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Rheumatology (Oxford, England) Oct 2019The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the prevalence of ADAbs in JIA studies; investigate the effect of ADAbs on treatment efficacy and adverse events; and explore the effect of immunosuppressive therapy on antibody formation.
METHODS
PubMed, Embase and the Cochrane Library were systematically searched to identify relevant clinical trials and observational studies that reported prevalence of ADAbs. Studies were systematically reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses and appropriate proportional and pairwise meta-analyses were performed.
RESULTS
A total of 5183 references were screened; 28 articles, involving 26 studies and 2354 JIA patients, met eligibility criteria. Prevalence of ADAbs ranged from 0% to 82% across nine biologic agents. Overall pooled prevalence of ADAbs was 16.9% (95% CI, 9.5, 25.9). Qualitative analysis of included studies indicated that antibodies to infliximab, adalimumab, anakinra and tocilizumab were associated with treatment failure and/or hypersensitivity reactions. Concomitant MTX uniformly reduced the risk of antibody formation during adalimumab treatment (risk ratio 0.33; 95% CI 0.21, 0.52).
CONCLUSION
The association of ADAbs with treatment failure and hypersensitivity reactions indicates their clinical relevance in paediatric patients with JIA. Based on our findings, we recommend a preliminary course of action regarding immunogenicity of biologic agents in patients with JIA. Further strategies to predict, prevent, detect and manage immunogenicity could optimize treatment outcomes and personalize treatment with biologic therapies.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antibody Formation; Antirheumatic Agents; Arthritis, Juvenile; Biological Factors; Child; Clinical Trials as Topic; Humans; Infliximab; Interleukin 1 Receptor Antagonist Protein; Methotrexate; Observational Studies as Topic
PubMed: 30809664
DOI: 10.1093/rheumatology/kez030 -
Clinical and Experimental Rheumatology Mar 2024The reported prevalence of coeliac disease (CD) in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) varies in previous studies. We aimed... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The reported prevalence of coeliac disease (CD) in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) varies in previous studies. We aimed to examine the prevalence of CD in patients with RA and JIA.
METHODS
We searched Medline, Embase, Cochrane and Web of Science Core Collection between 1 January 1990 and 31 October 2022. In our primary analysis, the prevalence of biopsy-confirmed CD in RA and JIA patients was investigated. In secondary analyses, the prevalence of serological markers for CD was examined. Pooled weighted prevalences of CD and serological markers with 95% confidence intervals (95%CI) were calculated and quality of included studies was assessed. Meta-regression analysis was performed on publication year, sample size, CD prevalence in the general population, proportion of females, and quality assessment score.
RESULTS
In this systematic review, 14 publications were deemed relevant for RA and 22 for JIA, with nine and 18 included in the primary analyses of CD prevalence, respectively. Among a total of 754 RA patients and 2077 patients with JIA, the weighted pooled prevalence estimates of biopsy-confirmed CD were 0.4% (95%CI=0.0-1.2) and 1.4% (95%CI=0.7-2.2), respectively. The pooled prevalence estimates of positive CD serology were 0.9% (95%CI=0.3-1.9) in RA and 5.4% (95%CI=2.5-9.2) in JIA.
CONCLUSIONS
In this meta-analysis, we found a pooled prevalence of biopsy-confirmed CD in patients with RA and JIA comparable to that in the general population. Routine screening for CD is not warranted in RA but could be considered in JIA patients with additional risk factors for CD.
Topics: Female; Humans; Arthritis, Juvenile; Prevalence; Celiac Disease; Arthritis, Rheumatoid; Biopsy
PubMed: 37933564
DOI: 10.55563/clinexprheumatol/b92b8a -
Pediatric Rheumatology Online Journal Oct 2021Juvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this...
BACKGROUND
Juvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this systematic review was to collect and cluster the information currently available on healthcare costs associated with JIA after the introduction of biological therapies.
METHODS
We comprehensively searched in MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Databases for studies from January 2000 to March 2021. Reviewers working independently and in duplicate appraised the quality and included primary studies that report total, direct and/or indirect costs related to JIA for at least one year. The costs were converted to United States dollars and an inflationary adjustment was made.
RESULTS
We found 18 eligible studies including data from 6,540 patients. Total costs were reported in 10 articles, ranging from $310 USD to $44,832 USD annually. Direct costs were reported in 16 articles ($193 USD to $32,446 USD), showing a proportion of 55 to 98 % of total costs. Those costs were mostly related to medications and medical appointments. Six studies reported indirect costs ($117 USD to $12,385 USD). Four studies reported costs according to JIA category observing the highest in polyarticular JIA. Total and direct costs increased up to three times after biological therapy initiation. A high risk of reporting bias and inconsistency of the methodology used were found.
