International Experts Reach Consensus on Uniform Dosing of Methotrexate for Psoriasis

Almost 200 experts addressed uniform methotrexate (MTX) dosing for patients with psoriasis in an international consensus statement published in JAMA Dermatology, following a survey study and conference.

Astrid van Huizen, MD, PhD, of the Department of Dermatology at Amsterdam University Medical Centers in the Netherlands, and colleagues, including the SPIN MTX Consensus Survey Study Group, conducted the research and facilitated the conference. The goal was to reach a consensus on uniform dosing guidelines for children and adults with psoriasis, including vulnerable patients.

When MTX was approved by the FDA for patients with psoriasis in the United States, there were no studies completed on the range of doses, the authors said.¹ Even now there is no uniform dosing guid-ance. “A global survey study conducted by Psoriasis International Network (which is currently named the Skin Inflammation and Psoriasis International Network [SPIN]), showed that starting doses differed from 5 to 22.5 mg per week,” van Huizen et al reported.²

With this survey study, researchers wanted to find an international consensus on MTX dosing for patients with psoriasis, and to discover and close knowledge gaps. Researchers said they examined 7 areas in the proposals: test dose; initiation dose; dose increase/decrease; form of administration; maximum dose; administration; and use of folic acid specified for adults, children, as well as vulnerable patients.¹

Following a systematic literature review that explored these topics, researchers created 21 pro-posals for MTX dosing and sent 3 rounds of modified electronic Delphi procedure study surveys to dermatology practitioners, dermatology residents, and psoriasis researchers between September 2020 and March 2021. Practitioners and residents had been recruited in June 2020 using SPIN and the European Academy of Dermatology and Venereology. “The participants worked mainly at a university hospital [97 (53.9%)] and were experienced in treating patients with psoriasis with methotrexate [163 (91.6%) had more than 10 years of experience],” researchers reported.¹

A total of 180 participants completed all 3 rounds of the surveys, which were created and distributed by Amsterdam University Medical Centers. A 9-point scale was used to evaluate proposals (1-3, disagree; 4-6, neither agree nor disagree; 7-9, agree). “Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree,” researchers said.¹

Van Huizen et al reported 11 proposals reached consensus in the first round of surveys, 3 did so in the second round, and 2 in the third round (16 total). Remaining proposals that did not reach consensus in the surveys were discussed at a June 2021 conference attended by 58 participants. Four more proposals reached consensus at the meeting, for a total of 20. Only 1 proposal did not reach consensus: “the proposal of an increased dosage of folic acid when increasing the dosage of MTX. During the consensus meet-ing, it was discussed that there was a lack of evidence and the available evidence was inconclusive,” researchers said.¹

In an interview with Dermatology Times®, van Huizen said the most significant takeaway from providers in practice was that no test dose of MTX is needed in adults, children, or vulnerable patients. “MTX can be started with 15 mg/wk in adults and 7.5 to 10 mg/wk in vulnerable patients. In children the MTX dosing should be based on square meter,” she said.

She added that folic acid should be supplemented once a week, 24 hours after taking MTX. “In our study, no consensus is reached whether the dosage of folic acid should be increased, when increasing the dosage of MTX. Furthermore, the evidence for the use of folic acid is controversial and dosing regimens strongly depend on availability,” van Huizen noted.

Van Huizen said that for next steps, the variability in treatment regimens might contribute to suboptimal treatment with MTX or can lead to early discontinuation of treatment due to limited efficacy or adverse effects. “With the publication of this consensus study we hope to raise awareness on the different used MTX dosages in daily practice and the need for a more uniform dosing regimen. Our published paper and presentations at international congresses on the 7th of July at the SPIN Congress in Paris can be included in reviews or implemented in guidelines and other supporting documents,” she told Dermatology Times®. Van Huizen also said it is challenging to define a vulnerable population. “We discussed elderly patients or patients with an impaired kidney function in our study group. In future research, it should be defined for which subpopulation a specific dosing schedule is needed,” she said.

For study limitations, van Huizen et al wrote that most respondents were from Europe, so investigators said surveying a more geographically diverse group of professionals may yield different results than respondents in non-Western countries. In addition, the authors said the study scope was limited because it did not include safety monitoring and screening of patients with psoriasis taking the drug. “We decided to focus on the dosing of MTX to prevent the survey being too extensive, because this could discourage participants from completing the survey rounds,” the authors said.¹

Van Huizen et al highlighted the study’s strengths: that participants were recruited from 7 continents and were academic professionals highly experienced in treating patients with MTX. They also noted the high 71.7% response rate (180 participants of 251 attempted recruitments). “Another strength is the design of this study; the anonymous eDelphi study avoided the possibility of dominance by any of the participants, but during the consensus meeting the proposals could also be discussed live,” researchers said.¹

The study authors emphasized that the current MTX guidelines should not apply to other inflammatory disorders or diseases such as alopecia areata, atopic dermatitis, and morphea. More high-quality studies should be completed to confirm these results, the study authors concluded.

References:

1. van Huizen AM, Menting SP, Gyulai R, et al. International eDelphi study to reach consensus on the methotrexate dosing regimen in patients with psoriasis. JAMA Dermatol. 2022;158(5):561-572. doi:10.1001/jamadermatol.2022.0434

2. Gyulai R, Bagot M, Griffiths CEM, et al. Current practice of methotrexate use for psoriasis: results of a worldwide survey among dermatologists. J EurAcad Dermatol Venereol. 2015;29(2):224-231. doi:10.1111/jdv.12495