Assessment Of Overall Disease Activity Research Articles

Development and initial validation of parent and child versions of the Juvenile Arthritis Disease Activity Score.

To develop parent- and child-centered versions of the Juvenile Arthritis Disease Activity Score (JADAS) and to provide preliminary evidence of their validity. Validation analyses were conducted on two large multinational datasets of patients with juvenile idiopathic arthritis (JIA) and included assessment of construct validity, internal consistency and structure, discriminative validity, responsiveness to change, and predictive validity. The parJADAS and patJADAS include four parent/patient-reported outcomes, each measured on a 0-10 scale: assessment of overall disease activity; rating of pain intensity; assessment of activity of joint disease; duration of morning stiffness. Both scores are calculated as the simple linear sum of the scores of their 4 components, which yields for both of them a global score of 0-40. The parJADAS and patJADAS demonstrated good construct validity, yielding high correlations with other JIA composite disease activity measures and moderate correlations with physician global rating and joint counts. Internal consistency was satisfactory, with Cronbach' s alpha > 0.80, and exploratory factor analysis showed that both indices are monodimensional. Both instruments discriminated well between different disease states, with discriminative ability being not affected by the presence of damage, proved able to predict important disease outcomes, and showed fair responsiveness to clinically important change, with standardized response mean of 0.71. Both parJADAS and patJADAS were found to possess good measurement properties and to serve as surrogate of physicians' evaluations. Regular home completion of the two instruments through digital technologies offers a suitable and pragmatic approach to deliver remote symptom monitoring and telehealth.

P172 Evaluating the use of patient reported outcome measures to assess intra-pandemic psoriatic arthritis disease activity and comparing them with pre-pandemic clinical assessments

Abstract Background/Aims In our department, patient reported outcome measures (PROMs), including RAPID-3 and PSAID12, were employed during the COVID-19 pandemic in asynchronous consultations for patients with psoriatic arthritis (PsA). We compared pre-pandemic DAS28-CRP with intra-pandemic PROMs to assess changes in disease activity since the pandemic. Whilst previous studies have primarily compared PsA PROMs with clinician-assessed scores (e.g. PASDAS), we compare PsA PROMs with clinicians’ overall assessment of disease activity; this judgement considers PROMs, serology studies and individual patient feedback. Finally, we assess whether patients with PROMs indicating active disease were followed up appropriately. Methods Clinician-assessed scores were collected between 01/01/2019-01/03/2020 (“pre-pandemic”). Between 01/12/2020-31/03/2022 (“intra-pandemic”), patient data from electronic surveys were analysed in a secure database for calculation of PROMs. These data, alongside blood results and patient comments, informed clinicians’ triage decisions. Clinical outcome data were collected from electronic patient records; ≤3 months follow-up appointment allocation was the target for patients with active disease (moderate/high disease activity). Data analysis was performed using r (version 4.2.2). Results In our pre-pandemic cohort (n = 393), 79.8% of patients were in remission (per DAS28-CRP). Conversely, the intra-pandemic cohort (n = 231) showed remission rates of 14.3% (per PSAID12) and 0% (RAPID-3). Indeed, 33.7% (based on PSAID12) vs 75.8% (RAPID-3) had moderate/high disease activity. These results were validated in a paired cohort (n = 38, score recorded in both windows). Disease activity worsened during the pandemic for 63.2% (PSAID12) and 97.4% (RAPID-3) of patients. PSAID-12 correlated positively with RAPID-3 (r = 0.52, p < 0.001), especially when RAPID-3 ≥6.5 (r = 0.75, p < 0.001). When comparing PROMs with clinicians’ assessment of PsA activity in our paired cohort, PSAID12 and RAPID-3 accurately reflected disease status in 70.6% and 58.8% of patients respectively. 3/9 and 9/27 patients with active disease, based on PSAID12 and RAPID-3 respectively, were seen within three months. Conversely, 7/10 patients who clinicians had deemed to have active disease were seen within three months. Conclusion Despite approximately 80% of patients being in pre-pandemic remission, the majority reported active intra-pandemic PsA. Whilst RAPID-3 skewed patients towards active disease, PSAID12 skewed patients towards remission/low disease activity. PSAID-12 and RAPID-3 have been previously correlated; however, here we suggest that they could be used interchangeably in patients with high disease activity. PSAID-12 was a better predictor of clinicians’ assessment of disease activity, although neither PROM correlated well with ≤3 months follow-up appointment allocation. Although RAPID-3 and PSAID12 helped inform clinicians’ decisions, neither alone sufficiently reflects patients’ disease states. Remote management is practicable, but future studies should validate these findings across a larger cohort and assess the utility of different PROMs across PsA disease activity categories. Furthermore, multivariate analysis is warranted to ascertain which (combination of) variable(s) (e.g., PROMs, serology results, tender/swollen joint count) best correlates with clinician judgement. Disclosure K. Song: None. D. Kurzeja: None. A. Verdiyeva: None. M. Mirza: None. M. Ashraf: None. L. James: None. R. Luqmani: None.