CONCLUSION
The costs of JIA are substantial, and the highest are derived from medication and medical appointments. Indirect costs of JIA are underrepresented in costs analysis.
Topics: Arthritis, Juvenile; Cost of Illness; Cost-Benefit Analysis; Health Care Costs; Humans
PubMed: 34627296
DOI: 10.1186/s12969-021-00641-y -
Journal of Medical Internet Research Feb 2022Juvenile idiopathic arthritis (JIA) management aims to promote remission through timely, individualized, well-coordinated interdisciplinary care using a range of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Juvenile idiopathic arthritis (JIA) management aims to promote remission through timely, individualized, well-coordinated interdisciplinary care using a range of pharmacological, physical, psychological, and educational interventions. However, achieving this goal is workforce-intensive. Harnessing the burgeoning eHealth and mobile health (mHealth) interventions could be a resource-efficient way of supplementing JIA management.
OBJECTIVE
This systematic review aims to identify the eHealth and mHealth interventions that have been proven to be effective in supporting health outcomes for children and young people (aged 1-18 years) living with JIA.
METHODS
We systematically searched 15 databases (2018-2021). Studies were eligible if they considered children and young people (aged 1-18 years) diagnosed with JIA, an eHealth or mHealth intervention, any comparator, and health outcomes related to the used interventions. Independently, 2 reviewers screened the studies for inclusion and appraised the study quality using the Downs and Black (modified) checklist. Study outcomes were summarized using a narrative, descriptive method and, where possible, combined for a meta-analysis using a random-effects model.
RESULTS
Of the 301 studies identified in the search strategy, 15 (5%) fair-to-good-quality studies met the inclusion criteria, which identified 10 interventions for JIA (age 4-18.6 years). Of these 10 interventions, 5 (50%) supported symptom monitoring by capturing real-time data using health applications, electronic diaries, or web-based portals to monitor pain or health-related quality of life (HRQoL). Within individual studies, a preference was demonstrated for real-time pain monitoring over recall pain assessments because of a peak-end effect, improved time efficiency (P=.002), and meeting children's and young people's HRQoL needs (P<.001) during pediatric rheumatology consultations. Furthermore, 20% (2/10) of interventions supported physical activity promotion using a web-based program or a wearable activity tracker. The web-based program exhibited a moderate effect, which increased endurance time, physical activity levels, and moderate to vigorous physical activity (standardized mean difference [SMD] 0.60, SD 0.02-1.18; I=79%; P=.04). The final 30% (3/10) of interventions supported self-management development through web-based programs, or apps, facilitating a small effect, reducing pain intensity (SMD -0.14, 95% CI -0.43 to 0.15; I=53%; P=.33), and increasing disease knowledge and self-efficacy (SMD 0.30, 95% CI 0.03-0.56; I=74%; P=.03). These results were not statistically significant. No effect was seen regarding pain interference, HRQoL, anxiety, depression, pain coping, disease activity, functional ability, or treatment adherence.
CONCLUSIONS
Evidence that supports the inclusion of eHealth and mHealth interventions in JIA management is increasing. However, this evidence needs to be considered cautiously because of the small sample size, wide CIs, and moderate to high statistical heterogeneity. More rigorous research is needed on the longitudinal effects of real-time monitoring, web-based pediatric rheumatologist-children and young people interactions, the comparison among different self-management programs, and the use of wearable technologies as an objective measurement for monitoring physical activity before any recommendations that inform current practice can be given.
Topics: Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Exercise; Humans; Infant; Quality of Life; Self-Management; Telemedicine
PubMed: 35107431
DOI: 10.2196/30457 -
JMIR Pediatrics and Parenting Dec 2020Considering the changing landscape of internet use and rising ownership of digital technology by young people, new methods could be considered to improve the current... (Review)
Review
BACKGROUND
Considering the changing landscape of internet use and rising ownership of digital technology by young people, new methods could be considered to improve the current model of juvenile idiopathic arthritis (JIA) management.
OBJECTIVE
This systematic review aims to evaluate the usability of eHealth and mobile health (mHealth) interventions currently available for young people living with JIA.
METHODS
The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to oversee this review. We systematically searched 15 databases for 252 potential studies; 2 authors independently screened all quantitative studies reporting the use of eHealth and mHealth interventions for young people (aged 1-18 years) diagnosed with JIA. Studies were excluded if they did not report outcome measures or were reviews, commentaries, or qualitative studies. Study methodological quality was scored using the Down and Black (modified) checklist. A narrative descriptive methodology was used to quantify the data because of heterogeneity across the studies.
