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Objective.To assess the validation status of echocardiography with continuous Doppler (echo-Doppler) as an outcome measure in pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc).Methods.Structured literature review on full-text English articles was performed using the PubMed and Cochrane databases. Assessment of validation of echo-Doppler was based on the OMERACT filter criteria with the domains truth (face, content, construct, and criterion validity), discrimination, and feasibility.Results.Out of 35 studies eligible for analysis, only 5 included well defined PAH-SSc subgroups (World Health Organization criteria). Echo was considered as having face validity based on expert opinion and high number of studies using echo for evaluation of patients with SSc. Echo was considered partially validated with respect to criterion validity based on significant correlations between echo measures and right-heart catheterization in patients with SSc at risk of PAH/PH. However, echo was found to lack specificity (lack of content validity), since measurements of echo pulmonary pressure may be influenced by left-heart disease and interstitial lung disease. Data from general populations of patients with scleroderma indicate that evaluation of pulmonary artery pressure by echo might not be available in all PAH-SSc patients because of technical factors. No studies enabling evaluation of the discriminant capacity over time and treatment of echo in PAH-SSc could be identified.Conclusion.Further studies are needed to fully validate echo-Doppler as an outcome measure in PAH-SSc. These studies would include cross-sectional analysis of baseline measures and longitudinal data of placebo and verum groups in randomized controlled trials of patients with PAH-SSc.

Objectives. Etanercept, a recombinant TNF receptor fusion protein, has been approved for the treatment of resistant polyarticular course juvenile idiopathic arthritis at a dosage of 0.4 mg/kg twice weekly in children older than 4 years. In adult patients, efficacy and safety of etanercept 25 mg twice weekly was comparable with 50 mg once weekly. Therefore, safety and efficacy of etanercept once weekly 0.8 mg/kg up to 50 mg s.c. was evaluated in a 3 month open label trial. Methods. Twenty patients 4 to 17 years old received 0.8 mg of etanercept per kilogram of body weight subcutaneously once weekly for 3 months in an open multicentre trial. Active polyarticular disease was defined by the presence of five or more active joints with swelling, alternatively with pain or tenderness combined with limitation of motion. Safety assessments were based on adverse events (AEs) reports. Efficacy was assessed using the PedACR30/50/70 criteria. Results. At the start of treatment the patients showed high disease activity. A rapid reduction of all disease activity parameters was observed. A PedACR30/50/70 response was reached by 75%/35%/10% of patients after 4 weeks, 90%/75%/35% after 8 weeks and 95%/75%/75% after 12 weeks of treatment. There were 37 AEs, none of them serious, with injection site reactions and minor infections being the most frequent. There was no drop out. Long-term follow-up of the patients will be carried out in the German JIA Registry. Conclusion. Treatment with etanercept once weekly using a double dosage leads to a significant improvement of disease activity in patients with active polyarticular course juvenile idiopathic arthritis and is well tolerated.

Juvenile systemic sclerosis is an orphan disease with an incidence of around 0.05 per 100,000 children. The mean age of onset is approximately 8 years, and 90% of pediatric patients have a diffuse subset. The organ involvement of pediatric patients differs from adult patients. Survival rates are significantly better in pediatric patients than in adult patients. Most patients who die in the first 5 years of the disease have a diffuse subset. Interestingly, the disease subset shifts when pediatric patients are reviewed in adult cohorts of systemic sclerosis patients, in which only around 40% of patients have diffuse subset. The pediatric-onset patients still have a low prevalence of anticentromere antibodies. There is a larger group of patients with overlap features in juvenile systemic sclerosis than in adult cohorts. There are also noticeable differences in organ involvement.

There have been steady efforts to develop a combined response index for systemic sclerosis (CRISS). A parallel and equally successful effort has been made by an Expert Panel on Outcome Measures in PAH related to Systemic Sclerosis (EPOSS) to measure effect in treatment of pulmonary arterial hypertension of systemic sclerosis (PAH-SSc). CRISS conducted a Delphi process combined with expert review to identify 11 candidate domains for inclusion in a core set of outcomes for SSc clinical trials: soluble biomarkers, cardiac, digital ulcers, gastrointestinal, global health, health related quality of life (HRQOL) and function, musculoskeletal, pulmonary, Raynaud’s, renal, and skin. Tools within domains were also agreed upon. Concentrating on one aspect of disease, PAH, EPOSS also conducted a Delphi process and judged the following domains as the most appropriate for randomized controlled trials in PAH-SSc: lung vascular/pulmonary arterial pressure, cardiac function, exercise testing; severity of dyspnea, discontinuation of treatment; quality of life/activities of daily living; global state; and survival. Possible useful tools within each domain were also agreed on. Patient derived, physician derived, and objective measures of response will be included and combined with the idea that each reflects different aspects of PAH (EPOSS) and overall disease (CRISS) although this assumption may not prove true and can be separated if statistically and clinically valid to do so. In either case, prospective studies will require measurement of all domains, and tools are required and will be developed to define appropriate combined measures of response. CRISS and EPOSS are being developed through the OMERACT process. Through Delphi process and literature review significant progress has been made for both indices, and prospective data are being collected.

The CD4 molecule is a relatively non-polymorphic 55 kDa glycoprotein expressed on a subset of T lymphocytes. A common African allele of CD4 has been identified by non-reactivity with the monoclonal antibody, OKT4. The genetic basis for the OKT4 − polymorphism of CD4 is unknown. In the present paper, the structure of the CD4 molecule from an homozygous CD4 OKT4− individual was characterized at the molecular level. The size of the CD4 OKT4− protein and mRNA were indistinguishable from those of the OKT4 + allele. The polymerase chain reaction (PCR) was used to map the structure of CD4 OKT4− cDNAs by amplifying overlapping DNA segments and to obtain partial nucleotide sequence after asymmetric amplification. PCR was then used to clone CD4 OKT4− cDNAs spanning the coding region of the entire, mature CD4 protein by amplification of two overlapping segments followed by PCR recombination. The nucleotide sequence of CD4 OKT4− cDNA clones revealed a G → A transition at bp 867 encoding an arginine → tryptophan substitution at amino acid 240 relative to CD4 OKT4+ . Expression of a CD4 OKT4− cDNA containing only this transition, confirmed that the arginine → tryptophan substitution at amino acid 240 ablates the binding of the mAb OKT4. A positively charged amino acid residue at this position is found in chimpanzee, rhesus macaque, mouse and rat CD4 suggesting that this mutation may confer unique functional properties to the CD4 OKT4− protein.

ObjectiveTo compare the efficacy and safety of celecoxib and naproxen in children with juvenile rheumatoid arthritis (JRA).MethodsIn this multicenter, randomized, double-blind, noninferiority study, subjects with JRA were randomized to receive a target dose of celecoxib 3 mg/kg bid or 6 mg/kg bid, or a target dose of naproxen 7.5 mg/kg bid for 12 weeks (maximum allowed dose = 600 mg total daily dose). The primary efficacy measure was the percentage of responders at Week 12 attaining the American College of Rheumatology pediatric 30% improvement criterion (ACR Pediatric-30).ResultsBoth celecoxib doses were at least as effective as naproxen at Week 12 [ACR Pediatric-30 treatment differences: celecoxib 3 mg/kg bid – naproxen = 1.36% (95% CI –13.08 to 15.80); celecoxib 6 mg/kg bid – naproxen = 13.02% (95% CI –0.22 to 26.25)]. Celecoxib 6 mg/kg bid had a numerically higher response rate than celecoxib 3 mg/kg bid at all postrandomization visits and a numerically higher response rate than naproxen 7.5 mg/kg bid at Weeks 4, 8, and 12. Improvement in each ACR Pediatric-30 core set measure was comparable to or numerically higher for celecoxib 6 mg/kg bid than naproxen or celecoxib 3 mg/kg bid. Adverse event rates were similar for all treatment groups, except that gastrointestinal adverse events were more common in the naproxen group, although the difference was not statistically significant.ConclusionCelecoxib 3 mg/kg bid and 6 mg/kg bid were at least as effective as naproxen 7.5 mg/kg bid in treating the signs and symptoms of JRA over 12 weeks. All treatments were generally well tolerated.

Methods 190 JIA patients were treated with abatacept for 4 months in an open-label lead-in period (Period A). ACR Pedi 30 responders (n = 123) were then randomized 1:1 to receive abatacept or placebo for up to 6 months in a double-blind withdrawal period (Period B). HRQOL was assessed by the Child Health Questionnaire (CHQ), sleep quality was measured by the Children's Sleep Habits Questionnaire (CSHQ), and pain by a 0–100 mm VAS. Mean change from baseline in each period was calculated and compared between the treatment groups (in Period B), and the change over time was examined.

Methods At each study site an independent ethics committee approved the protocol, and each patient's parent gave written informed consent (EudraCT No. 2007-00025534). 20 patients 4 to 17 years old were included and received 0.8 mg/kg bw. of etanercept subcutaneously once weekly for 12 weeks "Active" polyarticular disease was defined by the presence of five or more active joints. PedACR30/50/70 criteria were calculated.

Purpose of review Aim of the review is to summarize the current knowledge about clinical presentation and prognosis of patients with juvenile onset systemic sclerosis and compare it with that of those with adult onset systemic sclerosis. Recent findings Juvenile onset systemic sclerosis and adult onset systemic sclerosis have a different subtype and organ involvement pattern of the juvenile onset patients in the pediatric age is compared with that of adult patients. The juvenile onset patients have 90% diffuse subset, despite a 5-year survival of around 90%. The organ involvement pattern in both the groups becomes equal over the disease duration, but renal involvement is rare. The subset pattern equalizes over time too; the adult-aged juvenile onset patients have the same disease subset distribution, with around 40% diffuse subset patients, as the young adult onset patients, and this presents a survival bias presumably. The survival even after 20-year disease course seems more favourable for the juvenile onset patients. Summary Currently we are looking at two time windows: one at the first 5 years of the disease and the second at 20 years after the onset. We do not have the data on why and when the subset distribution changes occur.

