SAN FRANCISCO, CA—Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) who develop hypersensitivity reactions to infliximab, etanercept and adalimumab are more likely to have positive skin tests despite the absence of an overall relationship with antidrug antibody (ADA) levels, according to a study reported at the 2015 ACR/ARHP Annual Meeting.

“This study demonstrates that patients who exhibit a hypersensitive reaction to anti-TNF drugs produce notably positive results to skin testing without maintaining a direct relationship to serum levels of ADA,” reported lead study author Firas Doghanji, Physical Medicine and Rehabilitation, Ankara University Faculty of Medicine, in Ankara, Turkey, and coauthors.

Anti-TNF drugs can cause systemic or local hypersensitivity reactions, including “skin irritation, edema, erythema, urticaria, papulopustular rash, eczanthem, and skin peeling,” the researchers noted. In clinical practice, that can limit the use of biologics “and can sometimes even lead to termination of treatment,” Doghanji noted. In order to assess associations between serum ADA and local injection-site or systemic hypersensitivity during anti-TNF therapy, the study authors studied 69 patients diagnosed with AS and 46 patients diagnosed with RA, who were using infliximab, adalimumab, or etanercept.

Patients with anti-TNF-associated hypersensitivity reactions “were evaluated with skin prick (full strength)/ intradermal tests (1/1000 to 1/10 dilutions) with implicated anti-TNF agents,” the team reported. “Readings were conducted after 15 minutes and 24, 48, and 72 hours and considered positive if the size of the initial wheal had increased by at least 3mm in diameter and was surrounded by erythema.”

Overall, 28.6% of patients had a history of hypersensitivity reaction to the anti-TNF drugs. Hypersensitivity reactions were significantly associated with skin test positivity (P=0.001).   

“[A] statistically significant relation was identified between injection site reactions and skin test positivity in patients using etanercept and adalimumab (P=0.001 and P=0.02, respectively),” the researchers reported. “No relation was found between skin test positivity and the presence of ADA to anti-TNFs, and disease activity scores.”