The CADMUS trial showed improvements in moderate to severe psoriasis in adolescent patients 12 years or older treated with ustekinumab, a study showed.
Treatment of psoriasis in pediatric patients is complicated by the limited number of approved treatments, despite approximately one-third of patients developing psoriasis before the age of 20 years. A human monoclonal antibody that targets the p40 subunit of interleukin-12/23, known as ustekinumab, was found to be effective and safe in moderate to severe psoriasis in adults.
Dr. Ian Landells of Memorial University of Newfoundland in St. John’s and his colleagues presented the results of the CADMUS trial, a randomized phase III trial of ustekinumab for active psoriasis in patients aged 12-17 years (J Am Acad Dermatol. 2015;73:594-603).
Lori Farmer/Frontline Medical News
Patients aged 12-17 years with moderate to severe plaque psoriasis were included in the study.
Patients aged 12-17 years with moderate to severe plaque psoriasis as defined by a Physician’s Global Assessment (PGA) score of greater than or equal to 3, a Psoriasis Area and Severity Index (PASI) of greater than or equal to 12, or 10% or more of body surface area involved for at least 6 months were included in the study.
The investigators conducted a multicenter, double-blind placebo-controlled trial with patients randomly assigned to weight-based standard dosing (SD) or weight-based half-standard dosing (HSD) at weeks 0, 4, and 16, then every 12 weeks until week 40. Conversely, participants could receive placebo at weeks 0 and 4 with crossover at week 12 and 16, then every 12 weeks until week 40 with either SD or HSD. Early escape to topical steroids at week 8 to week 12 for patients with a PASI increase to more than 50% above baseline was considered.
The primary endpoint of the study was the proportion of patients who achieved a PGA 0/1 by week 12. Secondary endpoints included the proportion of patients with 75% improvement by PASI (PASI 75) and 90% improvement by PASI (PASI 90) at 12 weeks, and change in the Children’s Dermatology Life Quality Index (CDLQI) at 12 weeks.
Between March 2010 and January 2014, 110 patients were included in the study: 36 randomly assigned to weight-based SD ustekinumab, 37 to weight-based HSD, and 37 to placebo, with 18 participants crossing over to SD and 19 participants crossing over to HSD. One participant each from the HSD and SD achieved early escape at 8 weeks. A total of nine participants (8%) discontinued the study because of adverse events (n = 3), death in an automobile accident (n = 1), or an unsatisfactory response (n = 5).
After 12 weeks, there were significantly more participants receiving either SD (69%) or HSD (68%) achieving a PGA of 0/1 vs. placebo (5%, P less than .001 for both doses). About one-third of the treatment participants achieved a PGA of 0/1 by week 4. Likewise, in the treatment group, significantly more participants achieved a PGA of 0 by week 12 (SD, 47%; HSD, 32%; placebo, 3%; P less than .001 for both doses).
When treatment response by PASI was assessed, a PASI 75 and PASI 90 were achieved significantly more often in the treatment groups (P less than .001 for both) than among controls. A PASI score of 0 (cleared) was achieved in 39% of the SD group and 22% of the HSD group vs. 3% with placebo (P less than .001 and P = .014, respectively).
Participants treated with ustekinumab demonstrated improvements in quality of life that were maintained at 52 weeks.
At week 12, 44% of the SD group, 51% of the HSD group, and 57% of the placebo group reported one or more adverse events. At the conclusion of the study at week 60, 82% of the participants had reported adverse events. Most of the adverse events were under the category of infections and infestations, which the authors noted were consistent with those observed in adults treated with ustekinumab.
Dr. Landells and his colleagues wrote, “Patients in both the HSD and SD ustekinumab groups experienced robust and clinically meaningful improvements in disease activity.”
The study was funded by Janssen Research and Development. The authors reported multiple financial disclosures.