Uveitis occurs in 10%-15% of patients with juvenile idiopathic arthritis (JIA). If topical treatment fails, second-line agents are used to control the disease. However, some patients need the addition of tumor necrosis factor-alpha (TNF-alpha) antagonist (anti-TNF). We organized a cross-sectional cohort to investigate use and efficacy of anti-TNF treatment in patients with JIA-associated uveitis.The international pediatric rheumatology community was queried about the use and efficacy of anti-TNF in treatment of JIA-associated uveitis using an E-mail survey.Of the 33 responding centers following 884 patients with uveitis, only 15 centers, following 404 patients, were using anti-TNF for this indication. A total of 47 patients with JIA-related uveitis treated with anti-TNF because of an insufficient response to previous therapy were reported. The mean age of the patients was 12.5 years. The mean duration from onset of uveitis to start of anti-TNF treatment was 45.1 months. Three different anti-TNF agents were used: etanercept in 34 cases, infliximab in 25 cases, and adalimumab in 3 cases. In 12 of the 34 patients etanercept was inefficacious and patients were switched to infliximab. The final response was rated according to a composite index as 53%/12%/32%, and according to physician rating as 47%/12%/38% representing good, moderate, and poor, respectively, in the etanercept group; and 70%/30%/0% and 68%/24%/0% in the infliximab group. All 3 patients taking adalimumab were responders. Infliximab was statistically significantly more efficacious for the treatment of JIA-associated uveitis than etanercept (chi-square p = 0.004).Anti-TNF seems to be an effective treatment for refractory JIA-associated uveitis. In this cohort infliximab was more efficacious than etanercept.

Objective To develop criteria for the classification of systemic sclerosis (SSc) in children (juvenile SSc). Methods The study consisted of 3 phases: 1) collection of data on the signs and symptoms of actual patients with juvenile SSc that are useful for defining involvement of a particular organ; 2) selection of the parameters essential for the classification of juvenile SSc and preparation of a set of provisional classification criteria (PCC) using 2 Delphi surveys; 3) consensus conference consisting of 2 steps: discussion and rating of clinical profiles of 160 patients with definite juvenile SSc, possible juvenile SSc, or other fibrosing diseases as “having or not having juvenile SSc,” using nominal group technique, and defining those PCC with the best statistical performance and highest face validity by using the clinical profiles of patients with definite juvenile SSc as the gold standard. Results In phase 1, 55 centers submitted clinical data on 153 patients with juvenile SSc. A total of 48 signs and symptoms were derived from these patient data and were used to define 9 organ system categories (cutaneous, vascular, gastrointestinal, respiratory, renal, cardiac, neurologic, musculoskeletal, and serologic). During phase 2, these were reduced to 21 criteria (3 major criteria [Raynaud's phenomenon, proximal skin sclerosis/induration of the skin, and sclerodactyly] and 18 minor criteria) and combined to generate 86 different PCC. At the consensus conference, these 86 definitions were tested on the case profiles of 127 patients with juvenile SSc. The PCC with the highest ranking were proximal sclerosis/induration and at least 2 minor criteria. Conclusion These provisional classification criteria for juvenile SSc will help standardize the conduct of clinical research, epidemiologic and outcome studies, and therapeutic trials.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:28:15Z No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Made available in DSpace on 2014-02-26T17:28:15Z (GMT). No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Previous issue date: 2007-02-15 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:29:57Z No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Made available in DSpace on 2014-05-20T15:29:57Z (GMT). No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Previous issue date: 2007-02-15 Objective. To investigate the proxy-reported health-related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).Methods. In this multinational, multicenter, cross-sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.Results. A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 +/- 10.6 versus 54.6 +/- 4.0, P < 0.0001; psychosocial: 47.6 +/- 8.7 versus 51.9 +/- 7.59 P < 0.0001), with the physical well-being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score > 1 and a pain intensity rating > 3.4 cm on a 10-cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.Conclusion. We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well-being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health. Univ Genoa, Pediat Rheumatol Int Trials Org, IRCCS G Gaslini, I-16147 Genoa, Italy IRCCS G Gaslini, Serv Epidemiol & Biostat, Genoa, Italy Hop Necker Enfants Malad, Paris, France Univ Estadual Paulista, Botucatu, SP, Brazil Princess Margaret Hosp Children, Perth, WA, Australia Hanyang Univ, Med Ctr, Hosp Rheumat Dis, Seoul 133791, South Korea Univ Ziekenhuis Gent, Ctr Kinderreumatol, Ghent, Belgium Allgemeines Krankenhaus Eilbeck, Hamburg, Germany Inst Nacl Rehabil, Mexico City, DF, Mexico Wilhelmina Childrens Hosp, Utrecht, Netherlands Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland Fac Med 1, Prague, Czech Republic Gen Fac Hosp, Prague, Czech Republic Inst Madrileno Salud, Madrid, Spain Aristotle Univ Thessaloniki, Ippokration Gen Hosp, Thessaloniki, Greece Hop Univ Geneva, Geneva, Switzerland RAMS, Inst Rheumatol, Moscow, Russia Cerrahpasa Tip Fak, Istanbul, Turkey Cleveland Clin Fdn, Cleveland, OH 44195 USA HealthActCHQ, Boston, MA USA Univ Genoa, IRCCS G Gaslini, Genoa, Italy Univ Estadual Paulista, Botucatu, SP, Brazil

Publisher Summary This chapter discusses the epidemiology, diagnostic investigations, differential diagnosis, and treatment of juvenile systemic sclerosis (jSSc). It is a rare autoimmune disease of childhood, with a progressive course, and with a potentially fatal outcome. jSSc is characterized by cutaneous and visceral fibrosis. The disease shows a progressive course with a long-term fatal outcome. The clinical presentation of jSSc differs from the adult disease; limited subtype and CREST (calcinosis, Raynaud, esophageal dysmotility, sclerodactily, teleangiectasia) syndrome are rare. It is important to evaluate the patients regularly for internal organ involvement, in order to introduce the therapy as early as possible. There is no causal therapy for jSSc, but there is a large progress in the treatment of pulmonary hypertension. The diagnostic investigations involve radiological, functional, biochemistry, serology, or immunology. A medication to control the disease globally is not yet available: cyclophosphamide seems to be partially effective and autologous bone marrow transplantation seems to offer an effective rescue, if it is done before significant organ damage occurs. Physiotherapy plays an important role to decrease joint contracture and to keep up stamina.

Background Nailfold capillaroscopy is a useful investigation to identify patients with Raynaud9s phenomenon secondary to systemic sclerosis (SSc) because typical capillary changes can be clearly demonstrated in adults as well as in children. However, in juvenile-onset SSc the overall capillaroscopic pattern is called “scleroderma pattern”, the classification in “early”, “active” and “late” pattern (1) has never been applied, and differences in microvascular abnormalities between juvenile- and adult-onset SSc have never been explored. Objectives Microvascular abnormalities described as qualitative overall patterns by nailfold capillaroscopy in patients with juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods Data collected between June 2004 and April 2013 in the EUSTAR registry were examined with focus on capillaroscopy. In this case-control study, adult patients with juvenile-onset SSc with available data on capillaroscopy were matched with corresponding patients with adult-onset SSc having the same gender and autoantibody profile. Patients aged ≥65 year-old at disease onset were excluded. Results 30 adult patients with juvenile-onset SSc and 2108 patients with adult-onset SSc were included in the analysis. The mean age at the visit of patients with adult- and juvenile-onset SSc was 52.91±12.6 and 29.56±10.71 year-old respectively. Mean age at the onset of Raynaud9s phenomenon was 38.60±12.23 year-old in adult-onset and 11.36±5.12 year-old in juvenile-onset SSc. Similar distribution of modified Rodnan skin score between adult- and juvenile-onset SSc was observed (8.85±7.88 and 10.25±9.74 respectively). The majority of patients had a scleroderma pattern and it was equally distributed among early, active and late pattern in juvenile-onset SSc and adult-onset SSc. Results of univariate analysis showed that in patients with juvenile-onset SSc showed the presence of scleroderma pattern more frequently than adult-onset SSc (OR=2.44, p=0.17), even if not significant. No difference was observed in the distribution of early, active and late pattern between the two groups (OR estimates are near 1.0). Juvenile-onset SSc and adult-onset SSc shared similar capillaroscopy patterns and organ involvement, except for a slightly decreased frequency of oesophageal involvement (46.66% vs 66.22%) and increased lung fibrosis assessed by HRCT (18.13% vs 42.85%) in juvenile-onset SSc (OR=0.46 p=0.04 and OR 2.97, p=0.009 respectively). Conclusions This study is the largest series of adult patients with juvenile-onset SSc in which capillaroscopy has been performed and classified using the three qualitative patterns usually applied in adult-onset SSc. We showed that the microvascular involvement documented by nailfold capillaroscopy patterns in adulthood was similar in patients with juvenile- and adult-onset SSc. The possibility to use the same classification in three patterns applied in adults may be useful to standardise this examination. References Cutolo M, Pizzorni C, Tuccio M, Burroni A, Craviotto C, Basso M, et al. Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis. Rheumatology (Oxford). 2004;43(6):719-26. Disclosure of Interest None declared

