Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

BACKGROUND: Uveitis in juvenile idiopathic arthritis (JIAU) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first line therapy, and disease modifying anti-rheumatic drugs (DMARDs) are commonly used. However, treatment has not been standardized. METHODS: Interdisciplinary guideline were developed with representatives from the German Ophthalmological Society, Society for Paediatric Rheumatology, Professional Association of Ophthalmologists, German Society for Rheumatology, parents' group, moderated by the Association of the Scientific Medical Societies in Germany. A systematic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for anti-inflammatory treatment and final statements were discussed in a consensus meeting (Nominal Group Technique), a preliminary draft was fine-tuned and discussed thereafter by all participants (Delphi procedure). RESULTS: Consensus was reached on recommendations, including a standardized treatment strategy according to uveitis severity in the individual patient. Thus, methotrexate shall be introduced for uveitis not responding to low-dose (≤ 2 applications/day) topical corticosteroids, and a TNFalpha antibody (preferably adalimumab) used, if uveitis inactivity is not achieved. In very severe active uveitis with uveitis-related deterioration of vision, systemic corticosteroids should be considered for bridging until DMARDs take effect. If TNFalpha antibodies fail to take effect or lose effect, another biological should be selected (tocilizumab, abatacept or rituximab). De-escalation of DMARDs should be preceded by a period of  ≥ 2 years of uveitis inactivity. CONCLUSIONS: An interdisciplinary, evidence-based treatment guideline for JIAU is presented.

[Intra-articular injection of cortisone]. / Intraartikuläre Injektion mit Kortison.

Intra-articular injections with glucocorticoids are standard procedures according to therapy guidelines in many rheumatic conditions. There is increasing evidence from clinical trials on the treatment of rheumatoid arthritis that more patients will attain the target of remission using a combination of systemic medication and intra-articular injections with glucocorticoids compared to systemic medication alone. Intra-articular injections with glucocorticoids play an important role in the therapeutic management of pediatric rheumatic diseases. In many countries competency in performing intra-articular injections is among the important skills necessary for certification as a specialist in rheumatology.

[Current news from the BIKER register]. / Aktuelles aus dem BIKER-Register.

Innovative developments in the pharmacotherapy of juvenile idiopathic arthritis and especially biologics allow the formulation of new therapeutic targets, such as the rapid induction of remission with shortening of the period of active disease and therefore preventing damage and disability. These new therapies also represent a challenge to the monitoring of drug safety, the pharmacovigilance. For this purpose the Society for Paediatric and Adolescent Rheumatology has set up an early register to record achievements in treatment improvement and in addition to independently assess information on drug safety, acute tolerance and long-term safety.

Efficacy and safety of oral and parenteral methotrexate therapy in children with juvenile idiopathic arthritis: an observational study with patients from the German Methotrexate Registry.

OBJECTIVE: The German Methotrexate Registry has been collecting data concerning the efficacy and safety of methotrexate (MTX) treatment since 2005. The aim of this retrospective analysis is to compare oral and parenteral MTX treatment regarding efficacy and safety. METHODS: Inclusion criteria were diagnosis of juvenile idiopathic arthritis, MTX treatment for at least 6 months, a consistent route of administration of MTX, and no previous or concomitant treatment with biologic agents. Efficacy was measured by the American College of Rheumatology (ACR) pediatric (Pedi) criteria. Primary outcome was efficacy defined as the number of patients reaching ACR Pedi 30 improvement criteria after 6 months of treatment. Secondary outcome criteria were the ACR Pedi 50 and Pedi 70 criteria at 6 and 12 months, respectively. Analyses were performed with the intent-to-treat population. RESULTS: Of the 411 eligible patients, 259 (63%) received oral MTX and 152 (37%) received subcutaneous MTX. In both patient groups, a comparable weekly dose of MTX (0.4 mg/kg versus 0.42 mg/kg) was used, and a comparable number of patients received concomitant steroids. The primary outcome in both treatment groups was that a comparably high number of patients showed a clinical response according to the ACR Pedi 30 score after 6 months of treatment (73% versus 72%; P = 0.87). Twenty-two percent of patients with oral therapy and 27% with subcutaneous therapy had at least 1 documented adverse event. Discontinuation of treatment was observed in both groups with equal frequency, while significantly more patients with subcutaneous application discontinued MTX because of adverse events (11% versus 5%; P = 0.02). CONCLUSION: In this retrospective analysis, parenteral MTX was not superior to oral administration regarding efficacy and tolerability.

