DMARDs Cut Immunogenicity of Some Anti-TNF Drugs

Jani M, Barton A, Warren, RB, et al. The role of DMARDs in reducing the immunogenicity of TNF inhibitors in chronic inflammatory diseases.Rheumatology (2013) doi:10.1093/rheumatology/ket260 [published online: August 14, 2013]

A  literature review documents the evidence that certain tumor necrosis-alpha (TNFα) inhibitors can trigger production of antidrug antibodies in inflammatory diseases such as rheumatoid arthritis (RA), Crohn’s disease, psoriatic arthritis, and possibly ankylosing spondylitis. The result can be reduced serum levels and consequently diminished effectiveness of those biologics, leading to loss of therapeutic response over time.

However, the review also concludes that concomitant use of methotrexate (MTX) or other disease modifying anti-rheumatic drugs (DMARDs) can reduce such immunogenicity in patients with these disorders.  

Specific anti-TNF drugs cited as associated with anti-drug antibodies include infliximab and adalimumab. Infliximab induced these antibodies in 33% to 44% of RA patients in studies ranging from 12 weeks to six months in duration, and adalimumab triggered their production in 20% to 28% of patients in studies ranging from three to six years' followup. However, in these same studies concurrent use of MTX or of DMARDs such as prednisone or azathioprine was associated with reduced levels of these antibodies. One meta-analysis found that immunosuppressants, primarily MTX, reduced by 41% the proportion of patients taking infliximab and adalimumab who showed detectable antibodies against TNF inhibitors.

It’s unclear just how MTX reduces the immunogenicity of these inhibitors, but the review suggests that suppression of early T- and B-cell expansion may be one mechanism. A synergistic anti-inflammatory effect between DMARDS and biologics may also play a role.

The potential for MTX and other DMARDs to prolong the efficacy of anti-TNFs would not only have "significant cost implications," the review concludes, but would offer the "clear benefits" of longer disease-free remission for those patients who respond initially to TNF inhibitors.