Background Systemic juvenile idiopathic arthritis (sJIA) is a severe categori of JIA, which includes systemic features such as fever, rash, elevated inflammatory markers along with poly-arthritis. It is frequently resistant to treatment. Until recently, patients were treated mainly with large doses of glucocorticoids. Breakthroughs in understanding the pathogenesis of sJIA have led to the evaluation of biologics, which block the pro-inflammatory cytokines interleukin (IL)-1 or IL-6 and their receptors. Objectives To define the optimal biological agent for sJIA based on safety and efficacy data from randomised controlled trial (RCT). Methods Through a systematic literature search, sJIA RCTs evaluating biological agents were identified. The primary efficacy outcome was defined as 30% improvement according to modified JIA American College of Rheumatology response criteria (JIA ACR30). The primary safety outcome was defined as serious adverse events (SAEs). Outcomes were analysed by pairwise and network meta-analyses. Quality of evidence between biological agents was assessed by applying the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Results From the 493 citations original identified, 5 RCTs were eligible for inclusion – one for each of anakinra, canakinumab, and tocilizumab, and two for rilonacept: all vs. placebo. The canakinumab trial distinguished itself from the other trials, as it included patients having high systemic involvement and low joint involvement. Conversely, the tocilizumab trial included patients with more joint involvement compared with most other trials. While all evaluated biological agents were effective, the network meta-analysis indicated with low-quality evidence (due to indirect comparison and inconsistency) that rilonacept-treated patients were less likely to respond than those treated with canakinumab (modified JIA ACR30: odds ratio 0.10 [95%CI 0.02 to 0.38], P =0.001) or tocilizumab (0.12 [0.03 to 0.44], P =0.001). Risks of SAEs were similar among the biological agents (supported by very low-quality evidence) and not different from placebo. Conclusions Despite heterogeneous eligibility criteria and study designs across the 5 studies, and different modified JIA ACR30 criteria, this meta-analysis of short-term RCTs presents empirical evidence that canakinumab and tocilizumab are more effective than rilonacept. Our study also indicated that canakinumab should be considered mainly in patients with high systemic involvement and limited joint involvement, which to some extent also might be true for anakinra, whereas tocilizumab seems to be appropriate in patients with extensive joint involvement. Biological agents in sJIA seem safe and comparable with respect to SAE risk in the short term. We recognize that further data will be needed before these conclusions can be interpreted with high confidence. Protocol registration PROSPERO CRD42013004736 Acknowledgements We wish to thank The Oak Foundation for supporting the Musculoskeletal Statistics Unit, Parker Institute with unrestricted research grants. Disclosure of Interest S. Tarp Grant/research support from: paid to institute: AbbVie, Bristol-Myers Squibb, Mundipharma, and Roche, Speakers bureau: paid to institute: AstraZeneca, Pfizer, and Norpharma, G. Amarilyo Grant/research support from: Novartis, Consultant for: Novartis, I. Foeldvari Consultant for: Abbott, and Chugai, Speakers bureau: Pifzer, R. Christensen Grant/research support from: paid to institute: Abbott, Axellus, Bayer HealthCare Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Cambridge Weight Plan, Ipsen, Laboratoires Expanscience, MSD, Mundipharma, Norpharma, Pfizer, Roche, and Wyeth, Consultant for: paid to institute: Abbott, Axellus A/S, Bristol-Myers Squibb, Cambridge Weight Plan, Norpharma, Pfizer, Roche, Mundipharma, and Roche, J. Woo: None declared, N. Cohen: None declared, T. Pope: None declared, D. Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, BMS, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: AbbVie, Actelion, and UCB

Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Several publications in adults looked at the differences between limited and diffuse subtypes. There is rarity of data regarding this topic in pediatric jSSc. The juvenile scleroderma inception cohort (www.juvenilescleroderma.com) is a prospective standardized register for patients with jSSc. Objectives Comparison of features of patients with limited jSSc (ljSSc) and diffuse jSSc (djSSc) subtypes at the time of inclusion in the registry Methods Patients with jSSc were included worldwide into the juvenile scleroderma inception cohort. We compared the demographics and clinical features of the ljSSc and djSSc. Results Up till now 39 patients were enrolled, 29 with djSSc and 10 with ljSSc. 5 in the diffuse (17%) and 3 in the limited subtype (30%) had an overlap feature. The mean follow up of the patients in the cohort was 6.4 years in the djSSc and 5.3 years in ljSSc. 76% in the djSSc and 80% in the ljSSc group were female. The mean age at the onset of Raynaud9s Phenomenon was 8.7 years in the jdSSc and 12.9 years in ljSSc group while the mean age at the onset of the first non-Raynaud presentation was 9.1years in djSSc and 13.8 years ljSSc. At the time of the inclusion the mean modified Rodnan Skin Score was 19.6 in the djSSc and 7.5 in ljSSc. 70% of patients in both groups had already capillary changes, but 67% in djSSc and only 33% in ljSSc had already history of ulcerations and 32.1% presented with active ulceration in the djSSc and none in the ljSSc. 72% of djSSc and 50% of ljSSc had cardiopulmonary involvement. The two patients with pulmonary hypertension had djSSc. 27.5% in djSSc and 30% in ljSSc group showed signs of interstitial lung disease on imaging. All 3 patients with renal involvement had djSSc. In both groups 30% had gastrointestinal involvement. Around 80% had musculoskeletal involvement in both subtypes. Anti-Scl 70 positivity was found in 40% of djSSc and 37.5% in ljSSc. Only 1 patient in the djSSc group had anticentromere antibody. Conclusions We present the data on the first 39 patients with jSSc included in our cohort. Patients with djSSc and ljSSc differ in several characteristics. Patients with djSSc were younger at onset, had more often capillary changes and active ulcerations, pulmonary hypertension and renal involvement. The characteristics of the pediatric subtypes differs from adults with SSc. Disclosure of Interest None declared

Background Juvenile localized scleroderma (jLS) is an orphan disease. Only one large survey looked at the prevalence of extracutaneous involvement (EI), but without a standardised assessment protocol. Objectives Aim of our study was to assess retrospectively EI and comorbidities (CM) of patients with jLS. Methods We performed a retrospective chart review of consecutive patients with jLS seen in our centre for paediatric rheumatology from May 1999 until October 2014. We collected information regarding demographics, EI and CM. Results 108 patients were identified. 85 of them had at least one follow up appointment. Mean time of follow- up of the patients was 36.8 months. Mean disease duration to first visit was 50.4 months (n=101). 70 of the 108 patients (64.8%) patients were female. The subset distribution of jLS (n=108) was 28.7% linear scleroderma of the trunk/limbs and 21.3% linear scleroderma of the head (“en coup the sabre”); 24.1% mixed morphea, 9.3% circumscribed superficial morphea, 8.3% generalized, 7.4% circumscribed deep morphea and 0.9% pansclerotic morphea. Mean age at first visit was 12.6 years and 14 patients were older than 18 years old at the time of their first visit. 46 (43%) of the patients showed extracutaneous manifestations. 47 of the 85 were clinically screened for temporomandibular joint arthritis (TMJ) and 9 (19.1%) showed signs of TMJ- arthritis, of these 9 patients had arthritis on clinical exam, 8 on MRI. 3 patients of 72 (4.2%) who were followed and examined by an ophthalmologist developed anterior uveitis. As clinical consequences of the extracutaneous manifestations 5.5% developed lateral trusion at mouth opening, 4.6% decreased mouth opening, 22.2% contractures and 5.5% restricted joint range in non-TMJ. 13% developed length discrepancy of the effected limb and 5.5% leg dystrophy. No patient developed visual impairment. 49 of the 108 patients showed 43 different comorbidities: 7.4% had juvenile idiopathic arthritis, 0.9% rheumatoid arthritis, 6.5% were diagnosed with allergies and 6.5% of atopic eczema, 4% scoliosis, 3.7% migraine and 1.8% hashimoto-thyreoiditis. Conclusions This retrospective analysis shows a high incidence of patients with EI like TMJ- arthritis, arthritis and uveitis. We would recommend regular clinical investigations for assessment of arthritis, especially TMJ- arthritis and uveitis at least 6 monthly, as suggested from the PReS Scleroderma working group. The extracutaneous manifestations were most common in linear scleroderma of the trunk/limbs subtype. Disclosure of Interest None declared

Background Juvenile idiopathic arthritis (JIA) associated uveitis is one of the most severe comorbidities and occurs in around 10% of patients. There are currently no specific established outcome measures for JIA associated uveitis (JIAU). The SUN group made the first attempt to establish outcome measures for uveitis, which were not aimed at JIAU. Adopting part of it, we developed and proposed specific outcome measures for JIAU. Here we are presenting the results of the validation study. Objectives To prospectively validate the proposed outcome measures, if they fulfil the expected OMERACT criteria. Methods Patients were considered eligible, if they started a nonbiologic or biologic disease modifying agent, as indicated by active the uveitis. At baseline, follow up at 3 months and at 6 months following parameters were collected: demographics, rheumatologic assessment (JIA type, activity of arthritis, JIA-related disability), ophthalmologic assessment (duration of uveitis, activity and damage of uveitis, visual acuity, ocular complications, topical and systemic medications, surgical procedure, uveitis-related disability). Results 49 patients were included in the study and 35 patients had a complete follow-up for at least at 6 months. 34/49 (69%) of the patients were female. The mean age at inclusion into the study was 8.4 years (SD=3.4). 98% of the patients were Caucasian. At inclusion the median disease duration of JIA was 52 months for arthritis and 33 months for uveitis. All patients had anterior uveitis. The left eye was more frequently involved (95.3%) then the right eye (81%). Cellcount at baseline was +1 or more in 65.1% of the right eyes and 68.9% of the left eyes, and at 6 months only 22.6% in the right and 19.3% in the left eyes. The cell count before dilatation (p=0.008) and after dilatation (p

Background Juvenile systemic sclerosis (jSSc) is an orphan disease. We have currently new promising effective medication to treat systemic sclerosis, but no valid outcome measures to assess the activity of the disease. Objectives In the frame of the juvenile scleroderma working group of Paediatric Rheumatology European Society (PRES JSWG), we developed a provisional response index for jSSc. Methods The facilitating committee designed a 3-round Delphi-exercise to obtain a core set of disease activity measures in jSSc. In Round 1, they were asked to add unique items in 21 preleminary domains. Round 2 judged the items9 applicability and importance using a 1-10 scale. Previous respondents were asked to re-rate uncertain (score 4-7) items in Round 3. The aforementioned were followed by a face-to-face Nominal Group discussion to decide final items and domain structure. Results 52 participants of Round 1 suggested a total of 131 items for the 21 domains. In round 2, 56 responders rated the significance of the items. The Nominal Group accepted 11 main domains for further validation containing 41 items (see table 1). Conclusions We reached consensus and developed a Response Index, which should help to conduct clinical trials in jSSc. The validation of the JSSRI is planned in the frame of the Juvenile Scleroderma Inception Cohort. Disclosure of Interest None declared