P028 Impact of Juvenile Idiopathic Arthritis on schooling

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is one of the major causes of morbidity and physical disability. Due to frequent absences, children with chronic health impairments are also often confronted with educational difficulties. The aims of this study were to assess the impact of JIA on children’s schooling and to determine the factors that influence their school level. Methods This is a cross-sectional study including patients with JIA (ILAR criteria). A detailed questionnaire was completed for each participant by interviewing them or their parents as well as by information obtained from their medical records. Collected data included age, sex, subtype of JIA, disease duration, level of disability according to the Childhood Heath Assessment Questionnaire (CHAQ), visual analogue scale for patient’s overall assessment of disease activity (VASOA), duration of morning stiffness, tender joint counts (TJCs), swollen joint counts (SJCs), erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP), Disease Activity Score (DAS28) for polyarticular and oligoarticular JIA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for Enthesitis-related arthritis. Medications used for JIA treatment were also documented. Data on the school performance of patients and their siblings were obtained using telephone interviews (educational level, absenteeism, school delay by repetition, drop-out). Results A total of 43 patients with JIA were included, 25 female and 18 male, with a mean age of 26 years [12–51] and a mean disease duration of 237 months (5–496). The average age of the onset of the disease was 7.4 years [1.5–16]. The most common subtype was rheumatoid factor-positive polyarthritis (n = 18) followed by systematic (n = 8), oligoarticular (n = 8), rheumatoid factor-negative polyarthritis (n = 5) and Enthesitis-related arthritis (n = 4). The mean DAS28 was 3.02 [0.76 – 5.55] and the median CHAQ was 0.66 [0–3]. Twenty-nine of the children were receiving corticosteroid. Disease-modifying anti-rheumatic drugs were used by 38 of the 43 patients: methotrexate (n = 27), sulfasalazine (n = 8), leflunomide (n = 7), biotherapies (n = 16). Twenty patients had complications: Hip arthritis (n = 18), growth stunting (n = 14), uveitis (n = 5). Joint replacement was required in 11 cases. Four patients were illiterate, 14 had dropped out of school, 24 reported repeated absences due to illness. A year of schooling was repeated by 50.85% of patients. Eleven out of 32 patients over the age of 20 had an university level. Almost 80% of patients were exempted of physical education. There were no significant associations between the school-related problems, the socio-demographic characteristics and the various parameters of clinical and biological activity studied. Conclusion Our study suggested that JIA negatively affects schooling of children. More studies, with a larger sample of children, are needed to identify the variables associated with school failure in order to ensure the proper management of these patients and to increase their academic performance.

Whole-body magnetic resonance imaging vs. clinical evaluation of enthesitis in patients with spondyloarthritis

Whole-body magnetic resonance imaging vs. clinical evaluation of enthesitis in patients with spondyloarthritis

Differences in clinical phenotypes of primary Sjögren's syndrome depending on early or late onset.

