Usefulness of Low-dose Methotrexate Monotherapy for Treating Sarcoidosis

Abstract

Objective Methotrexate (MTX) is a cytotoxic agent that is commonly employed as an alternative to corticosteroids to treat sarcoidosis, although the proper use and efficacy of MTX as a single agent remain unclear. Methods The clinical records of patients newly diagnosed with sarcoidosis who were admitted to our institution between 2000 and 2009 were reviewed. Among these patients, 26 received 7.5 mg of MTX per week as a single agent, and the independent effects of MTX were analyzed. Results Six of the 26 patients (23%) exhibited an improvement of sarcoidosis-related lesions. The skin lesions demonstrated a relatively higher response rate (37%) than the pulmonary lesions (9%). Ten of the 26 patients (39%) experienced adverse effects, mostly mild hepatotoxicity. No severe adverse effects, including irreversible hepatotoxicity, were observed. Conclusion Although the efficacy of low-dose MTX monotherapy for sarcoidosis in this study was not high (23%), some patients exhibited definite improvements, and the drug proved to be safe, suggesting its possible benefits as a single agent for treating sarcoidosis.

Sarcoidosis

“…Of the 11 patients with cutaneous sarcoidosis treated with 7.5 mg of methotrexate weekly, 37% reported improvement in skin lesions. 152 A drawback to methotrexate use is that a therapeutic response takes 4 to 8 weeks and occasionally as long as 6 months. 150 Relapse frequently occurs after discontinuation so low-dose maintenance therapy is often necessary.…”

Sarcoidosis: Progression to the chronic stage and pathogenic based treatment (narrative review)

“…MTX can also polarize M0 to M2 via IL4-independent pathways. Thus, the desirable anti-inflammatory effects of MTX are leveled by an increased risk of fibrosis ( 70 , 71 ).…”

Potential immunotherapies for sarcoidosis

“…However, the optimal treatment dose and duration of therapy are not standardized due to lack of adequately powered randomized-controlled clinical trials. When used in the short term, CS can dramatically improve disease related symptoms, normalize molecular biomarkers, restore lung function, and x-ray findings 22,23 . However, their long-term effects/benefits are unclear in that they often fail to slow disease progression, prevent fibrosis, and there is no proof that they improve survival.…”

“…MTX is used clinically either as a “CS-sparing” agent or as the sole agent for patients requiring chronic immune suppression for sarcoidosis 22,23 . Evidence of clinical efficacy for MTX is extrapolated from a handful of trials, mostly retrospective and conducted in the setting of concomitant CS use, and demonstrating synergy with concomitant use ofMTX and CS.…”