Abstract
Spondyloarthritis (SpA) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by an aberrant immune response and inflammation with a key role for TNF in their pathogenesis. Accordingly, TNF-inhibiting therapy (TNFi) has dramatically improved the management of these diseases. However, about 30% of patients discontinue TNFi for lack of response, loss of response, and side effects and/or adverse events. Thus, the possibility to identify in advance those patients who will have a good response to TNFi would be extremely beneficial. The aim of this study was to investigate differences between males and females with either SpA or IBD in response to TNFi molecules, i.e., infliximab (IFX) and adalimumab (ADA), considering the reasons for TNFi withdraw. Data of 594 patients, 349 with IBD (M/F: 194/155) and 245 with SpA (M/F: 123/122), previously unexposed to TNFi, were collected. In the IBD group, the rate of female patients discontinuing ADA was significantly higher than that of male patients (p = 0.03). No difference emerged according to the distribution of reason for discontinuation. Otherwise, a similar discontinuation rate between female and male patients receiving IFX therapy was observed. In the SpA group, the overall discontinuation rate was not different between males and females both for ADA and IFX. However, in patients treated with ADA, males interrupted therapy more frequently than females due to lack of response (p = 0.03). In conclusion, the assessment of sex differences in TNFi response could help physicians personalize the therapeutic approach in a sex-oriented perspective.
Highlights
Chronic inflammatory diseases are a group of pathologies with different clinical features, but with shared pathogenetic mechanisms leading to a not resolving inflammation
The introduction of TNFinhibiting therapy (TNFi) has dramatically improved the management of SpA and inflammatory bowel diseases (IBD)
The rate (30/109, 27.5%) of male patients discontinuing IFX was significantly (p = 0.0018) higher than that discontinuing ADA (8/85, 9%). This observation suggested a better success of ADA than IFX treatment in male patients with IBD
Summary
Chronic inflammatory diseases are a group of pathologies with different clinical features, but with shared pathogenetic mechanisms leading to a not resolving inflammation. IBD is a group of chronic systemic diseases causing inflammation of the gastrointestinal tract. Several lines of evidence support a key pathogenic role for TNF in perpetuating chronic inflammation of SpA and IBD. The pathogenic effect of TNF is related to its ability to disrupt the integrity of intestinal epithelium and affect the activity of regulatory T cells and regulatory macrophages (Slebioda and Kmiec, 2014). In the treatment of SpA and IBD, corticosteroids and immunosuppressive agents are used to induce and maintain long-term remission. When these drugs fail to achieve sufficient disease control, biologic agents are used. About 30% of patients do not respond to TNFi at all or lose their initial response over time. The ability to identify in advance those patients who will have a good response to TNFi would be extremely beneficial
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