Physician Global Assessment Of Disease Activity Research Articles

Implementation of the Lupus Low Disease Activity State in Pediatric Rheumatology Care: The Role of the Visual Analog Scale.

We compared the measurement properties of a traditional physician global assessment of disease activity (PhGA) 10-cm visual analog scale (PhGA0-10) with that of the three-point numeric scale (PhGA0-3) in childhood-onset systemic lupus erythematosus (cSLE) as part of the childhood Lupus Low Disease Activity State (cLLDAS). We used a secondary data analysis from a convenience sample of 100 patients with cSLE followed every three months for up to seven visits. Ratings of PhGA0-10, PhGA0-3, parent assessment of patient well-being (ParGA) (range: 0= very poorly, 10 = very well), disease activity as measured by the SLE disease activity index 2000 (SLEDAI-2k), Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI, and the British Isles International Lupus Activity Group index (BILAG; A = 9, B = 3, C = 1, D/E = 0) were compared. After linear transformation of PhGA0-10 to a 0 to 3 range (tPhGA0-10), the frequency of PhGA0-3 ≤1 was assessed to estimate the impact of scale type on the scoring of the cLLDAS. In 600 visits, the median (range) scores of PhGA0-10, PhGA0-3, SLEDAI-2k, SELENA-SLEDAI, and BILAG were 2 (0-10), 1(0-3), 4 (0-28), 4 (0-32), and 2 (0-28), respectively. PhGA0-10 and PhGA0-3 ratings were strong to moderately correlated with (r = 0.73; P < 0.0001) and with more variability for PhGA0-3 ≥2. SELENA-SLEDAI and SLEDAI-2k scores were moderately correlated with PhGA0-10 (r = 0.56/0.54; P < 0.0001). ParGA values were weakly correlated with all other measures considered (all r = -0.19 to -0.34). There were 490 of 600 visits with PhGA0-3 ≤1 and 497 of 600 visits with tPhGA0-10 ≤1 (κ (SE) =0.59 (0.04), McNemar P = 0.4). PhGA0-3 and PhGA0-10 have comparable measurement properties and yield almost identical cLLDAS rates when used in cSLE.

Disease activity trajectories from childhood to adulthood in the population-based Nordic juvenile idiopathic arthritis cohort

ObjectivesTo identify long-term disease activity trajectories from childhood to adulthood by using the clinical Juvenile Arthritis Disease Activity Score (cJADAS10) in juvenile idiopathic arthritis (JIA). Second, to evaluate the contribution...

The importance of ultrasound examination in care of juvenile idiopathic arthritis patients: 9 months follow-up study.

Juvenile idiopathic arthritis (JIA) is a group of rare musculoskeletal disorders with chronic inflammation of joints, typically manifesting before the age of 16 years. The assessment of disease activity remains pivotal in JIA treatment decisions, particularly during clinical remission. While musculoskeletal ultrasound (MSUS) has shown promise in detecting subclinical synovitis, longitudinal data on MSUS features in JIA remains limited. The aim of this study was to evaluate the prevalence of subclinical synovitis observed in MSUS over a follow-up period in JIA patients. Additionally, it sought to assess the consistency and correlation between clinical findings, standardized composite clinical score (JADAS10), and MSUS-detected synovitis during 9 months follow-up. a prospective single-center study was conducted, enrolling all consecutive JIA patients (excluding systemic JIA) seen at the study center in one year period. At three-months intervals over a 9 months period (M0, M3, M6 and M9), patients underwent clinical examination, laboratory tests, and MSUS assessment. Data on demographic characteristics, disease profile, and treatment were collected. Patients were categorized into active disease (ACT) or remission (REM) groups based on Wallace criteria and JADAS10 scores using previously validated thresholds. The ultrasound assessments adhered to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) pediatric group, covering 40 joints, were performed by two ultrasonographers at every visit. Subclinical synovitis was defined as synovitis detected exclusively by MSUS. Spearman's correlation coefficients (rs) were used to evaluate the association between MSUS, clinical data, and outcome measures, such as active joint count (ACJ), patient's/parent's global assessment of disease activity (PaGA), physician's global assessment of disease activity (PhGA) and JADAS10. subclinical synovitis was evident in 5.2% of all joints and in 80.6% of the patients at baseline. During the follow-up period, signs of subclinical synovitis decreased to 3.8% of joints, however, the proportion of affected patients remained high (67.7%), with the majority in REM group. Despite the consistent strong correlation between PaGA and PhGA throughout the study (rs > 0.895; p < 0.001), both measures displayed moderate (rs = 0.647; p < 0.001) to weak (rs = 0.377; p = 0.04) correlations with MSUS findings. Notably, PaGA remained significantly correlated with MSUS at the M9 visit (rs = 0.377, p = 0.04), while PhGA showed no correlation (p = 0.094). The study results indicate the persistence of subclinical inflammation detected by MSUS in a significant proportion of JIA patients, even during clinical remission. Moreover, the findings suggest that conventional measurements of JIA activity may be insufficient for assessing patients in clinical remission.

