Guselkumab exhibits comparable efficacy to IL-17A, TNF inhibitors for psoriatic arthritis
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Guselkumab is comparable to interleukin-17A and subcutaneous TNF inhibitors for efficacy, and demonstrated a better PASI response relative to other drugs, in patients with psoriatic arthritis, according to a meta-analysis published in Rheumatology.
“Guselkumab is a monoclonal antibody currently approved for the treatment of psoriasis and also for psoriatic arthritis in some regions,” Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, in Seattle, and colleagues wrote. “Guselkumab offers a novel mechanism of action. It binds selectively to the p19 subunit of IL-23 with high specificity and affinity. The efficacy and safety of guselkumab 100mg every 8weeks (Q8W) and 100mg every 4weeks (Q4W) was demonstrated in the placebo-controlled DISCOVER-1 and DISCOVER-2 phase 3 trials, the first to evaluate the efficacy of a selective IL-23p19 inhibitor in PsA.”
“Although there are previous studies comparing IL-23 inhibitors in similar disease areas, such as the ECLIPSE trial evaluating guselkumab in psoriasis, few head-to-head studies comparing biologic and targeted interventions have been conducted in PsA,” they added. “Therefore, indirect comparisons are needed to inform the comparative efficacy and safety of guselkumab vs other targeted therapies.”
To compare the safety and efficacy of guselkumab (Tremfya, Janssen) to targeted therapies for PsA, Mease and colleagues conducted a network meta-analysis. The researchers performed a systematic literature review in January 2020 for randomized clinical studies, ultimately identifying and including 26 phase 3 trials in their quantitative analysis.
The trials enrolled adults with PsA and assessed a range of 13 targeted therapies, including the IL-17A inhibitors ixekizumab (Taltz, Eli Lilly & Co.) and secukinumab (Consentyx, Novartis); the IL-12/23 inhibitor ustekinumab (Stelara, Janssen); TNF inhibitors adalimumab (Humira, AbbVie), certolizumab pegol (Cimzia, UCB), etanercept (Enbrel, Amgen), golimumab (Simponi, Janssen) and infliximab (Remicade, Janssen); guselkumab; abatacept (Orencia, Bristol Myers Squibb); the small-molecule drugs apremilast (Otezla, Amgen) and tofacitinib (Xeljanz, Pfizer); and placebo.
Mease and colleagues used a Bayesian framework in their network meta-analyses to compare treatments in terms of American College of Rheumatology (ACR20/50/70) response, mean change from baseline van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI 75/90/100) response, adverse events and serious adverse events.
According to the researchers, guselkumab 100mg every 8weeks was comparable to IL-17A inhibitors and subcutaneous TNF inhibitors in terms of ACR20 response, with similar findings were for ACR50 and ACR70 responses. Regarding vdH-S score, guselkumab 100 mg every 8 weeks was comparable to other agents save for intravenous TNF inhibitors. Meanwhile, PASI 75 and 90 response data demonstrated that guselkumab every 8 weeks was superior to most other drugs, and comparable to other active agents for PASI 100.
Regarding safety, guselkumab 100 mg every 8 weeks ranked high in adverse and serious adverse events. However, comparative conclusions were uncertain, the researchers wrote. Researchers reported similar results for all outcomes regarding guselkumab 100mg every 4 weeks.
“Analyses suggest that guselkumab has joint efficacy (i.e., ACR and vdH-S score) comparable to IL-17A and subcutneous TNF inhibitors while offering particularly robust efficacy on skin manifestations through the placebo-controlled trial period,” Mease and colleagues wrote. “Guselkumab ranked highly in analyses of [adverse events] and [serious adverse events], but rarity of events led to significant uncertainty in pairwise comparisons. Overall, guselkumab offers favorable outcomes for patients with PsA by improving both rheumatological and dermatological outcomes coupled with a favorable safety profile.”
Perspective
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There has been a rapidly evolving landscape for the treatment of psoriatic arthritis over the past decade and rheumatologists have a broad number of treatment options from which to choose. Guselkumab is an IL-23 inhibitor that has been recently approved by the FDA for moderate to severe PsA based on two recent clinical trials, DISCOVER-1 and DISCOVER-2, and was previously approved for treatment of psoriasis.
Despite the growing number of treatment options in this space, there remains a lack of head-to-head data available. Therefore, this study done by Mease and colleagues was designed with the objective of comparing guselkumab given every 4 and 8 weeks to 13 existing PsA therapies through a network meta-analysis in the context of a systematic review.
It is interesting to see a network meta-analysis employed to compare multiple treatment options for PsA. This type of analysis allows for comparing multiple randomized control trials in a single analysis, as opposed to a conventional meta-analysis which is limited to comparing two interventions at a time.
The results of this multiple treatment comparison meta-analysis suggest guselkumab has comparable effectiveness to other targeted therapies currently available for PsA and appears to be superior for psoriasis. Given that guselkumab is the first approved specific IL-23 inhibitor, this study provides us with some useful information about this medication’s effectiveness for arthritis symptoms, skin disease and safety in context to currently available treatment options. It may also be a more favorable option for our PsA patients that have a significantly more considerable burden of psoriasis.
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