Therapy In Juvenile Idiopathic Arthritis Research Articles

P090 Real-world data on immuno-modulation therapies and body mass index in children and young people with juvenile idiopathic arthritis

Abstract Background/Aims There is some evidence that children and young people (CYP) with Juvenile Idiopathic Arthritis (JIA) who are overweight/obese have less favourable disease control and treatment outcomes. The aim of this study was to investigate any association between BMI and total number of immune modulation therapies used in CYP with JIA. Methods This was a retrospective observational study at a tertiary paediatric rheumatology centre. Cross-sectional data was captured in April 2022 from CYP receiving immunomodulation therapies for JIA. Data on diagnosis, treatments and weight/height at last routine follow-up was included. BMI was calculated for each patient and centile assigned using Royal College of Paediatrics and Child Health electronic BMI charts as follows: BMI ≥85th to 94th centile - overweight, ≥95th centile - obese, as per population monitoring British 1990 growth reference (UK90). Results 187 CYP were identified and 180 included (seven were excluded due to missing BMI data). Baseline demographic, disease and treatment data are summarised in Table A. 67% were female. Median (interquartile range (IQR)) age in years at diagnosis and follow-up was 4.3 (2.7, 8) and 11.9 (8.5, 14.4) respectively. At follow-up, 41.1% of CYP were either obese or overweight. The median (IQR) number of total immunomodulation therapies per patient according to BMI categories were: under/normal weight 2 (1, 3); overweight 3 (2, 3) and obese 3 (2, 5). The median (IQR) years of follow-up in under/normal weight, overweight and obese groups were 4.77 (2, 8.74); 5.27 (1.86, 7) and 5.5 (3, 9.1) respectively. Conclusion CYP that were overweight/obese received more therapies compared to under/normal weight. The high proportion (41%) of CYP in this study who were either overweight or obese is similar to prevalence (44.2%) for children in year six at school in this region. Corticosteroid use and limited physical activity is associated with inadequate control of joint inflammation and increased BMI but this data was not collected and is an important limitation, in addition to cross-sectional and retrospective study design. The overweight/obese group had longer follow-up and may have accumulated more therapies. Future research to evaluate optimal dosing of immunomodulation in CYP with high BMI is warranted. Disclosure K. Hartley: Grants/research support; NIHR BRC Internship. S. Jandial: None. F. McErlane: None. E. Sen: None. S. Sampath: None.

Tumor-necrosis factor α-rich environment alters type-I interferon response to viral stimuli in patients with juvenile idiopathic arthritis by altering myeloid dendritic cell phenotype

The balance between the tumor-necrosis factor α (TNFα) and type-I interferon (T1IFN) pathways is crucial for proper immune function. Dysregulation of either pathway can contribute to autoimmune diseases development. Even though TNFα blockade has shown promising results in various autoimmune diseases, the effect on the balance between TNFα and T1IFN is elusive. We used targeted anti-TNFα therapies in juvenile idiopathic arthritis (JIA) as an experimental approach to study the cross-regulation between TNFα and type-I IFN. We found that TNFα-rich environment affected viral defense through the attenuation of T1IFN responses and affected the phenotype and distribution of myeloid dendritic cells, which are engaged in early viral infections. Anti-TNFα therapy normalized the observed deviations in JIA patients. We hypothesize that the inadequate immune response caused by a high TNFα environment could be projected to more frequent or lengthy viral infections and possibly play a role in the process of JIA disease development.

Treatment of non-systemic juvenile idiopathic arthritis.

In the past two decades, the treatment of juvenile idiopathic arthritis (JIA) has evolved markedly, owing to the availability of a growing number of novel, potent and relatively safe therapeutic agents and the shift of management strategies towards early achievement of disease remission. However, JIA encompasses a heterogeneous group of diseases that require distinct treatment approaches. Furthermore, some old drugs, such as methotrexate, sulfasalazine and intraarticular glucocorticoids, still maintain an important therapeutic role. In the past 5 years, information on the efficacy and safety of drug therapies for JIA has been further enriched through the accomplishment of several randomized controlled trials of newer biologic and synthetic targeted DMARDs. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. A multinational collaborative effort has led to the development of the recommendations for the treat-to-target strategy in JIA. There is currently increasing interest in establishing the optimal time and modality for discontinuation of treatment in children with JIA who achieve sustained clinical remission. The aim of this Review is to summarize the current evidence and discuss the therapeutic approaches to the management of non-systemic phenotypes of JIA, including oligoarthritis, polyarthritis, enthesitis-related arthritis and psoriatic arthritis.