Paediatric rheumatologists do not score the physician's global assessment of juvenile idiopathic arthritis disease activity in the same way.

To assess the heterogeneity in factors affecting physician's global assessment of disease activity (PhGA) and in PhGA scoring of multiple JIA patient's case scenarios. An electronic web-based questionnaire of factors potentially considered in PhGA was sent worldwide to members of PRINTO and the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN). The respondents were asked to rate from 0 to 100 the relevance of 17 factors possibly affecting PhGA scoring and to derive a PhGA score of 17 detailed JIA patient cases. The median and interquartile range was used to measure the heterogeneity in the scoring. To demonstrate the consistency among the PhGA scores of the patient cases provided by multiple physicians, we assessed the inter-rater reliability using intra-class correlation. The questionnaire was completed by 491 respondents. A large individual variation was observed in the impact of different factors on PhGA when assessing JIA. For non-systemic JIA the presence of fever had the largest variation and swollen joint count had the smallest. For sJIA, the largest variation was seen in the presence of erosions and the smallest in the presence of fever. The intra-class correlation of the group for PhGA scoring of patient cases was 0.53 (95% CI 0.38, 0.72). In a sample of worldwide respondents, the scoring of the PhGA is divergent. Consensus on PhGA scoring guidelines is required to obtain a consistent assessment of patients.

Musculoskeletal Ultrasound and the Assessment of Disease Activity in Juvenile Idiopathic Arthritis.

To determine the frequency of subclinical synovitis on musculoskeletal ultrasonography (MSUS) in juvenile idiopathic arthritis (JIA) and correlate patient- and provider-reported outcome measures with MSUS synovitis. JIA patients with an active joint count (AJC) of >4 underwent a 42-joint MSUS performed at baseline and 3 months. B-mode and power Doppler images were obtained and scored (range 0-3) for each of the 42 joints. Outcomes evaluated included physician global assessment of disease activity (PhGA), patient global assessment of disease activity (PtGA), patient pain, Childhood Health Assessment Questionnaire (C-HAQ), and AJC. Subclinical synovitis was defined as synovitis detected by MSUS only. Generalized estimation equations were used to test the relationship between clinical arthritis (positive/negative) and subclinical synovitis (positive/negative). Spearman's correlation coefficients (rs ) were calculated to determine the association between MSUS synovitis and patient- and physician-reported outcomes. In 30 patients, subclinical synovitis was detected in 30% of joints. Clinical arthritis of the fingers, wrists, and knee joints was significantly associated with MSUS synovitis in these joints. PtGA and the C-HAQ had a moderate (rs =0.44, P= 0.014) to weak (rs =0.37, P=0.045) correlation with MSUS synovitis. There was a statistically significant strong correlation between MSUS synovitis and PhGA (rs =0.61, P=0.001), but a weak correlation with AJC (rs =0.37, P=0.048) at the follow-up visit. Subclinical synovitis was commonly observed in this cohort of JIA patients. The fair-to-moderate correlation of MSUS synovitis with patient- and provider-reported outcomes suggests that MSUS assesses a different, possibly more objective, domain not determined by traditional JIA outcome measurements.

