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Objectives To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). Methods Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. Results From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time (‘High’), the other rapidly evolving to low disease activity (‘Low’). In cluster A patients, peripheral manifestations predisposed to the ‘High’ trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR) = 2.1, 95% CI: 1.0, 4.4, P = 0.04 – Cox proportional-hazards model). Conclusion Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.

Objective To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in juvenile idiopathic arthritis (JIA) and to seek factors driving discordance. Methods The frequency of fulfillment of existing criteria was evaluated in information on 10,186 patients extracted from 3 cross-sectional data sets. Patients were divided up according to the functional phenotypes of oligoarthritis and polyarthritis. Concordance between criteria was examined using weighted Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. Results Criteria for ID were met by 28.6–41.1% of patients with oligoarthritis and by 24.0–33.4% of patients with polyarthritis. Criteria for LDA were met by 44.8–62.4% of patients with oligoarthritis and by 44.6–50.4% of patients with polyarthritis. There was a 57.9–62.3% overlap between criteria for ID and a 67.9–85% overlap between criteria for LDA. Parent and physician global assessments and acute-phase reactants were responsible for the majority of instances of discordance among criteria for ID (8.7–15.5%, 10.0–12.3%, and 10.8–17.3%, respectively). Conclusion We found fair concordance between criteria for ID and LDA in JIA, with the main drivers of discordance for ID being physician and parent global assessments and acute-phase reactants. This observation highlights the need for further studies aimed to evaluate the impact of subjective physician and parent perception of disease remission and of laboratory measures of inflammatory activity on the definition of ID.

Magnetic resonance imaging (MRI) features of active sacroiliac joint inflammation include joint space fluid and enhancement, but it is unclear to what extent these are present in normal children. To describe normal MRI appearances of pediatric sacroiliac joint spaces in boys and girls of varying ages. In this ethics-approved prospective study, 251 children (119 boys, 132 girls; mean age: 12.4 years, range: 6.1–18.0 years), had both oblique-coronal T1-weighted and short tau inversion recovery (STIR) sacroiliac joint MRI. Of these, 127 were imaged for other reasons and had asymptomatic sacroiliac joints (“normal cohort”) while 124 had low back pain with no features of sacroiliitis on initial clinical MRI review (“low-back-pain cohort”). Post-gadolinium T1-weighted sequences were available in 16/127 normal and 124/124 low-back-pain subjects. Three experienced radiologists scored high signal in the sacroiliac joint space on STIR (score 0=absent; 1=high signal compared to normal bone marrow present anywhere in the joint but not as bright as fluid [compared to vessels, cerebrospinal fluid]; 2=definite fluid signal in part of the joint; 3=definite fluid signal, entire vertical height, majority of slices) and, when available, joint space post-contrast enhancement (0=no high signal/enhancement; 1=thin, symmetrical, mildly increased linear high signal present in the joint space; 2=focal, thick or intense enhancement). Associations between joint signal scores, age, gender and sacral apophyseal closure were analysed. Increased signal on STIR (score 1–3) was present in 74.7% of pediatric sacroiliac joint spaces, as intense as fluid in 18.4%. There was no significant difference in proportion by gender, side or cohort, but girls showed peak signal earlier than boys (10 years old vs. 12 years old, respectively). On post-gadolinium T1-weighted sequences, a thin rim of increased signal was nearly universally seen in sacroiliac joint spaces without focal, intense or thick post-contrast enhancement. Sacroiliac joint spaces of most children demonstrate mildly increased signal on STIR, compared to normal bone marrow, and thin rim-like enhancement on post-contrast T1 images, likely related to cartilage. These findings should not be confused with sacroiliitis.

OBJECTIVE To evaluate changes in health-related quality of life (HRQoL) and disability in children with systemic juvenile idiopathic arthritis (JIA) or polyarticular JIA treated with tocilizumab. METHODS Secondary analyses of two double-blind, placebo-controlled trials of intravenous tocilizumab in children with active systemic JIA or polyarticular JIA were conducted. Patient-reported outcomes of disability (Childhood Health Assessment Questionnaire [C-HAQ]), HRQoL (Child Health Questionnaire Parent Form 50 [CHQ-P50], health concepts, physical summary score [CHQ-P50-PhS], psychosocial summary score [CHQ-P50-PsS]), pain, and well-being (100-mm visual analog scale [VAS]) were measured at weeks 0 and 12 for systemic JIA, weeks 16 and 40 for polyarticular JIA, and week 104 for both JIA subgroups. RESULTS The trial included 112 patients with systemic JIA and 188 patients with polyarticular JIA. In patients with polyarticular JIA, the mean ± SD C-HAQ score decreased from 1.39 ± 0.74 at baseline to 0.67 ± 0.65 at week 16 (P < 0.001). In patients with systemic JIA, the mean ± SD CHQ-P50-PhS improved more with tocilizumab therapy than with placebo at week 12 (7.3 ± 10.2 versus 2.4 ± 10.6) (P < 0.05). Almost all mean CHQ-P50 health concept scores, CHQ-P50-PsS, and CHQ-P50-PhS improved (P ≤ 0.002) by week 104 for patients with systemic JIA. Patients with polyarticular JIA and patients with systemic JIA showed significant reductions in disability (mean ± SD C-HAQ scores of -1.09 ± 0.71 and -1.17 ± 0.80, respectively), improvements in well-being (mean ± SD well-being VAS scores of -43.76 ± 26.61 and -51.53 ± 23.57, respectively), and decreases in pain (mean ± SD pain VAS scores of -41.56 ± 31.06 and -51.26 ± 26.79, respectively) (P < 0.001); in patients with polyarticular JIA and patients with systemic JIA who were treated with tocilizumab, 92.9% of polyarticular JIA patients and 96.8% of systemic JIA patients reported no more than minimal pain (a score of ≤35 mm on the VAS) at week 104. CONCLUSION Tocilizumab treatment was associated with significantly reduced disability and pain and improved HRQoL in patients with systemic JIA and polyarticular JIA.

