What is the best Disease-Modifying Antirheumatic Drug (DMARD) for inflammation?

From the Guidelines

Methotrexate is the most recommended DMARD for inflammation, particularly in conditions like rheumatoid arthritis, due to its strong disease-modifying properties and favorable tolerability profile. This recommendation is based on the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1. The guideline strongly recommends methotrexate over hydroxychloroquine or sulfasalazine for DMARD-naive patients with moderate-to-high disease activity, citing the amount of data supporting the disease-modifying properties of methotrexate monotherapy compared to hydroxychloroquine or sulfasalazine.

Some key points to consider when prescribing methotrexate include:

• Starting dose: 7.5-10mg once weekly, with gradual increases up to 20-25mg weekly as needed for symptom control
• Route of administration: oral or injection, with the latter often providing better absorption and fewer gastrointestinal side effects
• Folic acid supplementation: 1mg daily except on methotrexate day to reduce side effects
• Monitoring: baseline and periodic liver function tests, complete blood counts, and renal function assessment

The European League Against Rheumatism (EULAR) also recommends methotrexate as a preferred conventional synthetic DMARD (csDMARD) in patients with polyarthritis, particularly those with relevant skin involvement 1. If methotrexate is ineffective or poorly tolerated, alternatives include leflunomide, sulfasalazine, or hydroxychloroquine, though these may have different efficacy profiles depending on the specific inflammatory condition being treated. For more severe or resistant cases, biologics like TNF inhibitors might be considered as add-on therapy or alternatives.

From the Research

DMARD Options for Inflammation

• Methotrexate is considered a preferred disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis, with studies showing its effectiveness in reducing inflammation 2, 3.
• Combination therapy with methotrexate and other DMARDs, such as sulfasalazine and hydroxychloroquine, has been shown to be effective in controlling disease activity and preventing joint damage 2, 4.
• Biologic DMARDs, such as adalimumab, etanercept, and infliximab, have also been found to be effective in reducing inflammation and preventing joint damage when used in combination with methotrexate 2, 5.
• Leflunomide has been shown to be clinically efficacious and well-tolerated when used in combination with methotrexate or sulfasalazine 6.

Comparison of DMARDs

• Methotrexate has been found to have one of the best efficacy/toxicity ratios among DMARDs 3.
• Combination therapy with methotrexate and other DMARDs has been shown to be more effective than methotrexate monotherapy in reducing inflammation and preventing joint damage 2, 4.
• Biologic DMARDs have been found to be effective in reducing inflammation and preventing joint damage, but should be reserved for patients who fail to respond to traditional DMARD therapy 5.

Safety and Efficacy

• Methotrexate has been found to be generally well-tolerated, but can cause adverse events such as liver toxicity and bone marrow suppression 3.
• Combination therapy with methotrexate and other DMARDs can increase the risk of adverse events, and patients should be carefully monitored 2, 6.
• Biologic DMARDs have been found to be effective, but can also increase the risk of adverse events such as infections and malignancies 5.