Polyarticular Juvenile Idiopathic Arthritis Research Articles

P010 Clinico-epidemiological characteristics and outcomes of Juvenile Idiopathic Arthritis (JIA) patients in Kenya: data from the KAPRI registry

Abstract Background Pediatric rheumatic diseases pose a significant disease burden upon children and their families (1–3). They lead to physical disability and diminished quality of life (1–3). Determination of the burden and clinical characteristics of these diseases is a critical first step to improving access to care and optimizing use of existing health systems for the well-being of these patients (4). This is in line with the goal of the Bone and Joint decade (2000–2010) aimed at increasing recognition and understanding of the impact of musculoskeletal diseases (5,6). The Kenya Pediatric Rheumatology Registry (KAPRI) offers a unique opportunity to pioneer and spearhead a systematic and organized format to inform policy and better healthcare provision. Our objective was to determine the patient characteristics, clinical features and outcomes of Juvenile Idiopathic Arthritis (JIA) patients assessed at the Aga Khan University Medical College East Africa from March 2019 to December 2020. Methods Data of JIA patients on age, gender, laboratory and clinical features at diagnosis and treatment options offered were extracted from the database. A further detailed chart review was undertaken to determine the proportion of patients who achieved remission or minimally active diseases. Results Among the 207 patients enrolled thus far, 16 (7.7%) were diagnosed to have JIA. Majority of the patients were females (75%; n = 12) with a mean age of 7 years and 3 months (Range : 1 year—13 years 7 months). All patients had joint pain and swelling as the initial presenting complaints. Majority of the patients had polyarticular JIA (75%, n = 12). The other 4 patients were oligoarticular (n = 2) and systemic JIA (n = 2). Among the polyarticular JIA patients (n = 12), only 3 (25%) were rheumatoid factor (RF) positive and 1 was antinuclear antibody (ANA) positive. The oligoarticular and systemic JIA patients were all negative for antinuclear antibody, rheumatoid factor and cyclic citrullinated peptide antibodies (anti-ccp). Seven patients (43.8%) required biological therapies; tocilizumab (n = 2: systemic JIA), adalimumab (n = 2: polyarticular JIA), etanercept (n = 2: polyarticular JIA) andtofacitnib (n = 1: polyarticular JIA). One patient with systemic JIA on tocilizumab developed herpes simplex which was successfully managed with oral acyclovir. All the other patients did not develop any infections, allergic reactions or any other untoward events as adverse outcomes following the use of biological therapies. Five patients have attained remission as illustrated in the table below. Two patients have been lost to follow up. Conclusion Seronegative polyarticular JIA was the predominant form of JIA observed with a predilection to affect more girls and boys. Over a period of 2 years, remission has been attained among 31.25% of the patients (5 of 16) with use of synthetic disease modifying anti-rheumatic drugs and biological therapies.

P026 Efficacy and safety of Etanercept for the treatment of Juvenile Idiopathic Arthritis

Abstract Background Etanercept (ETN) is the first anti-TNF to have obtained FDA approval in 1999 for juvenile idiopathic arthritis (JIA) refractory to methotrexate. Currently, the indications of ETN cover the polyarticular JIA, the extended oligoarticular, and enthesitis-related arthritis. To assess the efficacy of Etanercept, as well as its tolerance in JIA. Material and methods We carried out a retrospective study of children with JIA according to the criteria of the ILAR classification and treated with Etanercept at the pediatric center of the CHU de Sétif since 2015. Nineteen children were included and considered to 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years on the criteria epidemiology, the efficiency criteria (joint Scores, uveitis, ESR, CHAQ), and the occurrence possible side effects. We defined the improvement of 30% (ACR 30), 50% (ACR 50), 70% (ACR 70), 90% (ACR 90), and 100% (ACR 100) as the improvement of minus 3 criteria out of 6 of 30%, 50%, 70%, 90%, 100%; patients must not have a worsening of > 30% of any of the 6 criteria. Results The epidemiological features were the following: 12 girls and 7 boys, 10 present polyarticular form, 6 present oligoarticular form, 2 cases with psoriatic arthritis, and a single case of enthesitis-related arthritis. ACR 30 is obtained in 75%, 84%, 88% of cases at 3 months, 6 months, and 1 year, respectively. The strongest responses were obtained in polyarticular, oligoarticular, and enthesitis-related arthritis. Complete remission was maintained in the majority of patients for varied durations depending on the follow-up. Furthermore, no clinical or biological adverse effects were noted. Conclusion The Etanercept has been dramatically effective in children with juvenile idiopathic arthritis, especially in the polyarticular subtype, oligoarticular, and enthesitis-related arthritis. Its overall tolerance is very good.