Objective To report the 2‐year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular‐course juvenile idiopathic arthritis (JIA). Methods Patients ages 2–17 years with active polyarticular‐course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open‐label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] 1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open‐label TCZ. At week 104 of the study, efficacy was assessed using JIA‐ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS‐71). Safety was assessed in the all‐exposure population per 100 patient‐years of exposure. Results Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent‐to‐treat group who received TCZ, JIA‐ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS‐71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient‐years and 11.1 per 100 patient‐years, respectively. The infection rate was 151.4 per 100 patient‐years, and the serious infection rate was 5.2 per 100 patient‐years. Conclusion Patients treated with TCZ for polyarticular‐course JIA showed high‐level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.

To determine patterns of variation of subchondral T2 signal changes in pediatric sacroiliac joints (SIJ) by location, age, sex, and sacral apophyseal closure. MRI of 502 SIJ in 251 children (132 girls), mean age 12.4 years (range 6.1–18.0), was obtained with parental informed consent. One hundred twenty-seven out of 251 had asymptomatic joints and were imaged for non-rheumatologic reasons, and 124 had low back pain but no sign of sacroiliitis on initial clinical MRI review. After calibration, three subspecialist radiologists independently scored subchondral signal changes on fat-suppressed fluid-sensitive sequences from 0 to 3 in 4 locations, and graded the degree of closure of sacral segmental apophyses. Associations between patient age, sex, signal changes, and apophyseal closure were analyzed. Rim-like subchondral increased T2 signal or “flaring” was much more common at sacral than iliac SIJ margins (72% vs 16%, p 90% of children. Iliac flaring scores were always lower than sacral, except for 1 child. Signal changes decreased as sacral apophyses closed, and were seen in

Chorea is considered a nonthrombotic manifestation of the antiphospholipid syndrome, often preceding thrombotic events in children. It can be present in up to 5% of pediatric patients with antiphospholipid syndrome. Immunomodulatory treatment regimens seem to be successful in these patients, emphasizing the underlying immunological etiology. Corticosteroids are considered first-line treatment, but chorea tends to be therapy-resistant and guidelines about second-line therapy in children are solely based on small case studies. We present a case of a therapy-resistant chorea, successfully treated with rituximab. Furthermore, we give an overview of the existing literature concerning rituximab for the treatment of chorea in children. Our findings indicate that rituximab can be considered a safe option to treat antiphospholipid syndrome-related chorea in children.

Objectives To characterize the frequency of PsA subtypes, estimate the severity based on damage and inflammation and estimate the impact of PsA on patients’ health-related quality of life. Methods We conducted a longitudinal observational study in 17 academic and non-academic centres in Belgium. Patients with PsA fulfilling Classification Criteria for Psoriatic Arthritis were recruited. Three visits were scheduled: at baseline (T0), at 1 year (±1 month; T1) and at 2 years (±1 month; T2) of follow-up. Demographics, clinical data and patient-reported outcome measures were collected at T0, T1 and T2. X-rays of the hands and feet were collected yearly (T0, T1 and T2). X-rays of the spine were collected at T0 and T2. Here we report on the burden of disease based on the clinical data and patient-reported outcomes. Results A total of 461 patients were recruited; 73.5% had combined peripheral and axial involvement and 13.7% had hip involvement. Plaque psoriasis was predominant (83.9%). At inclusion, 42.7% and 58.8% had no tender or swollen joints, respectively. Dactylitis and enthesitis were still present in 13.7% and 24.1% of the patients, respectively. Patients was treated with DMARDs (68%) and/or anti-TNF (44.2%). Forty-three per cent of the patients had a state of minimal disease activity and 62% considered the actual state as satisfactory. The mean HAQ score was 0.7%, with 32.5% of patients having a normal score ( Conclusion Despite the availability of different treatment options, including biologics (anti-TNF), a substantial number of patients have active disease and have a high disease burden.

Magnetic resonance imaging (MRI) features of active sacroiliac joint inflammation include joint space fluid and enhancement, but it is unclear to what extent these are present in normal children.To describe normal MRI appearances of pediatric sacroiliac joint spaces in boys and girls of varying ages.In this ethics-approved prospective study, 251 children (119 boys, 132 girls; mean age: 12.4 years, range: 6.1-18.0 years), had both oblique-coronal T1-weighted and short tau inversion recovery (STIR) sacroiliac joint MRI. Of these, 127 were imaged for other reasons and had asymptomatic sacroiliac joints ("normal cohort") while 124 had low back pain with no features of sacroiliitis on initial clinical MRI review ("low-back-pain cohort"). Post-gadolinium T1-weighted sequences were available in 16/127 normal and 124/124 low-back-pain subjects. Three experienced radiologists scored high signal in the sacroiliac joint space on STIR (score 0=absent; 1=high signal compared to normal bone marrow present anywhere in the joint but not as bright as fluid [compared to vessels, cerebrospinal fluid]; 2=definite fluid signal in part of the joint; 3=definite fluid signal, entire vertical height, majority of slices) and, when available, joint space post-contrast enhancement (0=no high signal/enhancement; 1=thin, symmetrical, mildly increased linear high signal present in the joint space; 2=focal, thick or intense enhancement). Associations between joint signal scores, age, gender and sacral apophyseal closure were analysed.Increased signal on STIR (score 1-3) was present in 74.7% of pediatric sacroiliac joint spaces, as intense as fluid in 18.4%. There was no significant difference in proportion by gender, side or cohort, but girls showed peak signal earlier than boys (10 years old vs. 12 years old, respectively). On post-gadolinium T1-weighted sequences, a thin rim of increased signal was nearly universally seen in sacroiliac joint spaces without focal, intense or thick post-contrast enhancement.Sacroiliac joint spaces of most children demonstrate mildly increased signal on STIR, compared to normal bone marrow, and thin rim-like enhancement on post-contrast T1 images, likely related to cartilage. These findings should not be confused with sacroiliitis.

