Editors' ChoiceAutoimmune Disease

The Biological Response to Biologics

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Science Translational Medicine  27 Apr 2011:
Vol. 3, Issue 80, pp. 80ec61
DOI: 10.1126/scitranslmed.3002541

Anti-tumor necrosis factor–α (TNF-α) therapy, such as monoclonal antibodies and soluble TNF-α receptor decoys, has revolutionlized the treatment of many autoimmune and inflammatory diseases. Anti–TNF-α therapies are routinely used to treat rheumatoid arthritis (RA) because TNF-α is recognized as the “master regulator” of the inflammatory response in organ systems affected by RA. Similar antibody-based therapeutics, or “biologics,” against other immune system modulators are available for diseases ranging from cancer to multiple sclerosis. However, an eventual loss of therapeutic activity has been reported for these biologics, and it is believed that patients develop antidrug antibodies, resulting in diminished treatment response.

Bartelds et al. studied the response of 272 RA patients to the anti–TNF-α drug adalimumab, specifically looking for a correlation with the development of anti-adalimumab antibodies. The authors showed that almost 30% of RA patients developed antidrug antibodies. Importantly, the presence of antibodies was linked to treatment failure, increased RA activity score (a measurement of joint pain and inflammation), and decreased ability to achieve clinical remission. The development of these antibodies occurred early (< 28 weeks) in two-thirds of RA patients, which correlated with decreased drug concentration in the bloodstream. It is unclear why some patients develop these antibodies, but Bartelds and colleagues speculate that individual genetic differences, concomitant use of other antirheumatic drugs, and temporal fluctuations in RA disease activity may be responsible.

The discovery of antidrug antibodies is important, especially for anti–TNF-α biologic therapy, because early detection of these antibodies will allow switching RA patients to another drug with a differing mechanism of action, such as methotrexate or TNF-α receptor decoys. Furthermore, identifying antidrug antibodies in response to other biologic drugs could help modify treatment regimens for many autoimmune and inflammatory diseases. In the near future, rheumatologists might be able to use our body’s own biological response to biologics to predict disease responsiveness earlier and to avoid irreversible damages to tissues, including joints, lungs, and kidneys.

G. M. Bartelds et al., Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA 305, 1460–1468 (2011). [Abstract]

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