Background Juvenile idiopathic arthritis (JIA) is one of the most common childhood rheumatic diseases. Adalimumab (ADA) is approved for moderate to severe polyarticular JIA (pJIA) in patients (pts) ≥4 yrs in Australia and Japan and for pts ≥2 yrs in the US and EU. Objectives To evaluate long-term safety and effectiveness of ADA in pts with moderately to severely active pJIA who are prescribed and treated with ADA in routine clinical practice. Methods This is an ongoing, multicenter, non-interventional, observational registry of pts with moderately to severely active pJIA who are treated with either ADA ± methotrexate (MTX) or MTX alone as part of their routine clinical care. 800 pts (500 ADA/300 MTX) were to be enrolled in the US, EU, and Australia. The follow-up observational period is 10 yrs from enrollment into one of the treatment arms. Observational adverse events (AEs) were recorded from the first day in the registry through last contact, irrespective of registry treatment duration. Clinical outcomes were assessed by 27-joint juvenile arthritis disease activity score (JADAS27), based on CRP. 5 yr interim data are presented. Results As of January 2014, enrollment is complete. 842 pts (540 ADA/302 MTX) were treated as of the March 28, 2014 cutoff. Mean pJIA disease duration at enrollment was 1.3 and 3.7 yrs and mean duration of study exposure was 643 and 653 days for MTX and ADA arms, respectively. Baseline mean AJC73 was 5.8 and 5.4 for MTX and ADA, respectively, and CHAQ-DI was 0.6 for both groups. Overall, 153 pts (50.7%) in the MTX arm and 132 pts (24.4%) in the ADA arm discontinued registry drug. Of those, 22 (7.3%) and 23 (4.3%) in the MTX and ADA arm, respectively, discontinued due to an AE, and 39 of the 153 pts in the MTX arm discontinued as they switched to the ADA arm. The observational AEs are summarized (Table). No deaths, malignancies, or opportunistic infections were reported. In the ADA arm, there were 13 (2.4%) pts with serious infectious AEs (abdominal abscess, acute tonsillitis, appendicitis, cellulitis, gastroenteritis, mononucleosis, viral meningitis, pneumonia, pyelonephritis, scarlet fever, subcutaneous abscess, tonsillitis, urinary tract infection, and varicella). Frequencies and rates of treatment-emergent AEs were similar to those reported for observational AEs. Mean JADAS27 improved from 12.1 at baseline to 9.4, 6.1, 5.1, 4.4 at months 1, 3, 6, and 12 for pts in the MTX arm and from 12.1 at baseline to 7.4, 5.5, 4.4, 4.5 in the ADA arm, respectively (observed data). Conclusions Overall, ADA is well-tolerated in these pts with active pJIA. No new safety signals were observed, and based on this interim analysis, the known safety profile of ADA remains unchanged. Acknowledgements AbbVie sponsored the study (NCT00783510), contributed with PRINTO and PRCSG to the design, and participated in data collection, analysis, and interpretation, and in the writing, review, and approval of the abstract. Medical writing support was provided by Jessica L. Suboticki, PhD, of AbbVie. Disclosure of Interest N. Ruperto Employee of: GASLINI Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Pharmaceuticals. NR has served on speaker9s bureau for Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, Janssen Biologics B.V., MedImmune, Roche, and Wyeth/Pfizer, H. Brunner Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Boehringer-Ingelheim, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UCB, and Genentech, Speakers bureau: Genentech Pharmaceuticals, C. Wallace Grant/research support from: Pfizer, Amgen, Consultant for: Amgen, Novartis, M. Toth: None declared, I. Foeldvari Consultant for: AbbVie, Novartis, J. Bohnsack Consultant for: Novartis, D. Milojevic Consultant for: Genentech, Novartis, E. Rabinovich Grant/research support from: UCB Pharma, Janssen Research & Development, LLC, Hoffmann-La Roche Inc., AbbVie, P. Vavrincova: None declared, D. Kingsbury Grant/research support from: AbbVie, K. Marzan Grant/research support from: AbbVie, P. Quartier Grant/research support from: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, Swedish Orphan Biovitrum; Participates on a data management committee of a phase 3 trial by Sanofi, Consultant for: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, Swedish Orphan Biovitrum, K. Minden Grant/research support from: Pfizer, Abbvie, Consultant for: Pfizer, Abbvie, Roche/Chugai, Novartis, Medac, Pharm-Allergan, Speakers bureau: Pfizer, Abbvie, Roche/Chugai, Novartis, Medac, Pharm-Allergan, E. Chalom Speakers bureau: AbbVie, G. Horneff Grant/research support from: AbbVie, Pfizer, and Roche and speaker9s fees from AbbVie, Novartis, Pfizer, Roche, R.-M. Kuester Grant/research support from: AbbVie, Wyeth/Pfizer, J. Dare Grant/research support from: AbbVie, AstraZeneca, Bristol-Myers Squibb, Horizon Pharma, Medac GmbH, UCB Biosciences, M. Bereswill Shareholder of: AbbVie, Employee of: AbbVie, H. Kupper Shareholder of: AbbVie, Employee of: AbbVie, J. Kalabic Shareholder of: AbbVie, Employee of: AbbVie, A. Martini Employee of: GASLINI Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals, Speakers bureau: Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, MedImmune, D. Lovell Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma, Genentech; served on data and safety monitoring boards for Amgen, Forest Research, Speakers bureau: Wyeth Pharmaceuticals

OBJECTIVE: To determine the clinical and immunologic features of systemic sclerosis (SSc) in a large group of children and describe the clinical evolution of the disease and compare it with the adult form. METHODS: Data on 153 patients with juvenile SSc collected from 55 pediatric rheumatology centers in Europe, Asia, and South and North America were analyzed. Demographic, clinical, and immunologic characteristics of children with juvenile SSc at the onset, at diagnosis, and during the disease course were evaluated. RESULTS: Raynaud's phenomenon was the most frequent symptom, followed by skin induration in approximately 75% of patients. Musculoskeletal symptoms were present in one-third of patients, and the most frequently involved internal organs were respiratory and gastrointestinal, while involvement of renal, cerebral, and cardiovascular systems was extremely rare. Antinuclear antibodies were present in the sera of 81% of patients. Anti-topoisomerase I (Scl-70) and anticentromere antibodies were found to be positive in 34% and 7.1% of patients, respectively. Involvement of the respiratory, gastrointestinal, and cardiovascular systems was more frequent and occurred earlier in patients who died than in those who survived. Compared with the adult form, juvenile SSc appears to be less severe, with the involvement of fewer internal organs, particularly at the time of diagnosis, and has a less characterized immunologic profile. CONCLUSION: This study provides information on the largest collection of patients with juvenile SSc ever reported. Juvenile SSc appears to be less severe than in adults because children have less internal organ involvement, a less specific autoantibody profile, and a better long-term outcome.

The scleroderma research community continued its focus on the development and proper validation of the outcome measures for clinical trials in scleroderma during the special interest group meeting at OMERACT 7. Deliberations focused on progress in the assessment of gastrointestinal disease, renal physiology, vascular damage, and the unique challenges inherent in studying pediatric patients with scleroderma.

To assess the effectiveness of methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) associated uveitis, which is still one of the most common causes of visual impairment.A retrospective chart review of patients with the diagnosis of uveitis associated with JIA between July 1, 2002, and December 31, 2002.Four hundred sixty-seven patients with JIA were followed. Thirty-eight had uveitis: 31 associated with oligoarticular JIA and 7 with psoriatic JIA. Twenty-five of the 38 patients received MTX; in 23 patients uveitis was the indication for MTX therapy. In the MTX treated group 46/50 eyes had uveitis, the mean (range) age at onset of uveitis was 7.82 years (1.8-15.8), and the mean age at onset of arthritis was 7.25 years (1.25-15.7). MTX treatment was started an average of 11.4 months (0-72) after the onset of uveitis. The mean MTX dose was 15.6 mg/m2. Remission occurred after 4.25 months (1-12). Mean duration of remission was 10.3 months (3-27). The total duration of MTX therapy was 661 months and patients were in remission for 417/661 months. In 6 patients MTX was discontinued after 12 months of remission. Four patients were still in remission after 7.5 months (1-14).MTX seems to be an effective therapy for JIA associated uveitis.

To describe a registry set up to monitor children treated with etanercept in Germany and Austria.Giannini's criteria, duration of morning stiffness, number of swollen, tender and contracted joints, adverse events, and reasons for discontinuation were assessed.322 patients with juvenile idiopathic arthritis (JIA) and 12 additional patients with non-JIA rheumatic diagnoses were included. Therapeutic efficacy was observed from one month after treatment was started. The number of patients with significant improvement and the degree of improvement increased during the first year. The mean (SD) number of tender and swollen joints decreased from 9 (9) and 8.4 (9) to 3.0 (6.5) and 4.5 (7) after one month, and to 2.2 (5.5) and 3.3 (5.5) after three months; morning stiffness decreased from 45 (65) minutes to 12 (30) and 7 (19) after one and three months (p0.001 for all). Using Gianinni's criteria of 30%, 50%, and 70% improvement, a therapeutic response in JIA patients was achieved in, respectively, 66%, 54%, and 30% after one month, 78%, 61%, and 38% after three months, and 83%, 72%, and 52% after six months. Therapeutic efficacy was lower in patients with systemic onset arthritis. Overall tolerability was good: in 592 patient treatment-years there were 69 reports of adverse events in 56 patients, including one CNS demyelination. There were no opportunistic infections or lupus-like reactions. Treatment was discontinued in 53 JIA patients, in 25 because of lack of efficacy.Etanercept treatment was safe and led to a significant improvement in most JIA patients resistant to conventional treatment.

A child with idiopathic systemic capillary leak syndrome had four episodes between 3 and 3 years 9 months of age, all characterized by the sudden onset of hypovolemic shock without any obvious triggering factor. Between the attacks she is well and free of symptoms. Early establishment of intravenous access facilitates volume replacement during the acute episodes.

Use of meloxicam as a selective COX-2 inhibitor for treatment of adult rheumatic diseases decreases the frequency of gastrointestinal (GI) side effects in comparison with nonselective COX inhibitors. Up to 50% of children with juvenile rheumatoid arthritis (JRA) also develop GI side effects through nonselective COX inhibitors. In this 12 week Phase I/II study, with an additional open extension lasting up to 52 weeks, the safety, efficacy, and pharmacokinetics of meloxicam in JRA were investigated.Meloxicam suspension 0.25 mg/kg once daily was given to 36 patients with JRA who required a nonsteroidal antiinflammatory drug. Safety evaluation and periodic measurement of efficacy were carried out using the Pediatric Rheumatology International Trials Organisation (PRINTO) criteria. Eighteen patients underwent pharmacokinetic (PK) evaluation.Thirty-one patients completed the study. Four were dropped due to administrative reasons. One patient, who found the drug ineffective, discontinued participation. A response was seen according to PRINTO outcome criteria in 44% of the patients at Week 4, 62% at Week 12, and 74% at Week 52. Drug related adverse events were observed in 5 patients. PK evaluation showed that the maximum plasma concentration Cmax of -34% and AUC(0-infinity) of -28% tended to be lower in younger children (2-6 years) versus older children. Plasma elimination half-life (13 h) was similar in all patients.Meloxicam suspension 0.25 mg/kg once daily seems to be effective and safe for treating active JRA over a period of 52 weeks.

There are currently no agreed recommendations on how to investigate children for gastrointestinal (GI) involvement in Juvenile Systemic Sclerosis (JSSc). The aim of screening is to detect disease early to facilitate early aggressive therapy and improve outcomes. GI involvement at diagnosis incurs a worse outcome [1]. Most deaths occur early in the disease course [1, 2].

Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Currently just retrospective data exist regarding evolvement of organ involvement. In the previous retrospective studies assessment of the organ involvement was not standardized. Our project is the first one, where data of jSSc patientes were collected prospectively and with a standardized assessment. Objectives To learn about the characteristics and evolvement of organ involvement in jSSc Methods Patients with jSSc were recruited worldwide and were prospectively assessed, using the proposed standardized patient assessment protocol. Data of the juvenile systemic sclerosis inception cohort have been contributed to the DeSScipher project which was funded by a grant of theEuropean Community9s Framework Programme 7 under grant agreement N° 305495.” Results 44 centers from 24 countries aggreed to participate on the project. The assent and consent forms were translated into the local native languages. Untill now 39 patients have been enrolled with a mean disease duration of 6.1 years. Thirty (77%) of the 39 patients were females. The mean age of the onset of Raynaud9s phenomenon was 9.7 years (2-16 years), the youngest 2 years old. The mean age at the onset of the non-Raynaud presentation of jSSc was 10.3 years (3.0-16.00years). 29 (74%) of the 39 have diffuse subtype. 5 in the diffuse (17%) and 3 in the limited subtype (30%) had an overlap feature. At the time of the inclusion the mean modified Rodnan Skin Score was 16.5. 26/37 had already capillary changes and 22/37 already history of ulcerations, 9/37 had active ulcerations at the time of the inclusion. 26/39 had cardiopulmonary involvement, 11/39 presented with signs of interstitial lung disease on imaging. Two patients had pulmonary hypertension. Three had renal involvement, but no renal crisis. 16/39 had gastrointestinal involvement and 11 of them esophageal involvement. 30/38 had musculoskeletal involvement. ANA positivity occurred in 30/36 and 12/30 of them were anti-Scl 70 positive. 1/23 had anticentromere positivity. Conclusions We present the data on the first 39 patients with jSSc included in our cohort. The current recruitment data confirms that pediatric patients are different from the adult patients, with a higher proportion of diffuse subset patients with 74% and of patients with overlap features. Disclosure of Interest None declared

Background Juvenile onset systemic sclerosis is thought to have distinct features compared to adult onset systemic sclerosis (SSc). There is currently little data on patients with juvenile onset of Raynaud9s phenomenon who subsequently develop SSc. Objectives To examine the characteristics of subjects in an adult cohort of SSc who developed juvenile onset Raynaud9s (JoR), defined as onset of Raynaud9s prior to the age of 16 years. Methods Data from patients registered in a Canadian adult SSc cohort were extracted. Baseline registry demographic, clinical and serological characteristics of patients with JoR were compared to those with adult onset Raynaud9s (i.e. onset after the age of 16 years; AoR). Chi-squared tests, Fisher9s exact tests and Mann Whitney U tests were used as appropriate. Kaplan Meier curves and Cox proportional hazard models were generated to compare survival of JoR and AoR subjects. P-values less than 0.05 were considered significant. All statistical analyses were performed with SAS v.9.2 (SAS Institute, USA). Results There were 78 JoR and 1311 AoR subjects. The proportion of females was similar in JoR (86%) and AoR (87%). Mean age of onset of Raynaud9s was 12.1±3.1 years in JoR compared to 42.8±13.5 years in AoR. Mean age of onset of the first non-Raynaud9s disease symptom was 28.8±16.0 years in JoR compared to 45.8±12.8 years in AoR. Mean disease duration at cohort entry was 16.7±12.3 years in JoR compared to 10.2±9.2 years in AoR. Limited cutaneous disease was more common in JoR compared to AoR (71.8% vs 63.1%, p=0.121), although anti-centromere antibodies were less common in JoR compared to AoR (24.2% vs 35.6%, p=0.060). Pulmonary hypertension was significantly less common in JoR compared to AoR (4.0% vs 18.3%, p=0.004). Scleroderma renal crisis was present equally in JoR and AoR (6.5% vs 4.8%, p=0.423), although anti-RNA polymerase III antibodies were significantly less common in JoR compared to AoR (4.4% vs 18.2%, p=0.016). Interstitial lung disease (35.9% vs 42.9%, p=0.222) and anti-topoisomerase I antibodies (18.2% vs 15.4%, p=0.546) were present equally in JoR and AoR. The prevalence of digital ulcers (26.9% vs 28.2%, p=0.804) and the number of gastrointestinal symptoms (4.2±3.2 vs 4.2±3.1, p=0.766) were also similar in JoR and AoR. HAQ (0.6±0.7 vs 0.8±0.7, p=0.005) and SF-36 PCS scores (42±12.1 vs 37.5±11.3, p=0.001) were significantly better in JoR compared to AoR. During follow up, 5/71 (7.0%) JoR and 185/1109 (16.7%) AoR subjects died. In unadjusted analysis, survival was significantly better in JoR compared to AoR subjects (log-rank p Conclusions Patients with juvenile onset Raynaud9s have distinct clinical profiles and better survival compared to those with onset of Raynaud9s after the age of 16 years. However, there was considerable uncertainty around the estimates and survival bias may have contributed to the results. Further studies in large samples of subjects with incident disease are needed to confirm these results. This contributes to the rationale for the emerging INSYNC (INternational Systemic sclerosis iNception Cohort) inception cohort. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2521

Background Remission and minimal disease activity have been proposed as treatment goal as both can be achieved. For both JADAS based definitions have been proposed. Methods This retrospective analysis used data of the German BIKER-registry the course of JADAS10 (Physician global assessment VAS 0–10-cm, Parent/patient global assessment VAS 0–10-cm, Active joint count 0-71, truncated at 10, normalized ESR [ESR-20/10], range 0-40) upon first biologic regimen. A JADAS Results 2111 JIA pts starting a first biologic were identified. 1830 received Etanercept (ETA), 209 Adalimumab (ADA) and 33 Tocilizumab (TCZ). Biologics not approved for first line therapy (Abatacept, Anakinra, Infliximab, Golimumab) were used in of 39 pts only. Therefore analysis of the latter patient cohorts seemed not reasonable. Baseline parameters differed for the chosen drugs group. Patients receiving ADA first more often have had chronic uveitis and were more often ANA positive. Age at onset, disease duration, distribution of JIA categories and pretreatments were comparable between ETA and ADA, while TCZ was used more frequently in systemic JIA (table 1). Disease activity indicators at baseline were highest in the ETA group followed by TCZ and lowest with ADA. ESR& CRP were highest in TCZ starters. Upon treatment, the median JADAS decreased in all JIA categories. After 12 months on treatment with ETA, depending of the JIA categories, 28% to 42% of pts had a JADAS Conclusions ETA is by far the most frequently used biologic in JIA pts. ADA is preferred in pts with a history of uveitis, while TCZ is preferred in systemic JIA. Minimal disease activity is reached by the majority of pts but remission only by a part. In summary, a treat to target approach seems reasonable in JIA patients. New therapeutic options are needed for JIA patients with refractory disease. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2336

Background Physical activity (PA) is essential for the social, emotional, and cognitive development of children and adolescents. There is limited knowledge on PA in patients with juvenile idiopathic arthritis (JIA). It is of clinical relevance to what degree JIA patients are physically active despite their disease-related functional limitations. Objectives To describe PA, to assess the relationship between PA and the burden of illness, and to analyse the trend over time regarding PA of adolescents with JIA. Methods Cross-sectional data of adolescents with JIA recorded in the national pediatric rheumatological database in the years 2000 to 2012 were considered for the analyses. PA was defined as doing sport at least three days a week. The data of the year 2012 were used to describe the frequency and duration of PA in adolescents, its influencing factors were analysed by linear regression. Whether PA had changed between 2000 and 2012 was determined using linear mixed models by West, Welch and Galecki. Results In 2012 a total of 2,641 adolescents with JIA (females 64%, mean disease duration 4 years) aged 13 to 17 were recorded. About 39% of the participants were physically active (32% girls, 50% boys). Significant differences regarding the frequency of PA were observed among the various JIA categories: patients with enthesitis-related arthritis were more frequently physically active than patients with rheumatoid factor-positive polyarthritis (47% vs 29%). Regardless of the JIA subtype patients who were physically active rated their functional status, intensity of pain, and overall well-being significantly better than physically inactive patients. Multivariate analysis showed that boys, patients with a low burden of disease and patients with an inactive disease did sports more often. Considering the whole cohort, JIA patients were physically active for a median of three hours per week. During the observation period, participation in physical education at school significantly changed. In 2000 only every 4th adolescent with JIA regularly participated in physical education compared to more than 50% in 2012. Conclusions The current recommendation [1] which advises daily PA of about 60 minutes is fulfilled only by about 40% of the adolescents with JIA. With regard to participation in physical education, a paradigm change took place, leading to fewer children extempted from school sports. References Janssen, LeBlanc (2010). Systematic review of the health benefits of physical activity and fitness in school-aged children and youth. Int. J. Behav. Nutr. Phys. Act. 7:40 Acknowledgements Funding: The National Pediatric Rheumatology Database has been funded by the German Children Arthritis Foundation (Deutsche Kinder-Rheumastiftung). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2562

