scholarly journals Biological treatment in systemic juvenile idiopathic arthritis: achievement of inactive disease or clinical remission on a first, second or third biological agent

RMD Open ◽  
2015 ◽  
Vol 1 (1) ◽  
pp. e000036-e000036 ◽  
Author(s):  
A. Woerner ◽  
F. Uettwiller ◽  
I. Melki ◽  
R. Mouy ◽  
C. Wouters ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Biological Treatment ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Biological Agent ◽  
Inactive Disease

scholarly journals POS0085 EVALUATION OF DURATION OF CLINICAL REMISSION IN CHILDREN WITH NON-SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS AFTER WITHDRAWAL OF ANTI – TUMOR NECROSIS FACTOR - ALPHA THERAPY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 250.1-250
Author(s):  
I. Tsulukiya ◽  
E. Alexeeva ◽  
T. Dvoryakovskaya ◽  
K. Isaeva ◽  
R. Denisova ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Inactive Disease ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Tnfα Inhibitors ◽  
Factor Alpha ◽  
Necrosis Factor

Background:Juvenile idiopathic arthritis (JIA) is the most common and prevalent rheumatic disease in childhood which is based on a chronic autoimmune inflammation. Inactive disease and remission are now the primary treatment goal in JIA and biologics have been playing an important role to reach this objective.The biologics of the first choice for the treatment of non-systemic JIA are the Tumor Necrosis Factor - alpha (TNFα) inhibitors; on this therapy patients can achieve clinically inactive disease and long-term remission.Currently, little is known about when or how to stop TNFα inhibitors, when a good clinical response is achieved, and therefore no guidelines are available.Objectives:To estimate the length of clinical remission after discontinuation of treatment with TNFα inhibitors in patients with non-systemic juvenile idiopathic arthritis.Methods:A total of 393 patients with JIA who were treated with TNFα inhibitors at the Rheumatology Department of the National Medical Research Center of Children’s Health (Moscow, Russia) were screened for inclusion in this retrospective study.Patients were treated with etanercept 1 times a week, 0.8 mg per kg of body weight per dose, with adalimumab 24 mg/m2 body surface area administered every other week until the end of therapy.Treatment was terminated abruptly. Inactive disease was defined according to the preliminary criteria of Wallace et al.[1]Results:77 patients (27—male, 50—female) with a mean age at diagnosis of 4 years (range 1–18 years) were included in the analysis. Of those, 69 of them discontinued TNFα inhibitors due to a long-term remission on treatment, 8 patients as a result of side effects, and there were excluded from our study.:allergic reaction (n = 5), development of uveitis (n = 1), alopecia (n = 1), recurrent infection (n=11).The clinical subtypes of JIA were RF-negative polyarticular JIA -28 (40,58%) oligoarthritis—38 (55,07%), enthesitis-related arthritis—3 (4,35%).TNFα inhibitors were started after a mean 46,43 (range 1–144) months of disease. The mean duration of therapy with TNFα inhibitors were 46,63 (range 10-113) months, with a mean duration of remission on medication 40,63 (range 6-107) months before withdrawal of TNFα inhibitors.40/69 (57,97 %) patients did not develop a disease exacerbation and remained in long-term remission off medication—more than 24 months.Early flares, that is less than 6 months after termination of TNFα inhibitors, were observed in 4/69 (5,8%) patients.29 (42,03%) patients restarted TNFα inhibitors after exacerbation, due to lack of improvement after no biological DMARDs. All patients in whom TNFα inhibitors were reinitiated responded satisfactorily.Conclusion:Among patients with JIA in whom TNFα inhibitors were discontinued after inactive disease was achieved, 57,97 % had disease in clinical remission more than 24 months after stopping anti-TNFα therapy. No association was observed between the duration of inactive disease prior to TNFα inhibitors cessation and the time to disease relapse. In addition, we also ob- served no correlation between the risk of flare and the length of anti-TNF α therapy after inactive disease was achieved. In our population, TNFα antagonists were withdrawn a median of 38 (4-107) months after inactive disease was achieved. Data from our experience with anti-TNF α agents in the treatment of JIA suggest that 57,97 % of patients can be successfully withdrawn from TNF α antagonists for at least 24 months.References:[1]Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, for the Childhood Arthritis and Rheumatology Research Alliance (CARRA), the Pediatric Rheumatology Collaborative Study Group (PRCSG), and the Paediatric Rheumatology Interna- tional Trials Organisation (PRINTO). American College of Rheumatology provisional criteria for defining clinical in- active disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2011;63:929–36.Disclosure of Interests:None declared.