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity

Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial

Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA). This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434. Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27-0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study. The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections. Pfizer.

Health-related quality of life and disability in adults with juvenile idiopathic arthritis: comparison with adult-onset rheumatic diseases

ObjectiveTo compare physical disability, mental health, fatigue and health-related quality of life (HRQoL) across juvenile idiopathic arthritis (JIA) categories in adulthood and between JIA and adult-onset rheumatic diseases.MethodsCross-sectional analysis nested...

Efficacy of tocilizumab for interstitial lung disease associated with polyarticular juvenile idiopathic arthritis

Efficacy of tocilizumab for interstitial lung disease associated with polyarticular juvenile idiopathic arthritis

O18 When joints vanish

O18 When joints vanish

P36 A case of refractory IBD-related scleritis

Case report - IntroductionScleritis is severe vision-threatening scleral inflammation, commonly presenting with a red, painful eye and can be classified using the Watson system. Posterior scleritis may present with associated anterior uveitis in many cases. Steroid therapy is often successful initially; however, further immunomodulation is usually required to control subsequent episodes which can be challenging. We present an 18-year-old, Caucasian girl with a left eye, sight-threatening, steroid-dependent posterior uveitis who required escalation of treatment to tocilizumab before inflammation could be suppressed.Case report - Case descriptionOur patient was diagnosed elsewhere with ulcerative colitis at the age of 12 and subsequently developed recurrent episodes of uveitis and scleritis which could be controlled with topical steroids. At the age of 16 she presented with an inflammatory arthritis and was treated with intravenous methylprednisolone before commencing sulfasalazine therapy. Due to persistent systemic and ophthalmic inflammation she was changed to adalimumab; however, this was also unsuccessful and methotrexate was added. By the age of 18 she had been steroid-dependent for 2 years and could not reduce daily prednisolone below 15mg without a deterioration in her left eye posterior scleritis with visual acuity compromise including episodes of complete visual loss causing high levels of anxiety. Due to the pain and deterioration in vision she struggled with her studies and school attendance, and withdrew from her passion for competitive sailing. With ongoing sight-threatening inflammatory changes she was referred for further tertiary assessment in 2019.During the following 4 months treatment was escalated rapidly. Methotrexate dose was increased, and adalimumab frequency reduced to weekly. There was a limited response, with further episodes of sight deterioration as a result of flares in inflammation. Response to tocilizumab treatment was seen after only two doses with good control of scleritis by 3 months of treatment when steroids were successfully weaned and stopped. Over 18 months of tocilizumab therapy the patient has only required one course of topical steroids for mild ocular inflammation which resolved without any other treatment required. She has successfully completed her degree, can complete daily gym training sessions and participate in regular sailing competitions.Case report - DiscussionPosterior scleritis is the most common scleritis in children and can be associated with anterior uveitis, concurrent anterior scleritis, disc swelling or retinal striae. Posterior scleritis has a higher rate of complications therefore is treated aggressively. Refractory cases such as this require biologic therapy and rituximab is often used. Despite the preference of two adult eye units for treatment with rituximab the rationale for tocilizumab included; recent high quality studies showing successful treatment of inflammatory bowel disease, its known benefit for anterior uveitis and case studies in adults with posterior scleritis. Tocilizumab is a recombinant monoclonal antibody that causes a blockade of interleukin-6 receptors. It is currently only approved by the Food and Drug Administration (FDA) for use in children with polyarticular or systemic onset Juvenile Idiopathic Arthritis (JIA). Our patient had a very positive experience with this drug, no side effects and rapid clinical improvement seen. As a result her quality of life and mental health improved quickly.Case report - Key learning pointsThis is a case of refractory, sight-threatening, steroid-dependent posterior scleritis on a background of inflammatory bowel disease and arthritis. As a result of this case our team reviewed current literature from other paediatric populations and adults with scleritis, informing the clinical decision to proceed with tocilizumab after control was unsuccessful with previous agents. The remarkable response demonstrated for our patient highlights the value tocilizumab can offer to the treatment options for similar refractory cases. This adds to the growing positive data published surrounding tocilizumab in children but further studies in paediatric populations are required to evaluate this in greater detail.