Objective.To develop and test shortened versions of the Manual Muscle Test-8 (MMT-8) in juvenile dermatomyositis (JDM).Methods.Construction of reduced tools was based on a retrospective analysis of individual scores of MMT-8 muscle groups in 3 multinational datasets. The 4 and 6 most frequently impaired muscle groups were included in MMT-4 and MMT-6, respectively. Metrologic properties of reduced tools were assessed by evaluating construct validity, internal consistency, discriminant ability, and responsiveness to change.Results.Neck flexors, hip extensors, hip abductors, and shoulder abductors were included in MMT-4, whereas MMT-6 also included elbow flexors and hip flexors. Both shortened tools revealed strong correlations with MMT-8 and other muscle strength measures. Correlations with other JDM outcome measures were in line with predictions. Internal consistency was good (0.88–0.96) for both MMT-4 and MMT-6. Both reduced tools showed strong ability to discriminate between disease activity states, assessed by the caring physician or a parent (P < 0.001), and between patients whose parents were satisfied or not satisfied with illness course (P < 0.001). Responsiveness to change (assessed by both standardized response mean and relative efficiency) of MMT-4 and, to a lesser degree, MMT-6, was slightly superior to that of MMT-8.Conclusion.Overall, the metrologic performance of MMT-4 and MMT-6 was comparable to that of the other established muscle strength tools, which indicates that they may be suitable for use in clinical practice and research, including clinical trials. The measurement properties of these tools should be further tested in other patient populations and evaluated prospectively.

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Flemish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 100 JIA patients (8% systemic, 33% oligoarticular, 24% RF negative polyarthritis, 35% other categories) and 99 healthy children, were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Flemish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research. ispartof: Rheumatology International vol:38 issue:Suppl 1 pages:187-194 ispartof: location:Germany status: published

Background The Assessment of Spondyloarthritis International Society (ASAS) definition for a ‘positive’ Magnetic Resonance Imaging (MRI) for sacroiliitis is well studied and validated in adults, but studies about the value of this definition in children are lacking. The aim of this study is to evaluate whether the adult ASAS definition of a positive MRI of the sacroiliac joints can be applied to children with a clinical suspicion of Juvenile Spondyloarthritis (JSpA). Methods Two pediatric musculoskeletal radiologists blinded to clinical data independently retrospectively reviewed sacroiliac (SI) joint MRI in 109 children suspected of sacroiliitis. They recorded global impression (sacroiliitis yes/no) and whether the adult ASAS definition for sacroiliitis was met at each joint. This was compared to gold-standard clinical diagnosis of JSpA. Additionally, MRI were scored according to’adapted’ ASAS definitions including other features of sacroiliitis on MRI. Results JSpA was diagnosed clinically in 47/109 (43%) patients. On MRI, sacroiliitis was diagnosed by global assessment in 30/109 patients, of whom 14 also fulfilled ASAS criteria. No patients with negative global assessment for sacroiliitis fulfilled ASAS criteria. Sensitivity (SN) for JSpA was higher for global assessment (SN = 49%) than for ASAS definition (SN = 26%), but the ASAS definition was more specific (SP = 97% vs. 89%). Modifying adult ASAS criteria to allow bone marrow edema (BME) lesions seen on only one slice, synovitis or capsulitis, increased SN to 36%, 32% and 32% respectively, only slightly lowering SP. Including structural lesions increased SN to 28%, but lowered specificity to 95%. Conclusion The adult ASAS definition for sacroiliitis has low sensitivity in children. A pediatric-specific definition of MRI-positive sacroiliitis including BME lesions visible on one slice only, synovitis and/or capsulitis may improve diagnostic utility, and increase relevance of MRI in pediatric rheumatology practice.

Background The anti–interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years. Methods Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2–17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing

Background Tocilizumab (TCZ) intravenous (IV) formulation was approved for the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) based on the results of a large phase 3 clinical trial. Physical function, measured by the Childhood Health Assessment Questionnaire–Disability Index (CHAQ-DI), and health-related quality of life (HRQOL), measured by the Child Health Questionnaire (CHQ), were evaluated. Objectives To examine measures of disability and HRQOL in patients with sJIA treated with TCZ IV for up to 2 years in post hoc analysis of data from the phase 3 trial of TCZ. Methods Changes within 3 months of treatment initiation with TCZ (baseline) were compared between TCZ- and placebo (PBO)–treated patients using CHAQ-DI, pain global assessment (Pain-GA), physician global assessment, and patient global assessment (Pt-GA) using analysis of variance adjusted for treatment group. Changes in CHAQ-DI overall and domain scores and changes in CHQ domain and summary scores from baseline to 2 years were compared for patients treated with TCZ using the unpaired t test. Results Patients with sJIA experienced clinically relevant improvement in physical function (CHAQ-DI) and reduction of pain (Pain-GA). Mean (SD) CHAQ-DI scores for patients treated with PBO and TCZ were 1.7 (0.8) for both groups at baseline and 1.2 (1.0) and 0.9 (0.8), respectively, at week 12 (week 12 mean difference, –0.2; median [range] change from baseline to week 12 difference, –0.3 [–0.6 to 0.0]). These patients also had significantly improved CHQ socialization, behavior, mental health, and psychosocial summary scores after 3 months compared with those receiving PBO (Figure 1). Improvement in all CHAQ-DI domains over 2 years was observed with TCZ treatment (Figure 2); improvement rates in patient well-being (Pt-GA) were 87.7%. Similar improvements in physical function were observed in patients with polyarticular JIA in the phase 3 trial that led to approval of TCZ IV in these patients (not shown). There was also significant improvement (p Conclusion Two years of TCZ treatment resulted in statistically significant and clinically relevant improvements in function and HRQOL in patients with sJIA. Disclosure of Interests Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

