P024 Efficacy and tolerance of methotrexate in patients with Juvenile Idiopathic Arthritis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
A Fazaa ◽  
F Rouatbi ◽  
S Miladi ◽  
K Ouenniche ◽  
L Souabni ◽  
...  

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease for children. The therapeutic management depends on several factors and is based on different treatments including methotrexate (MTX). The aim of our study was to determine the efficacy and safety of MTX in JIA. Methods This is a monocentric retrospective study of 37 patients followed for JIA according to the 2001 International League of Association of Rheumatology (ILAR) criteria and treated with MTX. Socio-demographic, clinical, paraclinical and therapeutic data were collected. Disease activity was assessed by the JADAS score. Highly active JIA was defined as JADAS superior to 25. Results There were 25 boys (67.5%) and 12 girls (32.4%) with a median age of 6.3 years [4–13]. The average duration of the rheumatic disease was 2.7 years [2.5–5.3]. The type of JIA was: oligoarticular in 22 cases (59.4%), polyarticular in 10 cases (27%), arthritis related to enthesitis in 3 cases (8.1%) and systemic in 2 cases (5.4%). Twenty patients (54%) received oral corticosteroid therapy for a mean period of 1.7 years [0.6–3] with a mean daily dose of 10 mg/day of prednisone or equivalent. Oral MTX was prescribed to all patients with a mean weekly dose of 10 mg/m2 body surface [10–15]. MTX was initiated after a mean period of 6.2 months [3.1–11.4] from diagnosis. The mean treatment duration was 50 months [34–66]. Observance of MTX was 80.5%. Remission with MTX was achieved in 28 patients (75.6%) after a mean treatment duration of 7.5 months [5–11], with a mean JADAS of 5.1 [3.5–10]. Despite good observance of MTX, eight patients (21.6%) continued to have high disease activity with a mean JADAS score of 32 [25–40]. Tolerance to oral MTX was good, with side effects occurring only with 5 patients (13.5%), such as epigastralgia in 2 cases (which disappeared after switching to the intramuscular administration), a skin reaction in one case, and hepatic cytolysis reversible when stopping the treatment in 2 other cases. Conclusion MTX still has a place in the therapeutic management of JIA and appears to be a well-tolerated and effective treatment.

2003 ◽  
Vol 28 (05) ◽  
Author(s):  
A Ronaghy ◽  
E Huijssoon ◽  
MA van Rossum ◽  
ABJ Prakken ◽  
GT Rijkers ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Liane D. Heale ◽  
Kristin M. Houghton ◽  
Elham Rezaei ◽  
Adam D. G. Baxter-Jones ◽  
Susan M. Tupper ◽  
...  

Abstract Background Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA). Methods In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach. Results in the JIA cohort were compared to normative Pediatric Bone Mineral Accrual Study data derived from healthy children using z-scores. Results At enrollment, PA z-score levels of study participants were lower than those in the normative population (median z-score − 0.356; p = 0.005). At enrollment, PA raw scores were negatively associated with the psychosocial domain of the Juvenile Arthritis Quality of Life Questionnaire (r = − 0.251; p = 0.023). There was a significant decline in PAQ-C/A raw scores from baseline (median and IQR: 2.6, 1.4–3.1) to 24 months (median and IQR: 2.1, 1.4–2.7; p = 0.003). The linear mixed-effect model showed that PAQ-C/A raw scores in children with JIA decreased as age, disease duration, and ESR increased. The PAQ-C/A raw scores of the participants was also negatively influenced by an increase in disease activity as measured by the JADAS-71 (p <  0.001). Conclusion Canadian children with newly diagnosed JIA have lower PA levels than healthy children. The decline in PA levels over time was associated with disease activity and higher disease-specific psychosocial stress.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 588.2-588
Author(s):  
G. Olivieri ◽  
F. Ceccarelli ◽  
F. Natalucci ◽  
F. R. Spinelli ◽  
C. Alessandri ◽  
...  

