scholarly journals FRI0456 EARLY IMPLEMENTATION OF TREATMENT WITH ETANERCEPT INCREASES THE LIKELIHOOD TO ACHIEVE REMISSION

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 825.1-825
Author(s):  
J. Klotsche ◽  
G. Horneff ◽  
P. Haas ◽  
I. Foeldvari ◽  
M. Niewerth ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Loss Of Function ◽  
American College Of Rheumatology ◽  
Early Implementation ◽  
Patient Reported ◽  
Permanent Loss ◽  
Treatment Data

Background:Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children and adolescents. A consistent therapy is required to avoid consequential damage and permanent loss of function. Biologic disease modifying anti-rheumatic drugs (bDMARDs) provide a well-accepted option for treatment of patients with a severe course of JIA. Etanercept (ETA) is still the most commonly prescribed bDMARD for JIA in Germany.Objectives:To analyze adherence to treatment with ETA with special attention on discontinuation after achieving an inactive disease and recurrence of active disease after ETA withdrawal.Methods:Data from two ongoing prospective, multicenter, non-interventional registries BiKeR and JuMBO were used for the analysis. JuMBO is the follow-up study to BiKeR and follows patients who have reached the age of 18. Both registers provide treatment data, individual trajectories of clinical data and outcomes from childhood into adulthood in JIA patients treated with bDMARDs and csDMARDs. Clinical disease characteristics, such as disease activity, were reported by the rheumatologists in addition to patient-reported outcomes at each six-months follow-up. Remission was defined as inactive disease defined by the Wallace Criteria (1).Results:Data from 2,500 patients who were included in BiKeR and had an age ≥18 at the time of analysis were considered. A subset of 1,535 were enrolled in JuMBO. The mean follow-up was 8.6 (SD 4.2) years for the JuMBO patients. The majority of them had polyarthritis (35%), followed by enthesitis-related arthritis (20%). A total of 1,779 (68.8% of 2,584) patients were ever treated with ETA, providing 2,178 ETA treatment courses. There were 1,724 (67%) patients with first, 338 patients with a second and 54 with a third course of ETA treatment course. 710 (41.2%) discontinued ETA by ineffectiveness in the first course with similar rates of discontinuation due to ineffectiveness in the first and second course. A total of 332 (+/-MTX, 19.3%) discontinued ETA after achieving remission in the first ETA course. Among those, 129 (38.9%) patients did not require treatment with any other bDMARD subsequently until last follow-up (3.9 years, SD 3.5), while 169 (50.9%) re-started treatment with ETA, 14 (4.2%) with adalimumab and 4 with other bDMARDs. The likelihood of discontinuing ETA due to an inactive disease was positively associated with a younger age (hazard ratio (HR) 1.08, p<0.001), persistent oligoarthritis (HR 1.89, p=0.004), a shorter duration between JIA onset and ETA start (HR 1.10, p<0.001) as well as a good response to therapy within the first six months of treatment (HR 1.11, p<0.001). 209 (of 332) had ETA monotherapy at withdrawal. Of those, 77% (n=161) experienced recurrence of disease with a mean time to flare of 12.1 (SD 13.7) months. 129 patients restarted bDMARD therapy (n=117 ETA). We could not identify any correlates for the risk of flare. 70% re-achieved remission and 20% again discontinued therapy thereafter.Conclusion:The study confirms the good effectiveness of ETA, even in the re-treatment of patients with JIA. Our data highlight the association of an early bDMARD treatment with a higher likelihood to achieve an inactive disease indicating a window of opportunity.References:[1]Wallace CA, Giannini EH, Huang B et al. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res 2011;63:929–36Disclosure of Interests:Jens Klotsche: None declared, 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, Peter Haas: None declared, Ivan Foeldvari Consultant of: Novartis, Martina Niewerth: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche

scholarly journals THU0502 EFFICACY AND SAFETY OF SECUKINUMAB TREATMENT IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 489.3-489
Author(s):  
I. Kriulin ◽  
E. Alexeeva ◽  
T. Dvoryakovskaya ◽  
K. Isaeva ◽  
A. Chomakhidze ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Psoriatic Arthritis ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Hla B27 ◽  
Serious Adverse Events ◽  
National Medical ◽  
Alternative Drug ◽  
Baseline Information

