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 Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mireia Castillo-Vilella ◽  
Nuria Giménez ◽  
Jose Luis Tandaipan ◽  
Salvador Quintana ◽  
Consuelo Modesto
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Therapeutic Approach ◽  
Primary Outcome ◽  
Hla B27 ◽  
Biologic Dmard ◽  
Relapse Rates ◽  
Subsequent Relapse

Abstract Background Juvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce. Methods We conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone. Results A total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206). According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%). Conclusions More than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

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 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 OP0161 PREDICTIVE VALUE OF MUSCULOSKELETAL ULTRASOUND IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS IN CLINICAL REMISSION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 97.2-97
Author(s):  
M. Mazzoni ◽  
S. Merlo ◽  
C. Morreale ◽  
A. Pistorio ◽  
S. Viola ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Remission ◽  
Structural Damage ◽  
Power Doppler ◽  
Musculoskeletal Ultrasound ◽  
Inactive Disease ◽  
Disease Flare ◽  
Subclinical Synovitis

Background:The accurate assessment of remission status in JIA patients is of utmost relevance to taper medications and prevent side effects from their long-term administration. In RA patients in clinical remission (CR), musculoskeletal ultrasound (MSUS) allows to detect persistent joint inflammation (subclinical synovitis), which predicts disease flare and structural damage progression. Although subclinical synovitis has been reported in a substantial proportion of JIA patients with inactive disease, its prognostic value is still being defined.Objectives:1) to investigate the prevalence of MSUS-detected subclinical synovitis in JIA patients in CR; 2) to establish which and how many joints should be scanned to reliably assess remission; 3) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis entails a risk of disease flare and whether it should affect the therapeutic strategy.Methods:135 consecutive JIA patients who met the Wallace criteria for CR were included in this 3-years prospective study. All patients underwent MSUS assessment of 56 joints at study entry and at 6 months follow-up visit. Joints were scanned for synovial hyperplasia, joint effusion and Power Doppler (PD) signal by two independent ultrasonographers. Patients were followed clinically for 3 years. A flare of synovitis was defined as a recurrence of clinically active arthritis. The association between clinical and MSUS variables with flare, was evaluated by adjusted logistic regression models.Results:135 patients (78.5% F; median age 11.3 y; median disease duration 5.7 y; median CR duration 1.4 y) were included. Fifty-seven/135 (42.2%) patients had persistent oligoarthiritis; 41/135 (30.4%) extended oligoarthiritis; 32/135 (23.7%) polyarthiritis; 5/135 (3.7%) systemic arthritis. Seventy-eight/135 (57.7%) patients were in CR on medication. Subclinical synovitis was detected in 32/135 (23.7%) patients and in 53/7560 (0.7%) joints. Subclinical tenosynovitis was present in 20/135 (14.8%) patients. Subclinical synovitis was found more frequently in the ankle and wrist joints. 58.6% of patients showed persistent subclinical synovitis at 6 month follow up MSUS examination. During the 3-year follow up 45/135 (33.3%) patients experienced a disease flare (median survival time 2.2 y). PD positivity in tendons was the stronger independent risk factor of flare on multivariable regression analysis (HR: 4.8; P=0.04). Other predictors of flare were the JIA subtype (oligo-extended form: HR: 2.3; P=0.031) and the status of CR on medication (HR: 3.7; P=0.002).Conclusion:our results confirm that MSUS is more sensitive than clinical evaluation in the assessment of persistent synovial inflammation in JIA patients. Subclinical tenosynovitis was the best predictor of disease flare. To date, the role of tenosynovitis in the diagnosis and prognosis of JIA has been poorly investigated. Our results further support the role of MSUS, especially of the wrist and the ankle, in monitoring JIA patients in clinical remission and to predict disease flare.References:[1]De Lucia O, et al. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018 Oct;77(10):1426-1431.[2]Filippou G, et al. The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound: the STARTER study. Ann Rheum Dis 2018;77:1283-9.Disclosure of Interests:None declared

