Efficacy, safety, and cost-effectiveness of the treatment in juvenile idiopathic arthritis

Medical treatment of juvenile idiopathic arthritis (JIA) consists of intra-articular glucocorticoid injections, conventional disease-modifying anti-rheumatic drugs (DMARDs), or biologic DMARDs (bDMARDs). Biologic (and conventional) DMARDs have specific targets in the immune system, and they may cause increased risk for infections or other adverse events. Biologics are more expensive than conventional DMARDs. It is not known which patients would benefit from early aggessive treatment with bDMARDs. The aims of this study were to compare the efficacy of biologic and conventional DMARDs, analyze the costs and cost-effectiveness of the treatments, and assess health-related quality of life (HrQoL) during one year from disease onset. Furthermore, we assessed the safety of bDMARDs. Patients and methods In the Aggressive Combination of Drug Therapy in Early Polyarticular JIA (ACUTE-JIA) study, 60 patients with new-onset polyarticular JIA were randomized into three treatment groups: the infliximab plus methotrexate group (hereinafter IFX+MTX), the triple therapy with hydroxychloroquine, sulphasalazine, and methotrexate group (hereinafter Triple), or the methotrexate monotherapy group (hereinafter MTX). The patients had eight study visits during one year from the onset of therapy. During these visits, efficacy was measured using the American College of Rheumatology pediatric criteria (ACR pedi); information on resource use was collected from medical records, and parental absenteeism was measured with a questionnaire. To measure HrQoL, parents filled out the Child Health Questionnaire during study visits. To assess the safety of bDMARDs, we collected data from medical records in 348 consecutive patients with JIA treated with bDMARDs from three tertiary centers. The number of adverse events (AEs) during bDMARD treatment, their severity, and time from onset of treatment were recorded. A subgroup of 292 patients was analyzed for the incidence of inflammatory bowel disease (IBD). Results The ACR pedi 75 target was achieved by 19/19 patients (100%) in IFX+MTX, compared with 13/20 (65%) in Triple and 10/20 (50%) in MTX (p<0.001 for IFX+MTX vs Triple or MTX). The mean time spent in clinically inactive disease (CID) in IFX+MTX was 26 weeks, compared with 13 in Triple and six in MTX (p=0.0014 for IFX+MTX vs MTX). During the first year from the onset of therapy, HrQoL improved in all treatment groups. Although there were significant differences in efficacy between therapies, HrQoL was similar in all groups. Changes in the Psychosocial summary score (PsS) were small. Significant differences in Physical Summary Score (PhS) were seen between each visit until week 24. In mixed models, the pain visual analog scale (pain VAS), cumulative time in remission, and the Child Health Assessment Questionnaire (CHAQ) contributed to PhS, while the CHAQ and gender contributed to PsS. In this intention-to-treat analysis, total societal costs within first year from disease-onset were largest in IFX+MTX – €21,164 (SD 4,158) – compared with €12,136 (5,286) in Triple, or €18,300 (8,635) in MTX. Medication and costs of intravenous administration were the largest cost components in IFX+MTX. Intra-articular glucocorticoid injections were the largest cost components in Triple and MTX. Mean incremental quality-adjusted life-years (QALYs) gained were 0.030, 0.039, or 0.069 for comparisons of IFX+MTX vs Triple, Triple vs MTX, or IFX+MTX vs MTX, respectively. Incremental cost-effectiveness ratios (ICER), i.e added costs as a ratio to added efficacy, were € 294,433 for IFX+MTX vs Triple, or €31,435 or IFX+MTX vs MTX. Triple was dominant compared with MTX, i.e it was less costly and more effective than MTX. In total, 1,516 patient-years (PYs) were included in analyses of AEs: 710 on etanercept (ETA), 591 on infliximab (IFX), 188 on adalimumab, 8 on rituximab, 5 on anakinra, 6 on tocilizumab, 6 on abatacept, and 1 on golimumab. The median follow-up time per patient was 51 months. Of the 2,902 AEs (191/100 PYs) observed, the most common were mild infections, reactions related with infusion or injection sites, or elevated liver enzymes. Of the patients, 319 (92%) had at least one AE, and 121 (35%) had at least one serious AE. However, 87% of these patients were able to continue medication without pausing or after a short pause. No malignancies or cases of tuberculosis were observed. In the subgroup of 292 patients, during 782 PYs, IBD occurred in four patients receiving biologics: three on ETA, and 1 on IFX. Conclusions Biologic therapy was effective in new-onset polyarticular JIA. IFX+MTX therapy was more costly than other treatments. At the willingness-to-pay level of £30,000, biosimilar IFX+MTX therapy could be considered cost-effective when compared with MTX monotherapy. The Triple therapy was a relatively effective and inexpensive treatment option. HrQoL was similar in all treatment groups. In a real-life setting, the safety profile of biologic therapy seemed acceptable, and AEs rarely led to the discontinuation of medication

