STOCKHOLM, Sweden — Long-term data on risankizumab (Skyrizi) in moderate to severe Crohn’s disease (CD) show that clinical remission and endoscopic response rates remain stable for up to 3 years, according to results of the FORTIFY extension study.
“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, told Medscape Medical News. In the most conservative analysis, “you see a benefit the longer you follow the patients…We haven’t seen this with many — if any — other compounds before.”
Ferrante, from University Hospitals Leuven, Leuven, Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents.
“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”
Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Ferrante. “And, importantly, this is true without any increased adverse effects.”
“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.
Ferrante presented the data (Abstract DOP 53) on February 23 at the 19th Congress of the European Crohn’s and Colitis Organization (ECCO).
Open-Label Extension up to 152 Weeks
The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD.
These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Ferrante also led that study.
Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n=872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n=275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months.
Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population.
For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.
The safety profile of risankizumab is consistent and supports long-term treatment, Ferrante said.
Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
‘Effective and Durable Option’
Providing comment, Tim Raine, MD, a consultant Gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.
“However, there are limitations with long-term extension studies,” he told Medscape Medical News. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.”
But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.
In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Raine.
“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted.
“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”
Dr Ferrante has declare research grants from: AbbVie, Amgen, Biogen, EG, Janssen, Pfizer, Takeda, and Viatris;
Consultancy fees from: AbbVie, Agomab Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, and ThermoFisher;
Speakers’ fees from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Falk, Ferring, Janssen-Cilag, Lamepro, MSD, Pfizer, Sandoz, Takeda, Truvion Healthcare, and Viatris.
Dr Raine has financial relationships with industry including receiving research/educational grants and/or speaker/consultation fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.
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