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 ◽  
...  
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 825.1-825
Author(s):  
J. Klotsche ◽  
G. Horneff ◽  
P. Haas ◽  
I. Foeldvari ◽  
M. Niewerth ◽  
...  

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


2014 ◽  
Vol 41 (6) ◽  
pp. 1163-1170 ◽  
Author(s):  
Carol A. Wallace ◽  
Edward H. Giannini ◽  
Steven J. Spalding ◽  
Philip J. Hashkes ◽  
Kathleen M. O’Neil ◽  
...  

Objective.To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA).Methods.Eighty-five children were randomized blindly to methotrexate (MTX), etanercept, and rapidly tapered prednisolone (MEP) or MTX monotherapy and assessed for CID over 1 year of treatment. Patients who failed to achieve intermediary endpoints were switched to open-label MEP treatment.Results.Fifty-eight (68.2%) of the 85 patients achieved CID at 1 or more visits including 18 who received blinded MEP, 11 while receiving MTX monotherapy, and 29 while receiving open-label MEP. Patients starting on MEP achieved CID earlier and had more study days in CID compared to those starting MTX, but the differences were not significantly different. Patients given MEP (more aggressive therapy) earlier in the disease course were statistically more likely to have a higher proportion of followup visits in CID than those with longer disease course at baseline. Those who achieved American College of Rheumatology Pediatric 70 response at 4 months had a significantly greater proportion of followup visits in CID, compared to those who failed to achieve this improvement (p < 0.0001). Of the 32 patients who met criteria for CID and then lost CID status, only 3 fulfilled the definition of disease flare.Conclusion.Shorter disease duration prior to treatment, a robust response at 4 months, and more aggressive therapy result in a higher likelihood and longer duration of CID in patients with poly-JIA. The original trial from which data for this analysis were obtained is registered on www.clinicaltrials.gov NCT 00443430.


2021 ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Elizaveta Krekhova ◽  
Tatyana Dvoryakovskaya ◽  
Ksenia Isaeva ◽  
Aleksandra Chomakhidze ◽  
...  

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).


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 489.3-489
Author(s):  
I. Kriulin ◽  
E. Alexeeva ◽  
T. Dvoryakovskaya ◽  
K. Isaeva ◽  
A. Chomakhidze ◽  
...  

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


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jens Klotsche ◽  
Ariane Klein ◽  
Martina Niewerth ◽  
Paula Hoff ◽  
Daniel Windschall ◽  
...  

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.


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 ◽  
...  

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.


Author(s):  
Nicolino Ruperto ◽  
Angelo Ravelli

The management of juvenile idiopathic arthritis (JIA) is based on a combination of pharmacological interventions, physical and occupational therapy, and psychosocial support. Ideally, the management is conducted by a multidisciplinary team composed by a paediatric rheumatologist, specialist nurse, physical therapist, occupational therapist, and psychologist. The treatment is aimed to achieve disease control, to relieve pain, to foster normal nutrition and growth, to maintain physical and psychological well-being, and to prevent long-term damage related to the disease or its therapy. First-line pharmacological interventions are based on non-steroidal anti-inflammatory drugs and intra-articular corticosteroids. Patients who are refractory to these therapies are candidates to receive disease-modifying anti-rheumatic medications, namely methotrexate or, in case of enthesitis-related arthritis, sulfasalazine. If therapeutic response is inadequate or suboptimal, the introduction of a biologic response modifier is considered. Systemic corticosteroids are used in selected instances, which include the management of extra-articular manifestations of systemic arthritis or the achievement of quick disease control while are awaiting the full therapeutic effect of a disease-modifying agent in patients with severe polyarthritis. To help physician select the safest and most effective treatment for JIA, the American College of Rheumatology (ACR) has issued a set of recommendations that were meant to be as evidence based as possible. The British Society for Paediatric and Adolescent Rheumatology (BSPAR) has developed the standards of care for patients with JIA, which are aimed to help the paediatric rheumatology teams to improve the service they provide.


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