Health-related quality of life during early aggressive treatment in patients with polyarticular juvenile idiopathic arthritis : results from randomized controlled trial

Background Juvenile Idiopathic Arthritis (JIA) may cause significant impairment in health-related quality of life (HrQoL), despite effective therapies. The aim of this study was to assess HrQoL during first-year treatment in patients with new-onset polyarticular JIA, and to compare treatment strategies. Methods In ACUTE-JIA Study, 60 patients with new-onset JIA were randomized to receive either infliximab with methotrexate (IFX+MTX); a triple therapy of methotrexate, hydroxychloroquine, and sulfasalazine (Triple); or methotrexate monotherapy (MTX). Efficacy was measured with American College of Rheumatology pediatric (ACRp) score, and juvenile arthritis disease activity score (JADAS). HrQoL was evaluated with Child Health Questionnaire (CHQ), which includes physical and psychosocial summary scores (PhS and PsS). Linear mixed models were utilized to compare groups over time. Results In the whole group of 60 patients, mean physical summary score (PhS) improved from 26.2 (SD 8.7) at week 0 to 49.7 (SD 13.2) at week 54 (p=0.046). Mean improvement of PhS was 20.3 (95% CI -15.5 to 56.2); 22.6 (-19.5 to 64.7); and 26.6 (-12.1 to 65.3) in IFX+MTX, Triple, and MTX, respectively. Changes in psychosocial summary score (PsS) were smaller: from 51.0 (SD 8.5) to 54.7 (6.3) (p=0.019) in all patients. No differences between the three treatment groups were detected in either of the measures. In multivariate analyses, Child Health Assessment Questionnaire (CHAQ), pain VAS, and time spent in inactive disease contributed to improvement in PhS; gender and CHAQ to PsS. Conclusions HrQol improved during the first year on therapy for JIA irrespective of the treatment strategy. The timing of change in the different dimensions of HrQoL varied; improvement occurred earlier in physical than psychosocial domains of HrQol.Peer reviewe

Economic evaluation of infliximab, synthetic triple therapy and methotrexate in the treatment of newly diagnosed juvenile idiopathic arthritis

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)-naive 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 (euro) 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 euro or 678 euro 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 euro, and for IFX + MTX vs MTX 31,435 euro 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.Peer reviewe

Pain-coping scale for children and their parents : a cross-sectional study in children with musculoskeletal pain

BackgroundIn 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.MethodsThe 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.ResultsThe 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.ConclusionsWe 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.Peer reviewe

