DISCUSSION
To our knowledge, this is the first study that has investigated
immunogenicity in both rheumatic (RA and SpA) and digestive (CD)
pathologies.
In our study, the presence of ADAbs was not correlated with disease
activity. However, the presence of ADAb was inversely correlated to the
trough levels of IFX and ADA.
Our study had some limitations. Firstly, the number of patients for each
pathology was not large. Besides, we did use the solid phase ELISA. It
is the simplest and most widely used method [13]. However, it can
give false positives due to its possible interaction with RF (frequently
associated with inflammatory conditions), but also false negatives as it
does not detect complexed ADAbs. It is a method that only allows the
determination of free ADAbs, thus we cannot differentiate between
neutralising and non-neutralising ADAbs [14,15].
Our results showed that IFX was the most immunogenic biologic (40%)
compared to ADA (25%), without a statistically significant difference.
Several authors agree that IFX is more immunogenic than ADA [16,17].
This could be explained by the fact that ADA, being a human antibody, is
less likely to form ADAbs than IFX which is a chimeric antibody [4].
Besides, we found that IFX which is administered through intravenous
courses, was more immunogenic than ADA which is administered
subcutaneously. Schellekens et al. compared the intravenous and
subcutaneous routes for Abatacept and found an increase in
immunogenicity in patients who received the intravenous route [18].
However, the subcutaneous route is known to be more immunogenic than the
intravenous route, as it exposes more antigen presenting cells such as
dendritic cells [19].
In our study, the combination of MTX with biologic in CD reduced
immunogenicity (p=0.04). The dose of MTX was higher in ADAbs- patients
in RA (p=0.04) and CD (p=0.005). This protective role of MTX on ADAbs
formation was not found in SpA. Maini et al. were the first to
investigate the role of MTX in reducing the immunogenicity of IFX in RA.
They included 101 patients receiving 1mg/kg or 3mg/kg or 10mg/kg of IFX,
and found that the combination of 7.5mg/week MTX reduced ADAbs formation
by 53%, 21% and 7% respectively [20]. In SpA, the question of the
role of synthetic DMARDs in immunogenicity has also been raised.
Plasencia et al. included 94 SpA patients and reported that ADAbs was
more frequently found in patients receiving IFX alone than in those
receiving it in combination with MTX (34% versus 11%). They also
reported that MTX delayed the formation of ADAbs during patient
follow-up, which may partly explain why other short-term studies have
not demonstrated a beneficial role for MTX in the immunogenicity of SpA
[21].
The exact mechanism behind the reduction of immunogenicity by DMARDs
remains unclear. Indeed, it is well known that immunomodulators such as
MTX interfere with the immune response, possibly inducing a decrease in
antibody production [22].