Faculty Opinions recommendation of Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial.

2021 ◽  
Author(s):  
Elizabeth Mellins
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Outcomes ◽  
Randomised Trial ◽  
Inactive Disease ◽  
Treat To Target ◽  
Target Drug ◽  
Drug Free

Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial

2018 ◽  
Vol 78 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Petra Hissink Muller ◽  
Danielle M C Brinkman ◽  
Dieneke Schonenberg-Meinema ◽  
Wytse Bastiaan van den Bosch ◽  
Yvonne Koopman-Keemink ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Combination Therapy ◽  
Adverse Events ◽  
Randomised Trial ◽  
Health Assessment ◽  
Treatment Strategies ◽  
Inactive Disease ◽  
Treat To Target ◽  
Etanercept Treatment ◽  
Drug Free

QuestionWhich is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?MethodsIn a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events.Results94 children (67 % girls) aged median (IQR) 9.1 (4.6–12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5–12), limited joints 2.5 (1–4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3–15.0) months in arm 1, 9.0 (6.0–12.8) months in arm 2 and 9.0 (6.0–12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0–6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar.ConclusionRegardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible.Trial registration number1574.

Update on the treatment of nonsystemic juvenile idiopathic arthritis including treatment-to-target: is (drug-free) inactive disease already possible?

2020 ◽  
Vol 32 (5) ◽  
pp. 403-413 ◽  
Author(s):  
Inge R. Klein-Wieringa ◽  
Danielle M.C. Brinkman ◽  
Rebecca ten Cate ◽  
Petra C.E. Hissink Muller
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Inactive Disease ◽  
Drug Free

scholarly journals How common is clinically inactive disease in a prospective cohort of patients with juvenile idiopathic arthritis? The importance of definition

2017 ◽  
Vol 76 (8) ◽  
pp. 1381-1388 ◽  
Author(s):  
Stephanie J W Shoop-Worrall ◽  
Suzanne M M Verstappen ◽  
Eileen Baildam ◽  
Alice Chieng ◽  
Joyce Davidson ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Inactive Disease ◽  
Treat To Target ◽  
Single Patient ◽  
Inception Cohort ◽  
Childhood Arthritis ◽  
Minimal Disease ◽  
Adolescent Rheumatology

ObjectivesMany criteria for clinically inactive disease (CID) and minimal disease activity (MDA) have been proposed for juvenile idiopathic arthritis (JIA). It is not known to what degree each of these criteria overlap within a single patient cohort. This study aimed to compare the frequency of MDA and CID across different criteria in a cohort of children with JIA at 1 year following presentation.MethodsThe Childhood Arthritis Prospective Study recruits children at initial presentation to paediatric or adolescent rheumatology in seven UK centres. Children recruited between October 2001 and December 2013 were included. The proportions of children with CID and MDA at 1 year were calculated using four investigator-defined and eight published composite criteria. Missing data were accounted for using multiple imputation under different assumptions.ResultsIn a cohort of 1415 children and adolescents, 67% patients had no active joints at 1 year. Between 48% and 61% achieved MDA and between 25% and 38% achieved CID using published criteria. Overlap between criteria varied. Of 922 patients in MDA by either the original composite criteria, Juvenile Arthritis Disease Activity Score (JADAS) or clinical JADAS cut-offs, 68% were classified as in MDA by all 3 criteria. Similarly, 44% of 633 children with CID defined by either Wallace's preliminary criteria or the JADAS cut-off were in CID according to both criteria.ConclusionsIn a large JIA prospective inception cohort, a majority of patients have evidence of persistent disease activity after 1 year. Published criteria to capture MDA and CID do not always identify the same groups of patients. This has significant implications when defining and applying treat-to-target strategies.

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 POS0241 VALIDATION OF THE ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE WITH A QUICK QUANTITATIVE C-REACTIVE PROTEIN ASSAY (ASDAS-QCRP) IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS (AXSPA): A PROSPECTIVE, NATIONAL, MULTICENTER STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 342.1-342
Author(s):  
F. Proft ◽  
J. Schally ◽  
H. C. Brandt ◽  
J. Brandt-Juergens ◽  
G. R. Burmester ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
High Disease Activity ◽  
Activity Score ◽  
Inactive Disease ◽  
Treat To Target ◽  
C Reactive Protein ◽  
Low Disease Activity ◽  
Reactive Protein