Previous research suggests that systemic involvement in primary Sjögren's syndrome (pSS) is a marker of disease prognosis. To evaluate pSS disease activity and the clinical phenotype of pSS patients depending on the age at diagnosis with long-term follow-up. The study group consisted of patients diagnosed with pSS based on the 2016 pSS classification criteria. The study group consisted of 46 patients with early-onset pSS (≤35 years of age) and 32 patients with late-onset pSS (≥65 years of age). The study group was identified from a total of 228 patients diagnosed with pSS. There were no differences regarding the frequency of eye and mouth dryness, focus score (FS) ≥1 or anti-SSA/SSB antibodies depending on age. Rheumatoid factor (RF) was more common among older patients (p > 0.05). In the overall assessment of disease activity using European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI), no differences related to age were observed on the first and last visit (after 36 months on average). Lymphadenopathy and changes in the hematology domain (p < 0.05) were more common in patients with the early-onset phenotype. Changes in the lungs and musculoskeletal system occurred regardless of age. Patients with early-onset pSS differ from those with late-onset pSS in terms of higher incidence of peripheral lymphadenopathy and cytopenia. The involvement of lung tissue and joints as well as dryness symptoms are common in pSS regardless of age. The RF plays a role in the pathomechanism of pSS development.

POS0830 FACTORS INFLUENCING PATIENT-REPORTED OUTCOMES IN ANCA-ASSOCIATED VASCULITIS

Background:Patient-reported outcomes (PROs) are currently poorly integrated in the clinical evaluation of disease activity in patients with ANCA-associated vasculitis (AAV).Objectives:To assess the distribution of the Patient Global Assessment (PtGA) in patients with AAV in stable remission, and to identify correlates of PtGA; to assess the discordance between PtGA score and PhGA.Methods:Patients with a diagnosis of AAV [eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, microscopic polyangiitis] in stable, complete remission (defined by a BVAS=0) and with a Physician Global Assessment (PhGA)=0 were included. A questionnaire including several aspects of disease captured by PROs was collected. PtGA on a 0-100 mm visual analogue scale (VAS) was assessed, with higher scores representing higher/worse levels of disease activity. Similarly, VAS for pain, chronic damage according to the patient’s opinion, general health (GH), fatigue, and sleep quality were collected. The worst symptom in the patient’s opinion affecting the overall assessment of disease activity was recorded. The Cragg Hurdle model was used to assess the predictors of PtGA.Results:65 patients were included, female 57%, mean age 61±12 years. Mean disease duration at enrollment was 8±6 years. Mean vasculitis damage index (VDI) was 4.4 ±2.3, with 45% of patients having a VDI ≥ 5. Despite having been classified as being in remission, PtGA was elevated in 37% of patients. We explored several correlates of PtGA. Higher degree of damage accrual (VDI) did not influence the patient’s evaluation of current disease activity. Similarly, we did not identify a correlation between older age, educational level, number of organ-systems involved, number of comorbidities, the number of previous major or minor relapses, higher disease duration, nor the type of AAV diagnosis (figure 1, panel A). Only sex significantly correlated with PtGA scores: 19 (51%) of female patients reported an elevated PtGA compared to only 5 (18%) of male (p=0.009). PtGA resulted to be significantly correlated with other (mostly modifiable) PROs including VAS pain, perception of the level of chronic damage accrual, GH, and fatigue (figure 1, panel B). The agreement between patients’ and physicians’ assessments of disease activity was 63%. Patients reported pain, followed by chronic respiratory symptoms to be the worst-experienced ongoing manifestations affecting their evaluation of disease activity.Conclusion:A significant proportion of patients with AAV considered to be in remission by the physician still declares to have persistent aspects of uncontrolled disease. PtGA is significantly influenced by persistent pain and fatigue, which warrant better assessment in the future.Disclosure of Interests:None declared

