Guselkumab efficacious in biologic-naïve patients with PsA, those unresponsive to TNFi
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Key takeaways:
- Guselkumab produced consistent effects among biologic-naïve patients with PsA and those responded inadequately to TNF inhibitors.
- Trials are now evaluating guselkumab in patients new to TNF inhibitors.
Guselkumab demonstrates consistent pharmacological effects across both patients naïve to biologics and those with an inadequate response to TNF inhibitors, according data published in Arthritis & Rheumatology.
“Patients with PsA who have had an inadequate response, defined herein as lack of efficacy, to [TNF inhibitors (TNFi)] represent a difficult-to-treat population,” Stefan Siebert, PhD, of the University of Glasgow, and colleagues wrote. “A better understanding of the immunologic characteristics of patients with PsA who are biologic-naïve or [had an inadequate response to TNF inhibitors (TNFi-IR)], and the differences between these patient types, may help optimize treatment strategies.”
To compare clinical responses to guselkumab (Tremfya, Janssen) among these two populations in PsA, Siebert and colleagues analyzed data from the phase 3 DISCOVER-1 and DISCOVER-2 trials, as well as the phase 3b COSMOS trial. Across the pooled cohort, participants who were biologic-naïve and those with inadequate response to TNF inhibitors were assigned to the following treatments:
- guselkumab 100 mg once every 4 weeks (84 biologic-naïve, 6 TNFi-IR);
- guselkumab 100 mg once every 8 weeks (84 biologic-naïve, 63 TNFi-IR); and
- placebo (83 biologic-naïve, 24 TNFi-IR).
Serum samples were collected from participants at baseline, week 4 and week 24, as well as from 43 healthy, matched volunteers. Clinical responses — measured via Psoriasis Area and Severity Index (PASI), Investigator’s Global Assessment of psoriasis (IGA) and ACR20 — were compared between biologic-naïve and those with inadequate response to TNF inhibitors.
According to the researchers, guselkumab once every 8 weeks demonstrated “early and sustained pharmacodynamic effects” in both subgroups. At week 24, patients in both groups treated with guselkumab saw significantly reduced levels of interleukin-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6 and BD-2 (greater than 1.4-fold difference, nominal P < .05), they added.
Compared with participants who did not respond to guselkumab, those who responded demonstrated significantly higher levels of the following biomarkers at baseline:
- IL-17A, IL-17F and BD-2 in biologic-naïve PASI90 responders;
- IL-22 and BD-2 in TNFi-IR PASI90 responders; and
- IL-17A and BD-2 in TNFi-IR IGA 0/1 responders.
Those elevated levels, as well as their associations with skin responses to guselkumab, “suggest greater dysregulation of IL-23/Th17 signaling” among patients who did not respond to TNFi, the researchers wrote.
“Overall, guselkumab treatment exhibited generally comparable and significant pharmacodynamic effects on IL-23/Th17-associated cytokines across participants with PsA who are biologic-naïve or have TNFi-IR,” Siebert and colleagues wrote.
“In both subgroups, levels of these cytokines at week 24 with guselkumab treatment reached or trended toward levels observed in healthy controls,” they added. “The associations between elevated baseline levels of IL-22, IL-17A, and BD-2 with achievement of robust skin response at Week 24 in TNFi-IR participants suggest IL-23p19-subunit inhibition with guselkumab may play an important role in modulating aberrant IL-23/Th17 cell–mediated signaling in this difficult-to-treat population. Further clinical evaluation of guselkumab efficacy in TNFi-experienced patients is ongoing.”
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