Monica Schwartzman, MD, on Medication Preferences Among Patients With PsA

From methotrexate to antitumor necrosis factor (TNF) inhibitors to interleukin-17 inhibitors and more, the array of therapeutic agents for the treatment of psoriatic arthritis (PsA) is greater than ever before. But what matters most to patients with PsA when considering medical therapy—symptomatic relief, low risk of adverse events, mode of administration, physician recommendation?

That’s the question Monica Schwartzman, MD, and colleagues wanted to answer when they designed and conducted a cross-sectional survey of patients with PsA.

Dr Schwartzman, a rheumatologist and internal medicine specialist with the Hospital for Special Surgery in New York-Presbyterian Weill Cornell in New York City, talked to us about the impetus for this study, what the results revealed, and how those results can be applied in clinical practice when caring for patients with PsA.

RALN:  What did you want to learn from the patients that you were surveying?

Dr. Schwartzman:   Psoriatic arthritis is an incredibly heterogeneous disease. This can make both identification and treatment extremely challenging, both on the patient and the provider side.

Over the last decade or so, our treatment armamentarium has expanded. We have a lot of different medications with different mechanisms of action that are effective in treating this disease, which allows patients to have the ability to have a choice in the medication used to treat their disease, whether it's based on the particular manifestations of their psoriatic arthritis or perhaps preferences regarding medications in their care.

When we were first starting to think about this, we noticed there was a paucity of data regarding patient medication preferences in psoriatic arthritis in the literature. We hypothesized that patient medication preferences would play a role in the management of their disease.

Our goal was to better understand what patients value with regards to their medications in psoriatic arthritis as well as evaluate different medication trends in psoriatic arthritis.

RALN:  What were the most commonly used medications you identified? What did you find patients had preferences for or against?

Dr. Schwartzman:  First, in terms of the most commonly used medications, we looked at 2 different time points. We first looked at the initial or the first medication patients use to manage their psoriatic arthritis. When I say medication, I'm talking about immunomodulatory and immunosuppressive medications.

We also looked at what they were on at the time the survey was administered, so their current medications. In terms of the first medications, we found that the most commonly used medications were antitumor necrosis factor (TNF) medication like adalimumab, etanercept, certolizumab, golimumab, and infliximab. The second most common was methotrexate, followed by apremilast.

Interestingly, we found about 10% of patients had never been on any medications for psoriatic arthritis. In terms of the medications patients were on at the time the survey was administered or their current therapies, the most common immunomodulatory or immunosuppressant medications remained the anti‑TNF alpha class.

The second most common were the anti‑interleukin (IL)‑17 class. Medications like ixekizumab and secukinumab. Methotrexate was the third most common.

We found that about a quarter of the patients were not on any immunosuppressant or immunomodulatory medications for their psoriatic arthritis at the time the survey was sent out, though most of those patients had been on medications for psoriatic arthritis previously.

RALN:  What did you conclude from that last piece of information? Were these patients in remission or had they given up on treatment? Were you able to conclude anything about why a quarter of them weren't on any kind of meds?

Dr. Schwartzman:  It's a good question. We weren't able, from our data, to find out the exact reasons patients weren't on medications. When we got our data, we did do this survey during the COVID 19 pandemic. Potentially, that might drive patients to maybe have stopped their immunosuppressant medications for psoriatic arthritis.

Among our patients overall, their disease activity was well controlled. Like you said, perhaps patients had well controlled disease and stopped medications for that reason. These are all hypotheses; we weren't able to definitively say why.

RALN:  I see. Certainly, the pandemic could have had a big effect.

Dr. Schwartzman:  Absolutely.

RALN:  Were you able to determine what patients had as their primary goals for their medical treatment? What factors did they describe as more or less important?

Dr. Schwartzman:  In terms of patients' values and preferences regarding their medication, we gave patients a whole slew of medication preferences that we had them rank on a 5‑point Likert scale from not at all important ranging to extremely important.

We found that the preferences most commonly rated extremely important focused on disease progression and pain, functional parameters, adverse event profile, and physician recommendation. We found that the preferences most commonly rated as not at all important were information from advertisements and peers.

RALN:  Your article notes that the median duration of skin symptoms among the survey respondents was 19 years. For joint pain, it was about 12 years. Clearly, you were seeing responses from people who've dealt with this disease for quite some time.

Could you determine or did you try to determine if there were significant differences in the types of medications prescribed for patients with PSA when they were first diagnosed versus today? Has there have been a trend toward or away from certain therapies?

You've already mentioned that the anti‑TNF class is pretty consistent. There have been some newer therapies that you've seen come to the fore, like the IL‑17 inhibitors.

Dr. Schwartzman:  That's a great question. We looked at medication trends in a couple of different ways. First, we looked at the initial medications used over time. We broke downtime into 5‑year blocks earlier than 2000, 2000 to 2005, 2006 to 2010, etc.