СИНДРОМ БЛАУ, ИЛИ МОНОГЕННЫЙ САРКОИДОЗ С РАННИМ НАЧАЛОМ: РОССИЙСКАЯ КОГОРТА ПАЦИЕНТОВ

Blau syndrome (BS) is a rare monogenic granulomatous autoinflammatory disease (a variant of genetically determined sarcoidosis) caused by a mutation of the NOD2/CARD15 gene, transmitted in an autosomal dominant manner and manifested by a triad of signs: dermatitis, granulomatous arthritis with pronounced exudative component and involvement of periarticular tissues, uveitis. Objective of the study: to present the variants of the clinical picture and the type of pathogenic variants (mutations) in patients with a rare monogenic granulomatous autoinflammatory disease – BS – in the Russian Federation, the clinical picture of which can mimic juvenile idiopathic arthritis. Materials and methods of research: the observational study included patients with BS who were observed in the children's department of the V.A. Nasonova Research Institute of Rheumatology from 2014 to 2021, the diagnosis of which was confirmed by the detection of a pathogenic mutation in the NOD2/CARD15 gene. Results: the study included 8 children: 6 boys and 2 girls. Ethnic Russians were 5 patients, 1 Jew, 1 of mixed origin (peoples of Dagestan/Russians), 1 Tatar female. The age of onset of the disease is from the first days of life to 2,5 years. Skin lesions were observed in 6 (75%) patients. Atypical arthritis (boggy arthritis) was observed in all patients, in all cases the wrist, ankle and knee joints were involved in the pathological process. Uveitis developed after all other manifestations and was detected in 6 (75%) patients. At the onset, 5 patients had anterior uveitis, 2 of them with subsequent involvement of the posterior segment; in 1 child, the first ophthalmic manifestation was posterior uveitis. In 5 patients, there was no increase in acute phase markers (ESR, C-reactive protein). 5 (62,5%) patients had variant p.R334Q (c.1001G>A), 2 (25%) had variant p.R334W (c.1001G>A), 1 patient had variant p.M513T (c.1538T>C) of the NOD2/CARD15 gene. Conclusions: BS can be encountered in the practice of a pediatric rheumatologist in Russia and requires differentiation from polyarticular juvenile idiopathic arthritis. Identification of the pathogenic variant of the NOD2/CARD15 gene plays a decisive role in the diagnosis.

Low-energy laser therapy application on knee joints as an auxiliary treatment in patients with polyarticular juvenile idiopathic arthritis: a dual-arm randomized clinical trial.

