Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay
Rattachement africain : nl, us, gb. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Patients with rheumatoid arthritis (RA) can be successfully treated with tumor necrosis factor (TNF) inhibitors, including the monoclonal antibody adalimumab. Once in remission, a proportion of patients can successfully discontinue treatment, indicating that blocking TNF is no longer required for disease control. To explore the dynamics of circulating TNF during adalimumab treatment, we developed a competition enzyme-linked immunosorbent assay that can quantify TNF in the presence of large amounts of TNF inhibitor, i.e., a "drug-tolerant" assay. In 193 consecutive adalimumab-treated patients with RA, we demonstrated that circulating TNF increased in average of >50-fold upon treatment and reached a stable concentration in time for most patients. A similar increase in TNF was found in 30 healthy volunteers after one dose of adalimumab. This implies that TNF in circulation during anti-TNF treatment is not primarily associated with disease activity. During treatment, TNF was in complex with adalimumab and could be recovered as inactive 3:1 adalimumab-TNF complexes. No quantitative association was found between TNF and adalimumab concentrations. Low TNF concentrations at week 4 were associated with a higher frequency of antidrug antibodies (ADAs) at subsequent time points, less frequent methotrexate use at baseline, and less frequent remission after 52 weeks. Also in healthy volunteers, early low TNF concentrations are associated with ADAs. In conclusion, longitudinal TNF concentrations are mostly stable during adalimumab treatment and may therefore not predict successful treatment discontinuation. However, early low TNF is strongly associated with ADA formation and may be used as timely predictor of nonresponse toward adalimumab treatment.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Dynamics of circulating TNF during adalimumab treatment using a drug-tolerant TNF assay
- Date Crossref
- 30/01/2019
- Éditeur
- American Association for the Advancement of Science (AAAS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Sanquin pays non établi dans la noticeOrganisation à but non lucratif
-
Reade pays non établi dans la noticeStructure de recherche
-
Amsterdam Neuroscience pays non établi dans la noticeStructure de recherche
-
Amsterdam UMC Location Vrije Universiteit Amsterdam pays non établi dans la noticeÉtablissement de santé
-
Amsterdam UMC Location University of Amsterdam Department of Immunopathology pays non établi dans la noticeÉtablissement de santé
-
Pfizer (United States) pays non établi dans la noticeEntreprise
-
King's College - North Carolina pays non établi dans la noticeUniversité ou école supérieure
-
King's College London pays non établi dans la noticeUniversité ou école supérieure
-
Amsterdam Rheumatology and immunology Center pays non établi dans la noticeInstitution
-
VU University Medical Center Amsterdam UMC pays non établi dans la noticeUniversité ou école supérieure
-
Academic Medical Center Amsterdam UMC pays non établi dans la noticeÉtablissement de santé
-
Collegeville Pfizer Inc. pays non établi dans la noticeUniversité ou école supérieure
Sanquin, Reade et Amsterdam Neuroscience, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.