What are anti-inflammatory medications that are not Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

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Last updated: May 11, 2025View editorial policy

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From the Guidelines

Corticosteroids are the most effective non-NSAID anti-inflammatory option, with prednisolone at a dose of 35 mg for 5 days being a recommended treatment for acute gout, as shown in high-quality evidence from the American College of Physicians guideline 1. When considering anti-inflammatory medications that are not NSAIDs, several options are available.

  • Corticosteroids, such as prednisone, dexamethasone, and methylprednisolone, are commonly used non-NSAID anti-inflammatories that work by suppressing the immune system and reducing inflammation through inhibition of inflammatory mediators.
  • Colchicine, often used for gout and other inflammatory conditions, works by interfering with neutrophil function and inflammatory pathways, with a recommended dose of 0.6mg once or twice daily.
  • Disease-modifying antirheumatic drugs (DMARDs) like methotrexate, hydroxychloroquine, and sulfasalazine also have anti-inflammatory properties without being NSAIDs.
  • Biologic agents such as TNF inhibitors, IL-6 inhibitors, and JAK inhibitors target specific inflammatory pathways and are typically used for autoimmune conditions when NSAIDs are contraindicated or insufficient. The American College of Physicians guideline recommends corticosteroids as a first-line therapy for acute gout due to their effectiveness and relatively safer profile compared to NSAIDs 1. Key points to consider when choosing a non-NSAID anti-inflammatory include:
  • Efficacy in reducing pain and inflammation
  • Potential side effects and contraindications
  • Cost and availability
  • Patient-specific factors, such as comorbidities and medication interactions.

From the FDA Drug Label

Methotrexate is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis, who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs). Methotrexate clearly ameliorates symptoms of inflammation (pain, swelling, stiffness)

Methotrexate is an anti-inflammatory medication that is not an NSAID. It is used to treat rheumatoid arthritis and has been shown to reduce symptoms of inflammation. 2 2

From the Research

Anti-Inflammatory Options

  • There are several anti-inflammatory options available that are not NSAIDs, including:
    • Disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide 3, 4, 5
    • Biologic DMARDs such as abatacept, adalimumab, etanercept, infliximab, rituximab, and tocilizumab 4, 5
    • Targeted synthetic DMARDs such as tofacitinib 4, 5
    • Glucocorticoids such as prednisone 3, 6, 7

Mechanism of Action

  • DMARDs work by modifying the immune system's response to inflammation, rather than just reducing symptoms 4, 5
  • Biologic DMARDs target specific molecules involved in the inflammatory process 4, 5
  • Glucocorticoids work by suppressing the immune system and reducing inflammation 3, 6, 7

Efficacy and Safety

  • The efficacy and safety of these options vary, with some being more effective or having more side effects than others 5, 6, 7
  • For example, methotrexate is a commonly used DMARD that can be effective in reducing inflammation, but may have side effects such as nausea and elevated liver enzymes 5, 6
  • Adding prednisone to methotrexate may help alleviate some of these side effects 6
  • Hydroxychloroquine is another DMARD that has been shown to be relatively safe and effective in reducing inflammation 5, 7

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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