Background The efficacy of SC abatacept (ABA) in patients (pts) with polyarticular-course juvenile idiopathic arthritis (pJIA) was shown in a 2-year (yr), Phase III, open-label international study (NCT01844518).1 However, it is unknown whether each individual pt within a treatment group consistently achieves the same efficacy endpoint at all time points. Objectives To investigate whether ABA efficacy is maintained by individual pts with pJIA over time. Methods In this subgroup analysis, pts in two age cohorts (2–5 yrs and 6–17 yrs) who achieved clinical response to weekly SC ABA (10 to Results A total of 219 pts entered the study (46 [21.0%] 2–5 yrs; 173 [79.0%] 6–17 yrs) and a subgroup of these pts achieved a clinical response at Day 113 (Table). Most pts who achieved JIA-ACR70, JIA-ACR100, JADAS71 MDA and JADAS71 ID at Day 113 sustained their response at Day 393 and at Days 393 and 645 in the 2–5-yr and 6–17-yr cohorts (Figure). Across cohorts, more than 75% and 60% of pts maintained a JIA-ACR 70 and JADAS71 MDA response through Day 645, respectively. Prior biologic (b)DMARD use was an important prognostic factor. In pts aged 6–17 yrs, sustained JIA-ACR70 response rate at Days 393 and 645 was 81% (57/70) in pts who did not have prior bDMARDs vs 57% (12/21) in pts who had prior bDMARDs (p=0.0715); sustained JADAS71 MDA response rate was 71% (37/52) vs 37% (7/19; p=0.0320). Prognostic factors for JIA-ACR100 response and JADAS71 ID in pts aged 6–17 yrs and for all outcomes in pts aged 2–5 yrs could not be determined due to low pt numbers. Conclusion The majority of individuals with pJIA who achieved stringent efficacy endpoints with weekly SC abatacept by Day 113 sustained that clinical endpoint over time. Prior bDMARD use may be a prognostic factor for sustained response over 2 yrs. Reference [1] Brunner HI, et al. Arthritis Rheumatol2018;70:1144–54. Acknowledgement Professional medical writing: Stacey Reeber, PhD, Caudex; funding: Bristol-Myers Squibb Disclosure of Interests Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus ( I perform consultancy activities on behalf of the Gaslini Institute for the companies listed below: AbbVie, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, R-Pharm. The money received for these activities are directly transferred to the Gaslini Institute’s bank account. Before March 2016, I was the head of the Pediatric Rheumatology Department at the G. Gaslini Hospital, where the PRINTO Coordinating Centre is located. For the coordination activity of the PRINTO network, the Gaslini Hospital received contributions from the industries listed in this section. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Daniel J Lovell Consultant for: Consulting fees and/or honoraria from Astra Zeneca, Wyeth Pharma, Amgen, Abbott, Pfizer, F. Hoffmann-La Roche, Novartis, UBC, Takeda, GSK, Boehringer, and Celgene

Background Diagnosis of axial spondyloarthritis (axSpA) often relies on a positive magnetic resonance image of the sacroiliac joints (MRI-SIJ). However, pitfalls in interpretation of MRI-SIJ were recently acknowledged (1). Thus reader’s expertise might be a source of heterogeneity in patient populations diagnosed with non-radiographic axSpA. Objectives We compared clinical characteristics of axSpA patients diagnosed in peripheral hospitals (MRI evaluation by local experts) versus an academic hospital (MRI central reading by trained radiologists and rheumatologists). Methods Patients originate from the Be-Giant cohort, a Belgian nationwide observational registry of axSpA patients diagnosed by expert opinion. Included patients fulfill the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA and are anti-TNF-α naive prior to inclusion. Patient enrollment started in 2010 and 2012 at the outpatient clinic of 1 academic and 7 peripheral hospitals respectively. Patients were free to visit a rheumatologist of their choice without necessity for referral by a general practitioner. Results By January 2019, 291 axSpA patients were included. Table 1 presents demographic and clinical characteristics according to the diagnostic echelon. The patient fraction fulfilling the imaging arm of the ASAS classification criteria was similar in both settings (75,4% vs. 88,7%, p = 0,21). However, because of a higher HLA B27 positivity rate in patients diagnosed in an academic versus peripheral hospitals (73,5% vs. 57,4%, p = 0,01), a significantly higher fraction of patients fulfilled both the clinical and imaging arm in the former diagnostic setting (63,0% vs. 37,7%, p = 0,01). Conclusion Patients diagnosed with axSpA in peripheral versus an academic hospital generally show similar demographic and clinical characteristics. In an academic center, patients diagnosed with axSpA are more likely to be HLA B27 positive and to fulfill both ASAS classification arms, indicating that rheumatologists in peripheral hospitals seem to assign more value to MRI findings compared to HLA B27 status in the diagnostic process. References [1] Varkas G, de Hooge M, Renson T, De Mits S, Carron P, Jacques P, et al. Effect of mechanical stress on magnetic resonance imaging of the sacroiliac joints: assessment of military recruits by magnetic resonance imaging study. Rheumatology (Oxford). 2018;57(3):508-13. Abstract THU0375 – Table 1 Continuous variables: mean (SD); other: counts(%). Disclosure of Interests Ann-Sophie De Craemer: None declared, Thomas Renson: None declared, Philippe Carron: None declared, Peggy Jacques: None declared, Jan Lenaerts: None declared, Lieve Gyselbrecht: None declared, Rik Joos: None declared, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Dirk Elewaut: None declared

Background Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure. Methods In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases) (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3 ' mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile. Results Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples. Conclusions Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis. Al Thrasher early career research Grant, the University of Antwerp; Hercules Foundation-Belgium; Research Foundation Flanders (FWO)FWO [151316, 1861219N]

Objective: Chronic pain is central to Juvenile Idiopathic Arthritis (JIA) and is predictive of impaired functioning. Whereas most work has focused on identifying psychosocial risk factors for maladaptive outcomes, we explored the idea that child and parental psychological flexibility (PF) represent resilience factors for adaptive functioning of the child. We also explored differences between general versus pain-specific PF in contributing to child outcomes. Methods: Children with JIA (8-18 years) and (one of) their parents were recruited at the department of pediatric rheumatology at the Ghent University Hospital in Belgium. They completed questionnaires assessing child and parent general and pain-specific PF and child psychosocial and emotional functioning, and disability. Results: The final sample consisted of fifty-nine children and forty-eight parents. Multiple regression analyses revealed that child PF contributed to better psychosocial functioning and less negative affect. Child pain acceptance contributed to better psychosocial functioning, lower levels of disability and lower negative affect, and also buffered against the negative influence of pain intensity on disability. Bootstrap mediation analyses demonstrated that parental (general) PF indirectly contributed to child psychosocial functioning and affect via the child’s (general) PF. Parent pain-specific PF was indirectly linked to child psychosocial functioning, disability, and negative affect via child pain acceptance. Conclusion: Our findings indicate that child and parental PF are resilience factors and show that pain acceptance buffers against the negative impact of pain intensity. Implications for psychosocial interventions that target (pain-specific) PF in children as well as in parents are discussed.

