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Guselkumab (Tremfya), an anti-interleukin (IL)-23 monoclonal antibody recently approved for the treatment of psoriatic arthritis (PsA), was shown to be superior versus placebo. However, there has never been a direct comparison of guselkumab to ustekinumab (Stelara), a monoclonal antibody targeting IL-12 and IL-23. While previous indirect comparisons only allowed for analyses up to week 24, a study presented at the American College of Rheumatology (ACR) virtual meeting used pooled trial data to up to week 52.

In this video courtesy of , , a consultant rheumatologist for St. James's Hospital in Dublin, describes the results and implications of the study.

Following is a transcript of his remarks:

This study took individual patients' data from the randomized controlled trials of these two agents, named DISCOVER 1 & 2 studies and the PSUMMIT trials. It was an indirect comparison and compared guselkumab every 4 weeks or every 8 weeks to ustekinumab 45 mg or 90 mg. There were 1,367 patients included in this study, and their main outcomes were ACR20 for joints and PASI [psoriasis area and severity index] 90 for the skin. So they found that guselkumab was better than ustekinumab, with an odds ratio of 1.9 for achieving ACR20, and an odds ratio between 2.6 and 3.2 for achieving a PASI 90.

So the results of this are not particularly surprising to me. I think we kind of knew that ustekinumab was probably not as good a drug as a lot of our other biologic agents in psoriatic arthritis, whereas guselkumab certainly is. And so I think the implications of this trial in and of itself are not surprising, perhaps not overly exciting. What I think is really important about this study is that somebody's done a head-to-head comparison -- an indirect one, at least, between these two drugs. And I think that's something we really need a lot more of in all of our diseases, but particularly in psoriatic arthritis.

We have this plethora of agents available to us now, all of which are very similar in efficacies when they've been compared to placebo in randomized controlled trials, but we don't really know which one to use in individual patients sitting in front of us. And we'd like to slice and dice the database and say, oh, they have this particular clinical feature, maybe this one is better. But these are really minimal differences that we're kind of extrapolating from the clinical trials.

And I really do think we need to have more head-to-head comparisons, whether they are done by pharmaceutical companies themselves, or whether this certainly is the sort of subject that would be very suitable to an investigator-initiated pragmatic trial, looking at very specific outcomes. And I think we do need more of that to better inform our decision making around these biologic drugs.

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