GOTHENBURG, Sweden - A psoriasis patient should not be considered a methotrexate nonresponder before a subcutaneous dose is tried, an expert panel from the International Psoriasis Council said at the annual congress of the European Academy of Dermatology and Venereology.
"Improvement in psoriasis with methotrexate is dependent on the blood level. And we know that absorption of methotrexate in the gastrointestinal tract is incomplete and quite variable from person to person, especially at higher doses. You can turn a patient into a responder by switching from oral to subcutaneous administration," said Dr. Knud Kragballe, professor of dermatology at Aarhus (Denmark) University Hospital.
Methotrexate is a dermatologic tradition, and most dermatologists were trained to administer the drug orally, said Dr. Kragballe. The oral form is easier to use than injectable methotrexate, and a logical starting place; however, some patients who do not get sufficient benefit because oral methotrexate’s bioavailability is about 30% less than that of the subcutaneous form, he added.
The switch is a straightforward matter. The subcutaneous dose is equivalent to the oral dose. If a patient is not showing sufficient benefit, for example, on 20 mg of oral methotrexate once weekly, try 20 mg subcutaneously once weekly, he said.
The widespread dermatologic reluctance to use subcutaneous methotrexate is partly a matter of training, but is also a function of the plethora of biologic agents available, according to Dr. Kragballe.
"I think it’s important to utilize the full potential of any drug before switching to another drug. We have too many cases dismissed as methotrexate nonresponders when the problem is the drug is not being used at the proper dose and route of administration," he said.
An audience show of hands indicated only a minority of attendees at the International Psoriasis Council–sponsored meet-the-experts session now utilize subcutaneous methotrexate. But the subcutaneous route is not the hassle many dermatologists imagine, according to Dr. Wolfram Sterry.
Dr. Wolfram Sterry
"We switched 3 or 4 years ago in my department, and now we do only subcutaneous methotrexate. That way you know 10 mg is 10 mg, and that’s it. I haven’t yet found a patient who is uncomfortable with subcutaneous administration," said Dr. Sterry, professor and chairman of the department of dermatology and allergy at Charité University Hospital, Berlin.
Dr. Craig Leonardi said that he, like Dr. Kragballe, typically starts patients on oral methotrexate because it is easier, and that’s how he was trained, but he doesn’t hesitate to shift to the subcutaneous form.
In the United States, another reason to favor subcutaneous methotrexate, besides better bioavailability, is that the cost is only about one-tenth that of tablets.
Dr. Craig Leonardi
"If a patient comes in who doesn’t have insurance and really can’t afford to pay for medications, subcutaneous methotrexate is the most cost-effective way to get the job done," said Dr. Leonardi a dermatologist and psoriasis specialist at St. Louis University.
International Psoriasis Council President, Dr. Alan Menter, commented that even though dermatologists have been using methotrexate for 40 years, the pharmacokinetics of the drug is still unclear.
Dr. Menter and his coworkers at Baylor University Medical Center, Dallas, where he is chief of dermatology, have been investigating a novel form of aminopterin – an antineoplastic drug closely related to methotrexate – which in preliminary phase I and II studies offered significant advantages over methotrexate: more predictable oral absorption, less uptake in cerebrospinal fluid, and less hepatotoxicity.
Dr. Alan Menter
Speaking of hepatotoxicity, Dr. Menter said he and his colleagues have not conducted a liver biopsy in years, even though they have patients who have been on methotrexate for 2 decades.
"I think our gastroenterologists can now scan livers and look at early fibrosis much better than we can," Dr. Menter said.
Panelists noted there is no consensus on how to give folic acid to patients on methotrexate. Dr. Leonardi has patients take 1 mg daily. He thinks it is easier for patients to follow a daily routine.
Dr. Kragballe, in contrast, gives folic acid once per week 2 days after the methotrexate. "But there’s no science behind it," he noted. The important thing is that every psoriasis patient on methotrexate be on folic acid.
All of the International Psoriasis Council panelists disclosed serving as consultants, speakers, and investigators for numerous companies that market psoriasis therapies.