Results from the ECLIPSE trial: does blocking IL-23 have better long-term outcomes in psoriasis?

Guselkumab demonstrated superior long-term responses compared with secukinumab in the treatment of moderate-to-severe plaque psoriasis in the first head-to-head trial (the ECLIPSE study) comparing an IL-23 inhibitor (guselkumab) to an IL-17 inhibitor (secukinumab); but there may be limitations to these data and more research is needed.

Prof. Kristian Reich (Georg-August-University Göttingen, Germany) reminded us that there are two main novel classes of drugs in psoriasis, the IL-17 and IL-23 inhibitors, and it will be interesting to discover what their similarities and differences might be in clinical outcomes [1]. The role that the cytokines play in the pathological cascade of psoriasis is very different; for example, while anti-IL-23 drugs can allow you to go to longer injection intervals, you have a very rapid onset of response if you block IL-17. What is also remarkable about this trial is that they use an unusual primary endpoint: the proportion of patients achieving a PASI-90 score at week 48. The reasoning behind this choice, Prof. Reich explained, was to get an idea about long-term disease control, which after all is more important to many patients than the response at 4 weeks.

The objective of the double-blind ECLIPSE study was to compare the efficacy and safety of guselkumab with secukinumab over 1 year of treatment for moderate-to-severe psoriasis, given that psoriasis is a chronic disease requiring long-term treatment. Patients were randomised to guselkumab 100 mg administered subcutaneously at weeks 0, 4, and 12; then every 8 weeks thereafter through week 44 (n=534); or secukinumab 300 mg subcutaneously at weeks 0, 1, 2, 3, and 4, and then every 4 weeks thereafter through week 44 (n=514). Primary and secondary endpoints were prespecified to be tested in a fixed sequence to control the overall Type 1 error rate. Patients were considered non-responders after discontinuing treatment for lack of efficacy, an adverse event, psoriasis worsening, use of a prohibited psoriasis treatment, if zero improvement was assigned, or if they had missing data.

The proportion of patients achieving PASI-90 response at all 7 visits from week 24-48 was 71.0% vs 61.5% in favour of guselkumab. Regarding safety, a higher Candida infection rate was observed in the IL-17 inhibition cohort -all easily treatable with standard oral therapy- which was to be expected from clinical experience. And whereas there were 3 cases of inflammatory bowel disease in the secukinumab group, there were also several reported de novo melanomas in the guselkumab, but the numbers are still too low to really draw any conclusions. Overall, both drugs had good safety profiles in this study. The take-home message was that we need more head-to-head trials like this one to see where these drugs are similar, and where there may be distinct advantages of choosing one drug over another.

Table: Expert clinical opinion of Prof. Reich – A profile of targeted therapies in psoriasisTNF, tumour necrosis factor; UST, ustekinumab; PPP, palmoplantar pustulosis; PsA, psoriatic arthritis.

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   1. Reich K, et al. P004, SPIN 2019, 25-27 April, Paris, France.

Posted on 21 June, 201924 March, 2021