Search

Background: Etanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN. Methods: In this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum. Results: Ninety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33–0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups — in MTX group [r = 0.35 (95% CI: 0.14–0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39–0.67)]. Conclusion: In the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.

Background: In a chronic pain-causing disease such as juvenile idiopathic arthritis, the quality of coping with pain is crucial. Parents have a substantial influence on their children’s pain-coping strategies. This study aimed to develop scales for assessing parents’ strategies for coping with their children’s pain and a shorter improved scale for children usable in clinical practice. Methods: The number of items in the Finnish version of the pain-coping questionnaire for children was reduced from 39 to 20. A corresponding reduced scale was created for parental use. We recruited consecutive patients from nine hospitals evenly distributed throughout Finland, aged 8–16 years who visited a paediatric rheumatology outpatient clinic and reported musculoskeletal pain during the past week. The patients and parents rated the child’s pain on a visual analogue scale from 0 to 100 and completed pain-coping questionnaires and depression inventories. The selection process of pain questionnaire items was performed using factor analyses. Results: The average (standard deviation) age of the 130 patients was 13.0 (2.3) years; 91 (70%) were girls. Four factors were retained in the new, improved Pain-Coping Scales for children and parents. Both scales had 15 items with 2–5 items/factor. The goodness-of-fit statistics and Cronbach’s alpha reliability coefficients were satisfactory to good in both scaled. The criterion validity was acceptable as the demographic, disease related, and the depression and stress questionnaires correlated with the subscales. Conclusions: We created a shorter, feasible pain-coping scale for children and a novel scale for caregivers. In clinical work, the pain coping scales may serve as a visualisation of different types of coping strategies for paediatric patients with pain and their parents and facilitate the identification of families in need of psychological support.

Background: Evaluation of costs and short-term cost-effectiveness of infliximab plus methotrexate (IFX + MTX); triple therapy of hydroxychloquine, sulphasalazine, and methotrexate (TRIPLE); or methotrexate monotherapy (MTX) in patients with new-onset polyarticular juvenile idiopathic arthritis (JIA). Methods: In a prospective multicenter study (ACUTE-JIA), costs and health outcomes of 60 randomized patients with new-onset disease-modifying anti-rheumatic drug (DMARD)-naïve polyarticular JIA were analyzed during the first year. A mapping algorithm was used to obtain utility values from Child Health Assessment Questionnaire (CHAQ). Wallace criteriae were used to assess clinically inactive disease (CID). Linear regression with non-parametric bootstrapping was used to adjust imbalances at baseline. Results: Using prices for IFX biosimilar, adjusted annual mean (SD) costs of treatment (€) were 21,164 (4158), 12,136 (5286), and 18,300 (8635) on IFX + MTX, TRIPLE, and MTX, respectively. Incremental cost-effectiveness ratio (ICER) for IFX + MTX as compared with TRIPLE or MTX were 3442 € or 678 € per additional month spent in CID. Mean (SD) quality-adjusted life years (QALYs) for IFX + MTX, TRIPLE and MTX were 0.755 (0.065), 0.725 (0.062), and 0.686 (0.124). ICER for IFX + MTX vs TRIPLE was 294,433 €, and for IFX + MTX vs MTX 31,435 € per QALY gained. Conclusions: In short-term, biosimilar IFX + MTX can be considered cost-effective when compared with MTX alone. TRIPLE was cost-effective when compared with MTX and showed cost advantage when compared with IFX + MTX. Cost per time spent in CID showed similar results than ICER evaluations. Trial registration: This trial was primarily registered with the Ethical Board of Helsinki District University Hospital (https://www.hus.fi), clinical trial number 211864, and later with ClinicalTrials.gov, number NCT01015547.

Introduction: The prevalence of immune-mediated diseases has increased in the past decades and despite the use of biological treatments all patients do not achieve remission. The aim of this study was to characterise the reasons for short interruptions during treatment with two commonly used TNF-inhibitors infliximab and adalimumab and to analyse the possible effects of the interruptions on immunisation and switching the treatment. Material and methods: This case-control study was based on retrospective analyses of patient records and a questionnaire survey to clinicians. A total of 370 patients (194 immunised cases and 172 non-immunised controls, 4 excluded) were enrolled from eight hospitals around Finland. Eleven different diagnoses were represented, and the largest patient groups were those with inflammatory bowel or rheumatic diseases. Results: Treatment interruptions were associated with immunisation in patients using infliximab (p < .001) or adalimumab (p < .000001). Patients with treatment interruptions were more likely to have been treated with more than one biological agent compared to those without treatment interruptions. This was particularly prominent among patients with a rheumatic disease (p < .00001). The most frequent reason for a treatment interruption among the cases was an infection, whereas among the control patients it was remission. The median length of one interruption was one month (interquartile range 1–3 months). Conclusion: Our results suggest that the interruptions of the treatment with TNF-inhibitors expose patients to immunisation and increase the need for drug switching. These findings stress the importance of careful judgement of the need for a short interruption in the biological treatment in clinical work, especially during non-severe infections.

We examined the association between cow’s milk allergy (CMA) and juvenile idiopathic arthritis (JIA). The material for this case-control study was collected from national registers of all children born in Finland between 2000 and 2010 and diagnosed with JIA (n = 1,298) and age-, sex-, and place-matched controls (n = 5,179). We identified 235 children with CMA; 66 of these children also had JIA. A conditional logistic regression analysis was performed to evaluate the association between CMA and JIA and to test whether exposure to antibiotics would be a covariate for this association. In boys (but not in girls), a diagnosis of CMA and the use of hypoallergenic formula in infancy were associated with the later development of JIA (odds ratio = 2.4, 95% confidence interval: 1.6, 3.6). The association was most evident in boys who were diagnosed with JIA before age 3 years or diagnosed with CMA with predominantly gastrointestinal symptoms. There was no statistically significant additive interaction between CMA and antibiotic exposure in the later development of JIA. These associations may reflect impaired maturation of intestinal immunity and integrity in boys with a risk of JIA. Predisposing factors related to JIA pathogenesis seem to display a sex-linked disparity.

Bacillus Calmette-Guerin (BCG) osteitis was more common in Finland than elsewhere at the time when universal BCG vaccinations were given to Finnish newborns. There is evidence that IL-17 plays a role in the defense against tuberculosis. The aim of this study was to evaluate the associations of IL17A rs4711998, IL17A rs8193036 and IL17A rs2275913 single-nucleotide polymorphisms (SNPs) with the risk of BCG osteitis after newborn vaccination. IL17A rs4711998, rs8193036 and rs2275913 SNPs were determined in 131 adults had presented with BCG osteitis after newborn BCG vaccination. We analyzed, using the HaploView and PLINK programs, whether allele or haplotype frequencies of these SNPs differ between the former BCG osteitis patients and Finnish population controls. Of the three IL17A SNPs studied, rs4711998 associated nominally with BCG osteitis; minor allele frequency was 0.215 in 130 BCG osteitis cases and 0.298 in 99 controls (p = 0.034). Frequency of the second common haplotype (GTA) differed significantly between BCG osteitis cases and controls (0.296 vs. 0.184, p = 0.040 after multi-testing correction). The GTA haplotype of the IL17A SNPs rs4711998, rs8193036 and rs2275913 was associated with osteitis after BCG vaccination.