Overdrive Podcast: Guselkumab Efficacy for Psoriatic Arthritis

In today’s episode, we sat down with Dr. Philip J. Mease to discuss his study, “Comparative effectiveness of guselkumab in psoriatic arthritis: results from systematic literature review and network meta-analysis.” Dr. Mease is the Director of Rheumatology Research at the Swedish Medical Center/Providence St. Joseph Health. We discuss a general overview of the current treatment landscape for psoriatic arthritis, challenges faced by rheumatologists when identifying appropriate treatment options, the importance of discovering that guselkumab has comparable efficacy with other treatments, and further research that Mease and his team plan on tackling next.

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Rheumatology Network: Hi, Dr. Mease, thank you for joining me today.

Philip Mease, MD: Yes, I'm happy to be here, Lana.

RN: Can you begin by giving me a general overview of the current treatment landscape for psoriatic arthritis?

PM: Yes. Fortunately, we have a number of different medications that have proven to be quite efficacious for treating all of the various clinical domains of psoriatic arthritis. Not only the arthritis component of it, but also skin disease, nail disease, spine disease, the phenomenon we called enthesitis, which is inflammation where tendons or ligaments insert into bone. And so, starting with the old drug, methotrexate, which we still very commonly use, and then now with the biologic and targeted synthetic DMARDs, such as the TNF inhibitors, the IL-17 inhibitors, the IL-12/23 inhibitor, and the drugs apremilast and abatacept and tofacitinib, which are oral jak inhibitors. This is a very good time, as I tell patients, to have the condition if only because we can really actually conceive of getting to remission or low disease activity state. And even when patients lose effect with 1 drug, we can switch to another and continue to achieve such an effect.

RN: Have you noticed any trends in treating psoriatic arthritis?

PM: Yes, what I've what I've noticed is that over time, some of the newer medications are slightly more targeted. They're more precisely hitting a specific cytokine for example, or place in the inflammatory cascade. And part of what's come with that is a slightly better safety profile with some of the newer medications. All of the medications do a modulation, if you will, of immune system overactivity, which leads to inflammation in all the various tissue domains.

RN: What are some of the challenges that rheumatologists face when trying to identify the most appropriate treatment option for their patients?

PM: Well, 1 thing is being aware and being educated about the different drugs and their mechanisms and their effectiveness and safety profile, and then being able to communicate that appropriately to patients so there can be shared decision making between the clinician as the patient in making an appropriate choice.

RN: Why is discovering that guselkumab demonstrated efficacy that was comparable to other treatment options, such as subcutaneous TNF inhibitors so important?

PM: Anytime that a new medication enters the market, it's important to know is it effective. How many of the clinical domains if not all, is the drug effective in and what is the overall safety profile because we don't want to be using medications that aren't effective or have a problematic safety profile. And so anytime we have a new entrant, it's important to scrutinize the relative efficacy and safety of the medication. And it's just part of the issue is that even though we have some very effective medications, such as the TNF inhibitors or the IL-17 ammeters, what often happens is that over time, the patient may lose benefit from 1 of these medications for a variety of reasons. And so, it's important to have medications that that we can switch to, from ones that the patient is already using. But also, if a new entrant has a favorable safety profile, to potentially use it earlier in the treatment cascade to take benefit from that safety profile.

RN: Were there any limitations or strengths of the study that you would like to elaborate on?

PM: So, this study was what we call a network meta-analysis. And increasingly, as more and more drugs become available to us, we want to know how does this drug stack up against a medication we're already using? How does it compare? The best way to determine that is to conduct a what we call a head-to-head trial, where we have 1 arm of the study of with patients receiving 1 drug and then versus another arm with the other drug, and then comparing a relatively comparable patient population in this regard. But head-to-head studies are very expensive. It requires lots of patients to do the study. And we don't always have the luxury of having a head-to-head trial in psoriatic arthritis. There really only have been 3 head-to-head trials thus far. One between methotrexate and etanercept, and then 1 between ixekizumab and adalimumab, and then 1 between secukinumab and adalimumab, and that's it. There have been more trials that are head-to-head in psoriasis, or rheumatoid arthritis. So, what do we do as clinicians to be able to compare medications? Or for that matter a for example, a payer body like an insurance company to help determine is this drug worth it. So, increasingly, we've seen these sophisticated network meta-analyses, where you do a statistical modeling method, wherein you use the placebo group as a reference arm, and then do pairwise comparisons between the placebo arm and then the treatment arm and then compare the comparable populations. For example, at a study with an IL-17 inhibitor or TNF inhibitor versus the new entrants, in this case guselkumab which is known as a P-19, interleukin 23 inhibitor. And so that's what this study was about. It has the natural limitation that it's not a head-to-head study. It's an indirect comparison. But nonetheless, its strength was that it compared all of the various clinical trials conducted in phase 3 for psoriatic arthritis treatments. That's all of the TNF inhibitors, all of the IL-17 inhibitors, looking at all the different dosing regimens, and so is very comprehensive in that regard.

RN: Does your team plan on doing any further research on guselkumab for psoriatic arthritis?

PM: Yes, there will be more studies with this medication coming along, including a study that is in planning stages for studying the ability of the drug to treat axial psoriatic arthritis or the spine aspects of the disease. It's been very rare to actually conduct such specific studies for clinical domains. So that's 1 important area, and I suspect that there will be others that we will see in the future, including possibly a head-to-head trial. I think that though it was very reassuring to see the results of this study, where guselkumab performed very well from the point of view of musculoskeletal benefit. It was quite effective in the skin benefits, and also showed very good safety profile, comparatively.

RN: Is there anything else that you'd like our audience to know about your research or psoriatic arthritis before we wrap up?

PM: Just to celebrate, if you will, the fact that psoriatic arthritis has really come into its own. It used to be researched in the shadow of rheumatoid arthritis. But now I think as people are appreciating how frequently it occurs in the overall population, the complexity of the disease in terms of the clinical domains that it represents, and we increasingly use, translating what we know in science, about the mechanisms of the disease to having effective treatments. It's a very good time for us to be able to treat patients with this debilitating disease.

RN: I agree. Dr. Mease, thank you so much for joining me today. I really appreciate it.

PM: Thank you for having me. Thanks, Lana.