What is the relationship between Methotrexate (MTX) and sarcoidosis?

From the Guidelines

Methotrexate is a recommended second-line treatment for sarcoidosis, particularly for patients with pulmonary, cutaneous, and neurosarcoidosis who have failed or cannot tolerate corticosteroids. The typical dosing regimen starts at 10-15 mg once weekly, which can be gradually increased to 15-25 mg weekly if needed, as suggested by the European Respiratory Journal study 1. Folic acid supplementation (1 mg daily) should be given concurrently to reduce side effects. Treatment duration typically ranges from 6-24 months, with response assessment after 3-6 months. Methotrexate works in sarcoidosis by inhibiting dihydrofolate reductase and promoting adenosine release, which suppresses the abnormal immune response and granuloma formation characteristic of the disease.

Some key points to consider when using methotrexate for sarcoidosis include:

• Monitoring for toxicity, including nausea, fatigue, and elevated liver enzymes, as noted in the study by Rahaghi et al. 1
• Regular laboratory tests, including complete blood count, liver and kidney function tests, every 4-8 weeks during treatment, as recommended by the European Respiratory Journal study 1
• Avoiding alcohol consumption to reduce hepatotoxicity risk, as suggested by the study by Baughman et al. 1
• Considering alternative treatments, such as infliximab, for patients who do not respond to methotrexate or have severe disease, as recommended by the European Respiratory Journal study 1

It is essential to weigh the benefits and risks of methotrexate treatment for each patient, considering factors such as disease severity, comorbidities, and potential side effects, as noted in the study by Baughman et al. 1. The decision to use methotrexate should be made on a case-by-case basis, taking into account the individual patient's needs and circumstances.

From the Research

Methotrexate and Sarcoidosis

• Methotrexate is a standard second-line agent for the treatment of sarcoidosis 2.
• The use of methotrexate in sarcoidosis has been associated with hepatic and hematologic toxicity, although the frequency of these complications is relatively low 3, 4.
• Studies have shown that methotrexate can be an effective treatment for sarcoidosis, with improvements in lung function and clinical symptoms observed in a significant proportion of patients 4, 5.
• Methotrexate has also been shown to have a steroid-sparing effect, allowing for the reduction or discontinuation of corticosteroids in some patients 4, 6.
• The safety and efficacy of methotrexate in sarcoidosis have been demonstrated in several studies, with the majority of patients tolerating the medication well and experiencing significant clinical benefits 3, 4, 5, 6.

Efficacy of Methotrexate in Sarcoidosis

• A study published in 1995 found that 33 of 50 patients with chronic sarcoidosis treated with methotrexate for at least 2 years experienced improvement in clinical symptoms, with 6 patients able to discontinue corticosteroids 4.
• A 2015 study found that 54% of patients with sarcoidosis refractory to previous treatment experienced improvement in their condition with methotrexate monotherapy, with improvements in spirometry and chest radiography observed in 63.2% and 54% of patients, respectively 5.
• A retrospective cohort study published in 2013 found that methotrexate and azathioprine had similar steroid-sparing potency and positive effects on lung function, with 70% of patients completing 1 year of therapy experiencing a reduction in daily prednisone dose of at least 10 mg 6.

Safety of Methotrexate in Sarcoidosis

• A 2003 study found that toxic reactions to methotrexate occurred in more than 10% of patients with sarcoidosis treated for more than 2 years, with the majority of these reactions being hepatic in nature 2.
• A 2020 study found that moderate elevation of alanine aminotransferase (ALT) was seen in 1.6% of patients treated with methotrexate, with white blood cell count of <1500 cells per cu mm seen in only 1 patient 3.
• A 1995 study found that the major toxic effects of methotrexate in sarcoidosis were hepatic, with 6 patients experiencing significant changes related to methotrexate that led to drug discontinuation 4.