Background:Anti-IL-17A biologic drug secukinumab (SEC) proved to be effective for treatment of psoriatic arthritis. However data about its efficacy in juvenile idiopathic arthritis (JIA) are restricted to off-label experience.Objectives:To evaluate the effectiveness and safety of SEC in JIA patients in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:25 patients started SEC therapy from 12/2017 to 11/2019 in single-center prospective study. 3 patients withdrew treatment: two patients (8%) due to AE (1 - allergy followed by MAS after first injection and 1 – leukopenia) and one patient (4%) – after 10 months of treatment due to secondary inefficacy. Among others, 14 patients which were successfully treated for 6 months or longer were included into analysis. At the baseline, information was collected on the characteristics of the onset of the disease, previous therapy and its success. Patients were monitored at least 1 time per year. At each visit, clinical and laboratory characteristics of JIA severity were assessed. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the C.Wallace criteria for inactive disease (WID) and clinical remission. AEs were assessed at each visit.Results:Among 14 patients received SEC for at least 6 months, 7 (50%) have enthesitis-related arthritis, one (7.1%) – persistent oligoarthritis, 4 (28.6%) – RF-negative polyarthritis, 2 (14.3%) – psoriatic arthritis. 6 patients (42.9%) were HLA-B27 positive. Median age of JIA onset was 8.8 (IQR 5:11), age at SEC initiation – 14 (9.9:16.1), disease duration before SEC start – 3.3 (2.7:5.8). 7 (50%) were biologics-naïve, 2 (14.3%) were previously treated with anti-TNF drug, 5 (35.7%) have 2 or more different biologics in anamnesis.SEC demonstrated high efficacy after the first injection resulting in JADAS-71 decreasing in all patients by median 4.3 (1.6:7.1) points and 7/7/5/2 patients (50%/50%/35.7%/14.3%) achieved ACR Pedi 30/50/70/90 response.After 6 months of treatment, WID was achieved by 7 (50%) patients, JADAS-71 decreased from baseline level 15.2 (12.7:20.5) to 0.8 (0:4.2) points, and 14/13/11/9 patients (100%/92.9%/78.6%/64.3%) achieved ACR Pedi 30/50/70/90 response. One patients who had active uveitis at SEC initiation remained with subactive uveitis; one patient with uveitis remission had not flare episodes during follow-up period. One patient (7.1%) had successfully treated evaluation of transaminases after 4-th injection.Conclusion:Secukinumab showed high effectiveness and safety in children with JIA and can be further used both as a first-line drug in JIA associated with HLA-B27, and as an alternative drug for the ineffectiveness of the standard treatment regimen with biologics. No serious adverse events were registered during follow-up period.Disclosure of Interests:Ivan Kriulin: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Elizaveta Krekhova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared

scholarly journals Fatigue in young adults with juvenile idiopathic arthritis 18 years after disease onset: data from the prospective Nordic JIA cohort

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ellen Dalen Arnstad ◽  
◽  
Mia Glerup ◽  
Veronika Rypdal ◽  
Suvi Peltoniemi ◽  
...  
Keyword(s):  
Young Adults ◽  
Juvenile Idiopathic Arthritis ◽  
Disease Onset ◽  
Poor Health ◽  
Inactive Disease ◽  
Fatigue Score ◽  
Severe Fatigue ◽  
Patient Reported ◽  
Active Disease

