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Personalized medicine in rheumatoid arthritis: How immunogenicity impacts use of TNF inhibitors

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  1. Hydroxychloroquine reduces IL-6 and pro-thrombotic status

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  2. The study of interactions between genome and exposome in the development of systemic lupus erythematosus

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  1. Therapeutic thresholds and mechanisms for primary non-response to infliximab in inflammatory bowel disease

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  2. Pattern recognition receptor polymorphisms in early periodontitis

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  3. Lewis and AB0 blood group-phenotypes in periodontitis, cardiovascular disease, obesity and stroke

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  4. Gasotransmitters and the immune system: Mode of action and novel therapeutic targets

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  • Caterina Bodio
  • Claudia Grossi
  • Francesca Pregnolato
  • Ennio Giulio Favalli
  • Martina Biggioggero
  • Antonio Marchesoni
  • Antonella Murgo
  • Matteo Filippini
  • Paola Migliorini
  • Roberto Caporali
  • Raffaele Pellerito
  • Francesco Ciccia
  • Piercarlo Sarzi-Puttini
  • Federico Perosa
  • Giuseppe Paolazzi
  • Ivana Hollan
  • Klaus Bendtzen
  • Pier Luigi Meroni
  • Maria Orietta Borghi
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Up to 40% of patients treated with tumor necrosis factor alpha inhibitors (TNFi) do not respond to therapy. Testing drug bioavailability and/or anti-drug antibody (ADAb) levels may justify dosage adjustment or switch to different drugs, enabling a personalized medicine approach. We report a multicenter cross-sectional study on different methods [ELISA and a cell based functional assay (reporter gene assay - RGA)] for drug/ADAb detection, and on the relationship between drug bioavailability and ADAb. 163 patients with rheumatoid arthritis (RA) treated with infliximab (IFX; n = 67), adalimumab (ADL; n = 49) or etanercept (ETA; n = 47) were tested for drug and ADAb levels. Furthermore, we report prospective data from additional 70 patients (59 RA and 11 juvenile idiopathic arthritis - JIA) tested for drug and ADAb levels at baseline (T0) and after 3 (T3) and 6 months (T6) of treatment with ADL or ETA only. IFX-treated patients were not included because of the increasing use of IFX biosimilars. Stringent inclusion criteria were used in order to avoid unwanted variables in both studies; none of the patients used TNFi before the study, and TNFi was used only in combination with methotrexate. Clinical response was defined according to EULAR response criteria. The two assays performed comparably in the comparison study. Accordingly, ELISA was selected for the prospective study because of its feasibility in the clinical setting. The cross-sectional study found ADAb in IFX and ADL treated groups only, that were associated with a decrease in pharmacological drug availability in the blood. Comparable results were found for the ADL-treated group in the prospective study which also showed a relationship between drug/ADAb levels and the loss of clinical response. Altogether our findings support drug and anti-drug Ab monitoring in the real-world clinical setting thus enabling individualized treatment and reducing disability in chronic inflammatory arthritis.

Original languageEnglish
JournalAutoimmunity Reviews
Volume19
Issue number5
Pages (from-to)102509
ISSN1568-9972
DOIs
Publication statusPublished - May 2020

    Research areas

  • Adalimumab/therapeutic use, Antirheumatic Agents/therapeutic use, Arthritis, Rheumatoid/drug therapy, Biosimilar Pharmaceuticals/therapeutic use, Cross-Sectional Studies, Etanercept/therapeutic use, Female, Humans, Infliximab/therapeutic use, Male, Middle Aged, Precision Medicine, Prospective Studies, Treatment Outcome, Tumor Necrosis Factor Inhibitors/therapeutic use, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Inflammatory arthritides, Immunogenicity, Anti-drug antibody, Precision medicine, Tumor necrosis factor inhibitors

ID: 61865294