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SAARDS – Slow-Acting Anti-Rheumatic Drugs

Slow-acting anti-rheumatic drugs, or SAARDs, are a class of medication that historically have been used to treat people with ankylosing spondylitis (AS), especially those with peripheral disease (joints in the arms and legs are affected). Today, most people with AS are now treated with other medications. SAARDs may also be called disease-modifying anti-rheumatic drugs (DMARDs), although this term was borrowed from rheumatoid arthritis. This class of medications was shown to be effective in reducing the inflammation and joint damage caused by rheumatoid arthritis, and doctors believed it may have a similar effect on people with AS. However, their effectiveness in AS has not been proven in clinical research, and these drugs do not act as “disease-modifying” agents in people with AS.1,2

Treatment guidelines for ankylosing spondylitis

The Spondyloarthritis Research and Treatment Network, in conjunction with the Spondylitis Association of American and the American College of Radiology have created treatment guidelines for people with AS. Their recommendations are that people with AS first be treated with non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDS have been shown to help reduce the pain and inflammation of AS. NSAIDs start to work quickly on pain, within a few hours of taking the medicine. The anti-inflammatory effects of NSAIDs take longer to realize. NSAIDs are readily available over-the-counter, but prescription-strength NSAIDs may be needed to relieve the pain and inflammation of AS. While NSAIDs can provide benefit and reduce the symptoms in people with AS, they can cause side effects, such as gastrointestinal problems.2,3

For people with active AS despite treatment with NSAIDs, or for those who cannot tolerate NSAIDs due to the side effects, doctors may prescribe a tumor necrosis factor (TNF) inhibitor. TNF inhibitors are a type of biologic medication, and they target the naturally occurring protein TNF that is elevated in people with AS. By blocking this protein, TNF inhibitors interrupt the inflammatory process and help reduce symptoms of AS. Another biologic targets interleukin 17-A (IL-17A), another protein that is involved in the inflammatory process. Biologics have demonstrated effectiveness in clinical trials, but they can cause side effects, including increasing the risk of infections, some of which can be serious.4

The treatment guidelines recommend against using SAARDs in people with AS, due to the lack of evidence in their benefit. However, the experts note in their recommendations that SAARDs may be used in certain cases, such as when the patient cannot tolerate or chooses not to take TNF inhibitors.4

Types of SAARDs

There are several SAARDs, including methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide.

Methotrexate is an antimetabolite or antifolate. It inhibits the metabolism of folic acid, which is critical in the production of DNA during cell replication. It also reduces a number of the factors the body produces that cause inflammation. Several studies have found that methotrexate has benefits in treating rheumatoid arthritis, but the research has not found a similar effectiveness in people with AS.5,6

Sulfasalazine is a sulfa drug. While the exact way it works isn’t fully understood, researchers believe that sulfasalazine or its metabolites (the substances it turns into when the body breaks it down) interfere with the inflammatory or immune system processes.7

Experts don’t know exactly how hydroxychloroquine works to treat autoimmune diseases, but researchers believe it may work by interfering with certain communications between the cells in the immune system.8

Leflunomide blocks the formation of DNA, which normally occurs as cells replicate. This action can reduce the inflammation produced by the immune system and help reduce pain and swelling.9

Written by: Emily Downward | Last reviewed: February 2019
  1. Akkoc N, van der Linden S, Khan MA. Ankylosing spondylitis and symptom-modifying vs disease-modifying treatment. Best Pract Res Clin Rheumatol. 2006 Jun;20(3):539-57. doi: 10.1016/j.berh.2006.03.003. Abstract.
  2. Ward MM, Deodhar A, Akl EA, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2015;68(2):282-98.
  3. NSAIDs (nonsteroidal anti-inflammatory drugs). American College of Rheumatology. Available at https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/NSAIDs. Accessed 1/15/19.
  4. A guide to biologic therapy. National Ankylosing Spondylitis Society. Available at https://nass.co.uk/wp-content/uploads/resources/Guide-to-Biologic-Therapy.pdf. Published 6/17. Accessed 1/18/19.
  5. Chen J, Veras MMS, Liu C, Lin J. Methotrexate for ankylosing spondylitis. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD004524. DOI: 10.1002/14651858.CD004524.pub4.
  6. Methotrexate prescribing information. Hospira, Inc. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011719s117lbl.pdf. Revised 10/11. Accessed 2/8/19.
  7. Azulfidine EN-tabs prescribing information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/007073s125lbl.pdf. Accessed 2/8/19.
  8. Hydroxychloroquine (Plaquenil) patient fact sheet. American College of Rheumatology. Available at https://www.rheumatology.org/Portals/0/Files/Hydroxychloroquine-Plaquenil-Fact-Sheet.pdf?ver=2018-11-08-142359-467. Accessed 2/11/19.
  9. Leflunomide (Arava). American College of Rheumatology. Available at https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/Leflunomide-Arava. Accessed 2/11/19.