International Experts Urge Uniformity in Methotrexate Dosing for Psoriasis

A close-up of bad psoriasis on a person’s arm
An international consensus establishes dosing recommendations of methotrexate for psoriasis treatment and identifies current knowledge gaps on the topic.

A consensus reached by nearly 200 international experts in dermatology supports specific methotrexate (MTX) dosing recommendations for the treatment of psoriasis in most adults with the disorder and certain dosing considerations for “vulnerable” patients and children. The consensus statement was published online in JAMA Dermatology.

According to the investigators of the SPIN MTX Consensus Survey Study Group, although MTX represents an effective systemic treatment for psoriasis, its US approval came before dose-ranging studies were performed. As a consequence, the investigators explained, there is no clear dosing regimen for the therapy, suggesting that the lack of uniformity may lead to inconsistent and suboptimal outcomes across the psoriasis population.

The SPIN study group therefore sought to establish an international consensus on the dosing of MTX for psoriasis and to identify current knowledge gaps on the topic. To reach this consensus, the working group performed a survey study which featured a modified electronic Delphi (eDelphi) procedure and was administered by the Amsterdam University Medical Center. A total of 180 participants worldwide completed the survey, which was conducted in 3 rounds.

Members of the SPIN working group identified 7 items related to MTX dosage: test dose, start dose, the increase or decrease of the dose, administration form, maximum dose, administration, and the use of folic acid. In combination with a literature review, clinical expertise and outcomes of the PIN survey were used to develop 21 proposals on the 7 items.

In each round, participants completed a survey which involved voting on the level of agreement with the proposals using a 9-point scale. A conference held in June, 2021 was convened to discuss proposals for which no consensus was reached. A total of 58 participants joined the meeting.

The participants of the initiative consisted of dermatologists, dermatology residents, as well as researchers who were conducting psoriasis research or in the process of relevant guideline development. Most of the participants in the survey worked at a university hospital (53.9%) and had experience with MTX therapy for patients with psoriasis. Approximately 92% of participants had more than10 years of experience prescribing MTX.

In round 1, consensus was reached on 11 proposals. In round 2, consensus was reached on 3 of the remaining 10 original proposals. For the third round, participants reached a consensus on 2 of 7 original proposals.

During the consensus meeting, the 5 remaining proposals were discussed, of which 4 proposals achieved consensus. Most of the participants agreed a test dosage was not needed for vulnerable patients and children when administering therapy with low-dose MTX. The participants agreed that lowering the initial dose could prevent idiosyncratic hepatotoxicity.

Some of the participants made comments regarding a lack of clear definitions for patients with frailty, so the description of “frail” patients was then switched to “vulnerable” patients. Based on this description, the participants concluded that there was no need for a specific maximum dosage in vulnerable patients, and the dose could be equivalent to the maximum dosage administered to adults.

Proposals discussed during the meeting involved the use of folic acid and whether the dose of this vitamin should be increased when the MTX dose is increased. Given the reportedly “controversial” nature of the evidence on this topic, the participants did not reach a consensus. However, a consensus was reached on a proposal discussing weekly administration of folic acid.

The working group also identified current knowledge gaps using the literature view, eDelphi study, and conference discussion on MTX dosing. Based on these knowledge gaps, the investigators suggested that potential future research should focus on MTX dosing in certain populations, such as children of various ages, as well as elderly or patients who have impaired kidney function. In addition, the investigators suggested that different doses of folic acid with different dosages of MTX should also be further studied.

Certain limitations remain, the working group stated. For example, the survey project did not include proposals on screening and safety monitoring of patients receiving MTX. Also, most of the respondents were from Europe, potentially limiting the generalizability of the consensus, the investigators wrote.

The working group also noted that it does not believe the consensus translates to other inflammatory diseases and disorders, including atopic dermatitis, morphea, and alopecia areata. “Other consensus projects can focus on the screening and monitoring of this drug, how often and which tests should be performed, and whether special precautions are needed in children, elderly individuals, and other subpopulations,” the investigators concluded.

Disclosure: Several authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


van Huizen AM, Menting SP, Gyulai R, et al. International eDelphi study to reach consensus on the methotrexate dosing regimen in patients with psoriasis. Published online March 30, 2022. JAMA Dermatol. 2022;10.1001/jamadermatol.2022.0434. doi:10.1001/jamadermatol.2022.0434