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

ObjectivesCombining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year.MethodsThe Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60 mg), COBRA Slim (MTX + prednisone step-down from 30 mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30 mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639).Results98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals.ConclusionsMTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed.Trial registration numbersEudraCT-number 2008-007225-39 and NCT01172639; Results.

Background Intravenous (IV) tocilizumab (TCZ) was approved in the, US (2011), EU (2013) and other countries for the treatment of systemic juvenile idiopathic arthritis (sJIA) patients (pts)≥2 years of age, based on a phase 3 study WA18221.1 US Food and Drug Administration approval resulted in postmarketing requirement to investigate TCZ in pts with sJIA Objectives Report safety results after completion of the optional extension period (OEP) of NP25737 (until 52 weeks from baseline or 2 years of age, whichever was longer). Methods NP25737 was a multicenter, open-label, single-arm study to evaluate the pharmacokinetics and safety of IV TCZ, 12 mg/kg every 2 weeks, for 12 weeks in pts aged Results Seven of 11 pts enrolled in the MEP continued to the OEP and received ≥1 dose of TCZ. Over the entire study period (n=11), the median number of TCZ doses was 11 (range, 2–26) and the median duration of TCZ exposure was 22 weeks (range, 4–58). Most pts (10/11; 91%) had ≥1 AE; most were mild or moderate in intensity and unrelated to study drug. The most common AEs were upper respiratory tract infection (6/11 pts, 55%), hypersensitivity, neutropenia, rash, viral upper respiratory tract infection, and vomiting (each in 3/11 pts; 27%). Seven serious AEs occurred in 5 of 11 pts (46%): 2 in the OEP (transaminases increased and histiocytosis hematophagic), 3 in the MEP (3 hypersensitivity events), and 2 in the safety follow-up of the MEP (sJIA flare and hand-foot-and-mouth disease). AEs leading to dose modification occurred in 5 of 11 pts (1 in the MEP, 4 in the OEP) mostly because of infections, neutropenia, and elevated liver enzymes, all mild or moderate in intensity. AEs leading to withdrawal occurred in 5 of 11 pts (46%): 1 in the OEP because of serious increased transaminases, 3 in the MEP because of serious hypersensitivity reactions to TCZ, and 1 in the MEP because of thrombocytopenia. No deaths were reported during the study. AE rates per 100 pt-years of exposure are reported in the table 1. Conclusions During the OEP of the study, long-term treatment with TCZ was well tolerated in sJIA pts aged References [1] De Benedetti F, et al. N Engl J Med2012;367:2385–2395. [2] Mallalieu NL, et al. Arthritis Rheumatol2017;69(suppl 10):abstract 2856. Acknowledgements This study was sponsored by F. Hoffmann-La Roche Ltd. Disclosure of Interest S. Wimalasundera Employee of: Roche, I. Calvo Penades: None declared, R. Cuttica Consultant for: Roche, Novartis, Lilly, GlaxoSmithKline, BMS, Janssen, Speakers bureau: Roche, Novartis, Lilly, GlaxoSmithKline, BMS, Janssen, H.-I. Huppertz: None declared, R. Joos: None declared, D. Milojevic: None declared, M. Rosenkranz: None declared, K. Schikler: None declared, T. Constantin: None declared, W. Douglass Employee of: Roche, C. Wells Shareholder of: Roche, Employee of: Roche, Y. Kimura Grant/research support from: Novartis, SOBI, Consultant for: Novartis, SOBI, C. Wouters: None declared

We present a patient in whom a combination of perinuclear antineutrophil cytoplasmic antibody-positive vasculitis, oligoarthritis, tendinitis, and myositis was considered to be associated with isotretinoin use. Discontinuation of the drug resulted in complete clinical and biochemical remission (normalization of perinuclear antineutrophil cytoplasmic antibody titer). Although we were unable to prove causality, no other underlying cause for the patient's course was found. We report this occurrence to bring it to the attention of physicians prescribing isotretinoin.

ObjectiveThis report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).MethodsIn this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0–16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16–48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety.ResultsAmong 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with ConclusionAlthough the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred.Clinical Trial RegistrationNCT01230827; Results.

ObjectivesTo compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial.Methods400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein ResultsData from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006).ConclusionsFor high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile.EudraCT number:2008-007225-39.