Lääkintämiehet rintamalla : Lääkintähuolto Suomen sodissa vuosina 1939–1945

Opinnäytetyön tarkoituksena oli koota tietoa lääkintähuollosta Suomessa talvi-, jatko- ja Lapinsodassa vuosina 1939–1945. Selvitimme, kuinka lääkintähuolto toteutui ja mitä haasteita vaikeat olosuhteet sodan keskellä aiheuttivat lääkintähuollolle. Aihe on erittäin tärkeä osa hoitotyön ja hoitotyön koulutuksen historiaa. Keskityimme työssämme lääkintämiesten ja lääkintäaliupseerien toimenkuvaan haavoittuneiden hoidossa ja käsittelemme myös heidän saamaansa koulutusta. Opinnäytetyö on tehty yhteistyössä Metropolia Ammattikorkeakoulun Hoitotyön koulutuksen museon kanssa. Tavoitteena oli kerätä opiskelijoille ja muille asiasta kiinnostuneille tietoa aiheesta ja myös siihen liittyvistä erityiskysymyksistä, kuten eri sairauksista, lääkeriippuvuudesta ja aseptiikasta sekä koota tieto selkeästi yhteen opinnäytetyössämme. Tietoja voidaan hyödyntää työ- ja opiskeluelämässä kohdatessa sodassa olleita tai haavoittuneita henkilöitä. Tieto on erittäin hyödyllistä myös lääkintähuollon historian kannalta; jotta ymmärtäisimme nykyajan hoitoa, on hyvä olla käsitys, kuinka asiat tehtiin aikaisemmin. Opinnäytetyön aineisto kerättiin kirjallisuuden, muistelmien ja artikkeleiden avulla ja lisäksi toteutimme haastattelun, joka on työssämme hyvin keskeisessä ja tärkeässä osassa. Haastattelimme jatkosodassa taistellutta ja haavoittunutta henkilöä ja tämän haastattelun ympärille rakensimme muun tiedon työssämme. Opinnäytetyön tulokset osoittavat, että lääkintämiehet ja lääkintäaliupseerit olivat talvi- ja jatkosodassa lähes ylivoimaisen tehtävän edessä. Poikkeukselliset olosuhteet toivat suuria haasteita hoitamiselle. Lääkintähuolto joutui koville, kun sota kaikkine kauhuineen oli läsnä jokapäiväisessä elämässä ja hyvin lähellä, sillä lääkintämiehet ja lääkintäaliupseerit toimivat usein etulinjassa, lähimpänä taisteluita. Olosuhteet olivat vaikeat ja oli pärjättävä hyvin vähillä apu- ja hoitovälineillä. Lääkintämiehet ja lääkintäaliupseerit tekivät tärkeää ja haastavaa työtä, jossa tarvittiin suurta rohkeutta ja paineensietokykyä.This thesis was undertaken to examine medical treatment and the impact of war on medical treatment during the Winter War, Continuation War and Lapland War in 1939-1945, Finland, which forms an important aspect of nursing history and education. We aimed to understand how medics and medical non-commissioned officers delivered medical care and treatment during such difficult and harrowing times, taking account of their education, training and overall experiences. This thesis is commissioned by Metropolia University of Applied Sciences, the Museum of nursing education. The findings of this thesis will be useful for students and those interested in this topic and in specific issues related to it, such as various diseases, drug addiction and aseptics. The information can also assist researchers who wish to collect a personal account from people who have a first-hand experience of war, having fought in the trenches and been wounded as a result. Finally, the research also contributes to a better understanding of medical history through gaining a deeper insight into past experiences, and shape future research directions. The data was collected using a combination of primary and secondary sources, including an interview, memoirs, and research literature. To gain deeper insight into medics perceptions, understandings and experience during the time, a one-to-one interview was conducted with an individual who fought and was wounded during the Continuation War. The results demonstrated that medical officers faced major challenges during the Winter and Continuation War, and it was almost impossible to administer adequate medical treatment during such difficult, pressurized circumstances. Medical treatment was under a lot of pressure when war, with all its horrors, was present in everyday life, and very close, as the medics and medical non-commissioned officers often worked in the front line, closest to the battles. They had to help and care for people with very little resources and treatment tools. The medics and the medical non-commissioned officers’ work was very important and challenging, and required great courage and resilience

Paediatric rheumatologists do not score the physician's global assessment of juvenile idiopathic arthritis disease activity in the same way

Objectives To assess the heterogeneity in factors affecting physician's global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient's case scenarios. Methods An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation. Results The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72). Conclusions In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients.Peer reviewe

Paediatric rheumatologists do not score the physician’s global assessment of juvenile idiopathic arthritis disease activity in the same way

Abstract Objectives: To assess the heterogeneity in factors affecting physician’s global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient’s case scenarios. Methods: An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation. Results: The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72). Conclusions: In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients