Efficacy and safety of canakinumab in patients with Still's disease: exposure-response analysis of pooled systemic juvenile idiopathic arthritis data by age groups

OBJECTIVES: To describe the efficacy, safety, and exposure-response relationship of canakinumab in a subgroup of patients with systemic juvenile idiopathic arthritis (SJIA) aged ≥16 years, representative of adult-onset Still's disease (AOSD) patients, and to compare this subgroup with those of children and young adolescents with SJIA by pooling clinical data collected during the development programme of canakinumab. METHODS: Safety and efficacy data on canakinumab-treated patients were pooled from 4 SJIA studies (NCT00426218, NCT00886769, NCT00889863, and NCT00891046). In the majority of patients, canakinumab was administered at 4 mg/kg every 4 weeks. Efficacy parameters (adapted American College of Rheumatology [aACR] paediatric and juvenile idiopathic arthritis [JIA] ACR responses), quality of life, C-reactive protein levels, safety, and exposure-response relationship were assessed over 12 weeks in 3 age groups (children 2-<12, young adolescents 12-<16 and older adolescents and young adults ≥16 years). RESULTS: Efficacy outcomes were analysed in 216 children, 56 young adolescents and 29 older adolescents and young adults. Efficacy parameters across 3 age groups were largely comparable. At Day 15, at least 50% of patients from each age group exhibited aACR ≥70 and ACR responses. The safety profile of canakinumab was similar across age groups. One death was reported. CONCLUSIONS: Pooled analyses from SJIA studies indicate that older adolescents and young adults SJIA patients show similar efficacy, safety, and exposure-response relationship on a weight-based dosing regimen as observed in children and adolescent SJIA patients. These analyses suggest that canakinumab may be an effective therapy in young adults with Still's disease

A177: Program Evaluation of the ACR/CARRA Inter‐Institutional Mentoring Program (AMIGO) in Pediatric Rheumatology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106776/1/art38603.pd

Sleep and fatigue and the relationship to pain, disease activity and quality of life in juvenile idiopathic arthritis and juvenile dermatomyositis

Abstract Objectives. To determine and compare the prevalence of disturbed sleep in JIA and JDM and the relationship of sleep disturbance to pain, function, disease activity and medications. Methods. One hundred fifty-five patients (115 JIA, 40 JDM) were randomly sampled and were mailed questionnaires. Sleep disturbance was assessed by the sleep self-report (SSR) and the children's sleep habits questionnaire (CSHQ). Fatigue, pain and function were assessed by the paediatric quality of life inventory (PedsQL) and disease activity by visual analogue scales (VASs). Joint counts were self-reported. Results. Eighty-one per cent responded, of whom 44% reported disturbed sleep (CSHQ > 41); there were no differences between disease groups. Poor reported sleep (SSR) was highly correlated with PedsQL fatigue (r = 0.56, P < 0.0001). Fatigue was highly negatively correlated with quality of life (r = À0.77, P < 0.0001). The worst pain intensity in the last week was correlated to sleep disturbance (r = 0.32, P = 0.0005). Fatigue was associated with prednisone and DMARD use. Conclusions. Sleep disturbance and fatigue are prevalent among children with different rheumatic diseases. Sleep disturbance and fatigue are strongly associated with increased pain and decreased quality of life. Strategies aimed at improving sleep and reducing fatigue should be studied as possible ways of improving quality of life for children with rheumatic illness

Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Objective: To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). Methods: A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. Results: Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. Conclusions: We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

Objective To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Results Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ = 0.76). Conclusion We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

A unique, interactive and web-based pediatric rheumatology teaching module: residents’ perceptions

BACKGROUND: The limited availability of pediatric rheumatologists for teaching in pediatric residency programs negatively impacts resident education about rheumatology. At present, there are no educational websites available for trainees to learn about pediatric rheumatology. We are planning to develop an interactive web-based teaching module to improve resident learning about rheumatology (“POINTER”: Pediatric Online INteractive TEaching in Rheumatology). The aim of this study was to perform a needs assessment of pediatric residents who will be using POINTER. METHODS: Pediatric residents (n = 60) at The Hospital for Sick Children were emailed an online survey. This was designed to assess prior use of online teaching modules, the utility of an online teaching module for rheumatology and which technologies should be included on such a site. RESULTS: Forty-seven residents participated in the survey (78.3% response rate). Ninety-one percent of the respondents thought that an interactive teaching website would enhance their learning and should include case-based teaching modules. Several web-based technologies were felt to be important for inclusion on the teaching modules. These included graphics and animation (86.4%), interactivity (93.2%), pictures (100%), live digital videos (88.9%) and links to articles and research (88.6%). CONCLUSIONS: An interactive web-based rheumatology teaching module would be well utilized by pediatric residents. Residents showed preference for case-based teaching modules as well as multimedia modalities for learning a detailed musculoskeletal examination