The benefits of physical therapy in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Recommended physiotherapy activity programs are essential for controlling JIA associated complications such as stiffness, deformity, muscle contractures, and cramps. It is uncertain if physiotherapy (PT) can significantly enhance prognosis and quality of life (QOL). In this review we focused on the specific effects of various PT on JIA manifestations. To conduct a literature review, the databases PubMed, Scopus, and DOAJ (last access in June 2023) were searched. The PubMed search returned a total of 952 articles, Scopus returned 108, and DOAJ returned no results. After screening, the final list included 18 papers on PT treatment for JIA patients. In children with JIA, targeted PT exercise may have the ability to improve strength, posture, aerobic conditioning, gait, functional mobility, and reduce pain.

Juvenile idiopathic arthritis-associated genetic loci exhibit spatially constrained gene regulatory effects across multiple tissues and immune cell types

Juvenile idiopathic arthritis (JIA) is an autoimmune, inflammatory joint disease with complex genetic etiology. Previous GWAS have found many genetic loci associated with JIA. However, the biological mechanism behind JIA remains unknown mainly because most risk loci are located in non-coding genetic regions. Interestingly, increasing evidence has found that regulatory elements in the non-coding regions can regulate the expression of distant target genes through spatial (physical) interactions. Here, we used information on the 3D genome organization (Hi-C data) to identify target genes that physically interact with SNPs within JIA risk loci. Subsequent analysis of these SNP-gene pairs using data from tissue and immune cell type-specific expression quantitative trait loci (eQTL) databases allowed the identification of risk loci that regulate the expression of their target genes. In total, we identified 59 JIA-risk loci that regulate the expression of 210 target genes across diverse tissues and immune cell types. Functional annotation of spatial eQTLs within JIA risk loci identified significant overlap with gene regulatory elements (i.e., enhancers and transcription factor binding sites). We found target genes involved in immune-related pathways such as antigen processing and presentation (e.g., ERAP2, HLA class I and II), the release of pro-inflammatory cytokines (e.g., LTBR, TYK2), proliferation and differentiation of specific immune cell types (e.g., AURKA in Th17 cells), and genes involved in physiological mechanisms related to pathological joint inflammation (e.g., LRG1 in arteries). Notably, many of the tissues where JIA-risk loci act as spatial eQTLs are not classically considered central to JIA pathology. Overall, our findings highlight the potential tissue and immune cell type-specific regulatory changes contributing to JIA pathogenesis. Future integration of our data with clinical studies can contribute to the development of improved JIA therapy.

Withdrawal of biologic therapy in juvenile idiopathic arthritis due to remission: predictors of flare and outcomes

ABSTRACT Objectives To investigate patients who flared after discontinuation of biological disease-modifying anti-rheumatic agents (bDMARDs) and identify risk factors associated with flare. Methods A multicenter study evaluating systemic and non-systemic juvenile idiopathic arthritis (sJIA and non-sJIA) patients whose bDMARDs were ceased after remission. Results A total of 101 patients whose bDMARDs were ceased after remission was evaluated. Children with sJIA had the lowest risk of flare and 11.1% of 36 sJIA patients experienced flare after a median of 9 (4–24) months of bDMARDs cessation with three of them flaring in the first year. High leukocyte counts in sJIA patients were associated with inactive disease at 1-year after the start of treatment (p = 0.004). In the non-sJIA group, 46.1% patients experienced flare after a median of 7 (1–32) months of biologic cessation, and of these, 25 flared in the first year. Antinuclear antibody positivity (p = 0.02), earlier disease onset (p = 0.03), long disease duration (p = 0.01), and follow-up (p = 0.02) and extended time from diagnosis to first biological onset (p = 0.03) were more common among patients with flare. Conclusions When considering discontinuation of bDMARDs, it should be kept in mind that the risk of exacerbation requiring re-initiation therapy is quite significant within the first year after discontinuation of therapy.

