Methotrexate, low-dose prednisone aids hair regrowth in patients with alopecia subtypes

Key takeaways:

• Methotrexate and low-dose prednisone combination allowed complete hair regrowth in up to 31% of patients.
• Only one patient taking methotrexate alone achieved complete hair regrowth.

Methotrexate and low-dose prednisone combination outperformed methotrexate alone in patients with chronic and recalcitrant alopecia totalis and alopecia universalis, according to a study.

Alopecia totalis (AT) and alopecia universalis (AU) are the most debilitating types of alopecia areata (AA) as they incur severe changes to a patient’s quality of life, according to Pascal Joly, MD, PhD, of the department of dermatology at Rouen University Hospital in Rouen, France, and colleagues.

“While many treatments have been successfully proposed in plaque-type AA, very few treatments are effective in chronic types of AT or AU,” Joly and colleagues wrote.

Methotrexate, an inexpensive oral treatment, may be an effective option for these alopecia subtypes. In this multicenter, double-blind, randomized clinical trial, researchers evaluated the efficacy and tolerance of methotrexate alone or combined with low-dose prednisone in patients with chronic and recalcitrant AT and AU.

Study design

The study included 89 patients aged 18 to 70 years with AT (n = 1) and AU (n = 88) from eight university hospital dermatology departments. Patients were eligible if they had evolving alopecia for more than 6 months, regardless of previous topical and systemic treatments.

The primary endpoint was defined as complete or almost complete hair regrowth, or a Severity of Alopecia Tool score of less than 10, at month 12 for those who received methotrexate alone for the study’s duration. Secondary endpoints included more than 50% hair regrowth by the end of the study, quality of life improvement and treatment tolerance.

Patients were randomly assigned to receive 20 mg or 25 mg of methotrexate (n = 45) or placebo (n = 44) for 6 months. The three patients taking methotrexate and the one patient taking placebo who experienced hair regrowth greater than 25% at 6 months continued their assigned treatment for an additional 6 months. The remaining patients who achieved less than 25% hair regrowth were again randomly assigned to receive their original methotrexate dose combined with oral prednisone, which was dosed at 20 mg per day for 3 months followed by 15 mg per day for 3 months, or methotrexate with placebo.

Study results

Results showed that the primary endpoint was achieved by one patient receiving methotrexate alone throughout the study.

As far as secondary endpoints, among the 16 patients assigned to methotrexate alone for 6 months followed by methotrexate plus prednisone through month 12, five achieved complete hair regrowth at the end of the study (31.2%; 95% CI, 11%-58.7%).

Further, when the researchers pooled the 35 patients who received methotrexate for 6 or 12 months plus prednisone for 6 months, seven (20%; 95% CI, 8.4%-37%) achieved complete hair regrowth by the end of the study.

Additionally, more patients who achieved a complete response experienced an improved quality of life vs. those who did not respond to treatment (P = .05).

The researchers also wrote that the combination methotrexate and prednisone treatment was “rather well tolerated,” with no severe adverse events. There were a total of 103 adverse events in 45 patients that were considered a grade 1 or 2, the most common being infections, mucocutaneous reactions, and nausea and vomiting. Fatigue and nausea caused two patients to discontinue treatment.

The 30 patients who discontinued the study was considered a limitation; however, the researchers considered all of these patients as treatment failures in their analysis.

“These results seem to be of the same order of magnitude as those recently reported with [Janus kinase] inhibitors, with a much lower cost,” Joly and colleagues wrote.

“This [study] has shown that the combination of methotrexate and low-dose prednisone can be considered as a therapeutic option in patients with recalcitrant types of AT or AU,” the researchers concluded.