Methotrexate Effective as Adjuvant for Treating Pemphigus Vulgaris

July 05, 2013

By Will Boggs, MD

NEW YORK (Reuters Health) Jul 03 - Methotrexate allows discontinuation of steroids in many patients with pemphigus vulgaris, a retrospective study suggests.

"Methotrexate should be considered as a first-line adjuvant treatment option for patients with pemphigus vulgaris," Dr. Kathleen D. Tran from New York University Medical Center, New York told Reuters Health. "As it takes some time to work, it may not be the best treatment for patients who need to be discontinued from glucocorticoids immediately -- but given time, it results in a marked steroid-sparing effect for the vast majority of patients and has an excellent safety profile."

Although methotrexate has been used for pemphigus vulgaris at least since 1968, only a few small studies have evaluated it, and none of them were randomized controlled trials.

Dr. Tran and colleagues reviewed their experience in 23 patients with pemphigus vulgaris who were treated with methotrexate between 2001 and 2012, using its steroid-sparing effect as a marker of clinical improvement.

As reported June 18 in the British Journal of Dermatology, the mean maximum daily dose of prednisone before treatment with methotrexate was 71 mg (range, 20-140 mg). Thirteen patients, or just over half (56.5%), had previously received immunomodulators other than methotrexate, but none were still taking them.

Maximum weekly methotrexate doses ranged from 15 to 25 mg (mean, 18.9 mg) after titration to a minimal effective dose.

All but two patients (21 patients, 91.3%) had improvement in blistering on methotrexate and could reduce their systemic corticosteroid dose. Sixteen (69.6%) were able to wean completely off prednisone after a mean of 18 months of methotrexate treatment (range, seven to 30 months).

In four of the five patients who could not be weaned completely, the mean prednisone dose needed to maintain symptom control was reduced by 86% from the baseline dose. The fifth patient was lost to follow-up.

Once weaned from prednisone, eight of 14 patients were able to reduce their weekly dose of methotrexate to a minimum maintenance dose (mean, 8.75 mg), and three patients were eventually weaned from methotrexate. All three remained in remission until they were lost to follow-up (after three and seven months) or until the end of the study period (26 months).

Two patients had to stop methotrexate due to adverse effects, and one patient had no benefit after two months of methotrexate up to a maximum weekly dose of 25 mg.

"The results of this study are similar to a study performed at our medical center about a decade earlier, which showed that prednisone could be weaned completely in six out of nine patients (67%) within six months," the researchers note.

"I would like other physicians to understand that this inexpensive, widely-available drug is an effective, underutilized, underappreciated treatment option for pemphigus vulgaris" Dr. Tran said. "I feel that methotrexate is often perceived as 'not as strong' as other systemic immunomodulators in autoimmune blistering disease, and perhaps the medical community also shies away from drugs that are perceived as 'old.' But at NYU Medical Center, we use it first-line in the vast majority of our pemphigus patients and find that the majority of our patients are eventually able to discontinue glucocorticoids completely as a result."

"Other systemic immunomodulators such as mycophenolate mofetil, dapsone, (and) azathioprine have all shown efficacy in pemphigus vulgaris," Dr. Tran added. "Unfortunately, studies comparing these immunomodulators head-to-head are lacking, and the factors leading physicians to choose one over the other are often strongly related to institutional bias."

SOURCE: http://bit.ly/14NZ0zG

Br J Derm 2013.

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