Urinary Soluble Alpha Chain of the Interleukin-2 Receptor as a Biomarker of Active Lupus Nephritis in Egyptian Children With Juvenile Systemic Lupus Erythematosus

Objectives This study aims to assess the urinary soluble alpha chain of the interleukin-2 receptor (sCD25) concentrations in patients with juvenile systemic lupus erythematosus (JSLE) and to evaluate its validity to be a possible marker of disease activity in patients with lupus nephritis (LN). Patients and methods We assessed sCD25 concentrations in urine samples obtained from 53 JSLE patients (15 males, 38 females; median age 11 years; range, 7 to 17 years) and 30 age- and sex-matched apparently healthy controls (10 males, 20 females; median age 10 years; range, 6 to 16 years). Concentrations were normalized according to urinary creatinine excretion. JSLE patients were subjected to clinical examination and assessment of overall disease activity by Systemic Lupus Erythematous Disease Activity Index (SLEDAI), while evaluation of LN activity was preformed using Systemic Lupus International Collaborating Clinics (SLICC) renal activity score.Results The JSLE patients had significantly higher normalized urinary sCD25 concentrations compared to the healthy controls (p=0.001). Patients with active LN had significantly higher normalized urinary sCD25 levels than active JSLE patients without LN (p=0.002) and JSLE patients with inactive disease (p<0.001). A significant positive correlation was found between normalized urinary sCD25 concentrations with different activity parameters such as proteinuria (p=0.004), SLEDAI (p<0.001), renal SLEDAI (p<0.001), and SLICC renal activity score (p<0.001). A significant negative correlation was found between urinary sCD25 and complement 3 (p<0.001).ConclusionUrinary concentrations of sCD25 were significantly elevated in JSLE patients, particularly in those with active LN. The remarkable association between urinary sCD25 concentrations and different renal disease activity parameters implies that urinary sCD25 can be a beneficial marker to monitor active nephritis in JSLE patients.

Performance of Surveillance MR Enterography (MRE) in Asymptomatic Children and Adolescents With Crohn's Disease.

MR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established. To determine whether MRE imaging features are associated with clinical recurrence. Retrospective. Pediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified. 1.5T including T2 -weighted single-shot fast spin echo, balanced steady-state free precession, diffusion-weighted, and contrast-enhanced multiphase T1 -weighted gradient recalled echo sequences. MREs were reviewed by three radiologists independently for mural thickening, T2 -weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's-related treatment escalation, surgery, or hospitalization. Fisher's exact test, Wald chi-square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features. Of 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T2 -weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786). MRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6-month period, indicating a potential role for surveillance imaging to assess for subclinical active disease. 3 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;50:1955-1963.

Development and validation of a composite disease activity score for measurement of muscle and skin involvement in juvenile dermatomyositis.

To develop a composite DAS for JDM and provide preliminary evidence of its validity. The Juvenile DermatoMyositis Activity Index (JDMAI) is composed of four items: physician's global assessment of overall disease activity; parent's/child's global assessment of child's wellbeing; measurement of muscle strength; and assessment of skin disease activity. The score of the JDMAI is the arithmetic sum of the scores of each individual component. Six versions of the JDMAI were tested, which differed in the tools used to assess the third and fourth items. Validation procedures were conducted using three large multinational patient samples including a total of 627 patients. The JDMAI was found to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha = 0.58-0.89), fair responsiveness to clinically important change (standardized response mean = 0.82-3.12 among patients improved) and strong capacity to discriminate patients judged as being in the state of inactive disease or low, moderate or high disease activity by the physician (P < 0.001) or whose parents were satisfied or not satisfied with the course of their child's illness (P < 0.001). Overall, the six versions of the JDMAI showed similar metrological performances in validation analyses. The JDMAI was found to possess good measurement properties in a large population of patients with a wide range of disease activity, and is, therefore, suitable for use in both clinical and research settings. The final version of the JDMAI will be selected after its prospective validation.