We found a couple of interesting trends. First was that methotrexate and other conventional synthetic DMARDs, which have been around for a long time— and rheumatologists have a lot of experience with these medications—were the most commonly used initial medications before the year 2000.

After 2000, novel biologics, so things like the anti‑TNF alpha medications, became the most commonly used initial therapy. Methotrexate use dramatically declined after 2015 as the initial immunosuppressant or immunomodulatory therapy in these patients.

This might reflect a perceived negative adverse effect profile from this medication, and as well as with our increasing options for medication for this disease that perhaps patients would choose other medications when they're presented with effective alternatives.

Maybe there is potentially an unmet therapeutic need that traditionally recommended first‑line agents like methotrexate don't address. We also looked at TNF-alpha medication use as initial therapy over time. As you mentioned, it was our most commonly used initial therapy.

Here, as you mentioned, with the newer classes between 2000 and 2006, anti‑TNF alpha therapy as initial therapy did start to decline. We started to see the rise of nonanti‑TNF alpha biologic medications. Things like the anti‑IL‑17 class or secukinumab and ixekizumab, as well as apremilast, starting to be used as initial therapy. The TNF-alpha medications did remain the most commonly used class through 2015.

One last piece that I think is very interesting is that we looked at the initial medication used before and after 2018, which is when guidelines were published by the American College of Rheumatology and National Psoriasis Foundation that brought in the recommendations for initial therapy to include not only methotrexate and anti‑TNF alpha medications, but also, other medications, like the anti‑IL‑17 class or small molecules, which the recommendations provide a caveat for—that these might be good options as initial therapy for those with contraindications to more traditionally used medications, patient preferences for oral medication or less frequent dosing, or perhaps, based on severity of the psoriasis.

We found that compared to earlier than 2018, after 2018 when these guidelines were published, a significantly higher percentage of patients' first medications were the anti‑IL‑17 class, compared to earlier, which was also seen with apremilast or the anti‑PDE4 class.

RALN:  What's the advantage of the IL‑17 and the PDE4 classes? What do they offer that patients have not had in previous medication therapies?

Dr. Schwartzman:  That's a great question. There's a study that came out, the SPIRIT head‑to‑head, which looked at anti‑IL 17 medication, ixekizumab. They compared it to an anti‑TNF, adalimumab. They found that they had similar efficacy.

However, the anti‑IL‑17 class had a...though it wasn't significant, there were less adverse effects compared to the adalimumab, which I think is very attractive to patients, given their rating of adverse effects as extremely important in their medication preferences.

Also, importantly, there are no boxed warnings for these medications. Whereas they are for the anti‑TNF alpha class, which speaks to their potential improved adverse effect profile.

RALN:  Do these drugs also work better in both respects, in terms of joint and skin alleviation of symptoms?

Dr. Schwartzman:   The anti‑IL‑17 class was not inferior to adalimumab in terms of their joint disease, and was found to be superior for skin disease. There are some advantages for this class, compared to the TNF-alpha medications and certain populations of patients.

RALN:  From this study and from others that have been done before yours, what do you think patients are looking for and would most want to see in any new therapeutic agents that may be coming along?

Dr. Schwartzman:  Based on the patients' readings of prevention or progression of disease, efficacy of medications remains paramount, which I don't think is a surprising attribute in a medication for patients to value. In terms of other important aspects of medications, adverse effect profile is something that is certainly significant.

This includes infection risk, which as we've touched on a little earlier in the current COVID pandemic, is something that is going to continue to be important to our patients.

RALN:  Is mechanism of administration an issue with these patients?

Dr. Schwartzman:  There's some data that showed that mode of administration, so whether they're pills, subcutaneous injections versus intravenous infusions, was significantly important to patients. Those data were sponsored by a pharmaceutical company. There is a little bit of a risk of bias in terms of mode of administration.

We were very interested to see if that data bore out with our patient population. We found that the patients were pretty evenly split across their ratings of mode of administration. I don't think it was something that we can say, from our data, factors into a patient's preferences. We can all imagine, from our clinical experience, that it does certainly come up.

RALN:  What's next for you, in terms of further research into these issues?

Dr. Schwartzman:  Next steps that we would be interested to see, we've looked at medication practices and patterns, as well as patient preferences. It would be important for us to look at the physician side to see what the physician preferences are in terms of choosing medications for our patients, prescribing medications, and prescribing medications for our patients.

It's important to ensure that both physicians and patients are both aligned in terms of therapy in order to ensure our patients have the most effective care.

RALN:   Thank you so much for joining us today. We look forward to speaking to you again in the future after you have conducted some additional research in this area.

Dr. Schwartzman:  Thanks so much. It was a pleasure being here.

Reference:

Schwartzman M, Abutalib Z, Mandl LA. Current medication practices and preferences among patients with psoriatic arthritis. J Clin Rheumatol. 2022;28(2):55-61.

DOI: 10.1097/RHU.0000000000001799