Background Tocilizumab (TCZ) is approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) based on clinical trials in patients (pts) ≥2 years of age. This study (NP25737) is the first for a biologic in sJIA pts Objectives To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of TCZ in sJIA pts Methods Pts with uncontrolled sJIA and symptoms for ≥1 month prescreening who failed treatment with corticosteroids and NSAIDs and had no history of allergy to TCZ or other biologics received open-label TCZ 12 mg/kg intravenously (IV) every 2 weeks (dose calculated at each visit based on body weight). Pts were treated up to week 12 and could continue until the age of 2 years or were treated for 1 year from baseline. End points included PK (primary) at week 12, PD and efficacy (exploratory), and safety. Comparison was made to exposures from a previous trial in sJIA pts ≥2 years of age (WA18221) that was the basis for approval of TCZ in sJIA. Results Eleven pts were enrolled; median (range) age was 16 (10–22) months and weight was 10.40 (6.8–11.5) kg. Serum TCZ concentrations, estimated using population PK analysis, peaked immediately after infusion; median (range) maximum concentration was 282 (195–347) μg/mL (steady state reached by week 12), and median (range) trough concentration was 34.3 (19.2–59.7) μg/mL. Peak and trough exposures were within the exposure range in older children (244 [109–382] to 54.3 [10.9–117] μg/mL; Figure). Observed mean±SD soluble IL-6 receptor levels were 47.65±16.40 ng/mL at baseline and 927.83±148.07 ng/mL at day 71. CRP levels were 250.81±425.11 mg/L and 2.80±3.56 mg/L, respectively. ESR levels were 59.40±27.47 mm/h and 2.00±1.00 mm/h, respectively. Mean±SD Juvenile Arthritis Disease Activity Score-71 improved from 22.27±10.09 at baseline to 3.66±4.66 at day 71. By week 12, 10 pts had 32 adverse events (AEs) and 4 withdrew due to AEs. Infections or infestations were the most frequently reported AEs (10 events, 9 pts). Five serious AEs (SAEs) occurred; 3 pts had SAEs of hypersensitivity that led to withdrawal; 1 of these pts then experienced SAEs of foot and mouth disease and sJIA flare after study withdrawal. No actual cases of MAS were reported, but 2 pts had laboratory abnormalities indicative of MAS according to 2016 criteria.1 No deaths occurred during the study. Conclusions TCZ exposures achieved in this study fell within the range of the previous trial in sJIA pts ≥2 years of age. This study provides evidence that TCZ is effective in sJIA pts References Ravelli A et al. Ann Rheum Dis. 2016;75:481–9. Disclosure of Interest N. Mallalieu Shareholder of: Roche, Employee of: Roche, J. Hsu Employee of: Roche, K. Wang Employee of: Roche, S. Wimalasundera Employee of: Roche Products Ltd., C. Wells Employee of: Roche Products Ltd., I. Calvo Penades: None declared, R. Cuttica Consultant for: Roche, Novartis, Lilly, GlaxoSmithKline, Bristol-Myers Squibb, Janssen, Speakers bureau: Roche, Novartis, Lilly, GlaxoSmithKline, Bristol-Myers Squibb, Janssen, H. Huppertz: None declared, R. Joos: None declared, Y. Kimura Consultant for: Novartis, SOBI, D. Milojevic: None declared, M. Rosenkranz: None declared, K. Schikler: None declared, T. Constantin: None declared, C. Wouters: None declared

Early diagnosis of spondyloarthritis (SpA) is becoming more important as new medical treatment options have become available to treat inflammation and delay progression of the disease. Increasingly, magnetic resonance imaging (MRI) of the sacroiliac joints is obtained for early detection of inflammatory changes, as it shows active inflammatory and structural lesions of sacroiliitis long before radiographic changes become evident. MRI of the sacroiliac joints in children is a useful tool for suspected juvenile spondyloarthritis (JSpA), even though it is not yet included in the current pediatric classification systems. Recognizing MRI features of pediatric sacroiliitis is a challenge. As most radiologists are not familiar with the normal MRI appearance of the pediatric sacroiliac joint, clear definitions are mandatory. Actually, the adult Assessment of Spondyloarthritis International Society (ASAS) definition for sacroiliitis needs some adaptations for children. A proposal for a possible pediatric-specific definition for active sacroiliitis on MRI is presented in this review. Furthermore, MRI without contrast administration is sufficient to identify bone marrow edema (BME), capsulitis, and retroarticular enthesitis as features of active sacroiliitis in JSpA. In selected cases, when high short tau inversion recovery (STIR) signal in the joint is the only finding, gadolinium-enhanced images may help to confirm the presence of synovitis. Lastly, we found a high correlation between pelvic enthesitis and sacroiliitis on MRI of the sacroiliac joints in children. As pelvic enthesitis indicates active inflammation, it may play a role in assessment of the inflammatory status. Therefore, it should be carefully sought and noted when examining MRI of the sacroiliac joints in children.

BACKGROUND: Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis.METHODS: We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedman's test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960.FINDINGS: Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35·5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0·0228). Median time to clinical remission was 41·9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2·45 fold [95% CI 1·2-5·0] increase with prednisone plus methotrexate; p=0·012). Median time to treatment failure was 16·7 months in patients allocated prednisone, 53·3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1·95 fold [95% CI 1·20-3·15] increase with prednisone; p=0·009). Median time to prednisone discontinuation was 35·8 months with prednisone alone compared with 29·4-29·7 months in the combination groups (p=0·002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study.INTERPRETATION: Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate.FUNDING: Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA).

Background: To determine the prevalence and diagnostic value of pelvic enthesitis on MRI of the sacroiliac (SI) joints in enthesitis related arthritis (ERA). Methods: We retrospectively studied 143 patients aged 6-18 years old who underwent MRI of the SI joints for clinically suspected sacroiliitis between 2006-2014. Patients were diagnosed with ERA according to the International League of Associations for Rheumatology (ILAR) criteria. All MRI studies were reassessed for the presence of pelvic enthesitis, which was correlated to the presence of sacroiliitis on MRI and to the final clinical diagnosis. The added value for detection of pelvic enthesitis and fulfilment of criteria for the diagnosis of ERA was studied. Results: Pelvic enthesitis was seen in 23 of 143 (16 %) patients. The most commonly affected sites were the entheses around the hip (35 % of affected entheses) and the retroarticular interosseous ligaments (32 % of affected entheses). MRI showed pelvic enthesitis in 21 % of patients with ERA and in 13 % of patients without ERA. Pelvic enthesitis was seen on MRI in 7/51 (14 %) patients with clinically evident enthesitis, and 16/92 (17 %) patients without clinically evident enthesitis. In 7 of 11 ERA-negative patients without clinical enthesitis but with pelvic enthesitis on MRI, the ILAR criteria could have been fulfilled, if pelvic enthesitis on MRI was included in the criteria. There is a high correlation between pelvic enthesitis and sacroiliitis, with sacroiliitis present in 17/23 (74 %) patients with pelvic enthesitis. Conclusions: Pelvic enthesitis may be present in children with or without clinically evident peripheral enthesitis. There is a high correlation between pelvic enthesitis and sacroiliitis on MRI of the sacroiliac joints in children. As pelvic enthesitis indicates active inflammation, it may play a role in assessment of the inflammatory status. Therefore, it should be carefully sought and noted by radiologists examining MRI of the sacroiliac joints in children.

