CHICAGO (FRONTLINE MEDICAL NEWS) – Subcutaneous risankizumab maintained clinical remission for half a year in 76% of Crohn’s disease patients who responded to it during an induction study.
The interleukin-23 antibody (ABBV-066; AbbVie) also maintained endoscopic remission in 52% of patients who entered the open-label maintenance phase of the 52-week study, Brian Feagan, MD, said at the annual Digestive Disease Week.
The results of the phase II trial are enough to propel the drug into further studies as a Crohn’s disease therapy. Both the induction and maintenance doses have yet to be determined for any subsequent studies, said Dr. Feagan of the Robarts Research Institute, University of Western Ontario, London.
The three-phase study enrolled 121 patients with moderate to severe Crohn’s disease. The first 12 weeks consisted of intravenous induction therapy; patients were randomized to monthly infusions of risankizumab 200 mg or 600 mg or placebo. The endpoint was deep clinical remission. Patients who achieved remission exited the study. Results of this study were published in April ( Lancet.2017;389:1699-09 ).
Phase II included only the patients who did not achieve deep clinical remission. They all received open label 600 mg risankizumab infusions every 4 weeks from weeks 14-26. The endpoints were clinical and endoscopic remission.
Phase III, on which Dr. Feagan reported, included the patients who achieved remission in phase II. These patients continued with subcutaneous risankizumab 180 mg every 8 weeks, from week 26-52.
Patients were an average of about 38 years old, with mean disease duration of 16 years. Their median Crohn’s Disease Activity Index (CDAI) score was around 300; their mean Crohn’s Disease Endoscopic Index score was 12. About a quarter had already taken at least one tumor necrosis factor–alpha inhibitor; half of those had taken at least two of those drugs.
At the end of the first induction period, 25 taking the study drug and 6 taking placebo achieved clinical remission (31% vs. 15%). Those taking 600 mg did better than those taking 200 mg (37% vs. 9%).
Patients who didn’t achieve deep clinical remission (a CDAI of less than 150 plus endoscopic remission) entered into the open-label reinduction phase; all received monthly 600-mg infusions from weeks 14 to 26. Of these, 62 achieved clinical remission and entered the open-label maintenance phase.
By week 52, the majority of patients were still in clinical remission, although this varied by the original treatment group: 76% of those first randomized to 600 mg, 59% of those randomized to 200 mg, and 79% of those randomized to placebo. Endoscopic remission was maintained in 52% of the 600-mg group, 23% of the 200-mg group, and 32% of the placebo group.
Deep remission occurred in a subset of patients: 43% of the 600-mg group, 13.6% of the 200-mg group, and 31.6% of the placebo group.
Dr. Feagan also said C-reactive protein levels remained suppressed in the maintenance period. Patients who entered that period had experienced a mean drop of about 9 mg/L in CRP. By week 52, this had risen slightly, but the median decrease was still around 8 mg/L from baseline measures.
There were 11 drug-related adverse events; these were severe in five patients, causing two to withdraw. There were 22 infections during the study, one of which was serious, but no cases of tuberculosis, cancer, or fungal or opportunistic infections.
“We did not see any new or unexpected safety signals,” Dr. Feagan said. “The drug was well tolerated and appears safe.”
This study showed a superior response for the 600-mg induction dose, but Dr. Feagan said the company may explore higher doses before making a final determination. Last November, the Food and Drug Administration granted Orphan Drug Designation to risankizumab for the investigational treatment of Crohn’s disease in pediatric patients. The company is also investigating it in psoriasis; it recently outperformed ustekinumab in a small phase II study of patients with moderate to severe psoriasis.
The study was funded by Boehringer Ingelheim. Dr. Feagan reported financial relationships with AbbVie and Boehringer Ingelheim.
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