Long-term efficacy and safety of canakinumab in the treatment of systemic juvenile idiopathic arthritis in Japanese patients: Results from an open-label Phase III study.

OBJECTIVES: The objective of the study was to report the efficacy and safety of canakinumab treatment in Japanese patients with systemic juvenile idiopathic arthritis (sJIA) over a 48-week study period. METHODS: Patients were administered canakinumab 4 mg/kg (maximum dose 300 mg) every 4 weeks, with no dose adjustments. The key outcome measures included adapted American College of Rheumatology paediatric (aACR pedi) 30/50/70/90/100 response, proportion of patients with inactive disease, and corticosteroid (CS) tapering. RESULTS: In total, 16/19 (84.2%) patients received canakinumab for ≥96 weeks reaching end-of-study (EOS) visit without premature discontinuation. Regardless of the level of joint involvement at baseline, high aACR pedi responses were observed throughout the study; at the EOS, aACR pedi 90/100 response rates were 84.2%/63.2%, respectively. The proportion of patients who successfully tapered CSs at EOS was 66.7% (12/18), of which 10 patients were steroid-free. The most common adverse events were infections (238.3 events/100 patient-years). Serious adverse events were observed in 52.6%. The event (n=1) adjudicated as possible macrophage activation syndrome was preceded by sJIA flare. No deaths were reported. CONCLUSIONS: Canakinumab treatment resulted in a sustained treatment response in sJIA patients over 48 weeks and was associated with CS tapering in majority of patients. No new safety findings were reported.

Canakinumab in systemic juvenile idiopathic arthritis: real-world data from a retrospective Italian cohort.

OBJECTIVE: The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA). METHODS: A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months. RESULTS: A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years. CONCLUSION: We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.

[Current aspects of antirheumatic therapy in pregnancy planning, during pregnancy and breastfeeding]. / Aktuelles zur antirheumatischen Therapie bei Kinderwunsch, Schwangerschaft und Stillzeit.

Active rheumatic disease is a known factor for increased fetomaternal risks during pregnancy. Remission or inactive disease should therefore be targeted to reduce these risks by using pregnancy-compatible antirheumatic drugs as recommended by international guidelines. Teratogenic antirheumatic drugs, such as mycophenolate, methotrexate, cyclophosphamide and thalidomide should be stopped about 3 months prior to conception. Leflunomide is a weak human teratogen that should be stopped and eliminated with cholestyramine prior to conception. Furthermore, drugs with limited data, such as apremilast and JAK inhibitors as well as new biologics should be avoided during gestation. Pregnancy-compatible drugs are the antirheumatic drugs hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, tacrolimus, colchicine, non-selective NSAIDs, low-dose prednisone/prednisolone and TNF inhibitors. These drugs as well as other biologics, such as rituximab can be used during lactation. In a preconception counselling visit, the benefits and the international recommendations of pregnancy-compatible antirheumatic drugs should be discussed with the patient and be weighed against the possible fetomaternal risks of an active disease to enable a shared decision-making.

Prediction of inactive disease and relapse in oligoarticular juvenile idiopathic arthritis.

OBJECTIVE: The aim of this study is to describe clinical features of patients with oligoarticular juvenile idiopathic arthritis (JIA) who achieved inactive disease at 3rd month and also to determine the predictors of relapse and extended course. METHODS: In the cohort study, 88 patients with oligoarticular JIA were retrospectively analyzed. The demographic data, clinical features, medications, relapse rates were recorded. Juvenile Arthritis Disease Activity Score (JADAS) and American College of Rheumatology Pediatric criteria were used to measure disease activity and treatment response at 3, 6 and 12 months. RESULTS: Fifty-nine (67%) patients were females and the mean age at diagnosis was 7.9 ± 4.3 years. The odds of achieving inactive disease (JADAS ≤1) at 3rd month were increased by a lower JADAS27 score at admission. Forty-one (48.8%) of 84 patients relapsed. Ankle involvement at onset, high JADAS27 score at admission, increased ESR at admission and presence of synovial hypertrophy in imaging were risk factors for occurrence of relapse. CONCLUSION: Our results show that a significant proportion of oligoarticular JIA patients relapse after inactive period. JADAS is a useful tool to guide the treatment decisions of patients who may be at risk of high disease activity and relapse.

Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the patterns of usage, efficacy and safety of tocilizumab in polyarticular JIA. METHODS: An observational study of 56 consecutive polyarticular JIA patients was conducted using patient charts and electronic JIA databases. Efficacy was assessed by tocilizumab survival, rates of low disease activity (LDA) and of inactive disease by 10-joint Juvenile Arthritis Disease Activity Score (JADAS-10), and of clinically inactive disease according to Wallace's preliminary criteria. Efficacy and rate of adverse events (AEs) were evaluated during a 24-month period after tocilizumab commencement. RESULTS: Tocilizumab was started on average as third-line biological agent (median, range first- to fourth-line) at a median disease duration of 5.2 years (interquartile range 3.0-7.7). Survival rates were 82% at 12 months and 64% at 24 months. The reasons for discontinuation were inadequate treatment effect in 50%, AE plus inadequate treatment effect in 37.5% and AE alone in 12.5%. LDA (JADAS-10 ⩽3.9) was reached in 58% at 12 months and in 84% at 24 months, inactive disease (JADAS-10 ⩽0.7) in 19% and 44%, and clinically inactive disease in 28% and 46%, respectively. The rate of AEs was 200.9/100 patient years and of serious AEs 12.9/100 patient years. CONCLUSION: Survival of tocilizumab was high and a large proportion of the treatment-resistant patients reached LDA at 12 months of treatment. The LDA rate continued to increase throughout 24 months. The rates of AEs and serious AEs were higher than in register studies but lower than in the originator study of tocilizumab.

Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy of biologic DMARDs (bDMARDs) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID), as remission-like surrogates, in axial SpA (axSpA). METHODS: Data from randomized controlled trials (RCTs), including long-term extensions, were included. A systematic literature review was performed using the MEDLINE database (first search May 2018, updated February 2020) and PICO criteria according to Patients-adults with radiographic or non-radiographic axSpA; Intervention-any bDMARD; Comparator-placebo and/or any different drug; Outcomes-ASAS-PR and/or ASDAS-ID as primary or secondary endpoints. Meta-analysis was performed after assessment of the homogeneity of study designs, populations and outcomes. RESULTS: After screening 155 references, a total of 22 RCTs and 28 long-term extensions were retrieved. ASAS-PR was the dominant remission-like definition used. Concerning TNF inhibitors, 14/17 RCTs provided evidence of efficacy in reaching remission at different time points: 12, 16, 24 and 28 weeks (ASAS-PR in 16-62% of patients and ASDAS-ID in 24-40% of patients). With a limited number of studies available, IL-17A inhibitors exhibited remission rates of 15-21% for ASAS-PR and 11-16% for ASDAS-ID at week 16. A meta-analysis regarding ASAS-PR was performed considering RCTs with a similar duration (12, 16 or 24 weeks). The relative risk for achieving remission was 3.864 (95% CI 2.937, 5.085). CONCLUSION: bDMARDs have a clear impact in axSpA remission evaluated by ASAS-PR. Nevertheless, these data show an unmet need for improved reporting of remission-like outcomes.

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

QUESTION: Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)? METHODS: In 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. RESULTS: 94 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. CONCLUSION: Regardless 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 NUMBER: 1574.

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

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.

Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA.

OBJECTIVES: To determine the reasons of methotrexate (MTX) discontinuation, frequency of adverse events (AE) and whether the time in inactive disease before MTX withdrawal disease is associated with the risk of disease flare. METHODS: Patients with juvenile idiopathic arthritis (JIA) beginning treatment with MTX were prospectively observed in the national JIA biologic register Biologika in der Kinderrheumatologie/Biologics in Paediatric Rheumatology and its follow-up register Juvenile arthritis Methotrexate/Biologics long-term Observation. Inactive disease was defined by a clinical Juvenile Arthritis Disease Activity Score ≤1, flare after MTX discontinuation by reoccurrence of at least moderate disease activity or restart of treatment with a disease-modifying antirheumatic drug . RESULTS: MTX treatment was initiated in 1514 patients after a mean disease duration of 2.1 years (SD=2.8). 40% of the patients experienced oligoarticular onset of JIA. MTX was discontinued in 982 (64.9%) patients. Ineffectiveness (36.9%) and achieving inactive disease (32.1%) were the most common reasons. Among the latter (n=316), 184 (58.2%) patients experienced a flare on follow-up. The likelihood of a flare was a function of time in inactive disease prior to MTX discontinuation (HR 0.95; 95% CI 0.92 to 0.97). Patients with inactive disease for longer than 12 months had a significantly lower flare rate (58 of 119, 48.7%; HR 0.48; 95% CI 0.34 to 0.69). The most frequently reported AE was MTX intolerance, including nausea, aversion and vomiting, accounting for 441 events (13.0 events/100 exposure years) in 307 (20.3%) patients. CONCLUSIONS: Patients who spent at least 12 months in inactive disease before MTX discontinuation had a significantly lower flare rate.