Objective To characterize the synovial immunopathologic features of juvenile-onset spondylarthritis (SpA) in relation to adult SpA and other forms of juvenile idiopathic arthritis (JIA). Methods Synovial biopsy samples were obtained from 10 patients with juvenile-onset SpA, 23 with adult SpA, 19 with rheumatoid arthritis (RA), 8 with juvenile polyarthritis, and 12 with juvenile oligoarthritis. Synovial immunopathologic features were studied by extensive histologic and immunohistochemical analyses. Results Synovitis in juvenile SpA was characterized by marked lining layer hyperplasia, clear hypervascularity, and pronounced inflammatory cell infiltration with lymphocytes and macrophages, independent of disease duration or time of sampling. The immunopathologic features of juvenile SpA resembled those of adult SpA in terms of hypervascularity and absence of RA-specific intracellular citrullinated proteins and HLA–DR4/human cartilage glycoprotein 39263–275 complexes, but differed markedly by a stronger lining layer hyperplasia and lower numbers of CD163+ macrophages. Accordingly, class prediction analysis failed to classify juvenile SpA synovitis in the SpA group. Comparison of juvenile SpA with other JIA subtypes showed a broad overlap, with the exception of slightly lower vascularity in juvenile polyarthritis and higher inflammatory cell infiltration in juvenile oligoarthritis. Unsupervised clustering analysis identified a subgroup of samples characterized by high plasma cell infiltration, which corresponded with active, longstanding JIA, mostly of the oligoarthritis subtype. Conclusion Despite some similarities with adult SpA, the findings with regard to lining layer hyperplasia and CD163+ macrophage infiltration are indicative of important differences in the synovial immunopathologic features of juvenile-onset SpA. The partial overlap with other JIA subtypes emphasizes the need for further biologic characterization of JIA in order to define pathophysiologic, rather than phenotypic, subgroups.

To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM).Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM.A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle.We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress.

Canakinumab (CAN), a selective, fully human, anti-interleukin-1β monoclonal antibody, has been shown to be efficacious in SJIA patients (pts) in 2 phase 3 trials: Trial 1 (4-wk, randomized placebo [PBO]-controlled) and Trial 2 (open-label CAN treatment [Part 1] followed by a randomized PBO-controlled withdrawal phase [Part 2]). In Trial 1, statistically significantly more CAN than PBO group pts achieved an adapted pediatric ACR 30 response and in Trial 2, CAN allowed successful reduction/discontinuation of steroids and significantly reduced risk of flare. Safety profile of CAN was in line with expectations for a biologic agent in active SJIA. The persistent disabling features of SJIA and chronic pain can have a negative impact on health-related quality of life (hrqol). These outcomes were evaluated in the CAN phase 3 program.

Background Psoriatic arthritis (PsA) is a common form of chronic arthritis strongly associated with the skin disease psoriasis. The gender distribution is considered equal but it is suggested that their might be gender related differences in disease expression, disease activity and outcome. The BEPAS cohort (Belgian Epidemiological Psoriatic Arthritis Study) is a large prospective multicenter real life cohort set up in 17 Belgian large academic and non academic rheumatology practices that offers a unique opportunity to study the disease patterns with their respective articular and skin involvement in this patient group Objectives (1) To assess gender-related differences in disease patterns and articular manifestations of psoriatic arthritis Methods A cross-sectional analysis at the inclusion visit was performed among the male and female patients included in the BEPAS cohort. They were evaluated for the demographics, the disease patterns at diagnosis and the presence of clinical articular and extra–articular manifestations at inclusion. Gender differences were evaluated by one way ANOVA or Chi –square testing. Results 461 patients including 263 male patients and 198 female patients with mean age: 52.79 years (±12.29) were recruited in the 17 centers from December 2012 to July 2014.There was no gender difference in rheumatoid factor, anti–CCP and extra-articular manifestations such as uveitis and inflammatory bowel disease Conclusions The disease patterns and clinical manifestations differ in several aspects between male and female PsA. They have a different clinical articular presentation at diagnosis: male patients have more polyarticular disease while female patients have more entheseal disease. Skin involvement is comparable except for male patients having more nail involvement. These differences might have impact on the disease evolution, severity and treatment decisions. Disclosure of Interest K. De Vlam: None declared, R. Lories Grant/research support from: MSD Belgium, S. Steinfeld Grant/research support from: MSD Belgium, F. Van Den Bosch Grant/research support from: MSD Belgium, A. Nzeusseu Toukap Grant/research support from: MSD Belgium, M. Malaise Grant/research support from: MSD Belgium, V. Taelman Grant/research support from: MSD Belgium, F. Van Bruwaene Grant/research support from: MSD Belgium, M. Van Den Berghe Grant/research support from: MSD Belgium, J. Lenaerts Grant/research support from: MSD Belgium, R. Joos Grant/research support from: MSD Belgium, P. Geusens Grant/research support from: MSD Belgium, S. Dall9Armellina Grant/research support from: MSD Belgium, I. Peene Grant/research support from: MSD Belgium, G. De Brabanter Grant/research support from: MSD Belgium, M. Van Den Berghe Grant/research support from: MSD Belgium, J. QU Grant/research support from: MSD Belgium, M. Maertens Grant/research support from: MSD Belgium, H. Leroi Employee of: MSD Belgium

Background Psoriatic arthritis impacts significantly function and quality of life. Although radiographic damage may be more important in rheumatoid arthritis both disability and quality of life are similarly impaired in both groups. Only few data in large cohorts are available to evaluate the impact of the articular and skin involvement in PsA. The BEPAS cohort is a unique opportunity to study cross-sectionally and longitudinally these aspects and their effect on disability and quality of life. Objectives (1) to estimate the severity of disease based on disease activity scores and active inflammation (2) to estimate the impact in terms of health-related quality of life of PsA in Belgium Methods A cross-sectional analysis at the inclusion visit was performed among all patients included in the BEPAS cohort and subsequently differences between male and female patients were studied. They were evaluated for the demographics, the disease activity at inclusion. Inflammatory parameters were captured at inclusion. HAQ and SF36 patient global assessment and physician global assessment were collected. Gender differences were evaluated by one way ANOVA or Chi –square testing. Results 461 patients including 263 male patients and 198 female patients with mean age: 52.79 years (±12.29) were recruited in the 17 centers from December 2012 to July 2014. Conclusions The differences in disease activity and consequently the burden of disease between male and female patients with PsA in the BEPAS cohort seem mainly based on the patient global assessment and enthesitis score. Swollen and tender joint counts as well as inflammatory parameters are not responsible for these differences Disclosure of Interest K. De Vlam Grant/research support from: MSD Belgium, R. Lories Grant/research support from: MSD Belgium, S. Steinfeld Grant/research support from: MSD Belgium, F. Van Den Bosch Grant/research support from: MSD Belgium, A. Nzeusseu Toukap Grant/research support from: MSD Belgium, M. Malaise Grant/research support from: MSD Belgium, V. Taelman Grant/research support from: MSD Belgium, F. Van Bruwaene Grant/research support from: MSD Belgium, M. Vanden Berghe Grant/research support from: MSD Belgium, R. Joos Grant/research support from: MSD Belgium, J. Lenaerts Grant/research support from: MSD Belgium, P. Geusens Grant/research support from: MSD Belgium, S. Dall9Armellina Grant/research support from: MSD Belgium, I. Peene Grant/research support from: MSD Belgium, G. De Branbanter Grant/research support from: MSD Belgium, M. Van Den Berghe Grant/research support from: MSD Belgium, J. Qu Grant/research support from: MSD Belgium, M. Maertens Grant/research support from: MSD Belgium, H. Leroi Employee of: MSD Belgium