Abstract Background To study fatigue in young adults with juvenile idiopathic arthritis (JIA) 18 years after disease onset, and to compare with controls. Methods Consecutive children with onset of JIA between 1997 and 2000, from geographically defined areas of Norway, Sweden, Denmark and Finland were followed for 18 years in a close to population-based prospective cohort study. Clinical features, demographic and patient-reported data were collected. Inclusion criteria in the present study were a baseline visit 6 months after disease onset, followed by an 18-year follow-up with available self-reported fatigue score (Fatigue Severity Scale (FSS), 1–7). Severe fatigue was defined as FSS ≥4. For comparison, Norwegian age and sex matched controls were used. Results Among 377 young adults with JIA, 26% reported severe fatigue, compared to 12% among controls. We found higher burden of fatigue among participants with sleep problems, pain, poor health, reduced participation in school/work, physical disability, active disease, or use of disease-modifying anti-rheumatic drugs (DMARDs)/biologics/systemic steroids. In contrast, participants without these challenges, had fatigue scores similar to controls. Active disease assessed at all three time points (baseline, 8-year and 18-year follow-up) was associated with higher mean fatigue score and higher percentage of severe fatigue compared to disease courses characterized by periods of inactive disease. Predictors of fatigue at the 18-year follow-up were female sex and diagnostic delay of ≥6 months at baseline, and also pain, self-reported poor health, active disease, and previous/ongoing use of DMARDs/biologics at 8 years. Conclusions Fatigue is a prominent symptom in young adults with JIA, with higher fatigue burden among participants with poor sleep, pain, self-reported health problems, active disease, or use of DMARDs/biologics. Participants without these challenges have results similar to controls. Patient- and physician-reported variables at baseline and during disease course predicted fatigue at 18-year follow-up.

scholarly journals Efficacy And Safety of Canakinumab As A Second-Line Biologic After Tocilizumab Treatment Failure in Children With Systemic Juvenile Idiopathic Arthritis: A Single-Center Cohort Study Using Routinely Collected Health Data

2021 ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Elizaveta Krekhova ◽  
Tatyana Dvoryakovskaya ◽  
Ksenia Isaeva ◽  
Aleksandra Chomakhidze ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Biologic Therapy ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Inactive Disease ◽  
Second Line ◽  
American College Of Rheumatology ◽  
Oral Corticosteroids ◽  
Biologic Dmard

Abstract Background: A significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (DMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.Methods: Patients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the pediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS‑71 =0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from outpatient medical records.Results: During the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at canakinumab initiation was 8.2 (interquartile range 4.0; 12.9) years, and median sJIA duration was 1.8 (0.8; 5.8) years; 37 (80%) patients received at least one non-biologic DMARD (oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (282; 404) days. During the follow-up, canakinumab was discontinued in one patient (due to tuberculosis detection) and the dose was reduced or the injection interval increased in four (9%) patients. In total, 27 (60%) patients continued to receive at least one non-biologic DMARD. Improvement according to the ACR30 criteria was achieved in 43 patients (96%; 95% confidence interval, 85–99), inactive disease in 42 (93%; 82–98), and clinical remission in 37 (82%; 69‑91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 adverse events (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.Conclusions: Short-term (about 12 months) canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA. Trial registration: CACZ885G2301E1 (G2301; NCT00891046 registered on April 29, 2009) and CACZ885G2306 (G2306; NCT02296424 registered on November 20, 2014).

scholarly journals Re-treatment with etanercept is as effective as the initial firstline treatment in patients with juvenile idiopathic arthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jens Klotsche ◽  
Ariane Klein ◽  
Martina Niewerth ◽  
Paula Hoff ◽  
Daniel Windschall ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Window Of Opportunity ◽  
Younger Age ◽  
Synthetic Dmards ◽  
Disease Modifying ◽  
Mean Time ◽  
Active Disease ◽  
Subsequent Risk

Abstract Objectives To determine (i) correlates for etanercept (ETA) discontinuation after achieving an inactive disease and for the subsequent risk of flare and (ii) to analyze the effectiveness of ETA in the re-treatment after a disease flare. Methods Data from two ongoing prospective registries, BiKeR and JuMBO, were used for the analysis. Both registries provide individual trajectories of clinical data and outcomes from childhood to adulthood in juvenile idiopathic arthritis (JIA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs (csDMARDs). Results A total of 1724 patients were treated first with ETA treatment course (338 with second, 54 with third ETA course). Similar rates of discontinuation due to ineffectiveness and adverse events could be observed for the first (19.4%/6.2%), second (18.6%/5.9%), and third (14.8%/5.6%) ETA course. A total of 332 patients (+/−methotrexate, 19.3%) discontinued ETA after achieving remission with the first ETA course. Younger age (hazard ratio (HR) 1.08, p < 0.001), persistent oligoarthritis (HR 1.89, p = 0.004), and shorter duration between JIA onset and ETA start (HR 1.10, p < 0.001), as well as good response to therapy within the first 6 months of treatment (HR 1.11, p < 0.001) significantly correlated to discontinuation with inactive disease. Reoccurrence of active disease was reported for 77% of patients with mean time to flare of 12.1 months. We could not identify any factor correlating to flare risk. The majority of patients were re-treated with ETA (n = 117 of 161; 72.7%) after the flare. One in five patients (n = 23, 19.7%) discontinued ETA again after achieving an inactive disease and about 70% of the patients achieved an inactive disease 12 months after restarting ETA. Conclusion The study confirms the effectiveness of ETA even for re-treatment of patients with JIA. Our data highlight the association of an early bDMARD treatment with a higher rate of inactive disease indicating a window of opportunity.