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

[Evidence and consensus based treatment guidelines 2010 for juvenile idiopathic arthritis by the German Society of Paediatric Rheumatology]. / Interdisziplinäre S2-Therapieleitlinie der Juvenilen Idiopathischen Arthritis (2. Auflage).

BACKGROUND: Treatment of Juvenile Idiopathic Arthritis (JIA) has improved quality of life in children and adolescents with JIA. Standardisation of care offers the chance to improve the quality of care of those patients. New studies have been published after completion of our last treatment guideline (2007). An updated consensus process is mandatory. METHODS: A systematic literature analysis in PUBMED (key words: juvenile idiopathic (rheumatoid) arthritis, therapy; limits: humans, published in the last 3 years, all child 0-18 years, clinical trial) revealed 17 relevant studies. Studies relating to diagnosis of JIA, Uveitis, vaccination, transition were excluded. Representatives nominated by scientific societies and organisations were invited to consensus conferences which were hosted by a professional moderator. The following societies were invited: Berufsverband der Kinder- und Jugendärzte (BVKJ), Deutsche Gesellschaft für Kinder- und Jugendmedizin (DGKJ), Deutsche Gesellschaft für Rheumatologie (DGRh), Deutsche Ophthalmologische Gesellschaft (DOG), Deutsche Rheuma-Liga Bundesverband, Verein zur Förderung und Unterstützung rheumatologisch erkrankter Kinder und deren Eltern, Vereinigung für Kinderorthopädie, Zentraler Verband der Physiotherapeuten und Krankengymnasten (ZVK). Consensus conferences were each attended by more than 95% of the nominated representatives. Consensus statements were confirmed by nominal group technique and Delphi method. RESULTS AND CONCLUSION: Updated consensus statements regarding drug therapy, symptomatic and surgical management of JIA were compiled and judged strictly by the criteria of Evidence-Based Medicine (EBM).

Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis.

AIM: To investigate the therapeutic value of azathioprine as monotherapy or combined with other immunosuppressive drugs for uveitis in patients with juvenile idiopathic arthritis (JIA). METHODS: A retrospective multicentre study including 41 children with JIA (28 (68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis. Azathioprine was used to treat uveitis that was active in patients receiving topical or systemic corticosteroids, methotrexate or other immunosuppressive drugs. The primary end point was assessment of uveitis inactivity. Secondary end points comprised dose sparing of topical steroids and systemic corticosteroids, and immunosuppression. RESULTS: At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as combination therapy. During the entire azathioprine treatment period (mean 26 months), inactivity was obtained in 16/26 patients (61.5%) with monotherapy and in 10/15 (66.7%) when combined with other immunosuppressives (p=1.0). With azathioprine, dosages of systemic immunosuppression and steroids could be reduced by ≥ 50% (n=12) or topical steroids reduced to ≤ 2 drops/eye/day in six patients. In three patients (7.3%), azathioprine was discontinued because of nausea and stomach pain. Conclusions Azathioprine may be reconsidered in the stepladder approach for the treatment of JIA-associated uveitis. The addition of azathioprine may also be beneficial for patients not responding properly to methotrexate.

IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA).

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a rare, but severe cause of childhood disability. Systemic onset JIA (SoJIA) accounts for approximately 5.8% of all JIA cases and is associated with cytokine dysregulation, including interleukin (IL-)1, IL-6 and tumour necrosis factor (TNF-)α. IL-10 is an immuno-regulatory cytokine, which in part regulates inflammation by controlling inflammatory cytokine expression. Dysregulation in IL-10 expression and certain single nucleotide polymorphisms (SNPs) in the IL-10 promoter were shown to be associated with autoimmune and infectious diseases. METHODS: Genomic DNA-samples from SoJIA patients from two German Paediatric Rheumatology centres, and healthy controls were analysed for three well defined IL-10 promoter SNPs (-1082G>A, -819C>T, and -592C>A). These SNPs are in tight linkage disequilibrium, and result in three predominant (or 'classical') haplotypes: ATA, ACC, and GCC. ATA and ACC are associated with low and medium, GCC is associated with high IL-10 expression. RESULTS: Here, we show a strong association of IL-10 promoter polymorphisms with SoJIA. We demonstrate a significantly increased frequency of low IL-10 expressing -1082A/A alleles, the medium IL-10 expressing ACC haplotype (p=0.01), and an enrichment of the rare GTC haplotype (p<0.001) in patients with SoJIA. Heterozygous -1082G/A alleles (p<0.001), and the GCC haplotype (p<0.001) on one allele protect from developing SoJIA. CONCLUSIONS: This suggests a central role of the immuno-regulatory cytokine IL-10 in the pathogenesis of SoJIA.