Factors affecting the discrepancy between patient and physician global assessment in early rheumatoid arthritis: The Ontario Best Practices Research Initiative.

We aimed to assess the prevalence and factors affecting the discrepancy between patient global assessment (PtGA) and physician global assessment of disease activity (PhGA) in patients with early rheumatoid arthritis (RA) at enrolment and after one year. Patients from the Ontario Best Practices Research Initiative (OBRI) were included. The discrepancy between PtGA and PhGA was calculated by simple subtraction (PtGA-PhGA). An absolute value ≥30 was considered discordant. Linear regression analysis was used to assess factors affecting PtGA, PhGA, and PtGA-PhGA discrepancy at enrolment and 1-year follow-up. A total of 531 patients with mean disease duration of 0.3 years were analysed. The discordance prevalence was 22.4% at enrolment and 20.3% after one year. PtGA was higher in the majority of the discordant cases. Multivariable regression analysis showed higher PtGA was significantly associated with higher pain score, tender joint counts (TJC28), ESR, and fatigue at enrolment and 1-year follow-up while PtGA was associated with higher swollen joint counts (SJC28) only at enrolment. Similar associations were found for PhGA, with the exception of fatigue, which was not a significant factor at one year. Multivariable analysis showed that higher discrepancy between PtGA-PhGA was associated with lower SJC28 and higher pain score at enrolment and lower SJC28 and higher pain and fatigue score at 1-year follow-up. Significant PtGA-PhGA discrepancy was found in approximately one-quarter of early RA patients. In the majority of these patients, PtGA was higher than PhGA. The main predictors of PtGA and PhGA remained the same after one year.

Juvenile Fibromyalgia in Patients With Juvenile Idiopathic Arthritis: Utility of the Pain and Symptom Assessment Tool.

To evaluate the proportion of children with juvenile idiopathic arthritis (JIA) who met criteria for comorbid juvenile fibromyalgia (FM) using the Pain and Symptom Assessment Tool (PSAT), and to identify clinical and demographic differences among JIA patients with and without juvenile FM. Patients ages 11-17 years with JIA were recruited from 4 North American pediatric rheumatology centers. Each patient completed the PSAT. Additional clinical and disease activity measures included pain visual analog scale, patient global assessment of disease activity (PtGA) and physician global assessment of disease activity (PhGA), the Functional Disability Inventory (FDI), and the Pain Catastrophizing Scale in children. Of 129 patients, 11 met criteria for juvenile FM. FDI scores were markedly higher in patients who tested positive for juvenile FM, with a mean of 24.8 compared to 6.9 in patients without juvenile FM (P < 0.001). Pain catastrophizing scores were also significantly higher, by ~14 points, in patients with juvenile FM. There was a significant tendency for patients to give higher disease activity scores than physicians, which was more marked among patients with juvenile FM. In patients with juvenile FM, PtGA scores exceeded PhGA scores by a mean of 3.7, compared to a mean of 0.7 among patients without juvenile FM (P < 0.001). A minority of JIA patients (8.5%) met criteria for juvenile FM. This group demonstrated markedly more functional impairment. PtGA scores were strikingly higher than PhGA scores among patients with JIA who met juvenile FM criteria, suggesting that providers might consider a more expansive approach to chronic pain and non-musculoskeletal symptom assessment and treatment in JIA patients.

Tofacitinib for the treatment of rheumatoid arthritis: a real-world study in China.

