A in a report published in the Journal of the European Academy of Dermatology and Venereology.
“The safety profile of secukinumab was similar to that reported in previous clinical trials, and no new or unexpected safety signals were observed,” according to Diamant Thaci, MD, of the Comprehensive Centre of Inflammation Medicine, University of Lübeck (Germany) and coauthors. Moreover, effectiveness in those who started treatment with secukinumab at baseline, they added, “was comparable to that observed in Phase 3 trials. High levels of effectiveness were observed also in subjects who had received previous biologic therapies, although the response rates were numerically lower, as might be expected in a difficult to treat population. In addition, lower baseline PASI [Psoriasis Area and Severity Index] in patients with prior biologic treatment could also reduce the relative decrease in PASI observed over the course of the study.”
They reported on an interim analysis of the first 1,988 patients enrolled in the PROSPECT study, an observational 24-week study conducted in Germany; 1,323 patients completed the 24 week study; total cumulative exposure to secukinumab was 746.3 patient-years. Their mean baseline PASI was 17.7, slightly lower than those in typical clinical trials, and most (91%) had received systemic therapies before.
Almost half the patients (46%) experienced an adverse event during treatment, and about 4% experienced a serious adverse event; only 1% of serious adverse events were considered related to the study drug. About 7% discontinued treatment with secukinumab because of an adverse event. The most common reasons for discontinuation were lack of benefit in 2.4%, psoriasis in 2.3%, and upper respiratory tract viral infection in 0.5%.
The most common adverse events were nasopharyngitis (8.7%), pruritus (2.9%), and headache (2.4%). Rates of neoplastic disorders and major cerebrovascular events were similar to published data, with 5 patients (0.3%) experiencing a major adverse cardiovascular event and 10 (0.5%) experiencing a malignancy. Four patients (0.2%) developed inflammatory bowel disease, 42 (2.1%) developed Candida infection, 2 (0.1%) developed hepatotoxicity, and 11 (0.6%) an injection-site reaction. There were three deaths, determined not to be related to secukinumab, the authors wrote.
Efficacy was also similar to that observed in earlier studies, they noted, with positive results regardless of concomitant medication. Overall, 44% of the cohort used concomitant medications.
Of the 829 patients using concomitant topical treatments, 73% had started before baseline. In all, 110 patients were also using conventional systemic medications and phototherapy; 77 started treatment before baseline. The most commonly employed concomitant therapies were topical steroids and phototherapy.
Overall, most patients (86%) achieved a PASI 75 by week 24, with 68.5% achieving a PASI 90, and 40% achieving a PASI 100 at that time point.
Secukinumab was most effective among the 83 patients who were naive to systemic therapies; in these patients, results at week 24 were as follows: PASI 75, 93%; PASI 90, 84%; and PASI 100, 66%. Among patients who had previously received a biologic, scores were slightly lower: PASI 75, 78%; PASI 90, 55%; and PASI 100, 29%.
“These interim data from PROSPECT confirm the effectiveness and safety of secukinumab in the routine clinical setting, in a large cohort of psoriasis patients with high disease severity,” the investigators concluded.
Initially approved in the United States in 2015, secukinumab, an interleukin-17A antagonist, is indicated for treating moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, adults with psoriatic arthritis, and adults with active ankylosing spondylitis.
The study was funded by Novartis, Germany; four authors are employees of the company. Dr. Thaci has served as an investigator and/or consultant for multiple pharmaceutical companies, including Novartis, AbbVie, Amgen, Arena, Biogen Idec, Boehringer Ingelheim, and Celgene. Other authors also disclosed serving as investigators, consultants, and/or speakers for Novartis and other companies.
SOURCE: J Eur Acad Dermatol Venereol. 2019 Sep 21. doi: 10.1111/jdv.15962.