Background Reaching inactive disease is the main target of therapeutic interventions in juvenile idiopathic arthritis (JIA). Furthermore, attaining a period of inactive disease early in the disease course has been shown to be predictive for the clinical course in the following years. ICON is a prospective longitudinal observation study carried out at 11 paediatric rheumatology centers in Germany where patients with a diagnosis of JIA ( Objectives To assess how many patients attain a state of clinically inactive disease during the first 12 months of paediatric rheumatology care, and to determine the percentage of time they spent with inactive disease during that time. Methods We analysed data of ICON patients who had completed the baseline and 12-month assessment. Inactive disease was defined according to the criteria by Wallace et al., i.e. absence of active arthritis, fever, exanthema, generalized lymphadenopathy, splenomegaly, serositis, active uveitis; normal ESR and physician9s rating of disease activity ≤0.5 (on a 21-point numeric rating scale from 0-10). Survival analysis was applied to calculate the cumulative time the patients spent with inactive disease during the first 12 months after enrollment. Results The analysis considered 488 patients (65% female) with a median age of 6 years at baseline and a median disease duration of 6 months. The population had oligoarthritis (52%), followed by polyarthritis (27%), enthesitis-related arthritis (10%), psoriatic arthritis (5%), and systemic arthritis (3%). Diagnosis of JIA was made two months (median) before baseline. About 3/4 of all JIA patients ever reached a state of inactive disease during the first year of observation with a median time from diagnosis to inactive disease of 8 months (IQR 4 – 11). Patients with systemic JIA reached a period of inactive disease in 93%, whereas patients with enthesitis-related arthritis reached this goal in only 52%. The percentage of time with inactive disease was 36% (mean, SD 34%) in all JIA patients during the first 12 months after enrollment, ranging from 20% (mean, SD 29%) in patients with enthesitis-related arthritis to 45% (mean, SD 30%) in patients with systemic arthritis. At the 12-month follow-up, 260 (53%) patients had an inactive disease of whom 102 (21%) were in remission on medication. Conclusions Under current treatment conditions, the majority of JIA patients reach a state of inactive disease during the first year of paediatric rheumatology care. Significant differences exist between the JIA categories not only in ever reaching a period of inactive disease, but also in the percentage of time the patients spent with inactive disease. Further analysis will show whether attaining inactive disease early in the disease course has an impact on patients9 long-term outcomes in this cohort. Disclosure of Interest C. Sengler: None declared, M. Niewerth: None declared, J. Klotsche: None declared, I. Liedmann: None declared, H.-I. Huppertz: None declared, D. Foell: None declared, G. Horneff Grant/research support: AbbVie, Pfizer, Chugai-Roche, I. Foeldvari: None declared, K. Minden Grant/research support: AbbVie, Pfizer, Consultant for: Pfizer, Abbvie, Roche/Chugai, Novartis, Medac, Pharm-Allergan DOI 10.1136/annrheumdis-2014-eular.4107

Background Due to low incidence rates, treatment data and guidelines in hereditary periodic fevers are limited. To complement published data from the autoinflammatory diseases PRINTO/Eurofever registry, an international noninterventional study of colchicine-resistant familial Mediterranean fever (crFMF), tumor necrosis factor-receptor-associated periodic syndrome (TRAPS), or hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) patients was conducted. Objectives To characterize the patient journey from disease onset to 1st use/eligibility of a biologic. Methods Chart review of adult/pediatric patients with clinically or genetically confirmed disease treated by a specialist (2008-12), with ≥12-mo follow-up post diagnosis. Eligible patients had inadequate response/intolerance to 1st-line treatment and received/were eligible for biologics. Eligible FMF patients had an inadequate response to colchicine as determined by physician (termed crFMF). Results 54 crFMF, 47 TRAPS and 38 HIDs patient records were analyzed. Time from symptom onset to diagnosis: 3.5-12.7 years. Only 33% and 46% of TRAPS and HIDS patients, respectively, received correct diagnosis before expert referral vs 69% with crFMF. Median times from disease onset to initiation of 1st biologic: 6.1 (crFMF), 5.9 (TRAPS) and 1.4 (HIDS) years. Initial and subsequent treatment as provided by specialists is reported here. All crFMF patients received colchicine: 6% subsequently had complete response (CR), 65% partial response (PR) and 29% no response (NR); 31 received 1st biologic plus colchicine (the 3 CR patients were deemed eligible by physician for a biologic due to CR loss, high colchicine dose, or continued severe symptoms). Of 47 TRAPS patients, initially 26 received a biologic; 21, corticosteroids. Of patients on corticosteroids, 34%, 42%, and 24% had CR, PR, and NR, respectively; 3 patients continued and 1 discontinued corticosteroids, and 17 switched to 1st biologic. Of 38 HIDS patients, initially 25 patients received a biologic (with 4 awaiting biologic) and 9 corticosteroids. Of patients on corticosteroids, 11%, 67% and 22% had CR, PR and NR, respectively; 3 patients continued and 6 switched to 1st biologic. Conclusions This analysis supports the need for greater awareness of such diseases, expedited referral to specialized centers, and development of standardized treatment algorithms, definitions of response, and guidelines. Disclosure of Interest S. Ozen Consultant for: Novartis, Speakers bureau: Biovitrium-SOBI, Novartis, J. Kuemmerle-Deschner Consultant for: Novartis, L. Cantarini Grant/research support: Novartis, SOBI, Consultant for: Novartis, SOBI, R. Cimaz: None declared, P. Quartier Grant/research support: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, SOBI, Consultant for: Abbvie, Chugai-Roche, Novartis, Pfizer, Servier, SOBI, Speakers bureau: Chugai-Roche, MEDIMMUNE, Novartis, Pfizer, A. Gul Grant/research support: Novartis, Consultant for: Novartis, Speakers bureau: Novartis, I. Kone-Paut Grant/research support: SOBI, LFB, Consultant for: Novartis, SOBI, Pfizer, Chugai, S. Spalding: None declared, A. Zeft Consultant for: Novartis, A. Simon Grant/research support: Servier, Consultant for: Novartis, Servier, SOBI, P. Hashkes Grant/research support: Novartis, Consultant for: Novartis, Paid instructor for: Novartis, V. Hentgen Consultant for: Novartis, Paid instructor for: Novartis, Pfizer, Roche, T. Kallinich Speakers bureau: Novartis, Pfizer, S. Savic Consultant for: Novartis, I. Foeldvari Consultant for: Novartis, Abbott, Chugai, Genzyme, J. Frenkel Grant/research support: European Union ERANET, Consultant for: Novartis, U. Machein Employee of: Novartis, A. Livneh: None declared, H. Lachmann Grant/research support: Novartis, Celtic, Consultant for: Novartis DOI 10.1136/annrheumdis-2014-eular.3251

Background Uveitis is one of the major extraarticular manifestations of JIA. Open studies demonstrate efficacy of Adalimumab (ADA) and Infliximab. It remains unclear if uveitis can occur as an adverse drug reaction, especially in pts. exposed to Etanercept (ETA). Methods The BIKER registry data base was used for analysis. Patient9s history of uveitis, JIA category, the first occurrence of uveitis and exposure to Methotrexate (MTX), ETA, ADA and steroids were searched for. The number of first uveitis events occurring in each treatment category, the no. of exposed patients and exposure time until event were calculated. Results Of 3467 pts, 1700 were exposed to ETA, 364 to ADA and 1403 to MTX only. 335 pts (9.4%) had a history of uveitis before. In 75 pts (2.2%) uveitis was reported as an adverse event. Pts. with a known history of uveitis were more likely to have a new uveitis event (n=22; 6.8%; OR 2.9 [1.5-5.5]; p To analyze the influence of drug treatment on the occurrence of a first uveitis flare pts9 treatments were categorised (table). Compared to the control group (MTX only) OR was significantly higher in pts receiving ETA monotherapy. It was not increased in combination with MTX. There were more uveitis events in pts on ADA±MTX in combination. Univariate analysis revealed that treatment with corticosteroids seems not to protect from uveitis, while MTX did. Pts. on ADA had significantly higher rates, while pts on ETA did not. Conclusions Risk factors for uveitis as an adverse event were history of uveitis and ETA mono therapy. MTX treatment did reduce the likelihood of uveitis whereas corticosteroids had no such effect. Few pts developed first uveitis when exposed to ETA with a rate comparable to the control group. Disclosure of Interest G. Horneff Grant/research support: Abbvie, Pfizer, Roche/Chugai, I. Foeldvari: None declared, K. Minden: None declared, K. Tenbrock: None declared, H. Huppertz: None declared, I. Becker: None declared DOI 10.1136/annrheumdis-2014-eular.2702

Background/Purpose: The outcome of children with JIA refractory to disease-modifying antirheumatic drugs (DMARDs) has improved significantly since Etanercept became available. The objectives were to analyse data from the German Biologics JIA Registry (BiKeR) and to report on practice changes of the last twelve years. Methods: Baseline demographics, pre-treatment, concomitant treatment, clinical characteristics and disease activity parameters and outcome have been prospectively documented in BiKeR since 2000. Efficacy was determined using the PedACR response criteria, the JADAS-10 and the proposed criteria for inactive disease on medication. Results: From 2000 to 2012 1678 children with JIA on Etanercept with a total of 11,474 visits have been enrolled in BiKer (3424.2 total patient-years). The median disease duration at treatment start decreased from 4.5 to 2 years. While initially children have been pre-treated with numerous antirheumatic agents, including cytotoxic agents, pre–treatment markedly decreased by a mean 6.3 (median 4.3) to 0.99 (median 1.0) DMARDssol;patient. Concomitant treatment initially consisted of corticosteroids in 83%, Methotrexate in 95% and other DMARDs in 45% of children compared to 40%, 74% and 6.7% respectively in 2012. At Registry start, 26% of newly enrolled children belonged to the systemic JIA category compared to only 1% in 2012. In contrast, the rate of children with enthesitis related arthritis increased from 2% to 16%. The median JADAS-10 in 2000 compared to 2012 was significantly higher at treatment start (24.4+/−6.8 vs. 13.3+/−6.2) and remained higher after 6 months on treatment (7.5+/−7.2 vs. 4.5+/−5.2). The number of patients that have reached a PedACR 70 after 12 months on treatment increased from 41% starting in 2000 to 51% of patients starting in 2012. Inactive disease within one year was documented initially in 20% of children and increased to 43% in 2012. Conclusion: In recent years, children with JIA have been treated earlier, received less pre- and concomitant treatment with corticosteroids as well as with DMARDs. Patients have shown a markedly better outcome reflected in the higher PedACR response, lower JADAS-10 and higher rate of patients with inactive disease after one year on treatment. These data suggest that early disease control and better pre–selection of patients who need biologics are important to improve outcome in children with JIA.