Patients with juvenile idiopathic arthritis (JIA) always experience persistent pain and stiffness which induces muscle weakness, fatigue, and functional limitations. This study evaluated whether applying low-energy laser therapy (LLT) on the knee joint could be an effective adjuvant intervention for patients with JIA. Sixty children with polyarticular JIA participated and were randomly allocated to receive either LLT (wavelength λ = 903nm; power output of 50 mW; and energy of 1.5J) plus exercises (LLT group) or exercises alone (control group). Pain, peak concentric torque of quadriceps muscles, fatigue, and functional status were measured by the visual analogue scale, isokinetic testing system, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, and Childhood Health Assessment Questionnaire, respectively pre- and post-intervention, and at 6-month follow-up. Per the mixed-model analysis of variance, the LLT group showed a statistically more favorable improvement in pain (P = .003, ηp2 = .014), fatigue perception (P = .004, ηp2 = .015), and functional status (P = .022, ηp2 = .09) across the three assessment occasions, as compared to the control group. However, no significant difference was demonstrated between both groups concerning peak concentric torque (all P > .05). Incorporation of LLT into the standard physical rehabilitation program for patients with JIA has the potential to induce more conducive improvements in pain, fatigue, and functional performance, but is not effective for improving muscle performance.

Interstitial lung disease occurring shortly after tocilizumab infusion in a patient with polyarticular juvenile idiopathic arthritis: a case report

BackgroundTocilizumab has been shown to be effective for treatment of juvenile idiopathic arthritis (JIA). To our knowledge, this is the first reported case of interstitial lung disease occurring shortly after tocilizumab infusion in a patient with JIA.Case presentationA 14-year-old female patient with polyarticular JIA developed interstitial lung disease after intravenous and subcutaneous administration of tocilizumab. Her condition improved with glucocorticoid therapy.ConclusionOur results suggest that increased interleukin-6 levels in the blood following tocilizumab treatment may be linked to development of interstitial lung disease.

Improved Disease Course Associated With Early Initiation of Biologics in Polyarticular Juvenile Idiopathic Arthritis: Trajectory Analysis of a Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans Study.

To investigate the effects of early introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) on the disease course in untreated polyarticular juvenile idiopathic arthritis (JIA). We analyzed data on patients with polyarticular JIA participating in the Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA) study (n = 400) and a comparator cohort (n = 248) from the Childhood Arthritis and Rheumatology Research Alliance Registry. Latent class trajectory modeling (LCTM) was applied to identify subgroups of patients with distinct disease courses based on disease activity (clinical Juvenile Arthritis Disease Activity Score in 10 joints) over 12 months from baseline. In the STOP-JIA study, 198 subjects (49.5%) received bDMARDs within 3 months of baseline assessment. LCTM analyses generated 3 latent classes representing 3 distinct disease trajectories, characterized by slow, moderate, or rapid disease activity improvement over time. Subjects in the rapid improvement trajectory attained inactive disease within 6 months from baseline. Odds of being in the rapid improvement trajectory versus the slow improvement trajectory were 3.6 times as high (95% confidence interval 1.32-10.0; P = 0.013) for those treated with bDMARDs ≤3 months from baseline compared with subjects who started bDMARDs >3 months after baseline, after adjusting for demographic characteristics, clinical attributes, and baseline disease activity. Shorter disease duration at first rheumatology visit approached statistical significance as a predictor of favorable trajectory without bDMARD treatment. Starting bDMARDs within 3 months of baseline assessment is associated with more rapid achievement of inactive disease in subjects with untreated polyarticular JIA. These results demonstrate the utility of trajectory analysis of disease course as a method for determining treatment efficacy.

Community poverty level influences time to first pediatric rheumatology appointment in Polyarticular Juvenile Idiopathic Arthritis

BackgroundThe impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.MethodsThis is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015–February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist.ResultsA total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level (< 20% vs ≥20%) yielded no significant differences with time to initial presentation to a pediatric rheumatologist (p = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67–0.99, p = 0.038) to be seen by a rheumatologist compared to patients with < 20% community poverty level, at the same time point, after adjusting for sex, race/ethnicity, insurance, education level, morning stiffness, RF status, and baseline CHAQ.ConclusionIn this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.

Functional Ability and Health-Related Quality of Life in Randomized Controlled Trials of Tocilizumab in Patients With Juvenile Idiopathic Arthritis.