Low prevalence of subclinical synovitis in patients with juvenile idiopathic arthritis (JIA) in long-term clinical remission on medication.

Subclinical synovitis is highly prevalent in patients with JIA in clinical remission (CR) with a short duration. The objective was to evaluate its prevalence by ultrasound (US) in patients with JIA in long CR during a one-year follow-up. In this prospective and longitudinal study, we included 76 patients with JIA according to ILAR with CR by the Wallace modified criteria and JADAS27 and compared them with 22 patients with active disease. Clinical and demographic characteristics were recorded. US evaluation was by 10-joint count. Differences in US evaluations were analyzed by the Mann-Whitney U test. There were no differences among the two group with regard to disease duration at enrollment, and age (p = 0.540 and p = 0.080, respectively), but JADAS 27, CHAQ, and acute phase reactants were significantly higher (p < 0.001) in the clinically active group. The prevalence of subclinical synovitis at baseline and the end of the study in the CR group was 18.4% and 11.8%, respectively, while it was 100% and 40.9% in the active disease group. Subclinical synovitis at baseline was significantly more prevalent in the clinically active group (elbow, p = 0.01; wrist, p = 0.001; MCP 2, p = 0.001; knee, p = 0.001 and ankle p = 0.001; and PD only in the ankle, p = 0.002). The concordance of inter-reader reliability in all evaluated joints was excellent (p = 0.001). Although the prevalence of subclinical synovitis is low in patients with JIA with long-term clinical remission on medication, a percentage of patients continue to have subclinical involvement that could predict the risk of relapse and structural damage. Key Points • Subclinical synovitis is less prevalent in JIA in long-term clinical remission compared to patients in short-term remission. • The persistence of imaging signs of inflammation in a significant percentage of patients may indicate the need for ongoing medication.

Withdrawal of biologic therapy in juvenile idiopathic arthritis due to remission: predictors of flare and outcomes.

OBJECTIVES: To investigate patients who flared after discontinuation of biological disease-modifying anti-rheumatic agents (bDMARDs) and identify risk factors associated with flare. METHODS: A multicenter study evaluating systemic and non-systemic juvenile idiopathic arthritis (sJIA and non-sJIA) patients whose bDMARDs were ceased after remission. RESULTS: A total of 101 patients whose bDMARDs were ceased after remission was evaluated. Children with sJIA had the lowest risk of flare and 11.1% of 36 sJIA patients experienced flare after a median of 9 (4-24) months of bDMARDs cessation with three of them flaring in the first year. High leukocyte counts in sJIA patients were associated with inactive disease at 1-year after the start of treatment (p = 0.004). In the non-sJIA group, 46.1% patients experienced flare after a median of 7 (1-32) months of biologic cessation, and of these, 25 flared in the first year. Antinuclear antibody positivity (p = 0.02), earlier disease onset (p = 0.03), long disease duration (p = 0.01), and follow-up (p = 0.02) and extended time from diagnosis to first biological onset (p = 0.03) were more common among patients with flare. CONCLUSIONS: When considering discontinuation of bDMARDs, it should be kept in mind that the risk of exacerbation requiring re-initiation therapy is quite significant within the first year after discontinuation of therapy.

Risk of flare in juvenile idiopathic arthritis: Is it related to the methotrexate treatment strategy or patient characteristics?