Background/Purpose: Based on the ACR 2011 recommendations for the treatment of juvenile idiopathic arthritis (JIA) with persistent oligoarticular course methotrexate (MTX) is indicated for children with high disease activity and features of poor prognosis or if they failed intraarticular glucocorticoid steroid injections. However, no report has been published on MTX outcome in this category. Therefore our aim was to evaluate the efficacy and safety of MTX in children with oligoarticular persistent JIA. Methods: Baseline demographics, clinical characteristics and disease activity parameters have been prospectively documented in the German JIA Register. Efficacy was determined using the PedACR response criteria and the JADAS-10. Safety assessments were based on adverse events reports from the responsible physician. Results: 343 patients with a total of 2039 visits were identified (894.7 total patient-years). 67% (n = 231) were females. The median age at JIA onset was 4.7 years (quartile (Q) 25/75 2.5/9.2). At treatment initiation the median age was 8.0 years (Q25/75 4.3/12.0) and the disease duration 1.1 years (Q25/75 0.5/3.1). ANA positivity has been found in 63.0%, HLB27 positivity in 11.1%. Prior to MTX therapy 90.1% of children have been treated with nonsteroidal anti-inflammatory drugs (NSAIDs), 46.1% have received intraarticular glucocorticoid steroid injections. 88.3 of children were treated concomitantly with NSAIDs, 11.5% with corticosteroids and 2.6% with other disease-modifying antirheumatic drugs. A high proportion of patients showed a significant response to treatment. Compared to baseline disease activity parameters at MTX initiation, at month 6 70.5%/61.0%/41.5%, at month 12 73.9%/63.9%/43.5% and at month 24 83.6%/80.0%/69.7% of patients met the PedACR response criteria of 30%/50%/70%. The median JADAS-10 at treatment start was 10.0 and decreased markedly to 2.1 at month 6, 1.4 at month 12 and 1.0 at month 24. At month 6 and month 12, 83 patients (33%) and 96 patients (42%) reached preliminary criteria for inactive disease. 113 children experienced 216 adverse events (AE) (24.7/100 patient–years). Four were reported as serious (0.4/100 patient–years (pj)). The most common reported AEs were nausea/vomiting (8.5/100 pj), abnormal liver enzymes (4.7/100 pj) and mild to moderate infections (3.6/100 pj). 48 children (14%) suffered from uveitis prior treatment. None of these patients flared with uveitis. Four new uveitis index cases (1.1%) were reported while on treatment. Treatment has been discontinued in 134 children for the following reasons: Inefficacy 3.2%, adverse events 9.8%, remission 24.3%, patients wish 16.5%, others 2.9%. 17 of 84 children (20.2%) who stopped MTX because of remission flared and re-started MTX. Conclusion: MTX appears to be highly effective in oligoarticular persistent JIA. The treatment is safe and well-tolerated. Few patients discontinued due to intolerance or inefficacy.

Juvenile systemic sclerosis (jSSc) is a rare disease of childhood, and the amount of published data is limited. It appears that its clinical presentation differs from adult disease and the limited form affects only very few children. The organ involvement pattern differs also from the adult form. Prognosis seems to be better with a 5-yr survival of 95% of the jSSc patients. The validation of the outcome measures for children with jSSc is currently in progress. Regarding effective treatment, there are no paediatric data and the paediatric rheumatologist needs to rely on the experiences in adult disease.

Background At least one third of the JIA patients as a whole experience a polyarticular course of disease which carries a high risk of persistent disease activity and disability. However, new therapeutic strategies hold promise for a better short- and long-term outcome of these patients. Objectives To examine changes in treatment and health status of patients with pJIA treated by paediatric rheumatologists over the past 12 years. Methods Data of patients with pJIA (rheumatoid factor [RF]-negative polyarthritis [PA], RF-positive PA, extended oligoarthritis), who were prospectively recorded in the national paediatric rheumatologic database in the years from 2000 to 2011, were considered for this analysis. The health status assessment of patients included physician- and patient/parent-reported outcomes: disease activity (measured by JADAS-10), functional capacity (measured by the CHAQ), pain and overall well-being (both measured by numeric rating scales from 0 to 10). Per year, a mean value was calculated for each health status parameter, with the patients recorded each year adjusted for age, sex, disease duration, treatment (MTX, biologics, corticosteroids), and time. The change of disease parameters over time and the influence of treatment on change were assessed by linear mixed models. Results Altogether, 10,310 cases with pJIA were recorded; the number of yearly included patients increased from 594 in 2000 to 1,517 in 2011. Over the years, the patients were treated increasingly more often with DMARDs in general and with biologics in particular. While in the year 2000, 70% and 2% of patients were treated with DMARDs and biologics, these were 79% and 32% in the year 2011, respectively. Moreover, pJIA patients were treated earlier in the disease course. In 2000, 52% and 1% received MTX and/or biologics during the first 12 months of the disease, in 2011 68% and 19%, respectively. Changes in treatment were coincided by changes in the health status of patients. Over the years, the adjusted mean annual JADAS-10 score significantly decreased from 10.3 to 8.1 (p=0.042), the CHAQ-score almost halved from 0.45 to 0.26 (p

Background The pedACR criteria are validated to analyse the response to a treatment but do not indicate the absolute disease activity nor the absolute improvement. This study correlates the JADAS 71 and 10 to the PedACR 30/50/70. Methods Data of the GERMAN BIKER-registry were used to compare the JADAS71 and -10 (Phy. global VAS 0–10cm, Par./pati. global VAS 0–10cm, Active joint count 0-71, Normalized ESR [ESR-20/10]) to the PedACR criteria. Results 7960 reports from 1470 JIA pts treated with Etanercept have been analysed. After 3 mths 75% of pts achieved a PedACR30. This number increased to 83% at mth 12 and remained stable thereafter. At mth 3, 45% of pts achieved a PedACR70. This number increased to 62% at mth 12. The median (range) JADAS71 decreased from 18 (0-85) to 4 (0-81) at mth 3, 3 (0-83) at month 6 and 3 (0-57) at month 12, the JADAS10 decreased from 17 (0-40) to 4 (0-35), 3 (0-35), and 3 (0-36). At patient-visits with a PedACR30 the median JADAS10 was 11 (0-29), for PedACR50 6 (0-26), for PedACR70 1 (0-19). In Patient-visit with a failure according to the PedACR the JADAS10 was 12 (0-37). The JADAS71 was 11 (0-49) for PedACR30 responses, 6 (0-47) for PedACR50, 1 (0-25) for PedACR70 response and 12 (0-84) for non-responders (figure). In pts not achieving PedACR30 the JADAS71 and the JADAS10 slightly decreased. In patients achieving a PedACR30/50/70 the JADAS71 decreased by 9.9, 12.3 and 16.7 points, while the JADAS10 decreased by 7.4, 10.0 and 14.9. 1116 (17%) pts achieved the prelim.criteria for inactive disease corresponding to a JADAS-score of 0. Conclusions The JADAS allows assessing of absolute disease activity and decreased corresponding to the PedACR. The change from baseline for each of the JADAS measures showed adequate ability to classify each of the PedACR accurately. Disclosure of Interest G. Horneff Grant/Research support from: Abbott, Pfizer, K. Minden Grant/Research support from: Pfizer, I. Foeldvari: None Declared

Background Juvenile localised scleroderma (jlSc) is an orphan disease. There are currently no guidelines regarding diagnosis, follow up and treatment. Objectives In the frame of the PRES scleroderma working group this consensus meeting was set up to gain consensus regarding these issues. Methods Members of the PRES scleroderma working group were invited to participate. Two pediatric dermatologists were invited. P. Clements was invited to moderate the meeting. A nominal group technique was used. 75% consensus was defined as agreement. Results The following agreements were reached: Diagnosis is based on clinical grounds by a rheumatologist or dermatologist, preferably pediatric, with a biopsy as a confirmatory measure if it is unclear based on clinical findings. If a biopsy is needed, a punch biopsy is appropriate. In the case of deep involvement, a deep biopsy is needed. Since progression to systemic sclerosis is unlikely, an evaluation for internal organ involvement, such as HRCT and echocardiogram, is unnecessary There are no laboratory studies needed to confirm the diagnosis. The group agrees there is no clear evidence for a pathogenic role of Borrelia, therefore we do not recommend investigation for Borrelia infection. In patients with sclerodermatous skin changes of the head (face and/or scalp) the following are suggested: MRI of the brain, preferably with contrast. In the absence of clear evidence, the group suggested to screen every 6 months for uveitis with slit lamp examination for the first 4 years of the disease. Dental assessment is strongly suggested, especially if the lesion crosses the maxilla and mandible. Temporomandibular joint assessment by a pediatric rheumatologist every 6 months is suggested. In the absence of clear evidence, the group suggested to screen every 12 months for uveitis with slit lamp examination for the first 4 years of the disease, if the lesion does not involves the face. All patients besides superficial circumscribed localised scleroderma (plaque morphea), especially those with linear disease, are suggested to be seen at baseline and every 12 months by both a pediatric rheumatologist and pediatric dermatologist, ideally in combined clinic. The group suggested using the LoSCAT (Localized Scleroderma Cutaneous Assessment Tool) to assess cutaneous activity and damage measures. There is a need to assess the quality of life of jLS patients. Conclusions Although there are no solid guidelines currently present as the “standard of care” for jLs, these suggestions are part of routine care for most physicians specializing in the care of pediatric localized scleroderma and are non-invasive measures. Disclosure of Interest None Declared

Background Etanercept turned out to be highly effective in juvenile idiopathic arthritis. The aim of this study was to use the German Biker Registry data base to analyse the performance after discontinuation of Etanercept because of remission. Methods Requested reasons for discontinuation were inefficacy, intolerance, remission or other reasons. Judgement about decision for discontinuation or restart of treatment was not influenced by the registry. The course during follow up was analysed until restart of Etanercept treatment. Results 1499 patients (pts) recruited into the registry have been identified. 208 (13.9%) pts discontinued treatment with etanercept due to “remission” of their disease including patients of all JIA categories: enthesitis related arthritis 17/79 (17%), extended oligoarthritis 40/275 (14.5%), systemic JIA 18/130 (13.8%), RF - polyarthritis 62/472 (13.1%) but significantly less frequently patients with RF+ polyarthritis (9/154 (5.8%); p=0.003, χ 2 -test). Data of 476 follow ups were available in 166 pts for a median of 17 months (0-110 months). 100 (46%) were followed for at least 12 months, 47 (22%) for at least 24 months, 31 (14%) for at least 36 months. 71 (34%) Patients restarted treatment with Etanercept due to a relapse. Treatment was restarted in 5 pts in the first month, 18 in the first 3 months, 31 in the first 6 months and 47 in the first 12 months after discontinuation of Etanercept. Kaplan Meier analysis revealed a median Etanercept free survival time of 38.2 months. Etanercept free survival time is significantly influenced by the total treatment time with etanercept and ongoing treatment with methotrexate. Treatment with corticosteroids at the time of discontinuation of etanercept or disease duration before initiation of Etanercept were without significant input. At the time when Etanercept has been first discontinued due to “remission” 118 (62%) patients fulfilled the “Wallace” criteria for inactive disease. However, this had no effect on the median survival time until retreatment. Conclusions Discontinuation of a successful treatment with Etanercept occurred frequently in JIA patients. Compared to the total cohort, patients with enthesitis related arthritis more frequently and patients with RF+ polyarthritis less frequently discontinued due to “remission”. The median drug free survival time was influenced positively by treatment with methotrexate and negatively by a longer period of time to reach “remission”. Further observation of these pts will demonstrate the total rate of permanently discontinuation of antirheumatic drugs. Disclosure of Interest G. Horneff Grant/Research support from: Pfizer, Abbott, H. Hupppertz: None Declared, I. Foeldvari: None Declared, K. Minden: None Declared