Tofacitinib has only been available in China for 2years to treat rheumatoid arthritis (RA). Our purpose was to compare real-world effectiveness of tofacitinib with that of disease-modifying anti-rheumatic drugs (DMARDs) in Chinese patients with RA. The records of patients with RA treated at Guangdong Provincial People's Hospital between July 2017 and September 2019 were retrospectively reviewed. Patients were divided into those treated with tofacitinib, biological DMARDs (bDMARDs), and conventional synthetic DMARDs (csDMARDs). Clinical disease activity index (CDAI), simplified disease activity index (SDAI), health assessment questionnaire-disability index (HAQ-DI), visual analog scale (VAS) pain score, patient global assessment of disease activity (PtGA), physician global assessment of disease activity (PhGA), and swollen joint and tender joint count were compared among the groups up to 12months of treatment. A total of 150 patients were included: 63 were treated with tofacitinib, 48 with bDMARDs, and 39 with csDMARDs. Tofacitinib was first-line treatment in 26.98% of patients, second-line treatment in 49.21%, and third-line treatment in 26.98%. Patients in the tofacitinib group had significantly higher disease duration (6.11 ± 6.97years) than those in the other groups. All disease indices in the three groups decreased with time, indicating improvement of symptoms, with no differences among the groups at 12months. Tofacitinib appeared to improve symptoms more rapidly than other treatments; however, differences in disease indices were not significant. This real-world study suggests that tofacitinib is rapidly effective and that the effects are sustained after 12months in Chinese patients with RA.

Extracutaneous involvement is common and associated with prolonged disease activity and greater impact in juvenile localized scleroderma.

The aim of this study was to evaluate factors associated with extracutaneous involvement (ECI) in juvenile localized scleroderma (jLS). A prospective, multicentre, 6-month observational study was performed. The data collected included disease features, global assessments, and subject symptoms. Bivariate and linear multilevel regression analyses were performed. A total of 86 jLS subjects (80% female, 80% Caucasian), median age of disease onset 7.7 years, were evaluated. Most had linear scleroderma or mixed morphea. Of the 86 subjects, 49 (57%) had 125 extracutaneous problems {median 2 [interquartile range (IQR) 1, 3] per subject} from nine organ systems. Most of these subjects had multiple musculoskeletal problems. ECI was associated with more extensive cutaneous involvement, higher number of symptoms, family history of autoimmunity, and ANA and RF positivity. Subjects with ECI had higher scores for physician global assessment of damage (PGA-D), and parental global assessment of disease impact, but not baseline physician global assessment of disease activity (PGA-A). Although subjects with ECI received more MTX and glucocorticoid treatment, they had a slower reduction in PGA-A scores and symptoms over time, suggesting a poorer response to treatment. In logistic regression modelling, female sex had the largest effect on parental impact scores. ECI occurred in the majority of subjects with jLS, and was associated with more medication use, longer treatment duration, higher PGA-D scores, and higher parental assessment of disease impact. Our findings suggest that jLS subjects with ECI have greater overall disease burden, both cutaneous and extracutaneous, and poorer response to treatment. More study of the treatment needs of this population is warranted.

Outcome Measures in Large Vessel Vasculitis: Relationship Between Patient-, Physician-, Imaging-, and Laboratory-Based Assessments.

To assess the relationship between measures of disease assessment in patients with large vessel vasculitis. Patients with giant cell arteritis (GCA) or Takayasu arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: 1) patient-reported outcomes (Multidimensional Fatigue Inventory, patient global assessment of disease activity [PtGA], Short Form 36 health survey [SF-36], Brief Illness Perception Questionnaire), 2) physician global assessment of disease activity (PhGA), 3) laboratory outcomes (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR]), and 4) imaging outcomes (PETVAS, a qualitative score of vascular 18 F-fluorodeoxyglucose-positron emission tomography activity). Analyses were performed on 112 patients (GCA = 56, TAK = 56), over 296 visits, with a median follow-up of 6 months. Correlation network analysis revealed assessment measures clustered independently by type of outcome. PhGA was centrally linked to all other outcome types, but correlations were modest (ρ = 0.12-0.32; P < 0.05). PETVAS, CRP level, and PtGA were independently associated with clinically active disease. All 4 patient-reported outcomes strongly correlated with each other (ρ = 0.35-0.60; P < 0.0001). Patient-reported outcomes were not correlated with PETVAS, and only PtGA correlated with CRP level (ρ = 0.16; P < 0.01). Patients whose clinical assessment changed from active disease to remission (n = 29) had a corresponding significant decrease in ESR, CRP level, and PETVAS at the remission visit. Patients whose clinical assessment changed from remission to active disease (n = 11) had a corresponding significant increase in CRP level and PtGA at the active visit. Measures of disease assessment in large vessel vasculitis consist of independent, yet complementary, outcomes, supporting the need to develop composite outcome measures or a standard set of measures covering multiple types of outcomes.

