Case-Based Approach for the Management of Rheumatic Diseases - Episode 15

Monotherapy vs Combination Regimens to Treat PsA

Transcript: Grace C. Wright, MD, PhD: As I mentioned, we have studies for some of these drugs as monotherapy, meaning you need only the biologic; you don’t need the background agent. In some patients, the combination is more effective. Even though the data say it should work as monotherapy, the combination may be better for that individual. That’s something you have to figure out. No data set is going to tell you if that person can do without that. When we look at apremilast, tofacitinib, and currently approved others in clinical trials in development for this, and the JAK inhibitor class, we also see agents that can be used as monotherapy. I always say, if she won’t or can’t take background agents, then find a drug that’s going to work well by itself. For data in rheumatoid arthritis, we talk about this a lot, but in psoriatic arthritis it becomes critical, especially since we tend to be dealing with a slightly younger population. We have young women who may be thinking of continuing or starting families, and many of those are agents we have to think through very carefully. But the data are there to help guide us, to say that I can use etanercept, secukinumab, or ixekizumab. I can use these agents without any background methotrexate and have a very good response.

I always say, never double biologic. Why? Because the data say that when you do, the likelihood of increased adverse events is enhanced, the most common thing being higher infections with very little in the way of increased efficacy. We just don’t have a cocktail combination that’s going to work and be safe and effective. When we talk about combination therapy, we’re often talking about an oral agent, a conventional synthetic DMARD [disease-modifying antirheumatic drug], combined with a biologic—not combining 2 biologics together, even if their MOA [mechanism of action] is different.

There are some interesting molecules being investigated that might have 2 different MOAs on the same molecule. That’s a different story because you’re going to study safety and efficacy of that combined bimodal pathway. But for me, to take drug 1 and drug 2 together, and they’re both biologics, I’m probably going to run into trouble with more adverse events and serious infections.

There are times when we have to combine agents, simply because they work better, and the most common background agent would be methotrexate, whether that’s a subcutaneous methotrexate injection, or oral methotrexate tablets. There are data that say, in some patients, the more recalcitrant the patient and the more advanced their disease, the heavier the weight of burden of the disease they have, they may need combination therapy. I always say, “What’s the goal?” The goal is to get you well. The goal is to have you functioning. The goal is to have you get up in the morning, and go, and not have to think, “Oh my gosh, I need 45 minutes just to move my hip.” That’s not the goal. Sometimes that goal has to be met by adding on additional therapies. Sometimes to do that we have to have background methotrexate. Not all the time, but sometimes for sure.

This is another big controversy in rheumatology. They say if 1 mechanism of action is not working, switch to another. Then we get into the discussion of, are you a primary nonresponder or a secondary nonresponder? Meaning that it worked really well and then stopped. The same class can work really well again, versus the person who takes that first thing, and there’s zilch. Absolutely no response. We like to switch when you see someone who’s just not responding to that pathway. Sometimes we don’t know what biologic pathway is driving an individual’s disease. We don’t have a really simple way of figuring that out right now. We can certainly research the lots of ways we can stratify things, but with a patient, it’s really trial and error. If I see that, and I’ve tried a TNF and it fails, maybe I’ll try a second TNF. If that fails, I should not be on to the fifth TNF. Because we have other choices, other classes, and a different pathway may work.

Transcript Edited for Clarity