title: Low pretreatment levels of myeloid-related protein-8/14 and C-reactive protein predict poor adherence to treatment with tumor necrosis factor inhibitors in juvenile idiopathic arthritis.
abstract: Two thirds of patients with juvenile idiopathic arthritis (JIA) treated with tumor necrosis factor (TNF)-alpha inhibitors respond initially, but only about one third of patients achieve clinical remission at follow-up. We evaluated the 1-year response and long-term treatment adherence to TNF inhibitor treatment in JIA patients naive to biologics and investigated if baseline myeloid-related protein (MRP)-8/14 and C-reactive protein (CRP) were predictive of treatment response. One hundred fifty-two patients were included in a unicenter observational, prospective study from 2002 to 2015, excluding patients with systemic-onset JIA. One-year treatment response was evaluated by American College of Rheumatology-pediatric (ACR-ped) and by the number of patients achieving inactive disease (ID). Medical charts were reviewed for reasons of treatment withdrawal. After one year of treatment ACR-ped 30, 50, 70, and 90 were achieved by 61, 55, 38, and 10 % of the patients, and 23 % achieved a status of ID. Treatment adherence: 51 % withdrew from treatment due to lack of clinical effect, while 32 % continued treatment or withdrew due to disease remission. Increased MRP-8/14 concentrations at treatment initiation was associated with ID after 1 year (OR 1.55, CI 1.06-2.25, p = 0.02). Treatment withdrawal due to lack of effect was associated with low baseline levels of both MRP-8/14 (685 vs. 1235 ng/ml, p < 0.001) and CRP (0.75 vs. 2.73 mg/l, p < 0.001), verified by multivariable logistic regression analysis (OR 0.51, CI 0.34-0.77/OR 0.63, CI 0.48-0.83). In conclusion, an association was found between ID after 1 year of treatment and increased baseline levels of MRP-8/14. Furthermore, low baseline MRP-8/14 and CRP concentrations were associated with treatment withdrawal due to lack of clinical effect.
authors: Department of Pediatrics, Naestved Hospital, Naestved, Denmark. mikel@dadlnet.dk.|Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. mikel@dadlnet.dk.|Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. mikel@dadlnet.dk.
authors: Mikel
authors: M
authors: Alberdi-Saugstrup
authors: Department of Pediatrics, Naestved Hospital, Naestved, Denmark.
authors: Susan
authors: S
authors: Nielsen
authors: Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Pernille
authors: P
authors: Mathiessen
authors: Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Claus Henrik
authors: CH
authors: Nielsen
authors: Department of Pediatrics, Naestved Hospital, Naestved, Denmark.|Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Klaus
authors: K
authors: Müller
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000737:chemistry*; D040501:Calgranulin A / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation; D008297:Male; D055118:Medication Adherence; D015999:Multivariate Analysis; D011446:Prospective Studies; D012044:Regression Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Biomarkers < methodology; Clinical trials < methodology; High-sensitivity CRP; Juvenile idiopathic arthritis < rheumatic diseases; Myeloid-related protein; TNF inhibitor