Secukinumab Therapy in Refractory Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA), the most common chronic rheumatologic condition in childhood, remains a cause of significant morbidity, particularly in those with spondyloarthropathy, including psoriatic arthritis (PsA) and enthesitis-related arthritis (ERA). While secukinumab was recently approved for the treatment of children and adolescents with ERA and PsA, there is limited published data on its use in JIA, particularly in refractory cases, despite its efficacy in the treatment of adult arthritis. We aim to examine the use of this therapy in JIA in a single pediatric rheumatology center. A retrospective chart review was performed and 10 JIA patients who received treatment with secukinumab were identified. Data extracted included disease activity, patient demographics, comorbidities, medications, and laboratory data. Seven ERA, 2 PsA, and 1 poly JIA patient were treated with secukinumab at our center between April 2011 and July 2021. These patients had notably resistant disease, with a mean disease-modifying antirheumatic drug (DMARD) failure rate of 3.8. One hundred percent of patients who underwent magnetic resonance imaging (MRI) after being on at least 3 months of secukinumab therapy demonstrated improvement in their MRI findings. One patient developed a flare of uveitis while on secukinumab therapy, with no other adverse events recorded in our patients. Secukinumab therapy was recently approved for children and adolescents with ERA and PsA, and may offer an efficacious option given its demonstrated improvement in imaging and joint examination, as well as qualitative reports of pain, even in those who have failed other therapies. However, caution may be warranted in those with a history of uveitis and warrants further study.

Ассоциации гена VDR с клиническими проявлениями, осложнениями и обеспеченностью витамином D на фоне ювенильного идиопатического артрита у детей

Objective. To conduct an association search between genetic variants (c.1206T>C, c.152T>C, c.1174+283G>A) of the VDR gene and clinical manifestations of juvenile idiopathic arthritis (JIA), need for genetically engineered biological drugs (GEBDs) and vitamin D status in children. Patients and methods. This study included 150 children (mean age: 9.11 ± 2.21 years) with JIA and 333 healthy controls. The determination of serum calcidiol concentrations was performed in all patients. Polymorphic variants of the VDR gene (c.1206T>C, c.1175-9G>T, c.152T>C, c.1174+283G>A) were tested by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique. Results. Carriers of the minor TT genotype of the genetic variant c.1206T>C(A>G) TaqI are 4 time more likely to develop systemic JIA, 5 time more likely to have high disease activity and uveitis, as well as 9.9 times more often require prescription of GEBDs. Carriers of the minor genotype TT of the genetic variant c.152T>C FokI are 7.7 times more likely to develop systemic JIA and 4.3 times – polyarticular JIA, 6.2 times more likely to have high disease activity and 5.6 times – uveitis, 8 times more often have a severe calcidiol deficiency and 4 times more often require prescription of GEBDs. Carrying the minor AA genotype of the BsmlI polymorphism (c.1174+283G>A) increases the risk of systemic-onset JIA by 17 times, high disease activity and uveitis – by 18 times, and need for GEBDs – by 15 times; carrying the AA and GA genotypes increases the risk of calcidiol deficiency by 5 times and severe calcidiol deficiency by 9 times. Conclusion. All studied genetic variants of the VDR gene verifiably affect the development of clinical manifestations, complications, calcidiol levels and response to therapy in JIA. Key words: VDR gene, juvenile idiopathic arthritis, children, vitamin D, autoimmune disease

Biologic Disease-Modifying and Other Anti-Rheumatic Drugs Use in Patients with Moderate-to-Severe Juvenile Idiopathic Arthritis Based on a Japanese Nationwide Claims Database.

PurposeBiologic disease-modifying anti-rheumatic drugs (bDMARDs) are highly effective and safe against juvenile idiopathic arthritis (JIA), which is classified into systemic JIA (sJIA) and the other JIA categories (non-sJIA) according to differences in clinical symptoms and pathophysiology. The purpose of the current study was to investigate trends in patterns of prescribing bDMARDs for moderate-to-severe JIA using a relatively large sample size in Japan.Patients and MethodsA descriptive epidemiological study based on a nationwide claims database in Japan was conducted from 2012 to 2018 using the “JMDC Claims Database” to explain annual changes based on the number of patients prescribed bDMARDs. Study drugs were identified based on the Anatomical Therapeutic Chemical codes, such as methotrexate, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs.ResultsFrom a database of 6,862,244 patients, the following exclusion criteria were applied: aged ≥16 years, without “M08” in their ICD-10 code as disease, and missing the information of prescription date in the database during the study period, resulting in a final number of 111 JIA patients. We found an increasing trend for adalimumab and tocilizumab and a decreasing trend for methotrexate. Differences in medication use between sJIA and non-sJIA patients were also evident, being consistent with national and international guidelines.ConclusionAlthough the introduction of bDMARDs has markedly improved the efficacy of JIA therapy, there are still many short- and long-term safety issues to be examined, including the risk of infection and potential risk of associated malignancy. Future studies are needed to clarify these issues.