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

Early Joint Replacement in Juvenile Idiopathic Arthritis: Trend Over Time and Factors Influencing Implant Survival.

To describe early prosthesis implantations in a cohort of patients with juvenile idiopathic arthritis (JIA) followed in a tertiary referral hospital and to analyze possible factors influencing implant survival. This was a retrospective cohort study. Charts of all patients with JIA who underwent total joint replacement at Gaetano Pini Hospital, Milan, Italy from January 1992 to June 2019 were retrieved, and relevant data were analyzed. Eighty-five patients met the inclusion criteria for this study, with a median follow-up period of 17.2 years. The median age at first prosthesis was 22.7 years. The total number of replaced joints was 198 over a period of 27 years. The hip was the most frequently replaced joint, accounting for almost two-thirds of the total number of implants; the other one-third refers mostly to knee implants. Polyarticular JIA and systemic JIA were the most represented JIA categories in the study cohort. A significant upward trend of the age at arthroplasty and of disease duration before arthroplasty over decades was found. The rates of implant survival at 5, 10, and 15 years were comparable (from 84% to 89%); 50% of implants lasted ≥20 years. We reported retrospective data on early joint replacement in a cohort of patients with JIA. We observed a progressive and significant upward trend of both age at arthroplasty and disease duration before the first arthroplasty over time. The JIA category, year of implant, and presence of complications significantly affected implant survivorship.

Juvenile Idiopathic Arthritis-Associated Chronic Uveitis: Recent Therapeutic Approaches.

Pediatric patients with early onset (before the age of 6 years), antinuclear antibody positive, oligoarticular or polyarticular juvenile idiopathic arthritis (JIA), and some children with no arthritis may develop chronic, anterior uveitis. Recent recommendations insist on the need to perform slit lamp examination every 3 months for at least 5 years in early onset JIA patients in order to diagnose uveitis before complications develop. Local steroid therapy is usually the first-line treatment. However, in patients requiring steroid eye drops for several months, systemic immunomodulatory therapy is indicated. Methotrexate (MTX) is then prescribed in most cases; however, some patients also need anti-tumor necrosis factor alpha monoclonal antibody therapy and, in some cases, other biologics to control uveitis and avoid long-term ocular damage. Expert ophthalmologists and pediatricians must be involved in taking care of such patients. Immunomodulatory treatment must not be too easily interrupted and may even be intensified in some cases, particularly if there is a need for optimal disease control before ophthalmologic surgery. In good responders to MTX and/or biologics, treatment must be maintained at least 1 year, possibly even 2 years after achieving remission before tapering treatment intensity.

Familial aggregation of juvenile idiopathic arthritis with other autoimmune diseases: Impact on clinical characteristics, disease activity status and disease damage.

To evaluate the impact of family history of autoimmune diseases (FHADs) on the clinical characteristics and outcome of juvenile idiopathic arthritis (JIA). We retrospectively reviewed children with JIA seen in 7 pediatric rheumatology clinics from 6 Arab countries. All included patients met the International League of Associations for Rheumatology classification criteria for JIA and had a disease duration greater than 1 year. Data were collected at the last follow-up visit and comprised clinical findings, including FHADs. Disease activity and disease damage were assessed by Juvenile Arthritis Multidimensional Assessment Report, and juvenile arthritis damage index (JADI) respectively. Disease activity was categorized as remission off treatment, remission on treatment, or active disease. A total of 349 (224 females) JIA patients with a disease duration of 5 (interquartile range 2.9-7.5) years were included. The most frequent JIA categories were polyarticular JIA and oligoarticular JIA, followed by systemic JIA. There were 189 patients with FHADs and 160 patients without FHADs. The most frequent FHADs were diabetes mellitus (21.2%), JIA (18.5%), rheumatoid arthritis (12.7%). Among patients with FHADs, 140/189 (74.1%) achieved clinical remission, while 131/160 (81.9%) patients without FHDs had clinical remission (odds ratio [OR]=1.2, 95% CI 0.97-1.5). Rate of consanguinity, enthesitis-related arthritis (ERA) and psoriatic arthritis were higher in patients with FHADs (OR=0.6, 95% CI 0.4-0.9 and OR=1.2, 95% CI 1.1-1.4). Also, articular JADI correlated significantly with presence of FHADs (OR=1.1, 95% CI 1.0-1.1). This study shows that autoimmune diseases cluster within families of patients with JIA with a high proportion of ERA and psoriatic arthritis. JIA patients with FHADs are likely to have more disease damage.

