We selected all patients who discontinued etanercept because of sustained good clinical response determined by the treating doctor. The outcome measures to assess disease activity consisted of the JIA core set of six response variables. 4 To evaluate the disease course we used the criteria for inactive disease on medication (IDM) or off medication (ID) and the criteria for clinical remission on medication (CRM) or off medication (CR) by Wallace.5 6 We defined erythrocyte sedimentation rate (ESR) values under 16 mm/h as normal and stated that a doctor's overall assessment score below 10 mm on a visual analogue scale (VAS) indicated no disease activity.7 Differences were tested with the Mann-Whitney U test using level of significance p,0.05.In all, 19 patients on the ABC register discontinued etanercept because of a sustained good clinical response. Most data on these patients were prospectively collected in the register, more detailed data on disease activity after etanercept discontinuation were collected retrospectively.Characteristics and disease course of each individual patient are shown in table 1.After discontinuation 10 patients (53%) retained remission over a median of 0.8 years (interquartile range (IQR) 0.5 to 2.8). They used etanercept longer (3.5 vs 2.1 years, p = 0.21) and showed a longer median period of CRM (1.5 vs 0 years, p = 0.004) compared to the nine patients who experienced flares. None of the juvenile arthritis psoriatica patients had psoriatic lesions and the enthesitis-related arthritis patient had no enthesitis. At last observation 4 of the 10 had reached the criteria for CR.Four out of five patients who discontinued etanercept without tapering experienced flares. In total nine patients developed a disease flare within a median of 0.7 years (IQR 0.1 to 1.1) after discontinuation of etanercept. All eight patients who resumed etanercept use after experiencing flares reacted promptly to treatment.This explorative study shows some important indicators for successful discontinuation of etanercept: prolonged CRM and careful tapering of etanercept. Rheumatoid factor positivity seems to be negatively related with sustained remission. This is all inline with data from rheumatoid arthritis treatment. 8 9 We suggest that patients with JIA should meet the criteria of CRM for at least 1.5 years before considering discontinuation of etanercept, and then taper it carefully.It is reassuring that patients regained effectiveness of etanercept after experiencing flares. A promising result is that four out of five patients with systemic JIA retained ID after discontinuation of etanercept. This last finding indicates that etanercept can be successful in systemic JIA, as we previously showed in results from our ABC register in which the same percentages of patients with systemic JIA meet the criteria of CRM compared to other subtypes after prolonged treatment. Competing interests: Wyeth International financially supported (unconditionally) the development and maintenance of the web-based ABC register.Ethics ...

Methotrexate (MTX) is the most commonly used disease modifying antirheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA), especially in polyarticular arthritis. At present no reliable prediction of individual response to MTX can be made. Identification of factors that influence the response to MTX could be helpful in realizing the optimal treatment for each individual patient.

Objective. Juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis and an autoimmune etiology. In several autoimmune diseases, including rheumatoid arthritis (RA), an association with the 4q27 locus has been reported. We undertook this study to investigate the possible role of the 4q27 locus in JIA.Methods. A case-control association study was conducted, with a total of 655 Caucasian JIA patients and 791 healthy controls divided into 2 independent sample sets. The rs6822844 marker in the 4q27 locus was genotyped.Results. In the first and larger sample set, a 5% decrease in T allele frequency was observed in patients compared with controls (allelic odds ratio Conclusion. Our findings suggest that the 4q27 locus, previously reported to be associated with RA, type 1 diabetes mellitus, celiac disease, and psoriatic arthritis, is also associated with susceptibility to JIA.

Apart from being a well replicated risk factor for RA, TRAF1/C5 also appears to be a risk factor for the rheumatoid factor-negative polyarthritis subtype of JIA and, more generally, seems to be associated with subtypes of JIA characterised by a polyarticular course.

PurposeTo evaluate whether immunomodulation can eliminate high sustained antibody levels, and thereby improve clinical outcome in classic infantile Pompe patients receiving enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA).MethodsThree patients (two cross-reactive immunologic material (CRIM) negative) with high sustained antibodies received a three-week treatment protocol with Rituximab and Bortezomib, followed by daily Rapamycin and monthly IVIG. Patients received 40 mg/kg/week rhGAA. Antibody titers were measured using ELISA. Neutralizing effects on cellular uptake were determined. Clinical efficacy was measured in terms of (ventilator-free) survival, reduction in left ventricular mass index (LVMI) and improvement in motor function.ResultsBefore immunomodulation anti-rhGAA antibody titers ranged from 1:156,250 to 1:781,250 and at last assessment from 1:31,250 to 1:156,250. Neutralizing effects of anti-rhGAA antibody titers (observed in two patients) disappeared. Infusion-associated reactions were no longer present. Immunomodulation resulted in substantial increases of aspartate transaminase, alanine transaminase, and creatine kinase levels. The two CRIM-negative patients who could walk at start of immunomodulation maintained their ability to walk; the patient who had lost this ability did not regain it.ConclusionsTo some extent, the immunomodulation protocol used in our study reduced antibody titers, but it did not eliminate them. Overall, there have been few reports on secondary immunomodulation, and various protocols have been applied. Future research should seek to identify the most successful immunomodulation protocol in patients with high sustained titers.Electronic supplementary materialThe online version of this article (10.1186/s13023-019-1039-z) contains supplementary material, which is available to authorized users.