The interleukin (IL)-23 inhibitor risankizumab (brand name Skyrizi) has been granted marketing authorisation by the European Commission for ulcerative colitis.
The indication covers the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy.
This marks the fourth approved indication for risankizumab after plaque psoriasis, psoriatic arthritis and Crohn’s disease.
Risankizumab selectively blocks IL-23 by binding to its p19 subunit. The recommended induction dose is 1,200 mg administered by intravenous infusion at Week 0, Week 4 and Week 8. Starting at Week 12 and every eight weeks thereafter, a recommended maintenance dose of either 180 mg or 360 mg administered by subcutaneous injection should be based on individual patient presentation.
‘Ulcerative colitis is a chronic, unpredictable and sometimes debilitating disease, and people living with the condition need sustained symptom relief,’ said Dr Edouard Louis, professor and head of gastroenterology at Liège University Hospital and dean of faculty at Liège University in Belgium. ‘This approval introduces a new treatment option to help patients with ulcerative colitis reach their long-term treatment goals.’
Risankizumab efficacy and safety
The EC approval of risankizumab is based on the results of two phase 3 clinical trials, INSPIRE and COMMAND, in which the primary endpoint was clinical remission. Secondary endpoints included mucosal healing and histologic endoscopic mucosal healing (HEMH).
In the INSPIRE induction trial, a significantly higher proportion of patients treated with risankizumab 1,200 mg IV achieved the primary endpoint of clinical remission (per Adapted Mayo Score) at Week 12 than patients receiving placebo (20% vs 6%; p<.00001).
Mucosal healing (defined as ES ≤1 without friability) was observed at Week 12 in 37% of patients treated with risankizumab 1,200 mg IV compared to 12% of those receiving placebo (p<.00001). In patients without previous biologic or JAK inhibitor failure, 48% of patients treated with risankizumab 1,200 mg IV achieved mucosal healing at Week 12 versus 14% of those receiving placebo.
Some 24% of patients treated with risankizumab 1,200 mg IV achieved HEMH (defined as Geboes score ≤3.1 and ES ≤1 without friability) at week 12 versus 8% of those receiving placebo (p<.00001).
In the COMMAND maintenance trial, a significantly higher proportion of patients who received risankizumab 180 mg or 360 mg SC achieved clinical remission at Week 52 than patients in the induction-only control group: 40% and 38%, respectively, versus 25% (p≤.01).
Some 51% of patients treated with risankizumab 180 mg and 48% of patients treated with 360 mg achieved mucosal healing at Week 52 versus 32% of patients in the induction-only control group (p<.001). In patients without previous biologic or JAK inhibitor failure, 60% of patients who received risankizumab 180 mg and 76% who received 360 mg achieved mucosal healing versus 36% of patients in the induction-only control group.
Some 43% of patients treated with risankizumab 180 mg and 42% receiving 360 mg achieved HEMH at Week 52 versus 23% in those treated with the induction dose only (p≤0.01).
Professor Louis, who was also a trial investigator, added: ‘Patients treated with Skyrizi in the INSPIRE and COMMAND clinical trials experienced significant improvements in clinical remission and mucosal healing. These are important findings as mucosal healing goes beyond symptom management to restoration of the intestinal lining and is associated with improved long-term outcomes.’
The safety profile of risankizumab in both trials was consistent with the safety profile observed in previous trials across other indications, with no new safety risks observed. The most common adverse events observed were Covid-19, anaemia, nasopharyngitis and arthralgia.