The value of the patient global health assessment in polyarticular juvenile idiopathic arthritis: a nested cohort study

ObjectiveThe objectives were: 1) to explore the discordance between the Patient Global Health Assessment (PtGA) scores, the Physician Global Health Assessment (PhGA) scores, and Pain scores; and 2) to explore whether the PtGA during disease remission is associated with future disease flare in pJIA.MethodsData from an NIH funded clinical trial (NCT00792233) evaluating flare were used (N = 137). PtGA, PhGA, and Pain scores were assessed. Flare was defined as any active arthritis. Spearman’s correlation coefficients were calculated, and multivariable logistic regression was performed.Results122 patients had records of flare status, of which 63 developed flare, and 42 of these patients had a visit immediately prior to flare. For study subjects with a visit immediately prior to flare, the PtGA, pain scores, and PhGA all increased at time of flare. For every unit increase in PtGA and Pain scores, there was a 9% and 23% higher odds of developing flare, respectively (p = 0.76, p = 0.40). For every unit increase in the PhGA score, there was a substantially lower odds of developing flare (p = 0.05).ConclusionOur results demonstrate that the PtGA and Pain scores are strongly correlated with each other and increased at the visit prior to flare, while the PhGA scores are not. Further, the PtGA and Pain score have some predictive value for flare, while the PhGA does not. These findings highlight the value of patient input in medical care and decision-making, and support the development and use of more sophisticated PROs in the care of JIA patients.

P455 Tofacitinib Therapy is Effective for Arthralgias Associated with Active Inflammatory Bowel Disease

Abstract Background Tofacitinib is an oral Janus kinase (JAK) inhibitor used to treat ulcerative colitis (UC). It is generally well tolerated and safe with mild to no side effects. Tofacitinib is FDA-approved for use in multiple inflammatory conditions such as rheumatoid arthritis, psoriasis and polyarticular course juvenile idiopathic arthritis as well as for ulcerative colitis (UC). Patients with UC often have extra-intestinal manifestations (EIMs) with up to 20% of patients having arthropathy. There are limited data describing the effect of tofacitinib therapy on EIMs in UC. The aim of this study is to determine whether tofacitinib therapy improves arthralgia in this patient population. Methods This retrospective study includes consecutive patients with active UC who initiated tofacitinib at our center since 2014 and remained on the therapy for at least 8 weeks. We reviewed electronic medical records to collect demographic and clinical data. Patients diagnosed with any EIM by the treating physician were included. Improvement in EIM symptoms was determined through patient reports or physician assessment. In the UC patients, a decrease in Simple Clinical Colitis Activity Index (SCCAI) of ≥ 3 was considered response and remission as a score of ≤ 2. In the CD patients, a 3-point reduction in Harvey Bradshaw index (HBI) was considered clinical response and a score of &amp;lt;5 remission. Results 112 patients were included in this cohort, with 36 (31 UC; 5 CD) having confirmed EIMs (32.1% of total). Basic demographic and clinical data are detailed in Table 1. 35 patients had peripheral arthralgia, 2 patients had primary sclerosing cholangitis (PSC) and 1 had pyoderma gangrenosum. 5 (13.9%) patients discontinued treatment during the induction phase due to lack of response. By 24 weeks, 26 (74.2%) out of 35 patients reported improvement in arthralgias, and 14 (40%) patients reporting resolution of joint symptoms. In terms of gastrointestinal disease activity, at week 24, 17/35 (48.6%) patients achieved clinical response and 11/35(31.4%) patients achieved clinical remission. There was no treatment effect noted on the other EIMs. Conclusion In our real world experience, treatment refractory IBD patients with peripheral arthralgia on tofacitinib showed significant improvement in joint symptoms, and this often paralleled improvement in gastrointestinal symptoms. This supports that tofacitinib is a suitable treatment for patients with IBD and concomitant peripheral arthralgia.

