Brigitte Bader-Meunier1, Roman Krzysiek2, Irène Lemelle3, Christine Pajot4, Aurélia Carbasse5, Sylvaine Poignant6, Isabelle Melki7, Pierre Quartier8, Laure Choupeaux9, Elodie Henry9, Jean-Marc Treluyer10, Alexandre Belot11, Salima Hacein-Bey-Abina12, Saik Urien10. 1. Service d'Immunologie-hématologie et Rhumatologie pédiatrique, Institut Imagine, Hôpital Necker, Assistance Publique Hôpitaux de Paris, France & Centre National de Référence RAISE, 149 rue de Sèvres, 75015 Paris, France. Electronic address: brigite.bader-meunier@aphp.fr. 2. Service d'Immunologie Biologique, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France; INSERM -UMR_S996, Université Paris-Saclay, Clamart, France. 3. Service d'Hémato-Onco Pédiatrie, CHRU Nancy, 54511 Vandoeuvre les Nancy, France. 4. Service de Néphrologie et Rhumatologie pédiatrique, Hôpital Purpan, Toulouse, France. 5. Service de Pédi atrie générale, Hôpital A de Villeneuve, Montpellier, France. 6. Service de Pédiatrie générale, Hôpital Mère-Enfants, Nantes, France. 7. Service de Pédiatrie générale, Hôpital Robert Debré, Paris, France. 8. Service d'Immunologie-hématologie et Rhumatologie pédiatrique, Institut Imagine, Hôpital Necker, Assistance Publique Hôpitaux de Paris, France & Centre National de Référence RAISE, 149 rue de Sèvres, 75015 Paris, France; Université Sorbonne Paris Cité, Paris, France. 9. Unité de Recherche Clinique Paris Descartes Necker Cochin, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Tarnier, Paris, France. 10. Unité de Recherche Clinique Paris Descartes Necker Cochin, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Tarnier, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, EA 7323, Paris, France. 11. Service de Néphrologie, Rhumatologie et Dermatologie pédiatriques, Hôpital Femme-Mère-Enfants, Hospices Civils de Lyon, France & Centre National de Référence RAISE, Bron, France; INSERM U1111, Université de Lyon 1, France. 12. Service d'Immunologie Biologique, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France; UTCBS, CNRS UMR 8258, INSERM U1022, Faculté de Pharmacie de Paris, Université Sorbonne-Paris-Cité, Université Paris- Descartes, Paris, France.
Abstract
OBJECTIVE: To investigate the relationship of clinical response of Juvenile Idiopathic Arthritis (JIA) to etanercept (ETN) with ETN levels, and the presence of anti-drug antibodies to ETN (ADAb). METHODS: Prospective study of JIA patients under 18 years old. Clinical and pharmacological data were collected at two visits. JIA clinical inactivity and activity were assessed according to the Wallace criteria and to the Juvenile Arthritis Disease Activity Score (JADAS). ETN and ADAb serum levels assessments were determined using ELISA-based assays. RESULTS: 126 patients were enrolled. The median duration of ETN treatment at inclusion was 569 days (range 53-2340). ADAb were undetectable (<10 ng/ml) in 171/218 (78%) samples and were > 25 ng/mL in 2/218 samples. No significant relationship between ETN concentration and the clinical inactivity status and JIA activity was found using either univariate logistic regression or multiple logistic regression analysis, adjusted on one individual descriptors, time since diagnosis, time of sampling, use of corticosteroids or methotrexate and classification of JIA. No correlation was found between the remission status and the detection of ADAb. CONCLUSION: This study did not demonstrate any correlation between JIA activity and circulating ETN levels in a large population of patients with JIA previously treated with ETN for at least 1.5 months. As described for adults, our study confirms that ETN is marginally immunogenic in pediatric patients. These results do not support the clinical usefulness of a monitoring of ADAb or ETN concentrations for the management of this group of JIA patients if they fail to achieve clinical inactive disease.
OBJECTIVE: To investigate the relationship of clinical response of Juvenile Idiopathic Arthritis (JIA) to etanercept (ETN) with ETN levels, and the presence of anti-drug antibodies to ETN (ADAb). METHODS: Prospective study of JIA patients under 18 years old. Clinical and pharmacological data were collected at two visits. JIA clinical inactivity and activity were assessed according to the Wallace criteria and to the Juvenile Arthritis Disease Activity Score (JADAS). ETN and ADAb serum levels assessments were determined using ELISA-based assays. RESULTS: 126 patients were enrolled. The median duration of ETN treatment at inclusion was 569 days (range 53-2340). ADAb were undetectable (<10 ng/ml) in 171/218 (78%) samples and were > 25 ng/mL in 2/218 samples. No significant relationship between ETN concentration and the clinical inactivity status and JIA activity was found using either univariate logistic regression or multiple logistic regression analysis, adjusted on one individual descriptors, time since diagnosis, time of sampling, use of corticosteroids or methotrexate and classification of JIA. No correlation was found between the remission status and the detection of ADAb. CONCLUSION: This study did not demonstrate any correlation between JIA activity and circulating ETN levels in a large population of patients with JIA previously treated with ETN for at least 1.5 months. As described for adults, our study confirms that ETN is marginally immunogenic in pediatric patients. These results do not support the clinical usefulness of a monitoring of ADAb or ETN concentrations for the management of this group of JIA patients if they fail to achieve clinical inactive disease.