December 18, 2018

Guselkumab is an IL-23 inhibitor; secukinumab is an IL-17A inhibitor

Guselkumab (Tremfya; Janssen), an interleukin (IL)-23 inhibitor, was found to be superior to secukinumab (Cosentyx; Novartis), an IL-17A inhibitor, in achieving Psoriasis Area Severity Index [PASI]) 90 responses in patients with moderate to severe plaque psoriasis, according to data from a Phase 3 head-to-head trial.

In the ECLIPSE study (N=1048), patients were randomized to receive guselkumab 100mg at weeks 0, 4, and 12 followed by every 8-week dosing or secukinumab 300mg at weeks 0, 1, 2 3, 4 followed by every 4-week dosing. The primary endpoint was the proportion of patients achieving a PASI 90 response at week 48.

Results showed that at 84.5% of patients treated with guselkumab achieved at least 90% improvement in their baseline PASI score vs 70% of patients treated with secukinumab (P <.001) at week 48. In addition, guselkumab was found to be noninferior to secukinumab in achieving PASI 75 response at weeks 12 and 48 (84.6% vs 80.2%; P <.001) but was not superior (P =.062). 

Other secondary endpoints included PASI 100 response and Investigator’s Global Assessment (IGA) scores of 0 and 1. At week 48, a greater proportion of guselkumab-treated patients achieved PASI 100 vs secukinumab-treated patients (58.2% vs 48.4%).  Also, 62.2% of patients receiving guselkumab achieved IGA score of 0 vs 50.4% of patients who received secukinumab; 85.0% and 74.9% of patients in the guselkumab and secukinumab  groups achieved IGA score of 1, respectively (all comparisons with nominal P ≤.001). Regarding tolerability, treatment discontinuation was seen in 5.1% of guselkumab patients and 9.3% of secukinumab patients. 

“The response-over-time curves show that maximum response rates with Tremfya are achieved after 6 months and are maintained over time through 1 year, achieving superiority at the primary endpoint of the study,” said lead study investigator Richard Langley, MD, FRCPC, Professor, Division of Clinical Dermatology & Cutaneous Science, Department of Medicine, Dalhousie University. “Results of the study confirm a slightly more rapid onset of response with Cosentyx, but importantly, in a chronic disease like psoriasis, these data provide new insights into comparative longer-term efficacy.”

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