Using Oral Systemic Agents for Psoriatic Arthritis Treatment



Mark Lebwohl, MD: Let me move on to the next class of therapy, which is traditional oral systemic agents like methotrexate. How often do you use that nowadays?

Philip J. Mease, MD: We use it frequently, and this is partly because it’s inexpensive and there’s no challenge at the insurance company level. There are potential adverse-effect issues that patients just don’t like. If they have nausea, mouth sores, or hair loss, they obviously don’t like it. There are restrictions on lifestyle. We encourage them not to drink too much alcohol while using methotrexate, and there is the need for blood testing and blood canal liver function test every 3 months. The drug is useful, but it comes with a little bit of baggage.

More often these days, we’re moving rather quickly through methotrexate onto either a biologic or a targeted synthetic disease-modifying antirheumatic drugs. We may keep some methotrexate in the background, especially to reduce what we call immunogenicity with the biologics. The patient may develop an immune reaction against the biologic agent, so sometimes methotrexate can abrogate that. It’s used, but increasingly we’re relying more on the newer, more effective and potentially safer medications.

Mark Lebwohl, MD: The adverse effect that has gotten dermatologists to not use it, and I would say rheumatologists have the experience with rheumatoid arthritis because they treat lots of patients with methotrexate. Psoriasis patients, unlike rheumatoid arthritis patients, are obese, so the liver is much more sensitive. That’s why for many years, we had guidelines before we had the drugs we have today. We had guidelines that called for frequent liver biopsies, which we don’t call for anymore, but we don’t use as much methotrexate because of the hepatotoxicity that we see.

The other adverse effects, which I noticed you didn’t mention but I know you’re aware of, are actually from a rheumatology study done years ago where they looked at double-blind placebo-controlled trials of methotrexate for primarily rheumatoid arthritis. The frequency of pancytopenia or death in well-controlled trials was 1.4%. That means if you treat 200 patients, you’re likely to endanger the lives of 3 of them, and that’s what really frightens us from using methotrexate. I would say, more than the liver, it’s the bone marrow toxicity.

Interestingly, insurers used to require that patients fail methotrexate. They no longer require it. They get it. We would write a letter saying, “Look, this drug kills people. You want me to give it to the patient, but would you take it?” We hardly ever have to write that letter anymore. There’s an occasional insurance company that insists on it, but we’re usually able to get around doing that.

I will say also, in terms of standard of care, our recent joint National Psoriasis Foundation/American Academy of Dermatology guidelines discuss all the treatments but make them all options to be used and do not say that you should use 1 over another and put it really squarely in the hands of the physician: Does the patient have liver disease? Are they obese? Do they have psoriatic arthritis?

On average, patients with psoriasis are obese. That’s a relative contraindication to the use of methotrexate, so our most recent guidelines are actually superb in doing that.

Transcript Edited for Clarity

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