Data from a 961-patient study shows that ustekinumab can induce and maintain remission for patients with moderate-to-severe ulcerative colitis.
Bruce E. Sands, MD
Patients with moderate-to-severe ulcerative colitis could turn to ustekinumab to achieve and maintain remission.
A team, led by Bruce E. Sands, MD, Icahn School of Medicine at Mount Sinai, evaluated ustekinumab as an 8-week induction therapy and 44-week maintenance therapy in a study that included 961-patients randomly assigned to receive either an intravenous induction dose of 130 mg [320 patients] of ustekinumab, a weight-range (based dose that approximated 6 mg per kilogram of body weight ), or a placebo (319).
The patients who then had a response to induction therapy after 8 weeks were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks ) or placebo (175).
The primary endpoint of the study was clinical remission (total score of ≤2 on the Mayo scale [range, 0-12, with higher scores indicating more severe disease] and no subscore >1 [range, 0-3] on any of the 4 Mayo scale components).
“The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P <.001 for both comparisons),” the authors wrote.
For patients who had a response to induction therapy with the drug and underwent a second randomization, the percentage of patients who had a clinical remission at week 44 was substantially higher for the patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than the patients assigned to a placebo (24.0%) (P =.002 and P <.001, respectively).
“Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis,” the authors wrote.
The investigators also found the incidence of serious adverse events was similar between the placebo group and those who were given ustekinumab.
There were 2 deaths (1 each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and 7 cases of cancer (1 each of prostate, colon, renal papillary, and rectal cancer, and 3 nonmelanoma skin cancers) among 825 patients who received ustekinumab.
There were no deaths and 1 case of testicular cancer among the 319 patients who received the placebo.
Recently, investigators conducted another study on ustekinumab, examining how it effects the microscopic manifestations of Crohn’s disease.
A team of investigators, led by Katherine Li, Janssen Research and Development, evaluated the effects of ustekinumab on histologic Crohn’s disease activity after analyzing the data of 251 patients in phase 3 induction and maintenance studies.
The investigators collected 2 endoscopic biopsy samples at weeks 0, 8, and 44 from the ileum, splenic flexure, and rectum and assessed histologic activity based on global histology activity scores (GHASs).
The mean GHAS was significantly reduced 8 weeks after ustekinumab induction treatment (10.4±7.0 to 7.1±5.9; P <.001). However, the same success was not found in the placebo group (9.2±6.4 to 7.8±6.2).
“In an analysis of data from participants in phase 3 induction and maintenance trials, we found histologic improvement in a greater proportion of patients given ustekinumab vs placebo,” the authors wrote. “The largest improvements occurred in patients who received ustekinumab maintenance therapy every 8 weeks.”
The study, “Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis,” was published online in The New England Journal of Medicine.