Background:The updated EULAR recommendations for the management of systemic lupus erythematosus (SLE) underline the use of Mycophenolate Mofetil (MMF) in the treatment of different disease related manifestations (1). Several randomized controlled trials have demonstrated the efficacy of MMF in lupus nephritis (LN) patients but only case series and open-labelled trials have analyzed the use of this drug in other than LN features. Moreover, no data are available about the MMF retention rate in a real-life setting.Objectives:The present study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a large monocentric SLE cohort. Secondly, we investigated the influence of MMF in disease activity changes and chronic damage progression.Methods:We performed a longitudinal study including all the SLE patients (ACR 1997 criteria) starting MMF treatment in our Lupus Clinic. Data about indications, mean dosage, duration of treatment and reasons for drug withdrawal were registered. The DRR was estimated using the Kaplan–Meier method. Disease activity and chronic damage were assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SLICC Damage Index (SDI), respectively.Results:The present analysis included 162 SLE patients (M/F 22/140, median age at the disease diagnosis 25.5 years, IQR 13). At the beginning of MMF treatment, we registered a median age of 34 months (IQR 21) and a median disease duration of 72 months (IQR 123). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%), followed by neuropsychiatric involvement (10, 6.2%), and others disease related manifestations (12, 7.4%; in particular skin involvement, hematological features, myositis, vasculitis). MMF was administered at a mean daily dosage of 2.1±0.6 grams; no differences in dosage were found between the different indications (p=ns).At the longitudinal analysis, we registered a median treatment duration of 30 months (IQR 55). Figure 1 reported data about DRR: in particular, at 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (NLN) (60.5%; p=ns). Interestingly, the DRR at 60 months was higher in the subgroup of patients treated for joint involvement (75.4%), even without reaching a statistically significant difference. During the observation period, 92 patients (59.2%) discontinued MMF (median treatment duration at discontinuation 25 months, IQR 35). Interestingly, the main cause of withdrawal was the achievement of persistent remission, observed in 20 patients (21.7%), followed by loss of efficacy (19 patients, 20.5%), drug intolerance and pregnancy planning (17 patients for both reasons, 18,4%). Furthermore, our analysis confirmed MMF efficacy, as demonstrated by the significant reduction in SLEDAI-2k values after 4, 12 and 24 months of treatment (p< 0.0001 for all the time-points in comparison with baseline). In addition, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in SDI values (baseline: 0.6, IQR 1; last observation: 0.93, IQR 1; p=ns).Conclusion:The evaluation of a large SLE cohort demonstrated a good retention rate for MMF. In particular, our results demonstrated that MMF is also a safe and effective drug for SLE manifestation other than LN, in particular for joint involvement. Moreover, it is able to control disease activity and to prevent the progression of chronic damage.References:[1]Fanouriakis A et al. Ann Rheum Dis. 2019 Jun;78(6):736-745.Disclosure of Interests:None declared


2021 ◽  
Vol 10 (8) ◽  
pp. 1771
Author(s):  
Violetta Opoka-Winiarska ◽  
Ewelina Grywalska ◽  
Izabela Korona-Glowniak ◽  
Katarzyna Matuska ◽  
Anna Malm ◽  
...  

There is limited data on the effect of the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) on pediatric rheumatology. We examined the prevalence of antibodies against SARS-CoV-2 in children with juvenile idiopathic arthritis (JIA) and a negative history of COVID-19 and the correlation of the presence of these antibodies with disease activity measured by juvenile arthritis disease activity score (JADAS). In total, 62 patients diagnosed with JIA, under treatment with various antirheumatic drugs, and 32 healthy children (control group) were included. Serum samples were analyzed for inflammatory markers and antibodies and their state evaluated with the juvenile arthritis disease activity score (JADAS). JIA patients do not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than healthy subjects. We found anti-SARS-CoV-2 antibodies in JIA patients who did not have a history of COVID-19. The study showed no unequivocal correlation between the presence of SARS-CoV-2 antibodies and JIA activity; therefore, this relationship requires further observation. We also identified a possible link between patients’ humoral immune response and disease-modifying antirheumatic treatment, which will be confirmed in follow-up studies.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 23.2-24
Author(s):  
V. Molander ◽  
H. Bower ◽  
J. Askling

