Additional clinical benefit of risankizumab in patients with delayed response

Crohn's patients who responded only after a risankizumab second induction kept a CDAI clinical response in 75.8% on subcutaneous 360 mg at week 52.

Most participants had a record with failure to anti-TNF treatment

The FORTIFY trial (NCT03105102) on risankizumab, a selective p19 anti-IL-23 antibody, in Crohn’s disease (CD) included so called ‘delayed responders’1. These patients only achieved clinical response after a second period of induction treatment with risankizumab over 12 weeks, after not attaining the outcome of a decrease of average daily stool frequency (SF) of at least 30% and/or a ≥30% reduction in their average daily abdominal pain score (APS), in phase 3 ADVANCE (NCT03105128) and MOTIVATE (NCT03104413). Prof. Geert D’Haens (Amsterdam UMC, the Netherlands) reported the 52 week FORTIFY maintenance results of the cohort of delayed responders, who were treated with subcutaneous risankizumab at a dosage of 180 mg or 360 mg in their second induction period.

The analysis included 63 patients with an average age between 38.5 and 40.4 years and 36.4% to 40% were women. The majority had a history of failure to anti-TNF treatment, but also previous therapy with vedolizumab or ustekinumab was observed. Mean Crohn's disease activity index (CDAI) in the group was 288.7 and 291.1 and mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) was 11.6 and 13.6.

2 induction treatments were needed before a significant drop in CDAI

At week 52, CDAI response was present in 53.3% (180 mg) and 75.8% (360 mg), while 56.7% and 66.7% achieved CDAI remission. Clinical remission rates in the SF/APS outcome were 43.3% on the lower and 54.5% on the higher dose. “Of course, the study was not powered to show a dose-response curve, but there is a numerical superiority for the higher dose of risankizumab 360 mg subcutaneous, but remember these are kind of refractory patients, they needed 2 induction treatments before they had a significant drop in their CDAI,” Prof. D’Haens commented. In the composite endpoint of deep remission (CDAI clinical remission plus endoscopic remission), rates of 40.0% and 39.4% were observed for the 180 mg and 360 mg regimens.

The safety summary did not reveal new safety risks and risankizumab was overall well tolerated.
“The findings underscore additional clinical benefit of initiating maintenance dosing of subcutaneous risankizumab, following intravenous induction even in the patients, who do not respond after 12 weeks,” Prof. D’Haens concluded.

  1. D’Haens G, et al. 52-weeks risankizumab subcutaneous maintenance dosing is efficacious and well tolerated in patients with moderate-to-severe Crohn’s disease who had delayed response to 12 weeks IV risankizumab induction. OP126, UEG Week 2022, Vienna, Austria, 8–11 October.