Feagan BG, et al. - This open-label extension study assessed the efficacy and safety of extended intravenous induction and subcutaneous maintenance therapy with risankizumab in patients with moderately to severely active Crohn's disease. Outcomes support the efficacy of the treatment in enhancing clinical response and remission rates at week 26. Most patients who were in clinical remission at week 26 remained remitted until week 52 with subcutaneous risankizumab.

Methods

• Researchers conducted this open-label extension study by recruiting all patients who completed the 12-week induction phase of the double-blind phase 2 induction study.
• Open-label intravenous therapy with 600-mg risankizumab was administered every 4 weeks for 12 weeks to patients who did not achieve deep remission, defined as clinical remission (Crohn's Disease Activity Index [CDAI] <150) and endoscopic remission (Crohn's Disease Endoscopic Index of Severity [CDEIS] ≤4, or ≤2 for patients with isolated ileitis), at week 12; patients in deep remission at week 12 entered a 12-week washout phase.
• Participants for the maintenance phase of the study comprised patients in clinical remission at week 26; these patients received open-label subcutaneous risankizumab (180 mg) every 8 weeks for 26 weeks.
• The proportion of patients in clinical remission (CDAI <150), and the proportion of patients who achieved clinical response (either CDAI of <150 or a reduction from baseline of at least 100 points) were included as the 26-week efficacy endpoints.
• The proportion of patients achieving clinical remission, clinical response, endoscopic response (>50% CDEIS reduction from baseline), endoscopic remission (as previously defined), mucosal healing, and deep remission were considered as the 52-week efficacy endpoints.
• Patients who received at least one dose of the study drug during the open-label phases of the study were assessed for safety.

Results

• The 12-week double-blind induction trial was completed by 108 patients; of these patients, six were in deep remission and entered the 12-week washout phase.
• Deep remission was not reported for 102 patients; of these patients, 101 received 12 weeks of 600-mg risankizumab treatment (original placebo group, n=33; 200-mg risankizumab group, n=34; and 600-mg risankizumab group, n=34); the other patient declined to continue the study.
• At week 26, clinical remission was achieved in 54 (53%) patients treated with 600 mg risankizumab.
• At week 26 vs week 12, clinical remission rates among patients included in the open-label extension trial were: 18 (55%) vs 6 (18%) of 33 patients in the original placebo group, 20 (59%) vs 7 (21%) of 34 patients in the original 200-mg risankizumab group, and 16 (47%) vs 9 (26%) of 34 patients in the original 600-mg risankizumab group.
• Risankizumab maintenance treatment was provided to 62 patients, including the 54 patients who achieved clinical remission at week 26, the six patients who had achieved deep remission at week 12, and one patient because of a protocol violation.
• At week 52, 44 (71%) patients maintained the clinical remission, 50 (81%) patients had a clinical response, 22 (35%) patients were in endoscopic remission, and 34 (55%) patients had an endoscopic response.
• Mucosal healing was achieved in 15 (24%) patients and deep remission in 18 (29%) patients at week 52.
• The patients well tolerated risankizumab with no report of new safety signals.
• Arthralgia (22%), headache (20%), abdominal pain (18%), nasopharyngitis (16%), nausea (16%), and pyrexia (13%) comprised the most frequent treatment-emergent adverse events (AEs).
• Most AEs were mild or moderate in severity were considered to be unrelated to study treatment.
• No treatment-related deaths were reported.