Background:Patients with rheumatoid arthritis (RA) are at increased risk for venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) (1). Several established risk factors of VTE, such as age, immobilization and comorbid conditions, occur more often patients with RA (2). In addition, inflammation may in itself also increase VTE risk by upregulating procoagolatory factors and causing endothelial damage (3). Recent reports indicate an increased risk of VTE in RA patients treated with JAK-inhibitors (4), pointing to the need to better understand how inflammation measured as clinical RA disease activity influences VTE risk.Objectives:To investigate the relationship between clinical RA disease activity and incidence of VTE.Methods:Patients with RA were identified from the Swedish Rheumatology Quality Register (SRQ) between July 1st2006 and December 31st2017. Clinical rheumatology data for these patients were obtained from the visits recorded in SRQ, and linked to national registers capturing data on VTE events and comorbid conditions. For each such rheumatologist visit, we defined a one-year period after the visit and determined whether a VTE event had occurred within this period or not. A visit followed by a VTE event was categorized as a case, all other visits were used as controls. Each patient could contribute to several visits. The DAS28 score registered at the visit was stratified into remission (0-2.5) vs. low (2.6-3.1), moderate (3.2-5.1) and high (>5.1) disease activity. Logistic regression with robust cluster standard errors was used to estimate the association between the DAS28 score and VTE.Results:We identified 46,311 patients with RA who contributed data from 320,094 visits. Among these, 2,257 visits (0.7% of all visits) in 1345 unique individuals were followed by a VTE within the one-year window. Of these, 1391 were DVT events and 866 were PE events. Figure 1 displays the absolute probabilities of a VTE in this one-year window, and odds ratios for VTE by each DAS28 category, using DAS28 remission as reference. The one-year risk of a VTE increased from 0.5% in patients in DAS28 remission, to 1.1% in patients with DAS28 high disease activity (DAS28 above 5.1). The age- and sex-adjusted odds ratio for a VTE event in highly active RA compared to RA in remission was 2.12 (95% CI 1.80-2.47). A different analysis, in which each patient could only contribute to one visit, yielded similar results.Figure 1.Odds ratios (OR) comparing the odds of VTE for DAS28 activity categories versus remission. Grey estimates are from unadjusted logistic regression models, black estimates are from logistic regression models adjusted for age and sex. Absolute one-year risk of VTE are estimated from unadjusted models.Conclusion:This study demonstrates a strong association between clinical RA inflammatory activity as measured through DAS28 and risk of VTE. Among patients with high disease activity one in a hundred will develop a VTE within the coming year. These findings highlight the need for proper VTE risk assessment in patients with active RA, and confirm that patients with highly active RA, such as those recruited to trials for treatment with new drugs, are already at particularly elevated risk of VTE.References:[1]Holmqvist et al. Risk of venous thromboembolism in patients with rheumatoid arthritis and association with disease duration and hospitalization. JAMA. 2012;308(13):1350-6.[2]Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44(2):62-9.[3]Xu J et al. Inflammation, innate immunity and blood coagulation. Hamostaseologie. 2010;30(1):5-6, 8-9.[4]FDA. Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate. 2019.Acknowledgments:Many thanks to all patients and rheumatologists persistently filling out the SRQ.Disclosure of Interests:Viktor Molander: None declared, Hannah Bower: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 901.2-901
Author(s):  
S. Kirchner ◽  
C. Sengler ◽  
J. Klotsche ◽  
I. Liedmann ◽  
M. Niewerth ◽  
...  

Background:Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in childhood. A multimodal treatment is needed to reduce pain, control inflammation and maintain joint functioning. Adherence to prescribed therapies is necessary for an optimal outcome. Measuring adherence in children with JIA and their caregivers by a validated questionnaire provides important information about benefits and problems with treatment.Objectives:To evaluate adherence in JIA patients and to validate the German version of both the parent adherence report questionnaire (PARQ) and the child adherence report questionnaire (CARQ).Methods:The PARQ and CARQ were translated from its original English version into German and cross-culturally adapted. Parents and children completed the PARQ and CARQ 4 years after enrolment in the Inception cohort ICON. These questionnaires measure child ability (by VAS 0-100, 100 = best) related to i) general level of difficulty in following treatment, ii) frequency of following treatment, iii) negative reactions in response to treatment [i)-iii) summarized to child ability total score], iv) perceived helpfulness of treatment, and 4 categorical questions on errors in medication behavior. Reliability was tested by re-administering the questionnaire after a mean of 13 days. Reproducibility was analysed using intraclass correlation coefficients (ICC). VAS scores were correlated with the Pediatric Quality of Life Inventory (PedsQL) treatment scale items for convergent validity, and with sociodemographic parameters for discriminant validity.Results:481 parents and 465 children completed the PARQ and the CARQ, respectively, 56 parents and 37 children took part in the re-test. The mean age at assessment was 10.1±3.7 years, mean disease duration was 4.7±0.8 years. The majority of patients suffered from oligoarthritis (49%), followed by rheumatoid-factor negative polyarthritis (30%). Treatment with a DMARD received 60% (MTX 46%), 28% received a biological drug, 16% both. Disease activity measured by the clinical juvenile arthritis disease activity score-10 (cJADAS-10) was 2.6 ± 3.4 (range 0 – 30, best = 0), functional status was good (mean CHAQ 0.2 ± 0.4). Exercise and splints were prescribed to 57% and 21% of patients, respectively.PARQ/CARQ mean child ability total scores for medication were 73.1 ± 23.3/76.5 ± 24.2, for exercise: 85.6 ± 16.5/90.3 ± 15.0, for splints: 72.9 ± 24.2/82.9 ± 16.5. About a third of parents and children reported any error in medication behavior. Perceived helpfulness was highest for medication (PARQ/CARQ 87.4 ± 20.6/83.6 ± 26.1) and lowest for splints. (PARQ/CARQ 80.8 ± 28.4/73.5 ± 33.6).ICCs related to medication indicated good to excellent concordance (PARQ ICC = 0.69 - 0.96; CARQ ICC = 0.53 - 0.75), to exercise moderate (PARQ ICC = 0.28 - 0.45; CARQ ICC = 0.67 - 0.93) and to splints disparate concordance (PARQ ICC = 0.01 - 0.90, CARQ ICC = 0.86 - 0.93).Scores for medications (PARQ: r 0.06 - 0.38, CARQ: 0.06 - 0.49), exercise (PARQ: r 0.03 - 0.30, CARQ: 0.01 - 0.34) and splints (PARQ: r 0.09 - 0.52, CARQ: 0.11 - 0.62) showed a fair to good correlation with the PedsQL scales. Gender and socioeconomic status were not associated with the level of adherence.Conclusion:The German version of the PARQ and CARQ appears to be a valuable tool to measure adherence in patients with JIA and to evaluate helpfulness of treatments.Acknowledgments:ICON is funded by the Federal Ministry of Research (FKZ:01ER0812)Disclosure of Interests:Sabine Kirchner: None declared, Claudia Sengler: None declared, Jens Klotsche: None declared, Ina Liedmann: None declared, Martina Niewerth: None declared, Daniel Windschall: None declared, Tilmann Kallinich Grant/research support from: Novartis, Consultant of: Sobi, Roche, Novartis, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Toni Hospach: None declared, Frank Dressler: None declared, J. B. Kuemmerle-Deschner Grant/research support from: Novartis, AbbVie, Sobi, Consultant of: Novartis, AbbVie, Sobi, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche


