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].