Background Psoriatic Arthritis is often considered to be predominantly peripheral presenting with arthritis, dactylitis and enthesitis. Consequently randomized controlled trials, screening procedures for early detection and treatment strategies largely focus on peripheral disease. Axial involvement is considered less common. The BEPAS cohort (Belgian Epidemiological Psoriatic Arthritis Study) is a prospective multicenter real life cohort set up in 17 Belgian large academic and non academic rheumatology practices that offers a unique opportunity to study the axial involvement in this patient group. Objectives (1) To estimate the prevalence of axial involvement in patients with PsA in general (2) to estimate the prevalence of inflammatory back pain in patients with PsA; (3) to estimate the influence of disease duration on spinal manifestations. Methods Patients included in the BEPAS cohort were evaluated for the presence of a clinical phenotype indicating axial involvement, the specific presence of spinal complaints (reported by patients) and the presence of inflammatory back pain according the Rudwaleit criteria. Demographics and clinical features were recorded. BASDAI and BASMI were calculated. Results Among the 461 recruited patients (mean age: 52.79 years (±12.29), male 57%) 157 patients (34,1%) fulfilled the Berlin Criteria for inflammatory back pain with a higher prevalence in female patients (40,5% vs 28,9%, p=0.007) at inclusion.A family history of ankylosing spondylitis is reported in 3.3% of the patients. Clinical characteristics and demographics are listed in table 1. Conclusions The BEPAS cohort reports a substantial contribution of inflammatory axial involvement to the clinical and inflammatory burden of disease in PsA patients. Inflammatory axial involvement is a common clinical phenotype in PsA patients reporting higher disease activity and worse health status occurring more frequent in female patients, contrasting with other spondyoloartropathies. Disclosure of Interest K. De Vlam: None declared, R. Lories Grant/research support from: MSD Belgium, S. Steinfeld Grant/research support from: MSD Belgium, F. Van Den Bosch Grant/research support from: MSD Belgium, A. Nzeusseu Toukap Grant/research support from: MSD Belgium, M. Malaise Grant/research support from: MSD Belgium, V. Taelman Grant/research support from: MSD Belgium, F. Van Bruwaene Grant/research support from: MSD Belgium, M. Van Den Berghe Grant/research support from: MSD Belgium, J. Lenaerts Grant/research support from: MSD Belgium, R. Joos Grant/research support from: MSD Belgium, P. Geusens Grant/research support from: MSD Belgium, S. Dall9Armellina Grant/research support from: MSD Belgium, I. Peene Grant/research support from: MSD Belgium, G. De Brabanter Grant/research support from: MSD Belgium, M. Van Den Berghe Grant/research support from: MSD Belgium, J. QU Grant/research support from: MSD Belgium, M. Maertens Grant/research support from: MSD Belgium, H. Leroi Employee of: MSD Belgium

To evaluate the efficacy and safety of apremilast, a novel, orally available small molecule that specifically targets phosphodiesterase 4, in the treatment of active psoriatic arthritis (PsA).This phase II, multicenter, randomized, double-blind, placebo-controlled study included the following: a 12-week treatment phase, with patients receiving placebo, apremilast 20 mg twice per day, or apremilast 40 mg once per day; a 12-week treatment-extension phase, with patients in the placebo group re-randomized to receive apremilast; and a 4-week observational phase after treatment cessation. The primary end point was the proportion of patients achieving the American College of Rheumatology criteria for 20% improvement (ACR20) at week 12. Safety assessments included adverse events (AEs), physical examinations, vital signs, laboratory parameters, and electrocardiograms.Of the 204 patients with PsA who were randomized to a treatment group, 165 completed the treatment phase. At the end of the treatment phase (week 12), 43.5% of patients receiving apremilast 20 mg twice per day (P0.001) and 35.8% of those receiving 40 mg once per day (P = 0.002) achieved an ACR20 response, compared with 11.8% of those receiving placebo. At the end of the treatment-extension phase (week 24),40% of patients in each group (patients receiving apremilast 20 mg twice per day, patients receiving apremilast 40 mg once per day, and patients in the placebo group re-randomized to receive apremilast) achieved the ACR20 level of improvement. Most patients in the treatment phase (84.3%) and treatment-extension phase (68.3%) reported ≥ 1 AE. Diarrhea, headache, nausea, fatigue, and nasopharyngitis were reported most frequently; most events were mild or moderate. No clinically relevant laboratory or electrocardiographic abnormalities were reported.Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. The balance of efficacy, tolerability, and safety supports further study of apremilast in PsA.

Purpose Treatment options for sJIA are limited. Excessive IL-6 production has been implicated in several manifestations of this disease. In a previous Japanese study, TCZ, an IL-6 receptor inhibitor, improved arthritis and systemic features of patients with refractory sJIA. We present efficacy and safety of TCZ in patients with active sJIA who were treated for ≥52 wks in the global, 3-part, 5-yr, phase 3, multicenter TENDER study. Methods

Background Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. Methods We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti–interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was