MPTH-48. INTER-INTERPRETER CONSISTENCY IN REVIEWING HISTOPATHOLOGY FROM PATIENTS WITH GLIOBLASTOMA AND RADIOGRAPHIC PROGRESSION FOLLOWING STANDARD RADIATION AND TEMOZOLOMIDE

As clinical and imaging assessments are often insufficient to determine if glioblastoma patients after standard treatment have true progression versus pseudo-progression, surgery is frequently recommended to obtain tissue to answer this critical question. However, inter-interpreter consistency of pathologic interpretation in this setting has never been formally addressed. 101 neuropathologists from 50 NCI-designated Cancer Centers were identified, mailed a case scenario, and asked to review histologic sections. The scenario involved a patient who underwent surgery within one year of diagnosis for progressive symptoms and imaging changes. Tissue sections were provided from 13 different cases. Neuropathologic evaluations requested the (1) percent active tumor, (2) percent treatment effect, (3) degree of cellularity, (4) degree of mitotic activity, and (5) overall assessment of disease activity (‘active tumor’ vs. ‘pseudo-progression’ vs. ‘unable to classify’). Fleiss’ kappa statistics were assessed for inter-interpreter consistency among all readers. The patterns of pathologists’ readings per patient case were also characterized. Responses were received from 48 pathologists (48%) at 30 centers (44 were neuropathologists). The kappa score for agreement in overall assessment of disease activity was 0.228 (95% CI: 0.22-0.24), which indicates marginal agreement. Percentages of maximum agreement in pathology assessment among the 13 cases ranged from 36%-98%. The pathology reading diversity in the overall assessment of disease activity (5) was highly consistent with the pathology reading diversity on percent active tumor (1) and percent treatment effect (2) with p=0.03 and 0.001, respectively. However, it was less consistent with cellularity (3) and mitotic activity (4). These data demonstrate marginal inter-interpreter consistency when experienced neuropathologists review the same images with an identical clinical scenario. This study strongly suggests that efforts to standardize pathologic interpretation in patients with glioblastoma with progressive imaging abnormalities post-therapy are critical to improving patient care and conduct of clinical research.

Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated.

ObjectiveThe Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM.MethodsWe assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients.ResultsAt 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of >0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of >0.2]; P < 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria).ConclusionThere was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met the other 3 criteria. Incorporating PGA as an essential criterion for clinically inactive disease helps prevent the misclassification of patients with active skin disease.

Contrast-enhanced MRI features in the early diagnosis of Juvenile Idiopathic Arthritis

ObjectivesTo determine whether clinical, laboratory or Magnetic Resonance Imaging (MRI) measures differentiate Juvenile Idiopathic Arthritis (JIA) from other forms of active childhood arthritis.Materials and methodsWe prospectively collected data of 80 treatment-naïve patients clinically suspected of JIA with active non-infectious arthritis of (at least) one knee for <12 months duration. Upon presentation patients underwent clinical and laboratory assessments and contrast-enhanced MRI. MRI was not used as a diagnostic criterion.ResultsForty-four (55 %) patients were clinically diagnosed with JIA, whereas in 36 (45 %) patients the diagnosis of JIA was discarded on clinical or laboratory findings. MRI-based synovitis was present in 27 (61.4 %) JIA patients and in 7 (19.4 %) non-JIA patients (P < 0.001).Five factors (male gender, physician’s global assessment of overall disease activity, joints with limited range of motion, HLA-B27, MRI-based synovitis) were associated with the onset of JIA. In multivariate analysis MRI-based synovitis proved to be independently associated with JIA (OR 6.58, 95 % CI 2.36-18.33). In patients with MRI-based synovitis, the RR of having JIA was 3.16 (95 % CI 1.6-6.4).ConclusionsThe presence of MRI-based synovitis is associated with the clinical onset of JIA. Physical examination could be supported by MRI, particularly to contribute in the early differentiation of different forms of non-infectious childhood arthritis.Key points• Juvenile Idiopathic Arthritis (JIA) is a diagnosis of exclusion.• Differentiating JIA and other forms of childhood arthritis can be difficult.• MRI-techniques have substantially improved evaluation of joint abnormalities in JIA patients.• MRI-based synovitis is significantly associated with the clinical onset of JIA.• MRI could support physical examination in the early differentiation of childhood arthritis.

