COPENHAGEN – The longest-ever clinical trials of etanercept and adalimumab for pediatric psoriasis show reassuring maintenance of efficacy, coupled with safety and tolerability profiles similar to what has been seen in long-term trials in adults, investigators reported at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Richard G. Langley presented outcomes from a 5-year open-label extension of an initial 12-week, multicenter, double-blind, randomized trial of etanercept or placebo in children and adolescents with moderate to severe chronic plaque psoriasis. The primary results were published more than 7 years ago (N Engl J Med. 2008 Jan 17;358[3]:241-51).
“This is the largest and longest follow-up of any biologic in children and adolescents to date. I think it’s encouraging data and should be reassuring to those of us who are managing this important population of pediatric patients in our conversations with parents and families,”said Dr. Langley, professor of dermatology at Dalhousie University in Halifax, Nova Scotia.
In the original 211-patient study, 57% of patients receiving etanercept (Enbrel) once weekly at 0.8 mg/kg to a maximum of 50 mg achieved a PASI 75 response at week 12, and 27% had a PASI 90. In the 69 patients who completed the full 264 weeks of follow-up, those response rates remained essentially unchanged.
Dr. Langley was quick to point out that this was an as-observed analysis, meaning results were counted only in those patients still participating at week 264. While conceding that the two-thirds dropout rate is an important study limitation, he added: “Notwithstanding that, what matters to us in the clinic are the patients we continue to treat and how they’re responding.”
Of note, most study discontinuations didn’t result from loss of response or adverse events, they were due to withdrawal of consent by families in which the patient began the study as a cooperative child and who as time went by turned into an independent and often willful teenager, he said.
No new safety signals arose over the course of 5 years. There were no opportunistic infections, no malignancies. The most common adverse events were the same ones seen in the original short-term study: upper respiratory infections, nasopharyngitis, and headaches. There was only one serious adverse event deemed by investigators as ‘possibly related’ to etanercept therapy: a case of cellulitis.
Dr. Diamont Thaci
Separately, Dr. Diamant Thaci and Dr. Kim A. Papp presented 52-week outcomes for different aspects of the pivotal phase III randomized trial which earlier in 2015 earned adalimumab (Humira) European Commission marketing approval as the first biologic agent indicated for treatment of children as young as age 4 years, as well as for adolescents. The multi-arm trial included 114 patients aged 4-17 years with moderate to severe plaque psoriasis.
Dr. Thaci reported on the 37 subjects initially randomized double-blind to 16 weeks of oral methotrexate at 0.1-0.4 mg/kg weekly. The 19 patients (51%) who were deemed nonresponders to methotrexate because of inadequate PASI response at week 16 were then switched to open-label adalimumab at 0.8 mg/kg every other week for the remainder of the 52 weeks.
After 16 weeks on adalimumab, the methotrexate nonresponders had a PASI 75 of 90% and a PASI 90 of 74%, and 79% of the subjects were rated clear or almost clear by Physician’s Global Assessment. At week 52, the PASI 75 rate was 79%, the PASI 90 rate was 58%, and 68% of patients were rated clear or almost clear, according to Dr. Thaci of University Hospital Schleswig-Holstein, in L<scaps>ü</scaps>beck, Germany.
The side effects of methotrexate and adalimumab were similar to those seen in adults. There were no serious adverse events. The infections that occurred during adalimumab therapy were “very banal things,” mostly nasopharyngitis and upper respiratory tract infections, the dermatologist said. There were no opportunistic infections, malignancies, or cases of tuberculosis during the phase III study.
This was an important analysis because it recapitulates daily clinical practice, he explained. In most of the world, when dermatologists deem it time for systemic therapy, they generally start out with methotrexate, reserving biologics for second-line therapy because of the cost.
Dr. Kim A. Papp
Dr. Papp reported on 39 patients on adalimumab at 0.4 mg/kg every other week, and 38 on 0.8 mg/kg every other week throughout the 52-week study. The response rate was essentially a flat line from week 16 to week 52, with PASI 75s of 44% at week 16 and 50% at week 52 in the low-dose group, and 58% and 56% in the high-dose group. Half of patients on 0.4 mg/kg were clear or almost clear at week 52, as were 56% on 0.8 mg/kg.