Objectives: The study aimed to determine the factors that increase the risk of disease flare in patients with juvenile idiopathic arthritis who stopped methotrexate (MTX) monotherapy following inactive disease (ID). Patients and methods: In the retrospective study, files of all juvenile idiopathic arthritis cases between April 1992 and June 2022 were examined. Patients who stopped MTX monotherapy following ID were evaluated. Patients with disease flare and persistent ID were compared. Juvenile idiopathic arthritis subgroup, age of symptom onset, autoantibodies, acute phase reactants, MTX method of use, and withdrawal strategy were recorded. Systemic juvenile idiopathic arthritis patients were excluded from the study due to different clinical symptoms, diagnosis, and treatment methods. Results: Files of 1,036 patients were evaluated, and 107 patients (88 females, 19 males; mean age: 5.9±4.2 years; range, 0.8-16.5 years) were included in the study. The median age at symptom onset was 4.8 (interquartile range [IQR]: 2-7.6) years. In terms of juvenile idiopathic arthritis subgroups, 52 (48.6%) had oligoarticular juvenile idiopathic arthritis, 43 (40.2%) had polyarticular juvenile idiopathic arthritis, and 12 (11.2%) had juvenile psoriatic arthritis. The patients reached ID in nine (IQR: 4.8-17.7) months after starting MTX, and MTX treatment was discontinued after one (IQR: 0.7-1.3) year following ID. The disease flare developed in 59 (55%) of the cases. The ID continued in 48 (45%) patients. In multivariate analysis, the risk of flare was associated with younger symptom onset (odds ratio [OR]=2.2, p=0.006), antinuclear antibody positivity (OR=1.6, p=0.03), higher erythrocyte sedimentation rate (OR=1.01, p=0.04), and C-reactive protein (OR=1, p=0.02) at the MTX onset. No difference was observed between the two groups regarding MTX dose, route of administration, prior and concomitant treatments, time to reach ID, and time and method of MTX discontinuation. Conclusion: In this study, the risk of flare was associated with patient's characteristics, rather than the administration and discontinuation method of MTX.

Systemic therapy in juvenile localized scleroderma.

INTRODUCTION: Juvenile localized scleroderma (JLS) is a rare sclerosing disorder of childhood which can result in permanent morbidity and functional disability, if not effectively treated. Treatment should be started in the inflammatory phase before the development of any complication and/or damage. AREAS COVERED: In this review, we will discuss how to assess disease activity and damage in JLS, and propose an escalation plan for systemic treatment, according to a treat-to-target concept. We will discuss the definition of inactive disease and how and when to discontinue medications. EXPERT OPINION: Before starting treatment, it is extremely important to assess baseline disease activity for treatment response to be adequately checked. Moreover, the activity of the extra cutaneous involvement is an important part of the assessment. Patients should be treated in the 'therapeutic window,' before significant fibrosis results. Most patients should receive systemic treatments; in these patients, Methotrexate should be used as the first-line disease-modifying anti-rheumatic drug (DMARD). However, methotrexate intolerance or non-response is an issue, and these patients should be proposed a treatment escalation according to results of latest studies. Future research can develop better prognostic markers to help to guide our decision.

Re-treatment with etanercept is as effective as the initial firstline treatment in patients with juvenile idiopathic arthritis.

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.

Early experience with teprotumumab for chronic thyroid eye disease.

PURPOSE: To report the first case of a patient with chronic thyroid eye disease (TED) treated with teprotumumab. OBSERVATIONS: A 50-year-old female with a 3-year history of Graves' disease presented with bilateral exophthalmos greatest on the left side. She was followed for 2 years with stable proptosis measurements (23mm OD, 28mm OS). Her clinical activity score (CAS) was 1 and there were no examination findings reflective of active inflammation. The patient underwent systemic treatment with teprotumumab and despite chronic TED and low CAS, she had notable improvement in proptosis (18mm OD, 22mm OS) and decrease in extraocular muscle volume as noted on orbital imaging. CONCLUSION AND IMPORTANCE: This case report suggests that teprotumumab may be used in patients with chronic TED and low CAS. Improvement in the proptosis and reduction in extraocular muscle volume suggest that teprotumumab may alter disease course even in patients with inactive or quiescent TED.