Research priority setting for paediatric rheumatology in the UK.

The evidence base that underlies the management of children and young people with paediatric rheumatic diseases is deficient. In this field, there are many crucial unanswered questions. The UK Paediatric Rheumatology Clinical Studies Group, supported by UK National Institute for Health Research Clinical Research Network: children and Versus Arthritis, elicited ideas for research priorities from paediatric rheumatologists, trainees, allied health-care professionals, nurse specialists, patients, parents of patients, carers, and charities. These ideas were collected through online surveys and face-to-face meetings. A modified Delphi process was used, which included online research priority ranking surveys and a consensus workshop. A longlist of 55 disease-specific research priorities and 37 general research priorities were voted on in the first survey. A list of 11 top general research priorities was produced. The top ten disease-specific research priorities were discussed in depth at a Delphi workshop to determine their final ranking. This Health Policy paper will help to guide clinicians, academics, and funding bodies to prioritise research in paediatric rheumatic diseases, specifically in areas of unmet patient needs.

Research progress in drug therapy of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. With the gradual expansion of the incidence of JIA in the population, the pathogenesis and treatment of JIA were further explored and analyzed, and JIA has achieved some success in drug therapy. A systemic literature search was conducted on PubMed, Cochrane Library, EMBASE, ISI Web of Science, the US National Institutes of Health Ongoing Trials Register, and the EU Clinical Trials Register. Through the searching of clinical trials of JIA in recent years, we summarized the progress of the clinical treatment of JIA. The main treatment drugs for JIA include non-steroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs and biological agents. So far, a variety of biological agents targeting the cytokines and receptors involved in its pathogenesis have been gradually approved for JIA in many countries. The application of biological agents in JIA showed good efficacy and safety, bringing unprecedented experience to children and adolescents with JIA. The potential and advantages of biologic agents in the treatment of JIA are significant, and the application of biologic agents in the treatment of JIA will be more and more common.

Comparison of efficacy between triamcinolone acetonide and triamcinolone hexacetonide for intraarticular therapy in juvenile idiopathic arthritis: a retrospective analysis

BackgroundThere are many FDA-approved corticosteroid preparations available for intra-articular injection, however triamcinolone hexacetonide is not one of them. It was the intraarticular drug of choice among pediatric rheumatologists up until approximately a decade ago, when production of this medication ceased. It can be obtained in the United States and Canada via importation from Europe, but it is not FDA-approved at this time. We wish to compare the duration of remission of intraarticular triamcinolone hexacetonide (TH) with that of triamcinolone acetonide (TA) in children with juvenile idiopathic arthritis (JIA) and demonstrate its safety in this population.MethodsThis retrospective chart review included 39 patients with JIA who received intraarticular corticosteroid injections (IACIs) from September 2018 to September 2019. These patients were reviewed and their life-time injections with either TH (41 joints) or TA (124 joints) was noted through May 30, 2021. Patients with concomitant systemic therapy initiation were excluded. The primary outcome was time to relapse. Relapse was defined by the presence of arthritis on physical examination by an attending rheumatologist. Kaplan–Meier curves and a log-rank test were constructed to compare the probability of time to relapse between IACI injections. Additionally, mixed effects cox regression models were constructed to account for multiple injections per participant.ResultsKaplan–Meier estimator of median relapse time in months was higher for TH. Based on the log-rank test, TA joints had a higher probability of experiencing a relapse during the study time (p value < 0.001). The hazard of time to relapse was reduced when comparing TH to TA in both unadjusted and adjusted mixed effects cox regression models [unadjusted hazard ratio (95% confidence interval): 0.184 (0.089, 0.381); adjusted hazard ratio (95% confidence interval): 0.189 (0.092, 0.386)].ConclusionsTH has longer duration of action than TA and is associated with less systemic side effects. It should be considered the drug of choice for intraarticular corticosteroid injections in children with JIA.

Considerations for the Primary Care Provider Caring for Patients with Juvenile Idiopathic Arthritis Receiving Biologic Therapy.

Juvenile idiopathic arthritis (JIA) is the most common rheumatologic condition in children. JIA is a chronic autoimmune disease with no known cure affecting more than 1 in 1,000 children. With the development of targeted biologic therapies for JIA in the late 1990s, the outlook for children with JIA dramatically improved. Since that time, many children have received biologic therapies, allowing for better disease control and even disease remission. Given the frequency of JIA and increasing use of biologic medications, primary care providers require a basic understanding about these medications and their side effects as well as how the primary care provider can best support the patients who are receiving biologic therapy. [Pediatr Ann. 2022;51(2):e54-e56.].

Juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is an umbrella term for arthritis of unknown origin, lasting for >6 weeks with onset before 16 years of age. JIA is the most common chronic inflammatory rheumatic condition of childhood. According to the International League Against Rheumatism (ILAR) classification, seven mutually exclusive categories of JIA exist based on disease manifestations during the first 6 months of disease. Although the ILAR classification has been useful to foster research, it has been criticized mainly as it does not distinguish those forms of chronic arthritis observed in adults and in children from those that may be unique to childhood. Hence, efforts to provide a new evidence-based classification are ongoing. Similar to arthritis observed in adults, pathogenesis involves autoimmune and autoinflammatory mechanisms. The field has witnessed a remarkable improvement in therapeutic possibilities of JIA owing to the availability of new potent drugs and the possibility to perform controlled trials with support from legislative interventions and large networks availability. The goal of drug therapy in JIA is to rapidly reduce disease activity to inactive disease or clinical remission, minimize drug side effects and achieve a quality of life comparable to that of healthy peers. As JIA can influence all aspects of a child's and their family's life, researchers increasingly recognize improvement of health-related quality of life as a key treatment goal.

Опыт успешного применения голимумаба у ребенка с ювенильным полиартритом

Objective of the Paper: Demonstration of a clinical case of successful use of golimumab in a child with juvenile polyarthritis. Key points. Juvenile polyarthritis is one of the most disabling clinical variants of juvenile idiopathic arthritis (JIA). In recent years, the range of medicines used in the therapy of JIA has significantly expanded. With the ineffectiveness of methotrexate, the appointment of genetically engineered biological drugs (GIBP) is shown, among which tumor necrosis factor α (TNF-α) inhibitors are most often used, one of which is golimumab. Conclusion. To date, for the treatment of juvenile polyarthritis, there is golimumab in the arsenal of medicines, which is human monoclonal antibodies to TNF-α, which allows to achieve an inactive phase of the disease with the ineffectiveness of the use of other GIBP. Keywords: juvenile polyarthritis, golimumab, children

Отмена ингибиторов фактора некроза опухоли-α при достижении лекарственной ремиссии ювенильного идиопатического артрита без системных проявлений

Juvenile idiopathic arthritis (JIA) is one of the most common and disabling rheumatic diseases in children. Pharmaceutical therapy for JIA can prevent the progression of the disease, achieve long-term remission, and significantly improve the quality of life in most patients. In cases where the initial therapy for JIA is not effective enough, it is recommended to escalate it, and vice versa, when remission is achieved, the de-escalation of therapy may be discussed. The latter is necessary due to the high risk of developing infectious complications and certain oncological diseases against the background of continuous biological treatment of JIA, as well as the negative impact of regular injections and/or infusions of medications on the quality of life, the interruption of educational process, the psychological burden of “lifelong” treatment with medications, and the economic burden on families and healthcare system. Currently, optimal regimens for the discontinuation of biopharmaceuticals, including TNFalpha inhibitors, remain a matter of debate. In this regard, the search for potential predictors of JIA exacerbation after withdrawal of biopharmaceuticals is relevant. Key words: juvenile idiopathic arthritis, biologic-free remission of JIA, tumor necrosis factor, inhibitors, etanercept, adalimumab, withdrawal, exacerbation, predictors

Адаптация и валидация шкалы непереносимости метотрексата MISS у детей с ювенильным идиопатическим артритом: одномоментное поперечное исследование

Background. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. First-line therapy for JIA includes methotrexate (MTX); however, it can cause adverse events, which necessitates early diagnosis of MTX intolerance. The Methotrexate Intolerance Severity Score (MISS) is one of diagnostic instruments that can be used for this purpose. Objective. To validate, customize, and implement the MISS questionnaire into clinical practice. Patients and methods. This cross-sectional study was conducted between January and May 2022 and included 100 JIA patients (32 boys and 68 girls) aged ≤17 years receiving MTX. We validated the MISS questionnaire to evaluate possible adverse events associated with MTX. We performed linguistic and cultural customization of the MISS questionnaire. To assess the reliability of the questionnaire, we calculated the Cronbach's alpha coefficient. Results. Cronbach's alpha coefficient showed that MISS is a reliable tool to detect MTX intolerance. We found that more than a quarter of patients had MTX intolerance with nausea being the most common complaint among the participants. Conclusion. Despite high MTX efficacy in clinical practice, patients often demonstrated poor treatment adherence due to MTXrelated adverse events. It is important to continue the implementation of the Russian version of MISS to ensure early detection of adverse events and timely initiation of adequate treatment. Key words: children, juvenile idiopathic arthritis, methotrexate, Methotrexate Intolerance Severity Score, drug intolerance

