Abstract

Immune-mediated inflammatory diseases (IMIDs), such as spondyloarthritis (SpA), psoriasis, Crohn's disease (CD), and rheumatoid arthritis (RA) remain challenging illnesses. They often strike at a young age and cause lifelong morbidity, representing a considerable burden for the affected individuals and society. Pioneering studies have revealed the presence of a TNF-dependent proinflammatory cytokine cascade in several IMIDs, and the introduction of anti-TNF therapy 20 years ago has proven effective to reduce inflammation and clinical symptoms in RA, SpA, and other IMID, providing unprecedented clinical benefits and a valid alternative in case of failure or intolerable adverse effects of conventional disease-modifying antirheumatic drugs (DMARDs, for RA) or non-steroidal anti-inflammatory drugs (NSAIDs, for SpA). However, our understanding of how TNF inhibitors (TNFi) affect the immune system in patients is limited. This question is relevant because anti-TNF therapy has been associated with infectious complications. Furthermore, clinical efficacy of TNFi is limited by a high rate of non-responsiveness (30–40%) in RA, SpA, and other IMID, exposing a substantial fraction of patients to side-effects without clinical benefit. Despite the extensive use of TNFi, it is still not possible to determine which patients will respond to TNFi before treatment initiation. The recent introduction of antibodies blocking IL-17 has expanded the therapeutic options for SpA, as well as psoriasis and psoriatic arthritis. It is therefore essential to develop tools to guide treatment decisions for patients affected by SpA and other IMID, both to optimize clinical care and contain health care costs. After a brief overview of the biology of TNF, its receptors and currently used TNFi in the clinics, we summarize the progress that has been made to increase our understanding of the action of TNFi on the immune system in patients. We then summarize efforts dedicated to identify biomarkers that can predict treatment responses to TNFi and we conclude with a section dedicated to the recently introduced inhibitors of IL-17A and IL-23 in SpA and related diseases. The focus of this review is on SpA, however, we also refer to RA on topics for which only limited information is available on SpA in the literature.

Highlights

  • Immune-Mediated InflammatoryDiseases—An OverviewImmune-mediated inflammatory diseases (IMID) is a term used to define a group of clinically heterogeneous, unrelated conditions that share common inflammatory pathways and derive from aberrant immune responses of the human adaptive or innate immune system

  • The study was performed on 155 SpA patients (117 treated with etanercept, 38 with infliximab) and clearly demonstrated that all the markers of inflammation tested, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score were significantly decreased after anti-TNF therapy

  • We showed that SpA patients carrying risk-associated alleles of genes in the IL-23/IL-17 pathway expressed high levels of genes involved in the differentiation and function of Th17 and Th1 cells, whereas the presence of protective alleles was associated with low-level expression of these genes

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Summary

Introduction

Immune-Mediated InflammatoryDiseases—An OverviewImmune-mediated inflammatory diseases (IMID) is a term used to define a group of clinically heterogeneous, unrelated conditions that share common inflammatory pathways and derive from aberrant immune responses of the human adaptive or innate immune system. Multiplex assay NK and B cell numbers reduced in patients vs controls, increased after anti-TNF therapy in responders.

Results
Conclusion
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