THU0579 Treating To Target with Canakinumab in Patients with Active Systemic Juvenile Idiopathic Arthritis: Results from The Long-Term Extension The Phase III Pivotal Trial

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 401.2-402 ◽  
Author(s):  
N. Ruperto ◽  
H.I. Brunner ◽  
P. Quartier ◽  
T. Constantin ◽  
E. Alexeeva ◽  
...  
2018 ◽  
Vol 77 (12) ◽  
pp. 1710-1719 ◽  
Author(s):  
Nicolino Ruperto ◽  
Hermine I Brunner ◽  
Pierre Quartier ◽  
Tamàs Constantin ◽  
Nico M Wulffraat ◽  
...  

ObjectivesTo evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA).MethodsPatients (2–19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population.Results144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed.ConclusionResponse to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab.Trial registration numbersNCT00886769, NCT00889863, NCT00426218 and NCT00891046.


2019 ◽  
Vol 46 (9) ◽  
pp. 1117-1126 ◽  
Author(s):  
Manuela Pardeo ◽  
Jianmei Wang ◽  
Nicolino Ruperto ◽  
Ekaterina Alexeeva ◽  
Vyacheslav Chasnyk ◽  
...  

Objective.To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ).Methods.Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112;ClinicalTrials.gov,NCT00642460) and pcJIA (n = 188;ClinicalTrials.gov,NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts.Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8–16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3–8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial.Conclusion.Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.


2013 ◽  
Vol 65 (9) ◽  
pp. 2486-2496 ◽  
Author(s):  
Daniel J. Lovell ◽  
Edward H. Giannini ◽  
Andreas O. Reiff ◽  
Yukiko Kimura ◽  
Suzanne Li ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 250.1-250
Author(s):  
I. Tsulukiya ◽  
E. Alexeeva ◽  
T. Dvoryakovskaya ◽  
K. Isaeva ◽  
R. Denisova ◽  
...  

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.


2021 ◽  
Vol 9 ◽  
Author(s):  
Xin Yan ◽  
Wenjing Tang ◽  
Zhiyong Zhang ◽  
Yu Zhang ◽  
Chong Luo ◽  
...  

Objective: We performed a single-center retrospective study to determine the different efficacy of tocilizumab (TCZ) in the early and late stages and in three phenotypic subgroups (monocyclic, polycyclic, and persistent) of systemic juvenile idiopathic arthritis (sJIA).Methods: Clinical and serological parameters of 77 sJIA patients treated by TCZ were collected from November 1, 2013 to May 1, 2019. Patients were grouped based on the duration group A < 6 months (n = 41) and group B > 6 months (n = 36) and divided into three phenotypes: monocyclic (n = 12), polycyclic (n = 14), and persistent (n = 51) course.Results: At baseline, group A had pronounced ESR, fever less active arthritis than group B (p < 0.05). After 12 weeks of therapy, TCZ alleviated fever, ESR, CRP, and systemic-onset juvenile arthritis disease activity score-27 (sJADAS27) in both group A and group B (p>0.05), while the efficacy of TCZ in relieving active arthritis in group A was better than that in group B (p<0.05). After 1 year of TCZ therapy, it showed that patients with monocyclic phenotype had the highest clinical response rate (91.7%, odds ratio = 0, 95% CI: 24–24, p = 0.00), followed by the polycyclic (28.6%, odds ratio = 2.1, 95% CI: 10.5–18.8, p = 0.00) and the persistent course (9.8%, odds ratio = 1.2, 95% CI: 9.5–13.8, p = 0.00).Conclusion: TCZ can quickly relieve fever and inflammation, especially when patients have less active arthritis with shorter disease duration. The long-term efficacy of TCZ is related to the phenotypes, among which the monocyclic is the best, and the persistent is the worst.


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