Research in context
Evidence before this study
We searched PubMed for publications of clinical trials and review articles using combinations and variations of the search terms “psoriasis”, “biologics”, “guselkumab and psoriasis”, “secukinumab and psoriasis”, “quality of life”, “efficacy standards for psoriasis”, “comparator or head-to-head psoriasis studies”, “psoriasis cytokines”, “interleukin (IL)-17 and psoriasis”, “IL-23 and psoriasis”, “IL-12/23 and psoriasis”, and “safety of biologics in psoriasis”. We also used other public search engines to retrieve relevant package inserts from companies. We did the searches from Oct 22 to Dec 4, 2018, and included materials published from Jan 1, 1999, to Dec 4, 2018. We observed from this search that although significant improvements in the efficacy of biologics for the treatment of moderate-to-severe psoriasis have been made, patients' desire for clear skin, and stable, long-term control is generally of greater relevance than an early response.
Until the past 4 years, dermatologists have had access to anti-tumour necrosis factor drugs and the IL-12/23p40 inhibitor, ustekinumab, for the treatment of moderate-to-severe psoriasis. Two novel classes of targeted biologic therapies are now available, the IL-17A inhibitors (first-in-class drug approved in 2015) and the IL-23p19 inhibitors (first-in-class drug approved in 2017), which are generally more effective. The first approved and available representatives of these classes are secukinumab (an IL-17A inhibitor) and guselkumab (an IL-23p19 inhibitor). Until now, there has been no comparison of these two novel classes in a head-to-head study. This information might also have relevance to a broader scope of health-care providers given the differential effects of these drug classes in other immune-mediated diseases such as inflammatory bowel disease and ankylosing spondylitis.
Added value of this study
The ECLIPSE study is the first head-to-head comparator trial between guselkumab and secukinumab. This study showed that guselkumab was superior to secukinumab for patients achieving an improvement of 90% or more in the Psoriasis Area and Severity Index (PASI 90) from baseline at week 48 (p<0·0001). This primary endpoint was assessed considerably later than was done in most pivotal phase 3 psoriasis trials. The proportions of patients with a response for other stringent longer-term efficacy endpoints (PASI 100, Investigator's Global Assessment [IGA] score of 0, and IGA score of 0 or 1 at week 48) were also numerically higher for guselkumab than for secukinumab, although formal statistical testing was not done. This report also provides a comprehensive assessment of efficacy over time in which clear differences were observed. Between week 3 and week 12, the proportions of patients achieving a PASI 90 response were higher in the secukinumab group than in the guselkumab group; at weeks 16 and 20 they were similar in the two groups; and from week 28 to 48 they were higher in the guselkumab group.
Both guselkumab and secukinumab were well tolerated. Although the proportion of overall adverse events and serious adverse events were similar in the two groups, some safety differences were observed. A higher proportion of patients with Crohn's disease was reported with secukinumab than with guselkumab, consistent with previous study findings and the approved label. A higher proportion of patients with non-melanoma skin cancers was reported for guselkumab than with secukinumab, which was not a known safety risk for guselkumab.
Implications of all the available evidence
The ECLIPSE study provides a comparison between the most effective classes of biologics used for treating moderate-to-severe psoriasis—generating valuable data for understanding the timeline and extent of efficacy of targeting IL-23p19 versus IL-17A—as well as a comparative safety profile, for a duration of nearly 1 year. This first ever head-to-head comparison of an IL-23p19 inhibitor (guselkumab) versus an IL-17A inhibitor (secukinumab), reported superior long-term efficacy for guselkumab at week 48. These findings should assist health-care providers in their decision making process when selecting a biologic for treating moderate-to-severe psoriasis.