Relationship between immunogenicity, hypersensitivity reactions and skin
tests against Infliximab, Etanercept and Adalimumab in patients with rheumatoid arthritis and ankylosing
spondylitis

Background/Purpose:

Anti-TNF drugs can cause systemic or
local hypersensitivity reactions.In this study, we aimed to investigate relationships
between serum antidrug antibody (ADA), systemic hypersensitivity or local
injection site reactionsduring anti-TNF drugs treatmentand to detect the role
of skin tests in the diagnosis of hypersensitivity reactions to anti-TNFs.

Methods:

According
to 1984 Modified New York Criteria and 1987 ACR classification criteria, 69 AS
patients who were using Infliximab, Adalimumab, and Etanercept (n=25, 21, and
23 respectively) and 46 RA patients who were using Infliximab, Adalimumab, and Etanercept
(n=9, 20, and 17 respectively) were enrolledin the study.Demographical data,
ESR and CRP levels in the serum of the patients were determined, and BASDAI for
AS patients and DAS28 for RA patients were assessed.Serum levels of anti-TNFs and ADA to these
agents were measured with ELISA methods (Progenika Biopharma SA, Derio Spain).
The patients withanti-TNF associated hypersensitivity reactions were evaluated withskin
prick (full strenght)/ intradermal tests (1/1000 to 1/10 dilutions) with
implicated anti-TNF agents..Readings were conducted after 15 min and 24, 48,
and 72 hoursand considered positive if the size of the initial wheal had
increased by at least 3 mm in diameter and was surrounded by erythema.

Results:

In total, 28.6% of patients had a
history of hypersensitivity reaction to the anti-TNF drugs. Statistically
significant relation was identified between hypersensitivity reactions and skin
test positivity in all patients (p=0,001) (Table 1). Statistically significant
relation was identified between injection site reactions and skin test
positivity in patients using Etanercept and Adalimumab (p=0,001, p=0,02
respectively). No relation was found between skin test positivity and the
presence of ADAto Anti-TNFs, and disease activity scores.Skin testswith
anti-TNFs results in significantly more positive in patients with normal drug
levelscompared with patients with low drug levels (table 2).

 Conclusion:

This study demonstrates that
patients whoexhibit a hypersensitive reaction to anti-TNF drugs produce notably
positive results to skin testing without maintaining a direct relationship to
serum levels of ADA. There is a need for more comprehensive studies in this
field.

Table 1.Relationship
allergic reactions and skin test positivity

Table 2.Relationship
between drug level and skin prick test