P084 DEEP REMISSION WITH DOUBLE BIOLOGIC THERAPY: A SUCCESSFUL CASE OF COMBINATION USTEKINUMAB AND VEDOLIZUMAB FOR SEVERE REFRACTORY CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S72-S72
Author(s):  
Ahmed Elmoursi ◽  
Courtney Perry ◽  
Terrence Barrett
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Combination Therapy ◽  
Clinical Remission ◽  
Biologic Therapy ◽  
Case Reports ◽  
Sigmoid Resection ◽  
Safety And Efficacy ◽  
Ileal Stricture

Abstract Background Stricturing Crohn’s disease (CD) constitutes a severe phenotype often associated with a high degree of morbidity (3). Surgical resection is first-line therapy for symptomatic strictures, but most patients relapse without subsequent medical therapy (4–5). Biologics are the mainstay for inducing and maintaining remission, but some cases are refractory despite maximum dosage of therapy. Reports of dual biological therapy (DBT) in refractory, stricturing CD are sparse, and prior case reports document only clinical remission (1). To contribute further knowledge regarding the use of DBT in stricturing CD, we present the case of a refractory CD patient who achieved deep remission with ustekinumab and vedolizumab. Case Presentation A 35 year old non-smoking, Caucasian male was referred to our clinic in 2014 for refractory CD complicated by multiple strictures. Prior to establishing care with us, he received two jejunal resections and a sigmoid resection. Previously failed therapies included azathioprine with infliximab, adalimumab, and certolizumab. He continued to progress under our care despite combination methotrexate/certolizumab, as well as methotrexate/golimumab. He underwent proctocolectomy with end ileostomy in 2015 and initiated vedolizumab q8weeks post-operatively. He reoccurred in 2018, when he presented with an ulcerated ileal stricture. He was switched from vedolizumab to ustekinumab q8weeks and placed on prednisone, but continued to progress, developing significant hematochezia requiring hospitalization and blood transfusions. Ileoscopy performed during hospital admission confirmed severe, ulcerating disease in the ileum with stricture. Ustekinumab dosing was increased to q4weeks, azathioprine was initiated, and he underwent stricturoplasty. Follow-up ileoscopy three months later revealed two ulcers in the neo- TI (Figure 1). Vedolizumab q8weeks was initiated in addition to ustekinumab q4weeks and azathioprine 125mg. After four months on this regimen the patient felt better, but follow-up ileoscopy showed two persistent ulcers in the neo-TI. Vedolizumab dosing interval was increased to q4weeks. After four months, subsequent ileoscopy demonstrated normal neo-TI (Figure 2). Histologic evaluation of biopsies confirmed deep remission of crohn’s disease. No adverse side effects have occurred with maximum doses of both ustekinumab and vedolizumab combination therapy. Discussion This case supports both the safety and efficacy of ustekinumab and vedolizumab dual biologic therapy for treatment of severe, refractory Crohn’s disease. While there are reports of DBT inducing clinical remission, this case supports efficacy for vedolizumab and ustekinumab combination therapy to induce deep histologic remission. Large practical clinical trials are needed to better investigate the safety and efficacy of DBT with vedolizumab and ustekinumab, but our case suggests this combination may be a safe and efficacious therapy for refractory CD patients.

scholarly journals Effect of first-line biologic initiation on glucocorticoid exposure in children hospitalized with new-onset systemic juvenile idiopathic arthritis: emulation of a pragmatic trial using observational data

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rosemary G. Peterson ◽  
Rui Xiao ◽  
Hannah Katcoff ◽  
Brian T. Fisher ◽  
Pamela F. Weiss
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Biologic Therapy ◽  
Tertiary Care ◽  
Pragmatic Trial ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Source Population ◽  
First Line ◽  
Eligibility Criteria ◽  
Over Time ◽  
New Onset