Background Juvenile localised scleroderma (jlSc) is an orphan disease. There are currently no guidelines regarding diagnosis, follow up and treatment. Objectives In the frame of the PRES scleroderma working group this consensus meeting was set up to gain consens regarding this issues. Methods Members of the PRES scleroderma working group were invited to participate. Two pediatric dermatologist were invited. P. Clements was invited to moderate the meeting. A nominal group technique was used. 75% consensus was defined as agreement. Results The group reached agreement on all discussed topic. Topical treatment is appropriate as therapy for small circumscribed superficial morphea lesions (plaque morphea) in non-cosmetically sensitive areas. Suggested topical treatment with best evidence: a.Tacrolimus 0.1% b, Vitamin D 0.005%; c. Topical steroids; d. Imiquimod Phototherapy is suggested for extending circumscribed superficial lesions, preferentially above the age of 12. UVA-1 is preferable; alternatively UVB narrowband can be used as an alternative. PUVA therapy should be avoided The group agreed that systemic treatment beyond topical treatment is suggested for active lesions in: a.linear scleroderma; b. Deep and pansclerotic morphea; c. Lesion in cosmetically sensitive areas; d. Lesions crossing joints; e. Generalized plaque morphea Consensus for first line systemic therapy among the group was unanimously agreed upon as methotrexate15 mg/m 2 /week, max 25 mg/week. a. Bridging therapy with glucocorticoids was suggested in this group, particularly in rapidly progressive and severe disease, such as lesions crossing the joints and cosmetically disfiguring disease. b. A glucocorticoid taper was suggested to be discontinued by 4 months (based on uveitis data). Physical and/or occupational therapy is recommended for any patient with decreased joint range of motion or muscle weakness. It was agreed that the aim of the treatment is to reach inactive disease If inactive disease is not reached after 6 months of systemic treatment or there is no improvement after 3 months of systemic treatment, it is recommended to switch systemic therapy There are currently no evidence based data to make suggestions in the case of methotrexate non-response, but there are possible options, such as mycophenolate mofetil, rituximab, tocolizumab …. Remission was defined by the group as 12 months of inactive disease on medication. The group agreed that after at least 12 months of inactive disease that systemic treatment can be stopped., based on case series. The group agreed to treat extracutaneous manifestations (ECM) associated with jLS according the treatment guidelines for the particular ECM (Uveitis, arthritis, seizures …). Conclusions Topical treatment of small superficial circumscribed morphea lesions and systemic treatment with MTX +/- corticosteroids for all other subtypes of jLS was unanimously agreed upon. The duration of treatment and alternative therapies require more investigation. Disclosure of Interest None Declared

Background Oligoarticular JIA (OA) is the most common subtype of JIA in Caucasian patients and may lead to a wide spectrum of outcomes. Clinical outcome predictors are required for a risk-adapted treatment of patients. Objectives To assess the 4-year outcome of patients with OA, and to identify clinical predictors for an unfavorable outcome (i.e., uveitis, active disease, and functional impairment at follow-up). Methods Patients with recent onset of OA (disease duration Results 544 patients with recent onset of OA and a 4-year-follow-up were identified in the PRD. At first documentation (5 months after disease onset), patients had a median age of 5 years and a median JADAS of 7.8 (IQR 4.3 to 11.0). Methotrexate (MTX) was given to 27% of the patients within the first year of disease. At the 4-year-follow-up 15% of the patients had developed extended OA and 16% uveitis. A JADAS of 0 (corresponding to inactive disease [1]) was recorded in 28% of cases, an acceptable symptom state (JADAS=1) in 11%, and a JADAS of ≥2 in 61%. The median CHAQ score was 0 (mean 0.13), with three quarters of the patients having a CHAQ score of 0. Neither age at onset, sex, presence of antinuclear antibodies (ANA), HLA-B27-positivity, nor JADAS at baseline had an influence on JADAS and CHAQ at follow-up. However, early treatment with MTX was significantly associated with a better outcome, i.e. with a lower disease activity (p=0.039) and a better functional status (p=0.015). ANA-positivity (p=0.036), young age (p=0.001) and the JADAS (p=0.012) at onset predicted uveitis at follow-up. With every point increase of the baseline JADAS the probability of uveitis at follow-up increased by 1.09. Patients with a JADAS >10 had a 2fold higher odds to have experienced uveitis at follow-up than those with a lower JADAS at baseline (OR=1.9; uveitis rate of 11.5% in patients with JADAS ≤10 vs. uveitis rate of 20% in patients with JADAS >10). Early MTX use, however, was a negative predictor for uveitis (p=0.019). Conclusions Disease activity at onset as measured by the JADAS seems to be a useful clinical outcome predictor, at least for uveitis. The JADAS may help to allocate patients to specific treatments, for example to an early MTX treatment. Early MTX therapy on the other hand improves the outcome of patients with OA which includes the prevention of uveitis. Supported by a grant from the child arthritis foundation. References Consolaro A, Bracciolini G, Ruperto N, Pistorio A, Magni-Manzoni S, Malattia C, Pederzoli S, Davi S, Martini A, Ravelli A. Remission, minimal disease activity and acceptable symptom state in juvenile idiopathic arthritis. Arthritis Rheum 2012 Jan 9 [Epub ahead of print] Disclosure of Interest None Declared

Background Uveitis is the most common extraartricular manifesation of juvenile idiopathic arthritis (JIA). Uveitis, a potentially blinding disorder, is present in approx 10-18% of JIA patients, with a wide spectrum of presentations. Despite advances in treatment of childhood arthritis there are no definitions for assessment of activity, damage and impact of JIA associated uveitis. Objectives The purpose of our efforts was to develop and gain consensus on such definitions Methods At the second consensus meeting of the MIWGUC group, using a Delphi method we developed definitions for activity, damage and impact of disease based on already published outcome measures [1]. Results Conclusions We will validate these proposed definitions propsectively in a JIA associated uveitis cohort. Based on the results, we will weight these measures to develop an overall scoring system. References Heiligenhaus, A., et al., Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: A consensus effort from the multinational interdisciplinary working group for uveitis in childhood (MIWGUC). Arthritis Care Res (Hoboken), 2012. Disclosure of Interest None Declared

Background Raynaud’s phenomenon (RP) can be the first symptom of a connective tissue disease in children, in particular juvenile systemic scleroderma (JSSC) or systemic lupus erythematosis (SLE). However, the prevalence of RP in healthy school children has been shown to be as high as 15%[1]. There are currently no guidelines or agreed management strategies amongst Paediatric Rheumatologists on how to differentiate primary from secondary RP or how often patients require evaluation. Objectives To develop consensus standards for good clinical practice for children with RP. Methods A consensus meeting was organized in the frame of the PRES scleroderma working group. A nominal group technique was used. 75% consensus was defined as agreement. Results The following agreements were reached: All patients with RP should be screened with an ANA test. All ANA positive patients should be screened for scleroderma-specific antibodies (e.g. anti-SCL 70 and anti-centromere antibodies). All patients with RP should be investigated by capillaroscopy. Capillaroscopy will be classified into “normal”, “aspecific changes” or “scleroderma pattern”. All patients who have additional symptoms pointing to a definite connective tissue disease should be evaluated according to disease specific guidelines. ANA-negative and capillaroscopy-negative patients should be followed-up at least every 6 months. ANA positive patients without disease-specific antibodies and with negative capillaroscopy findings should be followed-up at least every 6 months. ANA and disease-specific antibody positive patients should have organ specific evaluation according to symptoms, examination and relevant to that particular disease e.g. patients who are ANA and Scl-70 positive may need organ specific evaluation for JSSC as per the Juvenile systemic sclerosis inception cohort protocol (www.juvenile-scleroderma.com). ANA-positive patients, who have no disease specific antibody but have positive capillaroscopy results, should be followed-up at least every 3 months. ANA-negative patients with positive capillaroscopy result should be followed-up at least every 6 months. The group could not reach an agreement regarding treatment, due to a lack of data for the paediatric age group. The group agreed that implementation of adult recommendations for paediatric care might be reasonable, but robust paediatric trials are needed. Conclusions The group made a suggestion for a standard of good clinical practice for RP in children. Our aim is that this will facilitate a large multicentre prospective follow-up study of children with RP. References Jones, G.T., et al., Occurrence of Raynaud’s phenomenon in children ages 12-15 years: prevalence and association with other common symptoms. Arthritis Rheum, 2003. 48 (12): p. 3518-21. Disclosure of Interest None Declared

German evidenceand consensus-based guidelines 2011 for the treatment of juvenile idiopathic arthritis (JIA) Gregor Dueckers, Nihal Guellac, Martin Arbogast, Guenther Dannecker, Ivan Foeldvari, Michael Frosch, Gerd Ganser, Arnd Heiligenhaus, Gerd Horneff, Arnold Illhardt, Ruediger Krauspe, Matthias Schneider, Wolfram Singendonk, Helmut Sitter, Barbara Markus, Marianne Spamer, Norbert Wagner, Tim Niehues

Introduction While adalimumab is licensed for ankylosing spondylitis (AS), open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS (JoAS). Methods A total of 32 patients aged 12 to 17 years with severe, active and refractory JoAS were enrolled in a multicenter, randomized, double-blind, placebo-controlled parallel study of 12 weeks, followed by open-label adalimumab until week 24 for all patients. ASAS40 was used as the primary, and ASAS20, PedACR and single items were used as the secondary outcome measures for the intention to treat population. Results A total of 17 patients were randomized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo. Two patients (one of each group) discontinued prematurely due to insufficient efficacy and were labeled as non-responders. In the double-blind part, more patients on adalimumab achieved an ASAS40 at week 4 (41%), week 8 (53%) and week 12 (53%) than on placebo (20%, 33%, 33%), while differences at week 8 only reached borderline significance (P = 0.05). Also, at 4, 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group (53%/53%/29%; 59%/76%/41%; 53%/65%/53%) compared to placebo (27%/27%/7%; 27%/33%/13%; 33%/40%/27%). In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24. At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65% (P