A Long-term Survival after Surgical Treatment for Atypical Aortic Coarctation Complicating Takayasu Arteritis with Inactive Disease at the Diagnosis: An Appropriately Treated Autopsy Case.

The number of Takayasu arteritis (TAK) cases being diagnosed at an advanced age has increased, including some who develop ischemic lesions without inflammation of the involved arteries long after the onset of TAK. However, few histopathological analyses of such patients without immunosuppressive therapy have been reported. We herein report a 92-year-old woman with atypical aortic coarctation complicating TAK who underwent bypass graft surgery and survived for 23 years without immunosuppressive therapy. Microscopic findings at the autopsy revealed clear differences between the affected and unaffected arteries. This case suggests that inflammation severe enough to destroy the structure of the aorta may not inherently be sufficient to promote systemic atherosclerosis.

Physician practices for withdrawal of medications in inactive systemic juvenile arthritis, Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey.

BACKGROUND: We describe a Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey of North American pediatric rheumatologists that assesses physician attitudes on withdrawal of medications in systemic juvenile idiopathic arthritis (SJIA). METHODS: A REDCap anonymous electronic survey was distributed to 100 random CARRA JIA workgroup physician-voting members. The survey had three broad sections including: A) demographic information; B) physicians' opinions on clinical inactive disease (CID) in SJIA and C) existing practices for withdrawing medications in SJIA. RESULTS: The survey had an 86% response rate. 88 and 93% of participants agreed with the current criteria for CID and clinical remission on medications (CRM) respectively. 78% thought it necessary to meet CRM before tapering medications except steroids. 76% use CARRA SJIA consensus treatment plans always or the majority of the time. All participants weaned steroids first in SJIA patients on combination therapy, 47% waited > 6 months before tapering additional medications. 35% each tapered methotrexate over > 6 months and 2-6 months; however, 39% preferred tapering anakinra, canakinumab and tocilizumab more quickly over 2-6 months and favored spacing the dosing interval for canakinumab and tocilizumab. When patients are on combination therapy with methotrexate and biologics, 58% preferred tapering methotrexate first while others considered patient/family preference and adverse effects to guide their choice. CONCLUSION: Most CARRA members surveyed use published consensus treatment plans for SJIA and agree with validated definitions of CID and CRM. There was agreement with tapering steroids first in SJIA. There was considerable variability with tapering decisions of all other medications.

Effects of tapering tumor necrosis factor inhibitor on the achievement of inactive disease in patients with axial spondyloarthritis: a nationwide cohort study.

OBJECTIVES: To investigate the association between the extent of tapering tumor necrosis factor inhibitor (TNFi) and the likelihood of achieving inactive disease in patients with axial spondyloarthritis (axSpA) METHODS: We analyzed 1575 1-year follow-up interval data of 776 axSpA patients treated with TNFi for more than 1 year in a nationwide observational cohort. The decision on tapering TNFi was made by patients and their physicians. We quantified TNFi used during interval as a dose quotient (DQ). The intervals were classified into the heavy-tapering (DQ < 50), mild-tapering (DQ 50-99), and control groups (DQ = 100). Outcome variables included achieving Ankylosing Spondylitis Disease Activity Score-inactive disease (ASDAS-ID) and major clinical response of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) in the follow-up visit. The effects of TNFi tapering on the outcome were analyzed using the generalized estimating equation. RESULTS: At the baseline visit, 91.1% of the patients showed a high disease activity (ASDAS-CRP ≥ 2.1). DQ of each interval was significantly influenced by the ASDAS-CRP measure in the prior follow-up (P < 0.001). ASDAS-ID was observed in 42.3% of the intervals. A multivariable analysis showed that the likelihood of outcome achievement was comparable between the control and mild-tapering groups, but significantly decreased in the heavy-tapering group (vs. the control group, adjusted OR = 0.28, [95% CI, 0.08-0.94]). In contrast, the likelihood to achieve BASDAI50 response was not different among the groups. In the subgroup of patients who reached ASDAS-ID 1 year after TNFi treatment (n = 327), ASDAS-ID was observed in 66.1% of the subsequent intervals, and only the mild-tapering group showed a likelihood of target maintenance comparable with that of the control group (adjusted OR = 1.25 [0.41-3.80]). This likelihood decreased with an increase in ASDAS-CRP. CONCLUSION: Mild tapering of TNFi has efficacy comparable with that of the standard-dose treatment for ASDAS-ID achievement in patients with axSpA.