2009 ◽  
Vol 36 (4) ◽  
pp. 837-842 ◽  
Author(s):  
ANA FILIPA MOURÃO ◽  
JOANA CAETANO-LOPES ◽  
PAULA COSTA ◽  
HELENA CANHÃO ◽  
MARIA JOSÉ SANTOS ◽  
...  

Objective.Considering the relevance of tumor necrosis factor-α (TNF-α) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-α serum concentrations were associated with TNF-α −308 genotypes.Methods.Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at position −308 by restriction fragment-length polymorphism.Results.One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the −308 GA/AA genotypes and 76% the −308 GG genotype, similar to findings in controls. Patients with the −308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-α levels compared to those with the −308 GG genotype.Conclusion.TNF-α −308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
A. Raab ◽  
T. Kallinich ◽  
D. Huscher ◽  
I. Foeldvari ◽  
F. Weller-Heinemann ◽  
...  

Abstract Background Oligoarticular juvenile idiopathic arthritis (oligoJIA) is the most commonly diagnosed category of chronic arthritis in children. Nevertheless, there are no evidence- based guidelines for its treatment, in particular for the use of methotrexate (MTX). The primary objective of this analysis is to evaluate the outcomes in patients with persistent oligoJIA compared to those with extended oligoJIA and rheumatoid factor (RF) negative polyarthritis treated with methotrexate. Methods Patients with persistent or extended oligoJIA or RF negative PA recorded in the Biologics in Pediatric Rheumatology Registry (BiKeR), receiving methotrexate for the first time were included in the analyses. Efficacy was determined using the Juvenile Arthritis Disease Activity Score 10 (JADAS 10). Safety assessment included the documentation of adverse and serious adverse events. Results From 2005 through 2011, 1056 patients were included: 370 patients with persistent oligoJIA, 221 patients with extended oligoJIA and 467 patients with RF negative PA. Therapeutic efficacy was observed following the start of methotrexate. Over a period of 24 months JADAS-minimal disease activity (JADAS ≤2) was reached in 44% of patients with persistent oligoJIA, 38% with extended oligoJIA, 46% with RF negative PA, JADAS-remission defined as JADAS ≤1 was reached in 33% of patients with persistent oligoJIA, 29% with extended oligoJIA and 35% (RF negative PA). Patients with extended oligoJIA achieved JADAS remission significantly later and received additional biologic disease-modifying drugs significantly more often than patients with persistent oligoJIA or RF negative PA (p < 0.001). Tolerability was comparable. New onset uveitis occurred in 0.3 to 2.2 per 100 patient years. Conclusions Patients with persistent oligoJIA taking methotrexate are at least as likely to enter remission as patients with extended oligo JIA or polyarticular JIA. Patients with extended oligoJIA achieved JADAS remission significantly later. Within 2 years, almost half of the patients with persistent oligoJIA achieved JADAS-minimal disease activity.


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