Subcutaneous administration of risankizumab (marketed as Skyrizi) as induction therapy has demonstrated substantial improvements in both clinical remission and endoscopic response rates among patients suffering from moderately to severely active Crohn’s disease.
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At the 12-week mark, 55% of patients treated with subcutaneous risankizumab achieved clinical remission as defined by the Crohn’s Disease Activity Index (CDAI), compared to 29.6% of patients receiving a placebo injection. Additionally, endoscopic response rates were observed at 44% in the risankizumab group versus 14.3% in the placebo group, with both comparisons reaching statistical significance at a p-value threshold of less than 0.0001. Furthermore, the study identified higher response rates among patients who were treatment-naive to advanced therapies and among those who had previously experienced intolerance or an inadequate response to such treatments.
Patient Population and Prior Therapies
This double-blind, placebo-controlled study enrolled a total of 289 adult patients diagnosed with Crohn’s disease for a minimum duration of at least three months. To qualify for inclusion, participants were required to exhibit moderate to severe disease activity as measured by the Crohn’s Disease Activity Index (CDAI), with a Simple Endoscopic Subscore for Crohn’s Disease (SES-CD) of at least 6, or a score of 4 for those presenting with isolated ileal disease. All participants had previously experienced either intolerance or an inadequate response to conventional or advanced therapeutic regimens. Demographic analysis revealed an average age ranging from 38 to 40 years, with 43% of the cohort being female. Additionally, 61-65% of patients had a mean baseline CDAI above 300, and 7% had a mean baseline SES-CD of 13. Following randomization in a 2:1 ratio, patients were assigned to receive either subcutaneous risankizumab at a dose of 720 mg or a placebo injection.
Endoscopic Outcomes and Maintenance Phase
At the 12-week time point, endoscopic remission was observed in 27.7% of patients treated with risankizumab compared to 10.2% of those receiving placebo, with a statistical significance level of P<0.0001. Furthermore, rates of ulcer-free endoscopy were recorded at 26.2% in the risankizumab group and 10.2% in the placebo group, achieving statistical significance at P=0.0001. During the subsequent 24-week maintenance phase, patients who had initially responded to risankizumab induction therapy were administered subcutaneous risankizumab at a dose of 360 mg at weeks 12 and 20. Among the 134 patients who were risankizumab induction responders, 67.2% achieved clinical remission as defined by the CDAI by week 24, compared with the placebo responders' remission rate from the induction phase. Additionally, endoscopic response rates during the maintenance phase were substantially higher at 57.5% for the risankizumab group in comparison to 11.4% for the placebo group.
Subgroup Analysis and Long-Term Outcomes
In the study, about one-third of patients were anti-TNF naive, and two-thirds had prior anti-TNF exposure. Some had failed ustekinumab or JAK inhibitors, forming a medically refractory group. Long noted this during the American College of Gastroenterology meeting. At 24 weeks, endoscopic response rates were 57.5% with risankizumab versus 11.4% for placebo. Remission and ulcer-free rates followed similar patterns, with higher outcomes in the treatment-naive and intolerant subgroups. Adverse events were lower in the risankizumab group, though serious events remained rare in both arms. Long affirmed the treatment’s effectiveness, particularly in anti-TNF-naive patients, and intends to adopt the subcutaneous form in practice once this is available. The FDA approved risankizumab in 2022 for IV induction and subcutaneous maintenance therapy for Crohn’s disease. Based on the 12-week results from AFFIRM, AbbVie submitted an application to the FDA seeking approval for subcutaneous risankizumab as induction therapy—an option which would provide increased flexibility to our patients, Long pointed out.
Safety Profile and Regulatory Pathway
The incidence of treatment-emergent adverse events was comparatively lower among patients administered risankizumab, while the frequency of serious adverse events remained minimal in both the risankizumab and placebo treatment arms. Notably, only one patient in the placebo group discontinued treatment due to an adverse event. Risankizumab, classified as an interleukin-23 inhibitor, was granted FDA approval in 2022 for use as intravenous induction therapy followed by subcutaneous maintenance administration.
