What is the role of DMARDs in the treatment of reactive arthritis (ReA)?

Updated: Dec 24, 2020
  • Author: Carlos J Lozada, MD; Chief Editor: Herbert S Diamond, MD  more...
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In patients who have chronic symptoms or have persistent inflammation despite the use of the agents mentioned above, other second-line drugs may be used. Clinical experience with these DMARDs has been mostly in rheumatoid arthritis and in psoriatic arthritis. However, DMARDs have also been used in ReA, though their disease-modifying effects in this setting are uncertain.

Sulfasalazine has been shown to be beneficial in some patients. The use of this drug in ReA is of interest because of the finding of clinical or subclinical inflammation of the bowel in many patients. Sulfasalazine is more widely used in ankylosing spondylitis. In a 36-week trial of sulfasalazine versus placebo to treat spondyloarthropathies, patients with ReA who were taking sulfasalazine had a 62.3% response rate, compared with a 47.7% rate for the placebo group in peripheral arthritis. [105]

Methotrexate may be used in patients who present with rheumatoidlike disease. Several reports have shown good response, but controlled studies are lacking. Reports also describe the use of azathioprine and bromocriptine in ReA, but again, large studies have not been published. [106, 107] Patients with ReA who have HIV infection or AIDS should not receive methotrexate or other immunosuppressive agents.

Case reports have demonstrated the effectiveness of anti-TNF medications, such as etanercept and infliximab, [56, 96, 98, 108] though there remains a need for randomized, double-blind trials. The high concentrations of TNF-α in the serum and joints of patients with persistent ReA suggest that this cytokine could be targeted in patients who do not respond to NSAIDS and DMARDs. Anti−TNF-α therapy has been demonstrated to be effective treatment for ReA, with a corticosteroid-sparing effect. [109]

However, TNF-α antagonists can increase the risk of serious infection, and it is important to conduct infectious screening and monitoring with a high index of suspicion, as well as preemptive treatment, when such medications are used. [8] Anti-TNF medications can also be associated with severe glomerulonephritis, and it is recommended that renal function be closely monitored in patients treated with these agents. [14]

Interleukin (IL)-6 plays an important role in regulating immune response. Unregulated overproduction of IL-6, however, is pathologically involved in various immune-mediated inflammatory diseases, including ReA. Tocilizumab, a humanized anti–IL-6 receptor antibody, may provide clinical benefit in patients who are refractory to conventional therapy or anti-TNF therapy. [110] However, further clinical studies are required.

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