Patterns and determinants of response to novel therapies in juvenile and adult-onset polyarthritis

Author:

Triaille Clément123ORCID,Quartier Pierre456ORCID,De Somer Lien367,Durez Patrick18ORCID,Lauwerys Bernard R1,Verschueren Patrick69,Taylor Peter C10ORCID,Wouters Carine3467

Affiliation:

1. Pôle de Pathologies Rhumatismales Systémiques et Inflammatoires, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium

2. Department of Pediatric Hematology, Oncology, Immunology and Rheumatology, Cliniques Universitaires Saint-Luc , Brussels, Belgium

3. Division of Pediatric Rheumatology, Department of Pediatrics, University Hospitals Leuven , Leuven, Belgium

4. Department of Pediatric Immunology, Hematology and Rheumatology, Necker-Enfants Malades Hospital, AP-HP , Paris, France

5. Université Paris-Cité , Paris, France

6. Member of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases – Project ID No. 739543

7. Department of Microbiology and Immunology, University of Leuven , Leuven, Belgium

8. Department of Rheumatology, Cliniques Universitaires Saint-Luc , Brussels, Belgium

9. Department of Rheumatology, University Hospitals Leuven , Leuven, Belgium

10. Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford , Oxford, UK

Abstract

Abstract Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA (pJIA) and RA display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, the therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. The mechanisms and determinants of this heterogeneous response are diverse and complex, such that the development of true ‘precision’-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in pJIA in comparison with what is known in RA. Although some biomarkers have been identified that stratify with respect to the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment–response mechanisms. Consequently, we propose a pragmatic, patient-centred and clinically based approach, i.e. personalized instead of biomarker-based precision medicine in JIA.

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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