RESULTS
A total of 11 studies were included in this review, reporting 7 eHealth and mHealth interventions for young people (aged 4-18 years) living with JIA, targeting health issues such as pain, health-related quality of life, physical activity, and chronic disease self-management. The usability of the interventions was facilitated through training and ongoing support. The engagement was promoted by a combination of persuasive influences, and barriers preventing adherence were removed through personal reminders and flexible program schedules to cater to JIA and non-JIA illnesses or other commonly seen activities in childhood. The feedback obtained was that most young people and their parents liked the interventions.
CONCLUSIONS
The results of this review need to be considered cautiously because of the lack of rigorous testing and heterogeneity, which limits the detailed descriptions of data synthesis. Further research is needed to consider gender differences, associated costs, and the effectiveness of the interventions on health outcomes to better support young people living with JIA.
PubMed: 33258786
DOI: 10.2196/15833 -
Pediatric Rheumatology Online Journal 2014Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug in juvenile idiopathic arthritis (JIA). In JIA, it is important to start effective treatment... (Review)
Review
BACKGROUND
Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug in juvenile idiopathic arthritis (JIA). In JIA, it is important to start effective treatment early to avoid long-term sequelae, such as joint damage. To accomplish this goal, it is crucial to know beforehand who is going to respond well to MTX. In addition, MTX adverse effects such as MTX intolerance occur frequently, potentially hindering its efficacy. To avoid inefficacy of an otherwise effective drug, the physician should be timely aware of these adverse events. Consequently, to optimise treatment of JIA patients with MTX, predictors for efficacy and adverse events should be used in daily clinical practice. The aim of this study was to summarise the existing knowledge about such predictors.
METHODS
A systematic literature search was performed in PubMed, Embase and The Cochrane Library, and 1,331 articles were identified. These were selected based on their relevance to the topic and critically appraised according to pre-defined criteria. Predictors for MTX efficacy and adverse events were extracted from the literature and tabulated.
RESULTS
Twenty articles were selected. The overall quality of the studies was good. For MTX efficacy, candidate predictors were antinuclear antibody positivity, the childhood health assessment questionnaire score, the myeloid-related protein 8/14 level, long-chain MTX polyglutamates, bilateral wrist involvement and some single nucleotide polymorphisms (SNPs) in the adenosine triphosphate binding cassette and solute carrier transporter gene families. For MTX adverse events, potential predictors were alanine aminotransferase and thrombocyte level and two SNPs in the γ-glutamyl hydrolase and methylenetetrahydrofolate reductase genes. However, validation of most predictors in independent cohorts was still lacking.
CONCLUSIONS
Interesting candidate predictors were found, especially for MTX efficacy. However, most of these were not validated. This should be the goal of future efforts. A clinically relevant way to validate the predictors is by means of creating a clinical prediction model.
Topics: ATP-Binding Cassette Transporters; Adolescent; Antibodies, Antinuclear; Antirheumatic Agents; Arthritis, Juvenile; Biomarkers; Child; Child, Preschool; Humans; Methotrexate; Polyglutamic Acid; Polymorphism, Single Nucleotide; Predictive Value of Tests; Treatment Outcome
PubMed: 25525416
DOI: 10.1186/1546-0096-12-51 -
Seminars in Arthritis and Rheumatism Dec 2017The ideal goal of treatment for juvenile idiopathic arthritis (JIA) is disease remission. However, many sets of remission criteria have been developed and no systematic... (Review)
Review
OBJECTIVES
The ideal goal of treatment for juvenile idiopathic arthritis (JIA) is disease remission. However, many sets of remission criteria have been developed and no systematic review of remission in JIA exists. The current systematic review investigated (1) how remission has been defined across JIA clinical cohorts and (2) the frequency of remission overall and within disease categories.
METHODS
Studies using prospective inception cohorts published after 1972 were selected if they estimated remission in cohorts of ≥50 patients. Articles focusing on specific medical interventions, not defining remission clearly or not reporting disease duration at remission assessment were excluded. Studies were selected from Medline, Embase, PubMed and bibliographies of selected articles. Risks of selection, missing outcome data and outcome reporting biases were assessed.
RESULTS
Within 17 studies reviewed, 88% had majority female participants and patient disease duration ranged from 0.5 to 17 years. Thirteen sets of criteria for clinically inactive disease and remission were identified. Uptake of Wallace's preliminary criteria was good in studies recruiting or following patients after their publication (78%). Remission frequencies increased with longer disease duration from 7% within 1.5 years to 47% by 10 years following diagnosis. Patients with persistent oligoarticular and rheumatoid-factor positive polyarticular JIA were most and least likely to achieve remission, respectively.
CONCLUSIONS
Achievement of remission increased with longer disease duration, but many patients remain in active disease, even in contemporary cohorts. Multiple sets of outcome criteria limited comparability between studies.