Efficacy and Safety of Etanercept Biosimilars Compared With the Originator for Treatment of Juvenile Arthritis: A Prospective Observational Study.

ObjectiveAnalysis of etanercept biosimilars in pediatric patients with juvenile idiopathic arthritis (JIA) in comparison with the etanercept originator in terms of efficacy and safety.MethodsPatients diagnosed with JIA who started treatment with either the etanercept originator or a biosimilar after January 1, 2017, were selected from the German BIKER registry (Biologics in Paediatric Rheumatology Registry). Furthermore, patients who started therapy with the originator and switched to a biosimilar during the course of therapy were identified. For both patient groups, disease activity and safety were examined and compared separately.ResultsAfter January 1, 2017, 348 patients started treatment with the etanercept originator (n = 293) or a biosimilar (n = 55). Another 57 patients switched to a biosimilar during the course of therapy. A significant decrease or a stable remission of disease activity was observed in both patient groups. The safety profiles were comparable, and frequencies and types of adverse events (AEs) and serious AEs were similar in patients starting therapy with the originator or a biosimilar. Only injection site reactions occurred slightly more frequently under biosimilar therapy, without having an impact on therapy adherence. In patients who switched therapy, the AE rate per 100 patient‐years was comparable before (26.4) and after (32.1) the switch.ConclusionIn patients with JIA who require treatment with etanercept, the originator is still used much more frequently. However, our study highlights the equivalence of etanercept biosimilars for therapy for JIA. Increased use of these biosimilars in pediatric patients can therefore be recommended without hesitation.

Persistence and adherence to biologic therapies in juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that often requires biological therapy to control its activity. Medication persistence and adherence are important aspects on which we have scarce information. We performed a longitudinal, retrospective, and observational study based on data from the daily clinical management of JIA patients. We recorded clinical remission at 6 and 12 months. Persistence of biological therapy was evaluated using Kaplan–Meier curves, and adherence was assessed using the medication possession ratio (MPR). We included 68 patients who received biological therapy. Of these, 11 (16.2%) and 5 (7.4%) required a second and third drug, respectively. The persistence rate for biological therapy at 5 years was 64%, with no differences between the first and second lines. Adherence was high during the first year of treatment (MPR80: 96.3%) and also in the second and third years (MPR80: 85.2% and 91.8%, respectively). Persistence and adherence to biological therapy were remarkably high in our JIA cohort. Adherence to biological treatments could be related to a higher probability of fulfilling the Wallace remission criteria at 6 months, although this was not confirmed at 12 months.

Concerted Actions by PIICP, CTXII, and TNF-α in Patients with Juvenile Idiopathic Arthritis.

Joint destruction in juvenile idiopathic arthritis (JIA), initiated in the early, preclinical stage of the disease, is diagnosed on the basis of clinical evaluation and radiographic imaging. The determination of circulating cartilage-matrix turnover markers can facilitate the diagnosis and application of better and earlier treatment strategies for JIA. We have shown that 96 JIA patients have elevated levels of procollagen II C-terminal propeptide (PIICP), reflecting the extent of joint cartilage biosynthesis, and C-telopeptide of type II collagen (CTXII), a biomarker of the resorption of this tissue. Patients who did not respond to treatment had particularly high levels of these markers. JIA treatment resulted in the normalization of these markers in remissive patients, but not in those with active JIA. We showed correlations between examined variables and inflammatory process indicators, i.e., C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and tumor necrosis factor-α (TNF-α). The TNF-α of patients responding to treatment correlated with PIICP, especially in the patients before treatment (r = 0.898, p < 0.001). Significant changes in serum PIICP during JIA therapy suggest its potential diagnostic utility in the monitoring of disease activity and the possibility of its use in assessing treatment towards remission. Understanding changes in type II collagen metabolism over the course of the discussed arthritis may allow the implementation of both new diagnostic tools and new therapeutic strategies in children with JIA.