to 8 weeks’ placebo or upadacitinib 45 mg once daily; Week 8 responders were re-randomised [1:1:1] to 52 weeks’ placebo or upadacitinib 15 or 30 mg daily. Corticosteroid dose was kept stable during induction but tapered according to a protocol-defined schedule [or investigator discretion] during maintenance Weeks 0–8. Efficacy outcomes and exposure-adjusted, treatment-emergent adverse event [TEAE] rates were assessed for induction and maintenance stratified by corticosteroid use at induction baseline. Results Overall, 377/988 [38%] patients were receiving corticosteroids at induction baseline [placebo, n = 133; upadacitinib 45 mg, n = 244] and 252 [37%] of the 681 clinical responders who entered maintenance were on corticosteroids at induction baseline [n = 84 for each treatment]. Similar proportions of patients receiving upadacitinib achieved clinical remission per Adapted Mayo Score with and without baseline corticosteroids at Weeks 8 and 52. The total proportion of patients re-initiating corticosteroids was higher with placebo [24/84;29%] vs upadacitinib 15 mg [16/81; 20%)] and 30 mg [11/81; 14%]. During induction, patients receiving corticosteroids at baseline had higher rates of TEAEs, serious TEAEs, and serious infections vs those not receiving corticosteroids; however, TEAE rates were similar during maintenance after corticosteroid withdrawal. Conclusions Upadacitinib is an effective steroid-sparing treatment in patients with moderately to severely active ulcerative colitis. Clinicaltrials.gov identifiers: NCT02819635; NCT03653026