Two monoclonal antibodies targeting interleukin-17 proved effective and safe for moderate to severe plaque psoriasis, according to the results of two phase II clinical trials reported in the March 29 issue of the New England Journal of Medicine.
Both agents had a rapid onset of action and improved scores on the psoriasis area and severity (PASI) index, as well as on measures of dermatology-related quality of life and overall well-being, compared with placebo. Both agents also showed increasing efficacy at higher doses, indicating a dose-response effect, according to the industry-sponsored studies.
Brodalumab
In the first study, researchers assessed brodalumab (AMG 827), a human anti-interleukin-17RA monoclonal antibody that antagonizes the interleukin-17 pathway, in 198 patients at 23 international sites.
Dr. Kim A. Papp
The study patients were randomly assigned to receive 70 mg, 140 mg, or 210 mg of brodalumab (at weeks 1, 2, 4, 6, 8, and 10), 280 mg of brodalumab monthly, or placebo injections. A subgroup of 20 patients also underwent skin biopsy at baseline and at week 12, reported Dr. Kim A. Papp of Probity Medical Research, Waterloo, Ont., and his associates.
The mean patient age was 43 years, and the mean duration of psoriasis was 19 years. Most patients had previously received topical and systemic treatments, including phototherapy, and 35% had previously received biologic therapy.
The primary efficacy outcome – percentage improvement in PASI score at week 12 – was significantly greater in every brodalumab group than in the placebo group. Mean improvements were 45% with 70 mg, 85.9% with 140 mg, 86.3% with 210 mg, and 76% with 280 mg, and 16% with placebo.
"Similarly, a significantly higher percentage of patients in the brodalumab groups than in the placebo group [was] assessed as being clear of psoriasis (score of 0 on the physician’s global assessment) or as having minimal disease (score of 1) at week 12," Dr. Papp and his colleagues wrote (N. Engl. J. Med. 2012;366:1181-9)
In addition, the extent of the affected body-surface area was significantly smaller with active treatment than with placebo. Scores on the Dermatology Life Quality Index (DLQI) were significantly lower in the brodalumab groups, indicating that psoriasis had less of an impact on health-related quality of life. And scores on both physical and mental components of the SF-36 were significantly higher, indicating improved well-being, with brodalumab.
Among study patients who underwent skin biopsy, keratin 16 staining of the upper epidermis was reduced, and epidermal thickness and CD3 counts were decreased, at all doses of brodalumab except 70 mg. "This finding indicates a reversal of regenerative epidermal maturation, which is the essential pathological characteristic of psoriasis that causes epidermal hyperplasia and abnormal differentiation, with scaling and thickness as the clinical correlates," Dr. Papp and his associates noted.
At 16-week follow-up, which was 6-8 weeks after the final dose of brodalumab, PASI scores showed a diminished drug effect but were still better than those at baseline.
There were three serious adverse events, only one of which was related to the study drug. This was an asymptomatic case of grade 3 neutropenia, which resolved when the study drug was discontinued. A less serious case of neutropenia developed in another patient.