Alexis Ogdie, MD, on Treatment Burdens of Methotrexate and TNFis in PsA and RA

In this podcast, Dr Ogdie discusses research her team conducted into the treatment burden associated with methotrexate and antitumor necrosis factor inhibitors in both psoriatic arthritis and rheumatoid arthritis, including differences in perspectives among the 2 patient populations.

Alexis Ogdie, MD, is an associate professor of medicine and epidemiology, director of the Center for Epidemiology and Biostatistics, and director of the Penn Psoriatic Arthritis and Spondyloarthritis Program at the Hospital of the University of Pennsylvania in Philadelphia.

TRANSCRIPT:

RALN: Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, RALN. I'm delighted to be joined today by Dr. Alexis Ogdie, associate professor of medicine and of epidemiology at the Hospital of the University of Pennsylvania in Philadelphia. She's also director of their Center for Clinical Epidemiology and Biostatistics and director of the Penn Psoriatic Arthritis and Spondyloarthritis Program. Gee, do you need something further to do?

Dr. Alexis Ogdie:

Please, no, not at the moment at least.

RALN:

Well, it's great to have you back, and we appreciate you taking the time out of all of the many things that you're doing to talk to us about some new research you were involved in about the perspectives of the treatment burden of different types of therapies for psoriatic arthritis, and also rheumatoid arthritis, specifically methotrexate and antitumor necrosis factors or TNF inhibitors. To start off, what sparked your interest in this topic?

Dr. Alexis Ogdie:

Well, I think, first of all, this actually started a while ago. We have 2 paired papers, both in ACR Open Rheumatology, recently on this topic. The original question was, back a few years ago when we were doing the ACR treatment guidelines, we did a patient panel about methotrexate and other therapies to get a sense of what patients thought about individual therapies. And the thing that they kept saying was, "Methotrexate is so uncomfortable. I don't seem to get that much benefit from it, and I feel nauseous, I have fatigue. I have to plan, for my couple days after I take it, to be down for a little bit." And, of course, not everyone feels that way, but some patients were saying this, and we hear this quite a bit in clinic, so we were wondering how often do we really hear that?

And we think about methotrexate being, really, a cornerstone therapy in rheumatoid arthritis. Is it really different in PsA? Because we don't hear our RA patients complain about it as much, or at least that was the perception. The idea for this research was, first, to understand how frequent are the side effects to methotrexate in patients with rheumatoid arthritis versus psoriatic arthritis, and we had to compare that to another therapy, so we chose TNF inhibitors as being the other most common therapy used in those groups. And then we also then said, "All right, what are the different treatment burdens that people experience among people using methotrexate or TNF inhibitors?" Actually, patients had to experience both in order to give us some feedback on those. And then we broke those down into themes and looked at whether or not they were different between psoriatic arthritis patients and rheumatoid arthritis patients.

RALN:

Can you give us an overview of the study? How many patients were you looking at and just what were the parameters?

Dr. Alexis Ogdie:

Yeah. In the first study, which was a study of the side effects of methotrexate and TNF inhibitors in rheumatoid arthritis versus psoriatic arthritis, we had patients in the FORWARD data bank, which was previously known as the National Data Bank for Rheumatic Diseases, and patients that we utilized for that study were there around the time TNF inhibitors were available, so in the 2000s up to 2019, when we cut that dataset. And there were 116 patients with psoriatic arthritis and 4247 with RA who had newly initiated methotrexate, and then 124 with PsA and 4361 with RA, the newly initiated TNF inhibitor. And then we looked at the proportion who had side effects to one of those therapies over the course of the next one year after starting a therapy. That was in the first study. In the second study, it was just 25 from each group that we did a qualitative interview with.

RALN:

The difference in those numbers, is that attributable to the fact that RA is just simply much more common in the population than psoriatic arthritis?

Dr. Alexis Ogdie:

Well, it's 2 things. One is RA is more common than psoriatic arthritis, but also the National Data Bank for Rheumatic Diseases, when it was built, was an RA registry, and so it's just much more longstanding RA in that particular disease. And we formally stood up the Psoriatic Arthritis and SpA Registry in 2018, but there were patients in there following along with the RA questionnaires prior to that. It's just that it didn't really get its own name until then.

