, results from a multicenter, double-blind, parallel-group trial showed.
The more frequent dosing was also associated with comparable safety, consistent with the established secukinumab safety profile.
“Weight may have an impact on pharmacokinetics and, therefore, on the clinical outcome of biologic treatment for psoriasis,” Matthias Augustin, MD, and colleagues wrote in the study, published recently in the British Journal of Dermatology. “Dose optimization may be highly beneficial for patients with higher body weight,” they noted, adding that their study supports previous study findings and pharmacokinetic/pharmacodynamic modelling data, showing that secukinumab dosed every 2 weeks “leads to a clinically and statistically significant advantage in PASI 90 response,” compared with standard dosing every 4 weeks in patients who weight 90 kg (about 198 pounds) or more, after 16 weeks of treatment, which was maintained until week 52.
Dr. Matthias Augustin
For the study, Dr. Augustin, of the Institute for Health Services Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 331 patients with moderate to severe chronic plaque psoriasis who weighed 90 kg or more to receive secukinumab 300 mg every 2 weeks, or secukinumab 300 mg every 4 weeks. The mean age of the patients was 47 years, 75% were male, 92% were White, and their mean body weight was 111.1 kg, with a mean body mass index of 36.1 kg/m2.
Patients who did not achieve a Psoriasis Area and Severity Index (PASI) 90 at week 16 on the monthly regimen (Q4W) either remained on that regimen or were up-titrated to dosing every 2 weeks (Q2W). Of the 331 patients, 165 received Q2W dosing and 166 received Q4W dosing. The researchers found that, at 16 weeks, patients in the Q2W dosing group had significantly higher PASI 90 responses, compared with those in the Q4W group (73.2% vs. 55.5%, respectively; P = .0003; odds ratio estimate, 2.3).
At 52 weeks, a greater proportion of patients in the Q2W group maintained responses to several outcome measures, compared with those in the Q4W group, including PASI 75 (88.9% vs. 74.8%), PASI 90 (76.4% vs. 52.4%), and PASI 100 (46.7% vs. 27.3%) scores; Investigator’s Global Assessment score of 0 or 1 (75.9% vs. 55.6%); and Dermatology Life Quality Index scores of 0 or 1 (66.1% vs. 48.8%).
In addition, those who had not had a PASI 90 response at week 16 who were up-titrated to Q2W dosing demonstrated higher efficacy responses at week 32, compared with those who remained on the Q4W regimen, with PASI 90 scores of 37.7% versus 16.5%, respectively.
Both regimens were well-tolerated, consistent with the known secukinumab safety profile; safety was comparable in the treatment arms, and there was “no clear dose-response relationship seen” for the incidence of overall adverse events, serious AEs, and AEs leading to discontinuation of the study treatment, “or AEs related to the identified risks” of infections, hypersensitivity, neutropenia and potential risk of major adverse cardiovascular events, the authors wrote.
“Despite more frequent dosing, the incidence of Candida infections was numerically lower in the Q2W group versus the Q4W group,” although there were not many cases, three patients versus six patients, respectively.