FROM THE LANCET
Adalimumab appears to be a safe and effective treatment option for severe plaque psoriasis in children, outperforming methotrexate, based on the results of a phase III study, said Kim Papp, MD, PhD, of Probity Medical Research, Waterloo, Ont., and his associates.
“To our knowledge, this is the first randomized controlled study of either adalimumab or methotrexate in children and adolescents with psoriasis,” the researchers said, noting that the study did not include a placebo group because of ethical issues related to treating children with a severe chronic disorder.
The double-blind, phase III trial was done at 38 clinics in 13 countries with 114 children aged 4-17 years with severe plaque psoriasis who had not responded to topical therapy. They were randomized to receive 0.8 mg/kg (up to 40 mg total dose) adalimumab (38 patients), 0.4 mg/kg (up to 20 mg total dose) subcutaneously at week 0 and then every other week (39 patients), or 0.1-0.4 mg/kg once weekly of oral methotrexate (up to 25 mg per week total dose; 37 patients). There were four periods to the study: a 16 week period, followed by an up to 36-week withdrawal; a 16-week retreatment period; and a 52-week long-term follow-up. The first three periods were reported in this study.
At week 16 of the initial treatment period, an improvement of at least 75% in the Psoriasis Area and Severity Index (PASI75) score was reached by significantly more of the patients in the 0.8 mg/kg adalimumab group – 22 (58%) – than in the methotrexate group – 12 (32%). In the 0.4-mg/kg adalimumab group, 17 (44%) of patients reached a PASI75. The PASI75 response was rapid in the 0.8 mg/kg adalimumab group, a significant difference, compared with the methotrexate group. It was reached by week 4 (P = .002).
“At week 16, the 26% difference between adalimumab 0.8 mg/kg and methotrexate in the proportion of patients who achieved PASI75 was significant and clinically relevant,” Dr. Papp and his associates concluded.
At week 16 of treatment, the proportion of patients who achieved a physician global assessment (PGA) score of 0 or 1 (clear or minimal) was higher in the adalimumab 0.8 mg/kg group (23 of 38 [61%]) than in the methotrexate group (15 of 37 [41%]) or in the adalimumab 0.4-mg/kg group (16 of 39 [41%]) (P = .083). At week 16, the difference between the adalimumab 0.8-mg/kg and methotrexate groups was not significant, the investigators said (Lancet. 2017. doi: 10.1016/ S0140-673631189-3 ).
After the withdrawal period, PASI75 was achieved in 15 of 19 (79%) patients who were initial responders to adalimumab 0.8 mg/kg and 6 of 11 (55%) patients who were initial responders to adalimumab 0.4 mg/kg. PASI75 was achieved in six of eight (75%) patients who had responded to methotrexate treatment in the initial treatment period and who had loss of disease control in the withdrawal period.
During the initial treatment period, adverse events were reported by 26 of 38 (68%) in the adalimumab 0.8-mg/kg group, 30 of 39 (77%) in the adalimumab 0.4-mg/kg group, and 28 of 37 (76%) in the methotrexate group. Infections were the most frequently reported adverse events. Serious adverse events were infrequent, reported by three patients in the adalimumab 0.4-mg/kg group, and were not considered to be related to the study drug, the researchers said. Eleven severe adverse events were reported by 8 of the 114 (7%) children. Of these, headache was the most common. A case of urticaria during retreatment that led to discontinuation of adalimumab in the patient (who had received methotrexate in the first treatment period), was considered by the investigator as “probably related” to adalimumab.
“No new safety risks were identified in our study; however, longer-term data are needed to fully assess the safety profile of adalimumab in the pediatric population,” Dr. Papp and his associates commented.
“Our results showed better quality of life outcomes in children and adolescents treated with adalimumab compared with methotrexate. The mean 10.8-point change in PedsQL [pediatric quality of life inventory] from baseline to week 16 in the adalimumab 0.8-mg/kg group exceeded the minimal clinically important difference of 4.36, whereas the 1.9-point change in the methotrexate group did not,” they noted.
The study was funded by AbbVie, the manufacturer of adalimumab ( Humira ). Dr. Papp has served as a consultant for AbbVie and a number of other pharmaceutical companies, for which he has served as consultant or speaker or on advisory boards. His associates listed numerous similar disclosures. Two authors were AbbVie employees.