THU0356 Is there an Association between Skin and Joint Involvement in Patients with Psoriatic Arthritis Treated with Adalimumab? – Data-Analysis From a Large German Non-Interventional Study

BackgroundIn Psoriatic Arthritis (PsA) skin and joint manifestations usually occur in parallel. To explore the association between both, severity of skin disease, joint involvement as well as characteristics of joint...

AB0044 Correlation of peripheral il17 cytokine with activity parameters and ultrasound scores in rheumatoid arthritis

BackgroundIt is now recognized that some pro-inflammatory cytokines, such as IL-17, contribute to synovial neoangiogenesis and osteocartilaginous destruction in rheumatoid arthritis (RA). The serum concentration of this cytokine has also...

AB0023 Peripheral th17 cells in rheumatoid arthritis: correlation with the activity parameters of rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease regulated by T lymphocyte subsets. Th17 lymphocytes reportedly play significant roles in the development of this disease.ObjectivesWe investigated the correlation...

The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis

ObjectivesTo develop data-driven criteria for clinically inactive disease on and off therapy for juvenile dermatomyositis (JDM).MethodsThe Paediatric Rheumatology International Trials Organisation (PRINTO) database contains 275 patients with active JDM evaluated...

Functional status in severe juvenile idiopathic arthritis in the biologic treatment era: an assessment in a French paediatric rheumatology referral centre

To investigate the functional status of difficult-to-treat JIA patients, including patients receiving biotherapies, and to correlate functional status to disease activity. All JIA patients consecutively evaluated in a paediatric rheumatology referral centre (November 2008 to March 2009) were enrolled in an observational cross-sectional study. The Childhood HAQ (CHAQ), physician's assessment of overall disease activity, parent's assessment of well-being and pain, and active and limited joint numbers were measured. We enrolled 95 patients [27% systemic, 29% polyarticular, 22% enthesitis-related arthritis (ERA) and 23% oligoarticular JIA]. Median disease duration was 3.5 years. Treatment included NSAIDs (56%), MTX (23%), CSs (21%) and biologics (45%). Of all patients, 31 and 56%, respectively, had inactive and minimally active disease. The median CHAQ score was 0.375 (range 0-3). Most patients had no or mild functional disability (61%), impaired well-being (63%) or pain (55%); 10% reported severely impaired function and well-being, 19% severe pain. ERA patients reported worse well-being and pain. CHAQ scores correlated with disease activity. Long-lasting disease and biologic treatment were associated with better well-being and pain scores. Despite the high proportion of severe JIA patients in this cohort, CHAQ values are within the lower range of recent reports, probably related to new therapeutic approaches. Impaired function and well-being remain a challenge for at least 10% of the patients. Impaired well-being and pain in ERA patients require further study. The strong correlation between functional status and well-being underlines the importance of improving function to optimize quality of life.

Prospective validation of the provisional criteria for the evaluation of response to therapy in childhood-onset systemic lupus erythematosus.