POS0085 EVALUATION OF DURATION OF CLINICAL REMISSION IN CHILDREN WITH NON-SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS AFTER WITHDRAWAL OF ANTI – TUMOR NECROSIS FACTOR - ALPHA THERAPY

Background:Juvenile idiopathic arthritis (JIA) is the most common and prevalent rheumatic disease in childhood which is based on a chronic autoimmune inflammation. Inactive disease and remission are now the primary treatment goal in JIA and biologics have been playing an important role to reach this objective.The biologics of the first choice for the treatment of non-systemic JIA are the Tumor Necrosis Factor - alpha (TNFα) inhibitors; on this therapy patients can achieve clinically inactive disease and long-term remission.Currently, little is known about when or how to stop TNFα inhibitors, when a good clinical response is achieved, and therefore no guidelines are available.Objectives:To estimate the length of clinical remission after discontinuation of treatment with TNFα inhibitors in patients with non-systemic juvenile idiopathic arthritis.Methods:A total of 393 patients with JIA who were treated with TNFα inhibitors at the Rheumatology Department of the National Medical Research Center of Children’s Health (Moscow, Russia) were screened for inclusion in this retrospective study.Patients were treated with etanercept 1 times a week, 0.8 mg per kg of body weight per dose, with adalimumab 24 mg/m2 body surface area administered every other week until the end of therapy.Treatment was terminated abruptly. Inactive disease was defined according to the preliminary criteria of Wallace et al.[1]Results:77 patients (27—male, 50—female) with a mean age at diagnosis of 4 years (range 1–18 years) were included in the analysis. Of those, 69 of them discontinued TNFα inhibitors due to a long-term remission on treatment, 8 patients as a result of side effects, and there were excluded from our study.:allergic reaction (n = 5), development of uveitis (n = 1), alopecia (n = 1), recurrent infection (n=11).The clinical subtypes of JIA were RF-negative polyarticular JIA -28 (40,58%) oligoarthritis—38 (55,07%), enthesitis-related arthritis—3 (4,35%).TNFα inhibitors were started after a mean 46,43 (range 1–144) months of disease. The mean duration of therapy with TNFα inhibitors were 46,63 (range 10-113) months, with a mean duration of remission on medication 40,63 (range 6-107) months before withdrawal of TNFα inhibitors.40/69 (57,97 %) patients did not develop a disease exacerbation and remained in long-term remission off medication—more than 24 months.Early flares, that is less than 6 months after termination of TNFα inhibitors, were observed in 4/69 (5,8%) patients.29 (42,03%) patients restarted TNFα inhibitors after exacerbation, due to lack of improvement after no biological DMARDs. All patients in whom TNFα inhibitors were reinitiated responded satisfactorily.Conclusion:Among patients with JIA in whom TNFα inhibitors were discontinued after inactive disease was achieved, 57,97 % had disease in clinical remission more than 24 months after stopping anti-TNFα therapy. No association was observed between the duration of inactive disease prior to TNFα inhibitors cessation and the time to disease relapse. In addition, we also ob- served no correlation between the risk of flare and the length of anti-TNF α therapy after inactive disease was achieved. In our population, TNFα antagonists were withdrawn a median of 38 (4-107) months after inactive disease was achieved. Data from our experience with anti-TNF α agents in the treatment of JIA suggest that 57,97 % of patients can be successfully withdrawn from TNF α antagonists for at least 24 months.