The relationship between drug-induced immunogenicity and hypersensitivity reactions and skin tests related to infliximab, etanercept and adalimumab in patients with rheumatoid arthritis and ankylosing spondylitis.

Abstract

Background/aim: We aimed to investigate the relationship between serum antidrug antibodies (ADAbs), systemic hypersensitivity, or local injection site reactions to tumor necrosis factor (anti-TNF) drugs and to detect the role of skin tests in the diagnosis of hypersensitivity reactions (HSRs) against anti-TNFs.

Materials and methods: Sixty-nine ankylosing spondylitis (AS) and 46 rheumatoid arthritis (RA) patients taking infliximab (IFX), adalimumab (ADA), and etanercept (ETN) were enrolled. The demographical data, erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP) levels of the patients were determined, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) assessment for AS patients and DAS28 (disease activity score) for RA patients were assessed. Serum levels of anti-TNFs and ADAbs to these agents were measured with ELISA. These blood samples were taken 24 h before the next drug dose. The patients with anti-TNF-associated HSRs were evaluated with a skin-prick test (SPT) and intradermal test (IDT). Readings for the SPT and IDT were conducted after 15 min and 24, 48, and 72 h. Heel diameter of 3 mm or more greater than the negative control was considered positive for SPT, and if the size of the initial wheal had increased by at least 3 mm in diameter and was surrounded by erythema it was considered positive for IDT. Symptoms such as urticaria/angioedema and flushing were considered immediate-type HSRs. Findings developed at the injection site such as swelling and erythema were considered injection-site reactions (ISRs). An overall p < 0.05 was considered statistically significant.

Results: A statistically significant association was found between HSRs (immediate type and ISRs) and IDT reported by patients taking biological drugs (p = 0.001). In the subgroup analysis, a statistically significant association was found between ISRs and IDT in those taking ADA and ETN (respectively p = 0.012, p = 0.013). No relationship was found between skin test positivity and the presence of IgG ADAbs to anti-TNFs or disease activity scores.

Conclusion: This study demonstrates that patients who exhibit ISRs to anti-TNFs produce notably positive results to IDT without maintaining a direct relationship to serum levels of ADAbs.