To prospectively validate the provisional criteria for the evaluation of response to therapy in children with systemic lupus erythematosus (SLE). In this multicenter study, childhood-onset SLE patients (n = 98; 81 girls, 17 boys, 50% white, 88% non-Hispanic) were followed every 3 months for up to 7 visits (total number of visits 623). The 5 childhood-onset SLE core response variables were obtained at the time of each visit: 1) physician assessment of overall disease activity, 2) parent assessment of patient well-being, 3) Child Health Questionnaire, 4) proteinuria, and 5) global disease activity measure score, as measured by the European Consensus Lupus Activity Measure (ECLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or the Systemic Lupus Activity Measure (SLAM). Physician-rated relevant changes in the disease course (clinically relevant improvement, no change in disease, or worsening) between visits served as the criterion standard. Mixed models were used to assess the diagnostic accuracy of the 4 highest-ranked provisional definitions of response to therapy. There were 89 episodes of clinically relevant improvement between 2 consecutive visits, and 448 episodes without improvement. Irrespective of the choice of the global disease activity measure (ECLAM, SLAM, SLEDAI), sensitivities of all 4 highest-ranked definitions were low (all < or =31%), whereas their specificities were excellent (all >88%). Using logistic models, alternative definitions can be developed with both 80% sensitivity and specificity. The provisional criteria of response to therapy in childhood-onset SLE may have considerably lower sensitivity than previously reported. Additional validation in clinical trials is necessary to further evaluate the measurement properties of the provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology criteria for response to therapy in children with SLE.

Shifting Our Thinking About Uncommon Disease Trials: The Case of Methotrexate in Scleroderma

Randomized trials for uncommon diseases suffer from methodological challenges: difficulty in recruiting sufficient numbers of patients and low power to detect important treatment effects. Using traditional (frequentist) analysis, p values > 0.05 mean investigators are unable to reject the null hypothesis (of no treatment effect). The medical community often labels trials with p values > 0.05 as "negative." Our study demonstrates how Bayesian analysis conveys more relevant information to clinicians - using the example of methotrexate (MTX) in systemic sclerosis (SSc). Data from 71 patients with diffuse SSc (n = 35 MTX, n = 36 placebo) in the trial were reanalyzed using Bayesian models. We examined 3 primary outcomes: modified Rodnan skin score (MRSS), University of California Los Angeles (UCLA) skin score, and physician global assessment of overall disease activity. Using noninformative prior probability distributions, the probability of beneficial treatment effects for each outcome and the probability of simultaneous benefit in outcomes were computed. The probability that treatment with MTX results in better mean outcomes than placebo was 94% for MRSS, 96% for UCLA skin score, and 88% for physician global assessment. There was 96% probability that at least 2 of 3 primary outcomes were better on treatment. Bayesian analysis of uncommon disease trials allows for more flexible and clinically relevant interpretations of the data. From the trial data, clinicians can infer that MTX has a high probability of beneficial effects on skin score and global assessment.

Therapeutic effects of the anti-tumor necrosis factor monoclonal antibody, infliximab, in four children with refractory juvenile idiopathic arthritis

Objective To report the results of treatment with infliximab in patients with refractory juvenile idiopathic arthritis (JIA). Patients and methods A prospective study of four children with refractory JIA was carried out. Infliximab (100 mg) was administered in weeks 0, 2 and 6. Subsequently, the drug was administered every 8 weeks. The following parameters were assessed at the beginning and at the end of the follow-up period: number of joints with active arthritis, number of joints with a limited range of motion, physician overall assessment of disease activity, parent assessment of the child's overall well-being, pain assessment scores, and erythrocyte sedimentation rate. Improvement was rated according to the definition of the American College of Rheumatology (ACR 30). Paired sample tests were used for statistical analysis. Results Three girls and one boy aged between 10 and 16 years old with a history of JIA ranging from 1 to 9 years were included. The patients received infliximab for a period of 11 to 33 months (average 22 months). There was a significant decrease in the number of swollen joints (p < 0.05), joints with a limited range of movement (p < 0.04), pain score assessment (p < 0.005), physician overall assessment (p = 0.002), maternal evaluation (p < 0.001), the patient's own evaluation (p < 0.001), and duration of morning stiffness (p < 0.001). Both steroids and methotrexate dosages were reduced and no adverse effects or infections were registered. Conclusions Infliximab improved joint inflammatory indexes and clinical assessments. This improvement increased the quality of life of the patients and their families, suggesting that the use of biological therapy is a good option in refractory JIA.