Proposal for a definition for response to treatment, inactive disease and damage for JIA associated uveitis based on the validation of a uveitis related JIA outcome measures from the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC).

BACKGROUND: JIA-associated uveitis (JIAU) is a serious, sight-threatening disease with significant long-term complications and risk of blindness, even with improved contemporary treatments. The MIWGUC was set up in order to propose specific JIAU activity and response items and to validate their applicability for clinical outcome studies. METHODS: The group consists of 8 paediatric rheumatologists and 7 ophthalmologists. A consensus meeting took place on November 2015 in Barcelona (Spain) with the objective of validating the previously proposed measures. The validation process was based on the results of a prospective open, international, multi-centre, cohort study designed to validate the outcome measures proposed by the initial MIWGUC group meeting in 2012. The meeting used the same Delphi and nominal group technique as previously described in the first paper from the MIWGUC group (Arthritis Care Res 64:1365-72, 2012). Patients were included with a diagnosis of JIA, aged less than 18 years, and with active uveitis or an uveitis flare which required treatment with a disease-modifying anti-rheumatic drug. The proposed outcome measures for uveitis were collected by an ophthalmologist and for arthritis by a paediatric rheumatologist. Patient reported outcome measures were also measured. RESULTS: A total of 82 patients were enrolled into the validation cohort. Fifty four percent (n = 44) had persistent oligoarthritis followed by rheumatoid factor negative polyarthritis (n = 15, 18%). The mean uveitis disease duration was 3.3 years (SD 3.0). Bilateral eye involvement was reported in 65 (79.3%) patients. The main findings are that the most significant changes, from baseline to 6 months, are found in the AC activity measures of cells and flare. These measures correlate with the presence of pre-existing structural complications and this has implications for the reporting of trials using a single measure as a primary outcome. We also found that visual analogue scales of disease activity showed significant change when reported by the ophthalmologist, rheumatologist and families. The measures formed three relatively distinct groups. The first group of measures comprised uveitis activity, ocular damage and the ophthalmologists' VAS. The second comprised patient reported outcomes including disruption to school attendance. The third group consisted of the rheumatologists' VAS and the joint score. CONCLUSIONS: We propose distinctive and clinically significant measures of disease activity, severity and damage for JIAU. This effort is the initial step for developing a comprehensive outcome measures for JIAU, which incorporates the perspectives of rheumatologists, ophthalmologists, patients and families.

Flares of Disease in Children with Clinically Inactive Juvenile Idiopathic Arthritis Were Not Correlated with Ultrasound Findings.

OBJECTIVE: The validity of our current definitions for clinically inactive disease (CID) in juvenile idiopathic arthritis (JIA) based on physical examination is challenged by the development of advanced musculoskeletal imaging tools. We aimed to prospectively determine the prevalence of abnormal ultrasound (US) findings in children with CID in JIA and their clinical significance. METHODS: Children aged ≥ 4 years with CID and a history of arthritis from a single tertiary center were approached over 1 year. Standard US of knees, tibiotalar joints, subtalar joints, and wrists were performed at baseline and at a followup visit. US images were scored by 2 pediatric musculoskeletal radiologists. RESULTS: Forty children with CID were enrolled and followed clinically. The median duration of inactive disease was 1 year. The most common International League of Associations for Rheumatology JIA categories were extended oligoarticular JIA (30%) and rheumatoid factor-negative polyarthritis (38%). At baseline, among a total of 289 joints scanned, 24 joints (8%) had at least 1 abnormal finding in 18 (45%) of 40 subjects. When evaluated at the individual joint level against flares identified during followup exams, these baseline US findings had a sensitivity of 15% and a positive predictive value of 12%. The predictive performance of the second US was even less. CONCLUSION: Our study demonstrates that nearly half of children with CID had abnormal US findings in 1 of 8 commonly affected joints. These findings did not correlate with subsequent clinical flares in up to 2 years of followup.