Topics: Arthritis, Juvenile; Cohort Studies; Female; Humans; Male; Prospective Studies; Remission Induction; Remission, Spontaneous; Severity of Illness Index
PubMed: 28625712
DOI: 10.1016/j.semarthrit.2017.05.007 -
Open Access Rheumatology : Research and... 2019Depression and anxiety are prevalent in children with rheumatologic diseases, including juvenile idiopathic arthritis (JIA). However, prevalence rates and the... (Review)
Review
Depression and anxiety are prevalent in children with rheumatologic diseases, including juvenile idiopathic arthritis (JIA). However, prevalence rates and the relationship with disease outcomes, including quality of life are conflicting in the early literature. To review the current literature, determine gaps in our knowledge, and identify areas in need of further investigation, we conducted a systematic review of studies examining depression and anxiety symptoms among children with JIA and the impact these symptoms may have on disease outcomes and quality of life. Six electronic databases were searched up until January 2019. Of 799 potential articles, 60 articles were included with the main focus on 28 articles from 2009 to 2019, to concentrate on the most current evidence. We found that JIA patients experience symptoms of depression and anxiety similar to other childhood chronic diseases and at higher rates than in healthy children. Patients who experience these symptoms have worse quality of life, with some evidence pointing to depression and anxiety symptoms having a greater impact on quality of life than other disease features, such as active joint count. Family members of JIA patients experience high rates of anxiety and depression symptoms which may impact their child's mental health and pain symptoms related to JIA. Conflicting reports of associations between depression/anxiety symptoms and disease features/disease outcomes and a paucity of longitudinal studies investigating the impact of treatment on mental health symptoms indicate areas in need of further research to effectively identify patients at greatest risk of depression and anxiety and to better understand how to treat and prevent these symptoms in youth with JIA. Family mental health should also be considered in investigations concerning mental health and disease outcomes of children with JIA.
PubMed: 31807093
DOI: 10.2147/OARRR.S174408 -
RMD Open Sep 2022Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively...
A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases.
OBJECTIVES
Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases.
METHODS
A systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and observational studies. Meeting abstracts from ACR, EULAR conferences and results on clinicaltrials.gov were taken into consideration.
RESULTS
187 articles fulfilled the inclusion criteria. Evidence for positive effect of IL-6 inhibition was available in various inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, cytokine release syndrome due to chimeric antigen receptor T cell therapy and systemic sclerosis-associated interstitial lung disease. Newcomers like satralizumab and anti-IL-6 ligand antibody siltuximab have expanded therapeutic approaches for Castleman's disease and neuromyelitis optica, respectively. IL-6 inhibition did not provide therapeutic benefits in psoriatic arthritis, ankylosing spondylitis and certain connective tissue diseases. In COVID-19, tocilizumab (TCZ) has proven to be therapeutic in advanced disease. Safety outcomes did not differ from other bDMARDs, except higher risks of diverticulitis and lower gastrointestinal perforations. Inconsistent results were observed in several studies investigating the risk for infections when comparing TCZ to TNF-inhibitors.
CONCLUSION
IL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.
Topics: Adult; Humans; Antirheumatic Agents; Interleukin-6; Ligands; Receptors, Chimeric Antigen; COVID-19 Drug Treatment
PubMed: 36260501
DOI: 10.1136/rmdopen-2022-002359 -
Clinical Infectious Diseases : An... Nov 2013Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly administered to children and adolescents with juvenile idiopathic arthritis (JIA) and pediatric... (Review)
Review
Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-α inhibitors: systematic review of the literature.
Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly administered to children and adolescents with juvenile idiopathic arthritis (JIA) and pediatric inflammatory bowel disease (pIBD). Adult studies indicate that TNF-α inhibitors lead to an increased risk of serious infections compared to other disease-modifying antirheumatic drugs. We report herein a systematic literature review detailing the epidemiology and types of infections reported in children with JIA and pIBD treated with TNF-α inhibitors. The most frequently reported infections were mild and characterized as viral in etiology. Severe bacterial and fungal infections also occurred, but were less common and possibly associated with intrinsic risk factors and concurrent immunosuppressive therapy. Few pediatric patients developed Mycobacterium tuberculosis, likely due to effective screening. There were 8 infectious fatalities in children treated with TNF-α inhibitors. Overall, although rare, serious infections occur in immunocompromised children and adolescents with JIA and pIBD receiving TNF-α inhibitors.
Topics: Adolescent; Arthritis, Juvenile; Bacterial Infections; Child; Child, Preschool; Humans; Immunocompromised Host; Immunologic Factors; Infant; Inflammatory Bowel Diseases; Mycoses; Tumor Necrosis Factor-alpha; Virus Diseases
PubMed: 23899685
DOI: 10.1093/cid/cit489