Anti-drug antibodies in psoriasis: a critical evaluation of clinical significance and impact on treatment response

Abstract

TNF inhibitors and anti-p40IL12/23 monoclonal antibodies are efficacious treatments for moderate-to-severe psoriasis. However, the formation of anti-drug antibodies (ADA) with biologics may prevent patients from achieving a full clinical response. ADA have been reported in patients treated with etanercept, infliximab, adalimumab or ustekinumab at rates of 0–18.3%, 5.4–43.6%, 8.8–44.8% and 3.8–5.4%, respectively. Antibodies against etanercept have no apparent effects on clinical response, whereas antibodies against infliximab or adalimumab have been associated with diminished clinical response. The significance of ADA against ustekinumab is yet to be determined. Data regarding management strategies to counteract ADA formation and their effects are limited in psoriasis patients. However, some evidence suggests that concomitant immunomodulators such as methotrexate may suppress ADA development in psoriasis. ADA specific to one biologic do not appear to carry cross-linking potential with other biologic agents. ADA formation needs to be considered as a possible factor contributing to diminished response from biologic agents.

Keywords::

• adalimumab
• anti-drug antibodies
• etanercept
• infliximab
• methotrexate
• psoriasis
• ustekinumab

Financial & competing interests disclosure

AW Armstrong has served as an investigator, advisor and/or speaker to AbbVie, Amgen, Janssen, Ely Lilly, Merck, Pfizer and Modernizing Medicine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • In patients with psoriasis, the presence of anti-drug antibodies (ADA) has been associated with diminished clinical response to certain biologic agents.

• • Antibodies against etanercept are non-neutralizing and appear to have no significant effect on clinical response or treatment safety.

• • Antibodies against infliximab, adalimumab or ustekinumab have been associated with diminished clinical response.

• • The effect of concurrent administration of immunomodulators with biologics on ADA formation has been sparsely examined in psoriasis. However, data on other inflammatory diseases such as rheumatoid arthritis and Crohn’s disease have shown that concomitant immunosuppressive therapy can reduce the incidence of ADA.

• • Changing biologic agents may be one strategy in overcoming ADA-associated decreased clinical response because ADA do not carry cross-linking potential with multiple biologic agents.

• • Future research is needed to identify risk factors for ADA development and investigate management strategies for optimized treatment response.