Performance of the 2017 EUSTAR activity index in an scleroderma cohort

Assessment of disease activity in systemic sclerosis (SSc) is limited by the absence of a fully validated, multisystem measure of disease activity. The European Scleroderma Trials and Research Group (EUSTAR) SSc activity index (EScSG-AI) was recently revised, and a validation study within the EUSTAR cohort was performed. In this study, we evaluated the performance of the revised EScSG-AI in an external Australian cohort. The association between the EScSG-AI and the physician global assessment of disease activity (PhGA), both collected prospectively at each annual visit over up to 12years follow-up, was evaluated using Pearson's correlation coefficient and Cohen's kappa coefficient. Generalized linear modelling and time-dependent Cox regression analysis were performed to determine the association of disease activity measured by the EScSG-AI and the summed Medsger Severity Scale (MSS) and death, respectively. There was a moderate correlation between EScSG-AI and PhGA scores (r 0.42, p < 0.001) and moderate association between rising EScSG-AI and summed MSS (r 0.60, p < 0.001). High disease activity, measured by the EScSG-AI at any time during follow-up, was associated with a hazard ratio of 2.07 (95% CI 1.51-2.79) for mortality. The EScSG-AI has a moderate correlation with physician-assessed SSc disease activity. This suggests that the criterion and construct validity of the EScSG-AI are yet to be demonstrated in an external cohort of SSc patients. Key Points •There remains no gold standard measure of SSc disease activity. •The revised 2017 EUSTAR SSc disease activity index shows moderate correlation with physician-rated global disease activity. •Significant work remains to develop a validated multisystem measure of disease activity in SSc.

THU0111 PHYSICIAN’S GLOBAL ASSESSMENT OF DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS: WHAT DO WE REALLY MEAN?

Background:Physician’s global assessment of disease activity (PhGA) is included in some scores of disease activity and, demonstrably, plays a major role upon treatment decisions in rheumatoid arthritis (RA) [1, 2, 3]. Therefore, understanding the reasons underlying the physician´s assessment is crucial.Objectives:To understand the reasons underlying the physician´s assessment.Methods:Cross-sectional study, including consecutive RA patients followed in a Tertiary Rheumatology Department. Socio-demographic (age and gender) and clinical data were collected through a standardized protocol, including 28 tender (TJ28) and swollen (SJC28) joints count, C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Disease activity Score (DAS28-4v-CRP and DAS28-4v-ESR), PhGA and Patient Global Assessment of disease Activity (PGA) through a Visual Analogic Scale (VAS) 0-100mm, Health Assessment Questionnaire (HAQ), European Quality of Life-5 Dimensions (EQ-5D) and Hospital Anxiety and Depression Scale (HADS). Correlation between PhGA and other continuous variables was evaluated through Pearson´s Correlation Coefficient and variables with p&lt;0.05 in univariate analysis were included in multivariable linear regression (stepwise model).Results:392 RA patients (80.6% female, 65.3±12.6 years) were included. PhGA was weakly correlated with CRP (r=0.23), TJC28 (r=0.35), PGA (r=0.26), HAQ (r=0.31) and EQ5D (r=-0.21). Moderate correlations were observed with SJC28 (r=0.45) and DAS-4V-CRP (r=0.48). In multivariable analysis, SJC28 (β=4.14, 95%CI:3.16-5.12), CRP (β=0.22; 95%CI: 0.02-0.03), HAQ (β=4.46, 95%CI:1.50-7.42) and PGA (β=0.08; 95%CI:0.00-0.16) remained as independent correlates of PhGA (R2=0.27, p&lt;0,05).Conclusion:In this study, PhGA was associated with SJC28, CRP, HAQ and PGA, suggesting that physicians adopt a comprehensive reading of the disease into account. However, a large proportion of the variance of PhGA remains unexplained. Given its driving role in treatment decisions, the need to standardize and better understand PhGA seems to deserve a closer attention.

