John Tesser, MD: The concept of conventional DMARDs [disease-modifying anti-rheumatic drugs], I want to come to that for a second. It’s very interesting and you mentioned that not infrequently the payers demand that we start with conventional DMARDs. I alluded to them before; methotrexate, sulfasalazine, and leflunomide were to be used first. But, interestingly enough, none of those medications have an FDA [Food and Drug Administration]-approved indication for psoriatic arthritis or psoriasis for that matter. And so, there are intricacies involved with using those medicines. Nehad, I’m going to come to you and ask you to weigh in on if those are medicines appropriate for psoriatic arthritis in any form, in any manner, in any of its manifestations, and also for psoriasis? How do you want to pigeonhole them?

Nehad Soloman, MD: It’s interesting. As everybody was talking, I was taking a trip down memory lane. If you think about before 2001 and the treatment of psoriasis and psoriatic arthritis, we didn’t really have any biologic treatments or nonconventional therapies. I ask myself; how did we get into this mess in the first place with using methotrexate, sulfasalazine, and leflunomide? And the answer is that’s all we had. That’s it to start with. And, at that time, there were more breakthroughs because we adopted them from our rheumatoid arthritis experience. Again, it’s a bit naïve to think that because joint pain was inflammatory, and rheumatoid and psoriatic kind of look clinically the same, probably these drugs will work.

And the reality is we do know that methotrexate, although [it] doesn’t have the FDA indication for psoriasis, it works. But our dermatology colleagues shy away, and they look for alternative methods that may be safer and a little less burdensome as far as monitoring. Our dermatology colleagues were a bit more overzealous with liver biopsies periodically because of the concerns over liver toxicity. Where I use them, certainly if somebody is predominantly skin manifestations and mild joint manifestations, I still see value in methotrexate and leflunomide. Sulfasalazine, if somebody has more peripheral stuff, perhaps mild enthesitis, perhaps a little gun-shy from the injectable medications. But now we even have oral small molecules that are presumably safer than methotrexate and not as much monitoring of things like apremilast [Otezla], for example. And so, I tend to start to gravitate towards them.

But, in the end, in this sort of cost-conscious world, our third-party payers are always thinking about the bottom line literally. If we can get away with utilizing a conventional DMARD with benefit and save the system some money for a period of at least 3 months to trial it, it’s reasonable. But I think if somebody presents with more aggressive disease and high inflammatory markers, with extensive body surface area involvement of psoriasis, it very well may require more aggressive treatment upfront.

Now, the other piece to this is, as mentioned before, sometimes we’re overzealous and we start with biologics and we’re able to get them approved and we need just a little bit more push. And that little bit more could come at the hands of adding a conventional DMARD. I’ve seen that with IL-23s [Interleukin-23], for example, where I add methotrexate to just sort of get them over the hump with some mild manifestations. It did a 90% benefit for a patient but they’re just still looking for that extra 10%, for example. So that’s where I’m placing them. If it’s mild upfront, or if you’ve got patients that are somewhat resistant to treatment, we add them in combination.

John Tesser, MD: I appreciate the little bit of history you gave there of the field for that matter, the pre-biologic era which started in 1998 with the approval of etanercept, in the post-biologic era, with the approval of etanercept [Enbrel] and everything since then. The history of methotrexate is very interesting and actually antedates my jump into the field. Back in the 1950s, it was the dermatologists who were using it as pulse therapy once a week. Of course, methotrexate’s long history was used as chemotherapy in very high doses. But the dermatologists in the 1950s jumped on this and used it in doses 30 mg or 35 mg or more a week, and they were not following liver function tests. So that’s where we saw the unfortunate experience of outcomes in some of the patients developing cirrhosis. When that became known, obviously the dermatologists jumped out of that water fast and they’ve never jumped back in.

There were, interestingly enough, some rheumatologists who were beginning to use methotrexate. Back in the 1950s, there was a guy up in Spokane [Washington] and at the Cleveland Clinic, several people who were using it for RA [rheumatoid arthritis], but it never caught fire, and, of course, it would slow down because of this whole experience with cirrhosis in the dermatology field. But eventually, it came into play back in the late 1970s/early 1980s when the clinical studies were done and the LFTs [live function tests] were followed carefully and the doses were lower. We know the success that it has had. But I do want to point out; in general, conventional DMARDs do not have a place in axial disease.

Consequently, it’s never appropriate to start with a conventional DMARD if someone has back involvement, spine involvement, or sacroiliac involvement because you’re not going to get anywhere when you do that. I appreciate the add-on of using conventional DMARD to get over the hump with some of the patients, Nehad. It’s sort of backward from how we do things for RA. We start with a conventional DMARD. That’s our anchor drug and then we add the biologic to it. Here we may be going in the opposite direction, but it absolutely has value to look at it from that perspective.

This transcript has been edited for clarity.