Abstract Background Glucocorticoid exposure is a significant driver of morbidity in children with systemic juvenile idiopathic arthritis (sJIA). We determined the effect of early initiation of biologic therapy (IL-1 or IL-6 inhibition) on glucocorticoid exposure in hospitalized patients with new-onset sJIA. Methods We emulated a pragmatic sequence of trials (“pseudo-trials”) of biologic initiation in children (≤ 18 years) hospitalized with new-onset sJIA utilizing retrospective data from an administrative database from 52 tertiary care children’s hospitals from 2008 to 2019. Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial. Patients in the source population could meet eligibility criteria at several timepoints. Mixed-effects logistic regression was used to determine the effect of biologic initiation on in-hospital glucocorticoid exposure. Results Four hundred sixty-eight children met eligibility criteria, of which 19% received biologic therapy without preceding or concomitant initiation of immunomodulatory medications. This proportion significantly increased over time during the study period (p <  0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1380 assigned to the non-biologic arm. After adjustment, there was a trend toward decreased odds of glucocorticoid initiation in the biologic arm compared to the non-biologic arm (OR 0.39, 95% CI [0.13, 1.15]). Conclusion Biologic initiation in children hospitalized with new-onset sJIA significantly increased over time and may be associated with reduced glucocorticoid exposure. The increasing use of first-line biologic therapy may lead to clinically relevant reductions in treatment-related adverse effects of glucocorticoid-reliant therapeutic approaches.

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

Challenges of achieving clinical remission in a national cohort of juvenile-onset systemic lupus erythematosus patients

Lupus ◽  
2019 ◽  
Vol 28 (5) ◽  
pp. 667-674 ◽  
Author(s):  
N Abdelrahman ◽  
M W Beresford ◽  
V Leone ◽  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Remission ◽  
Immunosuppressive Treatment ◽  
Inactive Disease ◽  
Juvenile Onset ◽  
Time To Diagnosis ◽  
National Cohort ◽  
Onset Systemic Lupus Erythematosus

Background and objectives The multisystem involvement and variable course of juvenile-onset systemic lupus erythematosus (JSLE) make it difficult to assess disease activity over time. International consensus definitions of inactive disease and clinical remission have been proposed. The aim of this study was to determine the proportion of patients meeting these criteria in a large national cohort of JSLE patients and the association between achieving inactive disease and clinical remission with disease activity at presentation and time to diagnosis. Methods Patients diagnosed with JSLE aged ≤17 years with a minimum of 12 months follow-up participating in the UK JSLE Cohort Study were assessed against these criteria at baseline, 1 year and final clinic visit. Results A total of 218 patients with mean follow-up duration of 4.7 years were included and analyzed at baseline visit, of which 93 and 209 were available for analysis at the 1-year and the last follow-up visits, respectively. Eighty-five percent at 1 year and 62% at final follow-up still had active disease while only 6% and 9%, respectively, achieved inactive disease according to the proposed criteria. The majority of patients continued to require immunosuppressive treatment despite their prolonged follow-up with only two patients achieving clinical remission on medication and none off medication. A large number of patients did not meet the criteria for inactive disease due to isolated laboratory abnormalities such as reduced lymphocyte count. Isolated low lymphocyte count was the reason for not fulfilling the inactive disease criteria in 20/79 (25%) patients at 1 year and 14/130 (11%) patients at final follow-up visit. No statistically significant differences in relation to time to diagnosis and disease activity at presentation were found between patients achieving inactive disease compared to those who did not, at 1 year and final follow-up. Conclusion The majority of patients failed to achieve the proposed criteria for inactive disease and continued to require immunosuppressive treatment. This reflects the high burden of disease in JSLE despite immunosuppressive therapy. A significant proportion of patients had isolated laboratory abnormalities of potentially limited clinical significance, suggesting that some modifications of the proposed criteria may be required.

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