The economic burden of juvenile idiopathic arthritis-results from the German paediatric rheumatologic database.

OBJECTIVE: To estimate the cost of juvenile idiopathic arthritis (JIA) and to evaluate the influence of specific disease characteristics on the various costs domains. METHODS: Data on JIA outpatients (n=369) who were enrolled in the national paediatric rheumatologic database and completed a cost questionnaire were analysed. Direct JIA-related costs, families' out-of-pocket expenses and parents' income loss were calculated per patient and year, using physicians' reports, parents' 3-month recall, and average prices as the basis. RESULTS: The mean total cost of JIA was estimated to be 4,663 euro per patient per year. The highest costs were calculated for patients with seropositive polyarthritis and systemic arthritis (7,876 euro), and the lowest costs were seen for patients with persistent oligoarthritis (2,904 euro). Health-care costs accounted for 89% of total costs, and medication contributed to almost half of this value. A considerable amount of the cost was borne by the families, with a mean out-of-pocket cost of 223euro and a mean indirect cost due to time loss from work of 270 euros per year per family. Cost increased with disease activity and pain, disease duration, and time period from symptom onset to first paediatric rheumatologist visit; it also increased with the presence of uveitis. However, function, as measured by the Childhood Health Assessment Questionnaire, was the only factor significantly contributing to the variation in patient total costs. CONCLUSION: JIA imposes a significant economic burden. Medication (i.e. biologic drugs) contributes substantially to the total costs. However, these must be considered in the light of the patients' long-term outcomes.

Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis.

AIMS: Juvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children. METHODS: Multicentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs. RESULTS: Inactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by >or=50% (n=19) or topical steroids reduced to

Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication.

PURPOSE: To study the value of methotrexate (MTX) and the requirement for additional anti-inflammatory drugs for the treatment of severe chronic iridocyclitis associated with juvenile idiopathic arthritis (JIA). METHODS: Institutional study of 35 consecutive patients with JIA started on MTX as the single systemic immunosuppressive drug for the treatment of associated iridocyclitis. The clinical epidemiologic data, course of visual acuity (VA), development of complications, and the need for additional anti-inflammatory drugs were analyzed. RESULTS: Mean follow-up with MTX treatment was 27.6 months. Uveitic complications were present in 31 patients before MTX treatment. With MTX, quiescence of uveitis was obtained with (n=21) or without (n=4) additional topical steroids. Additional systemic immunosuppressive drugs were required in another 7 patients: cyclosporine A (n=4), azathioprine (n=1), infliximab (n=1), or etanercept (n=1). Three patients had active uveitis at the end of the follow-up period. During MTX therapy, uveitis first developed in the unaffected fellow eyes in 2 patients, and secondary glaucoma or ocular hypertension occurred in 7 patients. The VA deteriorated in 6, improved in 13, and was stable in the remaining eyes. CONCLUSIONS: The data suggest that MTX is very effective in controlling inflammation of uveitis in patients with JIA. However, additional topical steroids or systemic immunosuppressive drugs are often required.

[Juvenile idiopathic arthritis and uveitis: epidemiology including data from a national database]. / Juvenile idiopathische Arthritis und Uveitis: Epidemiologie einschliesslich der Daten aus der Kerndokumentation.

Uveitis is a potentially vision-threatening extra-articular manifestation of juvenile idiopathic arthritis (JIA) that manifests in approximately 13 % of all patients. According to the national ophthalmological and paediatric rheumatological database, one out of four children with JIA and uveitis develops ocular complications such as synechiae, band keratopathy, cataract, glaucoma and macula oedema. Independent risk factors of uveitis include the presence of a certain JIA subgroup, of antinuclear antibodies and age at onset. A late diagnosis, however, seems to be the relevant risk factor for uveitis complications in the course of the disease. The diagnosis of uveitis as early as possible is therefore the most important factor for a reduction of the morbidity of uveitis. Due to the usual lack of symptoms the diagnosis of uveitis requires, however, an examination by an ophthalmologist. This should be done immediately after the diagnosis of JIA and repeated in a risk-adapted manner during the follow-up.

