A combination of low-dose prednisone and methotrexate led to complete hair regrowth for up to 31% of patients with chronic alopecia areata totalis (AT) or alopecia universalis (AU), according to new findings.¹

These results are significant because they were found to be comparable to the results seen with JAK inhibitors but with a lower cost.

The main aim of this study was to assess the efficacy of methotrexate by itself or in combination with prednisone at a low dose for AT and AU patients, given that the conditions have fewer treatments than alopecia areata (AA).

This research was authored by Pascal Joly, MD, PhD, from the Department of Dermatology at Rouen University Hospital, Normandie University in France.

“Unlike most studies on severe types of AA, which included a significant proportion of patients with plaque-type AA, this academic double-blind RCT only included patients with AT and AU,” Joly and colleagues wrote. “Indeed, plaque-type AA is known to be less severe than AT and AU, whereas very poor therapeutic results have been reported in these later patients who have the highest therapeutic need.”

Background and Findings

The investigators conducted a randomized, double-blind clinical study, designed to determine both the effectiveness and tolerability of methotrexate. They would assess the drug as a standalone treatment or in combination with prednisone.

The team’s research was set up in 8 dermatology departments at university hospitals in the period between March of 2014 and December of 2016.

They included adult patients with AA or AU who had been diagnosed for over 6 months despite other topical and systemic treatments having been administered, enrolling 89 patients in total (39 male, 50 female; mean age, 38.6 years).

The investigators conducted their data analysis in the time between October of 2018 and June of 2019, randomly assigning participants to take either methotrexate (25 mg per week) or placebo for a period of 6 months.

The research team treated the participants who had over 25% hair regrowth at 6 months up until 12 months, and those with less than 25% regrowth were randomized again and then given either methotrexate and a placebo of prednisone or methotrexate and prednisone (20 mg per day for 3 months and 15 mg per day for 3 months).

By the end of the study, the team observed complete or almost complete hair regrowth (SALT score of <10) for 1 participant given methotrexate alone and also for 7 patients given methotrexate plus prednisone.

The near complete regrowth was reported in 5 of these 7 participants given methotrexate for 12 months and prednisone for 6 months.

The investigators concluded that participants who were able to get a complete response reported a greater improvement in quality of life, and the treatment was well-tolerated overall with only mild adverse effects having been reported.

“Importantly, the combination of prednisone with methotrexate was rather well tolerated, since corticosteroid-related adverse effects were rarely observed,” they wrote. “This good tolerance was likely related to the low dose of prednisone used. Additionally, the safety data of methotrexate are particularly well known, both in the short term and long term.”

References

1. Joly P, Lafon A, Houivet E, et al. Efficacy of Methotrexate Alone vs Methotrexate Plus Low-Dose Prednisone in Patients With Alopecia Areata Totalis or Universalis: A 2-Step Double-Blind Randomized Clinical Trial. JAMA Dermatol. Published online March 08, 2023. doi:10.1001/jamadermatol.2022.6687.