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 Factors Associated with Achievement of Inactive Disease in Children with Juvenile Idiopathic Arthritis Treated with Etanercept

2012 ◽  
Vol 40 (2) ◽  
pp. 192-200 ◽  
Author(s):  
NICOLETTA SOLARI ◽  
ELENA PALMISANI ◽  
ALESSANDRO CONSOLARO ◽  
ANGELA PISTORIO ◽  
STEFANIA VIOLA ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Disease Onset ◽  
Inactive Disease ◽  
Cox Regression Analysis ◽  
Factors Associated ◽  
Univariate Analyses

Objective.To evaluate the rate of inactive disease in children with juvenile idiopathic arthritis (JIA) treated with etanercept, and to identify clinical characteristics associated with attainment of inactive disease.Methods.Clinical charts of patients who were given etanercept between January 2002 and January 2011 were evaluated retrospectively. For each patient, all visits from initiation of etanercept to the last followup evaluation in which the patient was still receiving etanercept were examined to establish whether the patient had reached the state of inactive disease and to identify the first visit in which inactive disease was documented. Clinical characteristics associated with achievement of inactive disease were determined through univariate analyses and Cox regression procedures.Results.A total of 173 patients who received etanercept for a median of 2.2 years (range 0.5–10.5 yrs) were studied. Eighty-seven patients (50.3%) achieved inactive disease after a median of 0.6 years (range 0.1–2.5 yrs) of therapy. At last followup evaluation, 85 patients (49.1%) still had inactive disease and 70 (40.5%) were in clinical remission on medication. The probability of achievement of inactive disease after 6, 12, and 24 months of therapy was 24%, 46% and 57%, respectively. On Cox regression analysis, the attainment of inactive disease was associated with lack of wrist involvement and an age at disease onset < 3.6 years.Conclusion.Around half of our patients with JIA treated with etanercept achieved a state of inactive disease. Children who lacked wrist involvement and were younger at disease onset had a greater likelihood of achieving inactive disease.

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.

Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis

2016 ◽  
Vol 43 (11) ◽  
pp. 2068-2073 ◽  
Author(s):  
Carolina Birolo ◽  
Maria Elisabetta Zannin ◽  
Svetlana Arsenyeva ◽  
Rolando Cimaz ◽  
Elisabetta Miserocchi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Biological Agent ◽  
Treatment Modalities ◽  
Comparable Efficacy ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Ocular Complications ◽  
Significant Difference

Objective.Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)–associated uveitis refractory to anti–tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis.Methods.In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded.Results.Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile.Conclusion.ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

Anakinra in Systemic Juvenile Idiopathic Arthritis: A Single-center Experience

2015 ◽  
Vol 42 (8) ◽  
pp. 1523-1527 ◽  
Author(s):  
Manuela Pardeo ◽  
Denise Pires Marafon ◽  
Antonella Insalaco ◽  
Claudia Bracaglia ◽  
Rebecca Nicolai ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Primary Outcome ◽  
Late Onset ◽  
Disease Onset ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Inactive Disease ◽  
Single Center ◽  
Single Center Experience ◽  
Number Of Patients ◽  
The Ideal

Objective.To assess anakinra as a therapy for systemic juvenile idiopathic arthritis (sJIA) in a single-center series.Methods.We reviewed 25 patients with sJIA treated with anakinra for at least 6 months. The primary outcome was the number of patients who achieved clinically inactive disease at 6 months, according to preliminary criteria for inactive disease and clinical remission of JIA.Results.Among 25 patients evaluated, 14 (56%) met the criteria for inactive disease at 6 months and were classified as responders. For each individual patient, we compared the dose administered with the ideal dose of anakinra and we found that there was no relation with response. We also compared demographic characteristics and clinical and laboratory features at baseline in responders and non-responders: no differences were observed in relation with the number of active joints before starting anakinra or concomitant glucocorticoids treatment. The only variable significantly associated with response was the time from disease onset to receiving anakinra, with earlier treatment being associated with a better outcome.Conclusion.Anakinra is associated with rapid attainment of inactive disease in a significant portion of patients. We found that only the earlier treatment is associated with better outcome. However, formal studies on early treatment and on the pathophysiology and response to treatments, including anakinra, of early- and late-onset sJIA are needed to optimize the management of this challenging disease.

Proposed Core Set of Items for Measuring Disease Activity in Systemic Juvenile Idiopathic Arthritis

2017 ◽  
Vol 45 (1) ◽  
pp. 115-121 ◽  
Author(s):  
Elizaveta Limenis ◽  
Brian M. Feldman ◽  
Camille Achonu ◽  
Michelle Batthish ◽  
Bianca Lang ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Global Assessment ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Inactive Disease ◽  
Core Set ◽  
Activity Measures ◽  
International Experts ◽  
Disease Activity Measures ◽  
Active Joints

Objective.To date, there are no standardized disease activity tools for systemic juvenile idiopathic arthritis (sJIA). We developed a core set of disease activity measures for sJIA.Methods.We conducted a validation study in patients with sJIA recruited from 3 Canadian institutions. Disease activity scores were based on questionnaires, clinical factors, and laboratory measures. The physician’s global assessment was our criterion standard. We determined the strength of association of each item with the criterion standard. We then surveyed international experts to determine the top 10 items. Finally, we used the experts’ responses to generate a proposed core set of disease activity measures.Results.We enrolled 57 subjects — 26 with moderately or severely active disease, and 31 with mildly active or inactive disease. Items that most strongly correlated with the criterion standard were number of active joints (r = 0.79), parent’s global assessment of disease activity (r = 0.53), erythrocyte sedimentation rate (ESR; r = 0.62), and C-reactive protein (CRP; r = 0.61). The response rate from international experts was 82% (154/187). Items with the most votes, in descending order, were number of active joints, number of days with fever in the preceding 2 weeks, patient’s and parent’s global assessments of disease activity, sJIA rash, ESR, CRP, and hemoglobin level.Conclusion.We propose a core set of items for measuring disease activity in sJIA. Future research should be aimed at further validation of this core set in the international context.

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