Determinants of Patient’s Global Assessment of Disease Activity and Physician’s Global Assessment of Disease Activity in patients with rheumatoid arthritis: A post hoc analysis of overall and Japanese results from phase 3 clinical trials

Objectives: To assess the determinants of Patient’s Global Assessment of Disease Activity (PtGA) and Physician’s Global Assessment of Disease Activity (PhGA) in overall and Japanese patients with rheumatoid arthritis (RA) from two large randomized controlled trials.Methods: Post hoc analysis of overall and Japanese RA patients who had previous inadequate responses to methotrexate or who had no/minimal previous disease-modifying antirheumatic drug treatment. We examined correlations between PtGA/PhGA and tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), inflammatory markers, pain visual analog scale (VAS), and other patient-reported outcomes at baseline, Week 12, and Week 24. Determinants of PtGA/PhGA were identified.Results: In overall populations, pain VAS was the main determinant of PtGA, whereas TJC28 was the main determinant of PhGA in both studies. In Japanese populations, consistent with overall populations, pain VAS was the main determinant of PtGA in both studies; in contrast to overall populations, pain VAS and SJC28/TJC28 played an important role in PhGA.Conclusion: Pain was the most important determinant of PtGA, whereas determinants of PhGA varied between populations/studies and were mostly explained by pain/joint counts. Physicians should be aware of patients’ perceptions of disease activity when performing assessments/prescribing treatments.

FRI0138 A Psychometric Analysis of Outcome Measures in Trials of Peripheral Spondyloarthritis

BackgroundIn peripheral spondyloarthritis (pSpA), no specific efficacy endpoint has been developed representing improvement in arthritis, enthesitis, and/or dactylitis.ObjectivesTo assess the discriminatory aspects of disease activity measures and response criteria between...

AB0685 The systemic lupus erythematosus activity scoring tool (LAST) and the simplified clinical index (C-LAST) are simple and sensitive indices of disease activity as compared to the sledai selena modification

BackgroundSystemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with variable manifestations. New developments in the understanding and treatment of SLE mandated closer monitoring of the disease activity and its...

AB1186 IL-1beta inhibition with canakinumab in patients with systemic juvenile idiopathic arthritis: Efficacy and safety outcomes from a single-dose, placebo-controlled study

BackgroundIL-1β, a key inflammatory cytokine, appears to play a prominent role in systemic juvenile idiopathic arthritis (SJIA). Canakinumab (CAN), a fully human, anti-IL-1β monoclonal antibody selectively binds to IL-1β and...

SAT0271 Predictors of physical function and mobility in nonradiographic axial spondyloarthritis and ankylosing spondylitis

BackgroundThe definition of axial spondyloarthritis is evolving with a new ASAS classification. Maintenance of physical function and patient mobility are primary goals in the treatment of ankylosing spondylitis (AS) and...