Background:According to international recommendations, the Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred score for assessing disease activity in axial spondyloarthritis (axSpA) [1]. However, routine determination of C-reactive protein (CRP) to calculate ASDAS values takes hours to days. This limits the use of ASDAS in clinical routine and clinical trials and hinders the implementation of treat-to-target approaches in axSpA. Whereas quick quantitative CRP (qCRP) tests allow CRP assessment within a few minutes. In a pilot project the performance of qCRP-based ASDAS assessment (ASDAS-qCRP) was already investigated in a single center study of 50 newly diagnosed, bDMARD-naïve axSpA patients with promising results [2].Objectives:To validate the ASDAS-qCRP in a prospective, multicenter study of axSpA patients in a typical axSpA cohort with an appropriate sample size.Methods:The study was conducted in five centers in Germany. Consecutive adult (≥ 18 years) axSpA patients were included. In addition to a rheumatological assessment, including patient reported outcomes (PROs), routine CRP and erythrocyte sedimentation rate (ESR) were measured in the local labs. Additionally, a qCRP testing with the „QuikRead go instrument“ (Aidian Oy, Finland) was performed at the study center (measurement range 0.5 - 200 mg/l for hematocrit concentrations of 40 – 45%). Statistical analysis included descriptive statistics, cross tabulation and weighted Cohen´s kappa comparing disease activity categories, Bland-Altman plots and intraclass correlation coefficient (ICC) for ASDAS-CRP and ASDAS-qCRP.Results:In this study 251 axSpA patients were included between January and September 2020 (mean age: 38.4 years; mean disease duration: 6.2 years, 159 patients (63.3%) were male, 211 (84.1%) HLA-B27 positive and 195 (77.7%) were classified as radiographic axSpA). 143 patients (57.0%) were treated with bDMARDs. CRP and qCRP showed mean values of 2.12 and 2.17 mg/l, respectively. With the ASDAS-qCRP, 242 patients (96.4%) were assigned to the same disease activity category as compared to the ASDAS based on the conventional lab CRP measurement (Table 1). Weighted Cohen´s kappa was 0.966 (95%CI: 0.943; 0.988). ICC for ASDAS-CRP- and ASDAS-qCRP-values was 0.997 (95%CI: 0.994; 0.999). The agreement of ASDAS-qCRP and ASDAS-CRP is shown in a Bland-Altman plot (Figure 1).Table 1.Disease activity categories by ASDAS-qCRP vs. ASDAS-CRPASDAS-qCRP (n = 251)Inactive Disease(< 1.3)Low Disease Activity (1.3 - < 2.1)High Disease Activity (2.1 - 3.5)Very high Disease Activity (> 3.5)ASDAS-CRPInactive Disease(< 1.3)56 (22.3%)2 (0.8%)Low Disease Activity (1.3 - < 2.1)62 (24.7%)7 (2.8%)High Disease Activity (2.1 - 3.5)97 (38.6%)Very high Disease Activity (> 3.5)27 (10.8%)The fields highlighted in red indicate that disease activity categories do not match.ASDAS = Ankylosing Spondylitis Disease Activity Score, CRP = C-reactive protein, qCRP = quick quantitative CRPConclusion:The ASDAS-qCRP and ASDAS-CRP showed an almost perfect agreement on the assignment to disease activity categories (96%) with the important advantage of time. With ASDAS-qCRP, rheumatologists could base their clinical decision-making on a disease activity measurement by using a composite score immediately. ASDAS-qCRP, therefore, can be integrated in clinical routine and clinical trials in the future and may facilitate implementation of the treat-to-target concept in axial SpA.References:[1]Smolen JS, et al. Ann Rheum Dis. 2018 Jan; 77(1):3-17.[2]Proft F, et al. Joint Bone Spine. 2019 Jul 29.Figure 1.Bland-Altman plot for ASDAS-qCRP and ASDAS-CRPAcknowledgements:The authors would like to deeply thank Braun T, Doerwald C, Deter N, Höppner C, Lackinger J, Lorenz C, Lunkwitz K, Mandt B, Sron S and Zernicke J for their practical support and coordinating the study.Funding statement: The AQUA study was supported by an unrestricted research grant from Novartis. Testing kits were provided free of charge from Aidian Oy, Finland.Disclosure of Interests:None declared

scholarly journals Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes: a randomised trial

2012 ◽  
Vol 167 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Leo Niskanen ◽  
Lawrence A Leiter ◽  
Edward Franek ◽  
Jianping Weng ◽  
Taner Damci ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Aspart ◽  
Randomised Trial ◽  
Insulin Degludec ◽  
Treat To Target ◽  
Target Trial ◽  
Open Label ◽  
Biphasic Insulin ◽  
Biphasic Insulin Aspart 30

ObjectiveInsulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30).DesignSixteen-week, open-label, randomised, treat-to-target trial.MethodsInsulin-naive subjects with type 2 diabetes (18–75 years) and a HbA1c of 7–11% were randomised to twice-daily IDegAsp (n=61), AF (n=59) or BIAsp 30 (n=62), all in combination with metformin. Insulin was administered pre-breakfast and dinner (main evening meal) and titrated to pre-breakfast and pre-dinner plasma glucose (PG) targets of 4.0–6.0 mmol/l.ResultsMean HbA1c after 16 weeks was comparable for IDegAsp, AF and BIAsp 30 (6.7, 6.6 and 6.7% respectively). With IDegAsp, 67% of subjects achieved HbA1c <7.0% without confirmed hypoglycaemia in the last 4 weeks of treatment compared with 53% (AF) and 40% (BIAsp 30). Mean fasting PG was significantly lower for IDegAsp vs BIAsp 30 (treatment difference (TD): −0.99 mmol/l (95% confidence interval: −1.68; 0.29)) and AF vs BIAsp 30 (TD: −0.88 mmol/l (−1.58; −0.18)). A significant, 58% lower rate of confirmed hypoglycaemia was found for IDegAsp vs BIAsp 30 (rate ratio (RR): 0.42 (0.23; 0.75)); rates were similar for AF vs BIAsp 30 (RR: 0.92 (0.54; 1.57)). IDegAsp and AF had numerically lower rates of nocturnal confirmed hypoglycaemia vs BIAsp 30 (RR: 0.33 (0.09; 1.14) and 0.66 (0.22; 1.93) respectively).ConclusionsIDegAsp provided comparable overall glycaemic control to BIAsp 30 with a significantly lower rate of hypoglycaemia.

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.

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