Risankizumab as induction therapy induces clinical remission in UC

Induction therapy with risankizumab, a monoclonal antibody neutralizing interleukin-23p19, resulted in significantly higher clinical remission rates among patients with moderate-to-severe ulcerative colitis (UC) compared with placebo, according to the INSPIRE trial presented at AIBD 2023.

This phase III trial analysed 975 adults with moderate-to-severe UC (Adapted Mayo Score of 5–9 points) and an endoscopic subscore of 2–3 (per central review) who had intolerance or inadequate response to conventional and/or advanced therapies. Participants were randomly assigned to receive either risankizumab 1,200 mg intravenously (n=650) or placebo (n=325) at weeks 0, 4, and 8. The primary endpoint of the study was clinical remission (per Adapted Mayo Score, defined as SFS* ≤1 and not greater than baseline, RBS** of 0, and endoscopic subscore ≤1 without friability).

In the induction study, significantly more patients treated with risankizumab were in clinical remission at week 12 than those treated with placebo (20.3 percent vs 6.2 percent; p<0.00001), with a treatment difference of 14 percent between the treatment groups. [AIBD 2023, abstract S4]

A higher proportion of risankizumab-treated patients in both advanced therapy-naïve (29.7 percent vs 8.4 percent) and advanced therapy-IR (11.4 percent vs 4.3 percent) subgroups also achieved clinical remission at week 12 compared with placebo-treated patients.

Risankizumab recipients also demonstrated a significantly higher clinical response rate, as shown by per partial Adapted Mayo Score at week 4 (52.2 percent vs 30.5 percent; p<0.00001) and per Adapted Mayo Score at week 12 (64.3 percent vs 35.7 percent; p<0.00001), than placebo recipients.

Additionally, significantly more risankizumab- vs placebo-treated patients achieved the key secondary endpoints of endoscopic improvement and remission at week 12 (36.5 percent vs 12.1 percent and 10.6 percent vs 3.4 percent, respectively; p<0.00001 for both).

Patients on risankizumab also demonstrated a significant increase in HEMI*** (24.5 percent vs 7.7 percent; p<0.00001) and HEMR⁺ (6.3 percent vs 0.6 percent; p<0.00001) than those on placebo.

In terms of safety, the rates of adverse events (AEs) were lower in the risankizumab arm vs the placebo arm, with fewer serious AEs (2.3 percent vs 10.2 percent) and AEs leading to study drug discontinuation (0.6 percent vs 3.7 percent).

No adjudicated major adverse cardiovascular events, adjudicated anaphylaxis, or serious hepatic events were reported, the researchers noted.

However, one death occurred in the study arm due to COVID-19 pneumonia, which according to the investigator was not related to the study drug.

“Overall, risankizumab was superior to placebo as an induction therapy in patients with moderately to severely active UC for clinical remission and all secondary clinical, endoscopic, and endoscopic-histologic endpoints,” said the researchers.

“Risankizumab was well tolerated, and no new safety risks were observed,” they added.