Children with two subtypes of juvenile idiopathic arthritis responded well to initial treatment with secukinumab (Cosentyx), but were more likely to have a disease flare if they subsequently were switched to placebo, a phase III study found.
Patients randomized to secukinumab after 12 weeks following a 12-week open label period had a significantly longer time to flare and a 72% reduction in risk of flare compared with those given placebo (HR 0.28, 95% CI 0.13-0.63, P<0.001).
Following randomization, there were 21 flares in the placebo group and 10 in the secukinumab group, noted Nicolino Ruperto, MD, of the University of Genoa in Italy.
Enthesitis-related arthritis and juvenile psoriatic arthritis are two recognized subtypes of juvenile idiopathic arthritis, representing pediatric correlates of axial spondyloarthritis and adult psoriatic arthritis, respectively.
As Ruperto explained when reporting the study at the European League Against Rheumatism virtual congress, secukinumab has shown efficacy in these adult rheumatic conditions, so he and his team wanted to investigate whether the corresponding pediatric conditions might show similar responses.
Ruperto and his team of international colleagues enrolled 89 patients whose mean age was 13; 60% had enthesitis-related arthritis and 40% had juvenile psoriatic arthritis.
The study design, which was sponsored by Novartis, called for 12 weeks of open-label secukinumab, followed by randomization to secukinumab or placebo until flare occurred, with follow-up to week 104. Patients in the placebo group were switched to open-label secukinumab at the time of flare, which was defined as a 30% worsening in signs and symptoms. This has been a typical study design in pediatric patients with chronic diseases, intended to minimize exposure to placebo, Ruperto noted.
The children in the study had high levels of disease at baseline, with a mean Juvenile Arthritis Disease Activity Score of 15.07. They had an average of 7.7 joints with active arthritis, and enthesitis scores of 2.6. Two-thirds were receiving concomitant methotrexate.
During the open-label phase of the study, all patients received subcutaneous secukinumab in doses of 75 or 150 mg depending on body weight at weeks 1, 2, 3, 4, 8, and 12. Following randomization at week 12, secukinumab or placebo was given every 4 weeks.
After 12 weeks of open-label secukinumab treatment, 90.4% of patients had achieved a 30% improvement on the criteria of the American College of Rheumatology (ACR) and entered the randomized phase.
Also at week 12, ACR50, 70, 90, and 100 responses were seen in 86.7%, 69.9%, 39.8%, and 25.3% of patients, respectively, while inactive disease was observed in 36.1%.
By week 104, 89.2% of patients in the secukinumab group had ACR30 responses, compared with 64.9% of patients remaining in the placebo group. “But the median time to flare in the placebo group was 453 days, highlighting the prolonged biologic effect of secukinumab,” Ruperto said.
In addition, inactive disease persisted at week 104 in 47.2% of the secukinumab group and 37.8% of the placebo group.
Among patients with enthesitis-related arthritis, 73.9% had complete resolution of this symptom.
Regarding safety, 91.7% in the secukinumab group had any adverse event (AE), as did 92.1% of those in the placebo group. Three patients on secukinumab discontinued treatment because of AEs, as did five on placebo.
Most adverse events were minor infections, gastrointestinal complaints, and headache. This was consistent with the known safety profile of secukinumab in adults, Ruperto noted.
“This is a very important study,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University in Munich, Germany, who moderated the session.
One concern however, he said, was that 22% of patients in the study reported diarrhea. Anti-IL-17 treatment has been associated with reactivation or de novo development of inflammatory bowel disease, and Schulze-Koops asked if there might be a connection.
“Most cases of diarrhea were self-resolving, and at least yet it does not appear to represent inflammatory bowel disease,” Ruperto said.
The study was sponsored by Novartis.
Ruperto reported financial relationships with Novartis, Ablynx, AstraZeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli-Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Pfizer, R-Pharma, Sinergie, Sobi, UCB, a, Sinergie, Sobi, and UCB; co-authors also reported multiple relationships with industry.