scholarly journals S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis

2018 ◽  
Vol 45 (4) ◽  
pp. 547-554 ◽  
Author(s):  
Faekah Gohar ◽  
Janneke Anink ◽  
Halima Moncrieffe ◽  
Lisette W.A. Van Suijlekom-Smit ◽  
Femke H.M. Prince ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Serum Concentration ◽  
Treatment Response ◽  
Therapy Group ◽  
Univariate Analysis ◽  
S100 Protein ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Baseline Serum ◽  
Potential Biomarker

Objective.Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response.Methods.S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded.Results.Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133–440 ng/ml] and MTX (median 220, IQR 100–440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125–615) ng/ml versus 150 (IQR 87–233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150–624) ng/ml versus 151 (IQR 83–201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10.Conclusion.Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.

scholarly journals Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register

2008 ◽  
Vol 68 (5) ◽  
pp. 635-641 ◽  
Author(s):  
F H M Prince ◽  
M Twilt ◽  
R ten Cate ◽  
M A J van Rossum ◽  
W Armbrust ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Adverse Events ◽  
Rheumatoid Factor ◽  
Serious Adverse Events ◽  
American College Of Rheumatology ◽  
Systemic Jia ◽  
Long Term Follow Up ◽  
Remission Criteria

Objective:We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis (JIA) subtypes.Methods:At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept. Disease activity was evaluated (at start of the study, after 3 months and then yearly) according to the JIA core set of the American College of Rheumatology paediatric definition for 30, 50 and 70% improvement (ACR Pedi 30, 50 and 70). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded.Results:We included 146 patients with JIA with a median follow-up of 2.5 years per patient (range 0.3–7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid factor positive, 38% polyarticular rheumatoid factor negative, 19% oligoarticular extended, 3% enthesitis-related and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first 3 months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long term. Serious adverse events rate was low (0.029 per patient year).Conclusions:Etanercept is effective and safe in JIA, even for a large proportion of the patients with systemic JIA. The greatest improvement occurred in the first 3 months of treatment, and was sustained for a long time in most patients (up to 75 months).

Predicting Which Children with Juvenile Idiopathic Arthritis Will Have a Severe Disease Course: Results from the ReACCh-Out Cohort

2016 ◽  
Vol 44 (2) ◽  
pp. 230-240 ◽  
Author(s):  
Jaime Guzman ◽  
Andrew Henrey ◽  
Thomas Loughin ◽  
Roberta A. Berard ◽  
Natalie J. Shiff ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Prediction Models ◽  
Severe Disease ◽  
Inactive Disease ◽  
Joint Involvement ◽  
Disease Course ◽  
Active Joint ◽  
Random Samples ◽  
Patient Reported ◽  
Distinct Disease

Objective.We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis.Methods.Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included. Multivariable cluster analysis, r2, and silhouette statistics were used to identify distinct disease courses. One hundred candidate prediction models were developed in random samples of 75% of the cohort; their reliability and accuracy were tested in the 25% not used in their development.Results.Four distinct courses were identified in 609 subjects. They differed in prioritized variables, disability scores, and probabilities of attaining inactive disease and remission. We named them Mild (43.8% of children), Moderate (35.6%), Severe Controlled (9%), and Severe Persisting (11.5%). A logistic regression model using JIA category, active joint count, and pattern of joint involvement at enrollment best predicted a severe disease course (Controlled + Persisting, c-index = 0.87); 91% of children in the highest decile of risk actually experienced a severe disease course, compared to 5% of those in the lowest decile.Conclusion.Children in this JIA cohort followed 1 of 4 disease courses and the probability of a severe disease course could be estimated with information available at diagnosis.