RALN:

What did you find out from these patient interviews about how they assess the burden of methotrexate versus anti-TNFs?

Dr. Alexis Ogdie:

First, from just looking at the data among that large group of patients, we found that methotrexate-related side effects were reported by 44.8% of patients with psoriatic arthritis versus 29.4% with RA. There was a difference there. And, for TNFs, it was very similar. It was 24% and 23%, so not much different for TNF inhibitors. It did seem like patients with psoriatic arthritis were reporting more side effects with methotrexate, and that was actually, when we adjusted for other things, that was still there, although the statistical significance went away when you added obesity. That is explanatory in that more patients with psoriatic arthritis are obese, and it is possible that patients with obesity are having more side effects from methotrexate. We do know that they can have more liver function test abnormalities from it, but they reported more symptom side effects as well.

Then, when we did the qualitative study and we talked to patients about their experiences, then we first just got, "What are, overall, some of the things you've experienced with a variety of different therapies that you've been on?" And they talked about a variety of different things, including the challenges with planning work and daily life around treatment burden. Planning for the days after methotrexate was a really common theme, so you take your methotrexate on a Friday night so you don't have to worry about working through the weekend when you don't feel good, or some people said, "I really want the weekend," and so they would take it on Tuesday so they would be able to have a full weekend.

They also talked about, if you had to drive to go get an infusion, that really disrupts things. There's essentially a cost to that in terms of work participation. Challenges with accessing and administering therapies, that was more specific to the biologics, as were financial or economic impact. And then the family planning and breastfeeding considerations with methotrexate, and then also just more side effect burdens, again, like the symptoms and the fatigue and so on, those came up as themes with methotrexate.

RALN:

Your article mentions that treatment discontinuation was high among patients with PsA due to lack of effectiveness. Was that consistent between these two types of therapies or was it more pronounced, for instance, for methotrexate than for the anti-TNF therapies?

Dr. Alexis Ogdie:

In the quantitative study, we couldn't really examine effectiveness appropriately because we don't have joint counts in that particular data set. Discontinuation was more often reported by PsA patients, particularly with methotrexate, and they noted lack of efficacy, especially in the qualitative study. We didn't have great data around that. The difference between the 2, which is in the qualitative study, they were saying, "It didn't work as well for me," and that's what we had heard in that original focus group with patients when we were considering the treatment guidelines as well. But I think, if you're going to tolerate treatment burden, that has to be countered by something, and I think the efficacy probably is better in rheumatoid arthritis, which is one of the reasons it's been used as a therapy for so long in RA, and so you can tolerate the treatment burden if the efficacy is worth it. In psoriatic arthritis, I'm not sure that that balance is true and the patients were essentially saying to us, "It wasn't worth it to me, that minimal efficacy or what I did get from it."

RALN:

Have you found any indicators as to why that is the case? Why doesn't methotrexate work as well in PsA as in RA?

Dr. Alexis Ogdie:

Well, it hasn't been studied in a rigorous manner, so we've been basically studying it from these retrospective studies. If you had a prospective study where you're enrolling people and really measuring things at the same time point, and, actually, I think some of the Danish and Norwegian studies could get at this and do the comparisons, they've done those comparisons, but really for the adverse effects, in particular, liver disease. And I think that they are different diseases, and so you might not be as effectively treating the synovial inflammation in PsA as you could be in RA. Additionally, in psoriatic arthritis, you add this burden of the skin. And so sometimes, actually, the skin is more easily treated with the methotrexate than the joints sometimes, but sometimes not always, you get more of the skin disease, and I think the patient wants both to be improved, which is understandable.

RALN:

You mentioned earlier the issues of cost and access and having to go in for infusions and things like that that could be factors in discontinuing treatment. Were some of those problems related to patients’ inability to get either of these medications covered by their insurance?

Dr. Alexis Ogdie:

Yeah. Methotrexate is easy to get, so that's very cheap and, in fact, you can really get it without insurance because it's a very inexpensive medication if you're getting just the oral tablets. Even the injectable methotrexate that's not the one that they've branded, you can get a vial of methotrexate for really cheap. But, yes, they brought up the squabbles with the insurance company, the going back and forth and needing a new prior authorization, the calling for the copay card, the copay card ran out, "I got to get a new copay card, then I got a charge for a thing." It's complicated.