Methotrexate and Corticosteroids in the Treatment of Localized Scleroderma: A Standardized Prospective Longitudinal Single-center Study

To evaluate the effectiveness of a uniform single-center treatment protocol composed of high-dose methotrexate (MTX) and oral corticosteroids in a pediatric localized scleroderma (LS) cohort. Thirty-six patients with LS were recruited. Patients with active disease, defined as erythematous lesions and/or new lesions, or expansion of existing lesions, were started on oral prednisone 2 mg/kg/day (maximum 60 mg/day) and subcutaneous (SC) MTX at 1 mg/kg/week (maximum 25 mg/week). Prednisone was tapered and kept at 0.25 mg/kg/day for 12 months. MTX SC was continued for 24 months, and then switched to oral administration to complete 36 months of therapy. Modified LS Skin Severity Index (mLoSSI) and the physician global assessment of disease activity (PGA-A) were used as outcome measures. Twenty-five patients with LS were female with a median age at onset of 7.86 years [interquartile range (IQR) 4.63-11.91]. Median disease duration from onset until start of this treatment regimen was 19.2 months (IQR 8.96-35.35). Median duration of followup was 36.40 months (IQR 29.39-45.36). All patients demonstrated significant improvement in mLoSSI at median 1.77 months (IQR 0.76-2.37, 95% CI 1.54, 2.01). PGA-A followed the same trend. No significant adverse reactions or flares were observed during therapy. This single-center LS treatment protocol was effective and well tolerated. Clinical outcome in LS is affected by dose and route of administration of immunosuppressive regimens. Daily tapering dose of corticosteroids and parenteral MTX were effective in controlling LS activity without significant adverse reaction. This regimen should be considered as one of the therapies for LS clinical trials.

Informing Response Criteria for Psoriatic Arthritis. I: Discrimination Models Based on Data from 3 Anti-Tumor Necrosis Factor Randomized Studies

To develop statistical models, based on the analysis of data from phase III randomized placebo-controlled trials of tumor necrosis factor-alpha (TNF-alpha) inhibitors over a 24-week period, that may inform the definition of response measures for clinical trials in psoriatic arthritis (PsA). Data from phase III randomized controlled trials with anti-TNF agents were used. A training set using baseline and 24-week data from 2 trials was used to derive the models, which were then tested on a dataset using baseline and interim data from the third trial, and baseline and interim data from the first 2 trials. Logistic regression, tree analysis, and factor analysis were considered in the development of the models. Receiver-operating characteristic curves were constructed and area under the curve (AUC) calculated to assess performance of the models. Two models were derived. One was based on differences between baseline and last-visit values, which identified the current 68 tender joint count (TJC68), baseline and change in C-reactive protein (CRP), and the measure with the highest difference among the patient and physician global assessment of disease activity (GDA), patient assessment of pain and the Health Assessment Questionnaire (HAQ). The second model was based on percentage change from baseline and included TJC68, CRP, physician GDA, patient global assessment of arthritis pain, and HAQ. Both models provided high AUC of at least 0.8 for both the training and testing sets. Models for discriminating joint disease response patterns in PsA were derived from data from randomized controlled trials. These models can now be used to inform further consideration of response measures for trials.

7.4 Improvements in individual disease components are sustained with long-term adalimumab therapy for polyarticular Juvenile Idiopathic Arthritis

To control symptoms and prevent increasing disability in children with active polyarticular Juvenile Idiopathic Arthritis (JIA), long-term, effective treatment that controls all aspects of the disease is necessary. Individual ACR Pedi response criteria were analyzed for the 128 patients who entered the open-label extension (OLE) of the Phase III study of adalimumab in the treatment of polyarticular JIA. Measurements of disease activity were performed at each visit, including active joint count (AJC), number of joints with limitation of passive motion (LOM), parent's or patient's assessment of patient's pain (PaP), disability index of the Children's Health Assessment Questionnaire (CHAQ DI), and physician's global assessment of disease activity (PhDA). Observed data were examined for those patients who had been treated with adalimumab throughout the study and reached more than 1 year in the OLE (Week 56; 75% of entering patients had data available). Patients entering the study had active polyarticular JIA, with clinically significant joint involvement, limitation of motion, pain, and disability in performing daily living activities. Long-term treatment with adalimumab provided marked improvements in disease activity (Table ​(Table1).1). The established safety profile for adalimumab remained consistent. Table 1 Improvements in JIA with adalimumab therapy Long-term treatment with adalimumab substantially improves multiple aspects of polyarticular JIA.