scholarly journals American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis

2011 ◽  
Vol 63 (7) ◽  
pp. 929-936 ◽  
Author(s):  
Carol A. Wallace ◽  
Edward H. Giannini ◽  
Bin Huang ◽  
Lukasz Itert ◽  
Nicolino Ruperto ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Inactive Disease ◽  
American College Of Rheumatology

scholarly journals Serum Calprotectin (S100A8/A9): A Promising Biomarker in Diagnosis and Follow-up in Different Subgroups of Juvenile Idiopathic Arthritis

2021 ◽  
Author(s):  
Céline La ◽  
Phu Quoc Lê ◽  
Alina Ferster ◽  
Laurence Goffin ◽  
Delphine Spruyt ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Added Value ◽  
Response To Treatment ◽  
Inactive Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Minimal Disease ◽  
Active Disease

Abstract IntroductionIn the management of juvenile idiopathic arthritis (JIA), there is a lack of diagnostic and prognostic biomarkers. This study assesses the use of serum calprotectin (sCal) as a marker to monitor disease activity, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA. MethodsEighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 non-pediatric healthy controls. An enzyme-linked immunosorbent assay (ELISA) method was used to quantify sCal with a commercial kit.ResultsPatients with an active disease compared to healthy controls and to patients with inactive disease showed an 8-fold and a 2-fold increased level of sCal respectively. sCal was found to be correlated with the CRP and even more strongly with the ESR. Evolution of DAS28 scores correlated well with evolution of sCal, as opposed to evolution of CRP. With regard to CRP, sCal could differentiate forms with active oligoarthritis from polyarthritis and systemic forms. However, sCal brought an added value compared to the CRP as a prognosis marker. Indeed, patients with active disease and reaching minimal disease activity (according to JADAS) at 6 months following the test had higher sCal levels, while patients with inactive disease had higher sCal levels if a flare was observed up to 3 to 9 months following the test.ConclusionsThis study confirms the potential uses of serum calprotectin as a biomarker in the diagnosis and follow-up of JIA.

A dysregulated interleukin-18–interferon-γ–CXCL9 axis impacts treatment response to canakinumab in systemic juvenile idiopathic arthritis

Rheumatology ◽  
2021 ◽  
Author(s):  
Tanja Hinze ◽  
Christoph Kessel ◽  
Claas H Hinze ◽  
Julia Seibert ◽  
Hermann Gram ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Complete Response ◽  
Interferon Γ ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Serum Samples ◽  
Open Label ◽  
Baseline Serum ◽  
Ifn Γ

Abstract Objectives The monoclonal IL-1β antibody canakinumab is approved for the treatment of systemic juvenile idiopathic arthritis (SJIA). Its efficacy has been proven in several trials, but not all patients show a complete and sustained response to therapy. We aimed to analyse the association of baseline serum biomarkers with treatment outcome in patients with SJIA treated with canakinumab. Methods Serum samples from 54 patients with active SJIA without recent macrophage activation syndrome (MAS) treated with canakinumab in an open-label response characterization study were subjected to a multiplexed bead array assay. Interesting targets from these analyses were validated by ELISA. Clinical treatment outcomes included modified paediatric ACR (pACR) 30 and 90 responses, clinically inactive disease (CID) within 15 days of treatment and sustained complete response, defined as pACR100 or CID within 15 days of treatment plus no future flare or MAS. Results In canakinumab-naïve patients most biomarkers were elevated when compared with healthy controls at baseline and some rapidly decreased by day 15 [IL-1 receptor antagonist (IL-1RA), IL-6, IL-18 and S100A12]. Responders had higher IL-18 and IFN-γ levels and lower chemokine (C-X-C motif) ligand 9 (CXCL9) levels at baseline, emphasized by the IL-18: CXCL9 and IFN-γ: CXCL9 ratios. These ratios had significant accuracy in predicting treatment responses. Conclusion Differential regulation of the IL-18–IFN-γ–CXCL9 axis is observed in patients with SJIA. Higher IL-18: CXCL9 and IFN-γ: CXCL9 ratios at baseline are associated with a better clinical response to canakinumab treatment in SJIA. Future studies are needed to validate these findings and determine their generalizability to patients with recent MAS.

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