[Other rheumatic diseases with uveitis besides juvenile idiopathic arthritis]. / Andere entzündlich rheumatische Erkrankungen mit Uveitis neben der juvenilen idiopathischen Arthritis.

In childhood and adolescence, uveitis is part of the clinical spectrum of many inflammatory-rheumatic diseases. Besides juvenile idiopathic arthritis juvenile, ankylosing spondylitis, infection-associated arthritides, infantile sarcoidosis, systemic vasculitides, inflammatory bowel diseases, hereditary autoinflammatory syndromes and the TINU syndrome have to be excluded. These inflammatory diseases can be differentiated clinically in connection with immunogenetic and molecular genetic investigations. Early diagnosis of uveitis as well as the underlying diseases is mandatory for an early treatment and therefore for a good prognosis.

Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide study in Germany: suggested modification of the current screening guidelines.

OBJECTIVES: To analyse the prevalence and complications of uveitis and their predictors in a large cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Data of 3271 JIA patients as classified by International League of Associations for Rheumatology (ILAR) criteria included in a national database during 1 yr were analysed. RESULTS: Uveitis prevalence was 12% of all JIA patients. The most frequent were oligoarthritis extended (25%) and persistent (16%). JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs 7.0 yrs) or ANA-positive (86% vs 42%) than the patients without uveitis. Predictors of uveitis included age at onset (P= 0.03) and ANA-positivity (P< 0.01) besides the presence of a certain JIA subgroup (P= 0.04). Uveitis was clinically silent in 75% of the oligoarthritis but in none of the enthesitis-related arthritis patients. The median onset of uveitis was 5.5 months after arthritis manifestation. In 73%, 77% and 90%, uveitis developed within 1, 2 and 4 yrs after arthritis, respectively. Anterior uveitis was the most common anatomic type of uveitis (83%). Uveitis complications at mean follow-up of 5.6 yrs were common (56%), and predictors for complications included presence of complications at first visit (P< 0.001) and uveitis manifestation before arthritis (P= 0.001), but not ANA positivity. CONCLUSIONS: The JIA subgroups markedly differ with respect to the prevalence and course of associated uveitis. Ophthalmological screening should be initiated early after arthritis onset and the intervals be related to the JIA subgroup. A modification of the current screening guidelines is suggested.

Two mathematical models for predicting dispersion of particles in the human lung.

The dispersion of particles in the human lung is modeled as a series of virtual mixing tanks. Using the experimental results of Scherer et al. (1975, J. Appl. Physiol., 38(4), pp. 719-723) for a five-generation glass lung model, it is shown that each generation of the glass lung behaves like an independent virtual mixing tank. The corresponding resident time distribution is shown to have a variance approximately equal to the square of the average time a particle spends in the generation. By assuming that each generation of the human lung behaves as an independent virtual mixing tank, the realistic lung data provided by Weibel (1963, Morphometry of the Human Lung, Spinger-Verlag, New York) are used to validate this assumption in two ways. First, the half-width of the exhaled particle concentration profile is obtained. Second, a system of differential equations, with the concentration of particles in each mixing tank as its solution, is derived and solved numerically. This gives the exhaled concentration profile. Both techniques yield similar results to each other, and both give excellent agreement with the experimental data. The virtual mixing tank approach allows the complex mixing that occurs in the branching pathways of the lung to be more simply modeled. The model, thereby derived, is simple to change and could lead to enhancements in the understanding of the underlying processes contributing to the ventilation of the lung in health and disease.

[Structural quality of rheumatology clinics for children and adolescents. Paper by a task force of the "Society of Pediatric and Adolescent Rheumatology" and of the "Association of Rheumatology Clinics in Germany"]. / Strukturqualität von kinder- und jugendrheumatologischen Akutkliniken und -abteilungen. Projektgruppenarbeit der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) und des Verbandes Rheumatologischer Akutkliniken (VRA).