Biologics are very difficult for patients to deal with, and I think as time has gone on, I think it's gotten harder, not easier, and so we do see that sometimes. I saw a patient the other day who discontinued their biologic because they're like, "I can't deal with it anymore. I just don't want to deal with those people on the phone all the time," and it's so frustrating and anxiety-provoking. I think that really is a burden that we don't think about as much. We think about it as par for the course, but, to a patient, that's really impactful.

RALN:

Based on what I've heard from other physicians in all of the autoimmune domains, it's a burden on the physician and the office staff as well.

Dr. Alexis Ogdie:

Absolutely, yes, it is, for sure. And we have a specialty pharmacist, so we're very lucky. But, even, then you're like put in the prescription again, put in the prescription again, put it in the prescription again. You're constantly sending it a different place. You send it to the wrong place, a new pharmacy now. Yeah, it's a constant battle, and writing letters and doing peer-to-peers, and I think this is all getting so much more complicated than it was before.

RALN:

Have you had any difficulty with your patients being able to access methotrexate since the Dobbs decision?

Dr. Alexis Ogdie:

Actually, there was an 8th grader who did an interview with me the other day because she was studying this in Texas. In Pennsylvania, we really haven't had much of a problem with that, or New Jersey or even Delaware, so, fortunately, no, but I think that is a big question. And she was interested in this topic because people are losing access to medicine, and I'm very worried about that because methotrexate is a good drug and it's cheap. If you don't have access to those higher-level therapies that are expensive, then you're really discriminating against people who already have health care disparities and already things stacked up against them. It's a big problem that I hope we will get past.

RALN:

Granted that this was a small sample from a much larger study, did you find that it provided you some information that you think can be applied now to the clinical care of patients with these diseases?

Dr. Alexis Ogdie:

I do. One of the things we also try to point out in the paper is that we think of adverse events as we're talking about a new therapy that's coming out, but what we don't think about is counseling about treatment burden, and so really trying to bring to light that these are 2 different things. In trials, we only measure adverse events and using an ontology that comes from oncology. These have been built up from other disease areas. And it makes sense, it's important to measure, but what is probably equally important to measure is the impact on quality of life, the impact on daily functioning, how people are managing the medicines, how that impacts decisions they're making in their day-to-day life. I think those are things that we need to be thinking about building into trials, especially pragmatic trials moving forward, but we also need to think about these things when we counsel the patients.

I think this has made me much more aware of counseling about these. Then, when I'm talking about the medicine, the first thing I'm doing is going through and talking about side effects, traditional side effects, or adverse events that could happen. Once we land on a side effect profile that seems reasonable to the patient or a therapy that they they're going to choose to go with, then I talk about the treatment burden, "Okay, you're going to have to deal with the insurance company. This is how things are going to go."

We made a handout about what the process looks like and that there are many unknowns in this process. "It's going to be frustrating at times. Make sure you plan ahead. Let us know as soon as you hear something." We're trying to counsel about those things. With the methotrexate, it's knowing that sometimes taking it at night is better than taking it in the morning, and helping people think through how they might manage the nausea, for example. While that's more of a traditional side effect, the timing and all those kinds of things are helpful to talk through with patients too.

RALN:

How would you advise practicing clinicians to proceed in light of what you've found out here? Clearly, you've covered some of this already in talking about counseling the patient beyond just adverse effects, talking about treatment burden. Is there anything else that you would suggest?

Dr. Alexis Ogdie:

I think that is what I would suggest, thinking about that there's adverse events and there's treatment burden, being open to hearing about those things from the patient, about the treatment burden, and helping them think about ways to reduce those barriers or make it better. In that paper, we have this figure that talks about what are the different themes that are associated with treatment burden. And I think that's kind of a helpful figure in terms of thinking about what is treatment burden, and it's just a framework that you can use to think through how might this medicine affect this patient.

RALN:

Is this going to lead to additional studies with your group?

Dr. Alexis Ogdie:

I hope so. One of the things that we've been thinking about is how do we build this into medication trials or studies? We haven't done that yet, but I think that's something to think about for some of the next steps.

RALN:

Okay. Well, this is really interesting and I look forward to getting back to you on this at a later date, and thanks very much for your time today.

Dr. Alexis Ogdie:

Thank you so much. So nice to talk to you.