Rheumatic diseases in childhood and adolescence differ from those of adulthood according to type, manifestation, treatment and course. A specialized therapy, starting as early as possible, improves the prognosis, can prevent long-term damage and saves the costs of long-term care. Only a specialized pediatric care system can guarantee optimum quality of the processes involved and the results for rheumatology in childhood and adolescence within a global financial system. This requires adequate structural quality of the specialized clinics and departments for pediatric rheumatology. The management of rheumatic diseases in childhood and adolescence is comprehensive and requires a multidisciplinary, specialized and engaged team which can cover the whole spectrum of rheumatic diseases with their various age-dependent aspects. In order to guarantee an adequate, cost-efficient routine, a specialized center which concentrates on inpatient care should treat at least 300 patients with pediatric rheumatic diseases per year. The diagnoses should be divided among the various disease categories with at least 70% of them involving inflammatory rheumatic diseases. For the inpatient care of small children, an accompanying person (parent) is necessary, requiring adequate structures and services. Patient rooms as well as diagnostic (radiography, sonography, etc.) and therapeutic services (physiotherapy, occupational therapy, pool, etc.) must be adequate for small children and school children as well as adolescents. Suitable mother-child units must also be provided and a school for patients is required within the clinic. A pediatric rheumatologist must be available 24 h a day, and it must be possible to reach other specialists within a short time. For painful therapeutic procedures, age-appropriate pain management is obligatory. A continuous adjustment of these recommendations to changing conditions in health politics is intended.

[Transition clinic--it is not always a simple segue in rheumatology for adults]. / Transition-Clinic -- Der nicht immer einfache Ubergang in die Rheumatologie für Erwachsene.

Chronic inflammatory rheumatic diseases with onset in childhood often persist into adulthood and result in a considerable number of patients in impairments of body functions and structures, activities at the individual level and participation in society. Continuation of health care beyond adolescence is, therefore, necessary. Its provision should be of high quality, coordinated, uninterrupted, patient-centred and developmentally appropriate to ensure smooth transitions between children's and adult services and positive outcomes of transition for the young people themselves. Existing research is very persuasive on the need to improve transitions for young people with rheumatic diseases. To achieve effective transition, not only disease specific, but also aspects of growth and development have to be taken into account. Paediatric and adult rheumatologists should establish close cooperation and implement specific transition programs to meet the special health care needs of these patients.

[Epidemiology of uveitis in juvenile idiopathic arthritis from a national paediatric rheumatologic and ophthalmologic database]. / Epidemiologische Daten zur Uveitis bei juveniler idiopathischer Arthritis aus einer bundesweiten pädiatrischen und ophthalmologischen Datenerhebung (Uveitis-Modul der Kerndokumentation).

BACKGROUND: Uveitis is a frequent and potentially vision-threatening manifestation of juvenile idiopathic arthritis (JIA). There are only a few population-based studies providing data on the frequency and severity of uveitis. METHODS: Documentation of patients with JIA was collected in a national database. An analysis of the paediatric rheumatologic and ophthalmologic data collected from all patients that were included in 2002 was performed. RESULTS: Uveitis was documented in 12 % of a total of 3271 JIA patients: extended oligoarthritis (25 %), persistent oligoarthritis (16 %), seronegative polyarthritis (4 %), seropositive polyarthritis (2 %), psoriatic arthritis (10 %), enthesitis-related arthritis (ERA) (7 %), systemic arthritis (1 %), other arthritis forms (11 %). Ophthalmologic data were available from 115 uveitis patients (28 %). Mean age at onset of uveitis was 5.2 (SD 3.2) years. JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs. 7.0 years), and were more often girls (74 vs. 63 %) or ANA-positive (86 vs. 42 %) than the patients without uveitis. Uveitis complications were present in 45 % at initial presentation of uveitis. After a mean duration of 5.6 years, complications were noted in 56 %, and included band keratopathy (29 %), posterior synechiae (27 %), cataract (26 %), glaucoma (8 %), and macula oedema (6 %). Final visual acuity was less than 20/50 in 31 % and less than 20/200 in 12 % of eyes. In patients with uveitis, immunosuppressive or immunomodulatory drugs were used significantly more often than in patients without uveitis (75 % vs. 43 %). CONCLUSIONS: The nationwide data documents the spectrum of uveitis in patients with JIA, the complications and the therapy for uveitis. The high rate of uveitis complications at the time of diagnosis points out the need for early ophthalmologic screening and therapy, and for a close collaboration between ophthalmologist and paediatric rheumatologist.

The German etanercept registry for treatment of juvenile idiopathic arthritis.

OBJECTIVE: To describe a registry set up to monitor children treated with etanercept in Germany and Austria. METHODS: Giannini's criteria, duration of morning stiffness, number of swollen, tender and contracted joints, adverse events, and reasons for discontinuation were assessed. RESULTS: 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 (p<0.001 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. CONCLUSION: Etanercept treatment was safe and led to a significant improvement in most JIA patients resistant to conventional treatment.