Composite Disease Activity Measures Research Articles

Nitisinone attenuates progression of aortic stenosis in patients with alkaptonuria: an analysis of the SONIA 2 study

Abstract Background/introduction Alkaptonuria (AKU) is a rare metabolic disorder caused by a defective enzyme, resulting in deposition of unmetabolised homogentisic acid in various connective tissues throughout the body (also termed "ochronosis"). Ochronosis of the aortic valve leading to progressive aortic stenosis is a rare but serious complication. Nitisinone decreases urinary and serum homogentisic acid levels and has been shown to improve morbidity and slow disease progression in AKU but the effects of this treatment on the progression of aortic stenosis have not yet been described. This review extrapolated from the data set of the SONIA 2 study, a 4-year multi-centre, randomised controlled trial investigating the effect of nitisinone on a composite clinical measure of AKU disease activity, but looked more specifically at measures of aortic stenosis disease progression. Methods Data was obtained from echocardiograms performed on 138 patients at baseline, 12, 24, 36 and 48 months of follow-up. In measuring the degree of aortic stenosis, the peak trans-aortic velocity (Vmax) was examined. A linear mixed effects regression model was used to assess the association between treatment and Vmax and to ascertain the difference in this measure at baseline and 48 months between the treatment and control groups. The mixed effects model incorporated both fixed effects for population parameters (age, sex, baseline Vmax, follow-up time) and treatment; and random effects, to account for intra-subject correlation of longitudinal observations of Vmax, inter-subject variability of baseline measurements of Vmax, and centre. Results At baseline, 19/138 patients (13.8%) had aortic stenosis, as classified by echocardiogram findings in accordance with the European Society of Cardiology (ESC) guidance on valvular heart disease, with 9/19 having mild aortic stenosis, 6/19 having moderate aortic stenosis and 4/19 having severe aortic stenosis. 25/138 had aortic sclerosis (see figure 1). The prevalence of aortic valve disease increased with age. From the 4-year follow-up period, 613 longitudinal observations of 138 subjects across all sites were obtained. At baseline, the difference in Vmax between the control and treatment groups was 0.063 m/s [95% CI: -0.054 m/s to 0.18 m/s] and did not reach statistical significance (p=0.23). At the end of the 4-year treatment period, the difference in Vmax was 0.10 m/s [95% CI: -0.0007 m/s to 0.20 m/s] and was statistically significant (p=0.05) (see figure 2). Conclusion Nitisinone slowed progression of aortic stenosis in patients with AKU. This may be grounds for timely initiation of nitisinone in those deemed to be at high risk, as identified by echocardiography. Of note, this is the first time that any medical therapy has ever been shown to affect the natural history of aortic stenosis.

Exploratory analysis of the potential disconnect between objective inflammatory response and clinical response following certolizumab pegol treatment in patients with active axial spondyloarthritis

IntroductionThis post hoc analysis evaluated the relationship between objective measures of inflammation and clinical outcomes following 12 weeks of certolizumab pegol (CZP) treatment in patients with active axial spondyloarthritis (axSpA).MethodsWe...

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.

P175 The Psoriatic Arthritis Impact of Disease 12-item questionnaire can replace other patient-reported outcome measures to facilitate disease monitoring in clinical practice

Abstract Background/Aims The Psoriatic Arthritis Impact of Disease 12-item questionnaire (PsAID-12) was developed and validated to improve assessment of disease activity from the patient’s perspective. Several patient-reported outcome measures (PROMs) are relevant to PsA but completing several questionnaires at each clinic visit creates a time and administrative burden for patients and clinicians. Furthermore, the Minimal Disease Activity (MDA) for assessing disease activity in PsA requires the Health Assessment Questionnaire (HAQ) to be collected; however, a Canadian study found that PsAID-12 can replace HAQ in the MDA using a cut-off of < 3.7. A previous study also found sex-specific differences in PsAID-12 scores, with scores being higher in females. The aim of this study was to assess whether PsAID-12 correlates well and could replace other PROMs in clinical practice, and to validate previously published findings related to the use of PsAID-12 instead of HAQ in determining MDA, and sex-specific differences in PsAID-12 scores. Methods Clinical data were collected from 75 consecutive patients attending a PsA clinic in a tertiary centre at their first review in 2023. Clinical characteristics, PROMs, examination findings, and measures of disease activity were recorded. Correlation with PsAID-12 was assessed using Spearman’s rank correlation coefficient. Sex-specific differences were assessed using Mann-Whitney U tests. Bonferroni correction was used to adjust for multiple comparisons. Results PsAID-12 scores were significantly correlated with all PROMs, and with composite measures of disease activity (DAPSA, MDA), but not with clinical measures of disease activity (TJC, SJC, PASI, BSA), or acute-phase reactants (CRP, ESR). PsAID-12 scores were not affected by age or disease duration. There was no sex-dependent difference in PsAID-12 scores; however, female patients had significantly higher HAQ and HAD scores. MDA scores using PsAID-12 correlated significantly with MDA scores using HAQ. Conclusion PsAID-12 is a suitable replacement for other PROMs in clinical practice, and for HAQ when determining MDA status to reduce the time and administrative burden on patients and clinicians, and to facilitate monitoring of disease activity in patients with PsA regardless of age or disease duration. Contrary to previous studies, there were no sex-dependent differences in PsAID-12 scores. Disclosure R.M. Hum: None. K. Hasanein: None. L.T. Hao: None. J.C. Williams: None. A. Cheung: None. A. Adhikarla: None. A. Choyce: None. A. Newton: None. C. Clegg: None. A. Barton: None. P. Ho: None.

Efficacy of risankizumab across subgroups in patients with active psoriatic arthritis: a post hoc integrated analysis of the phase 3 KEEPsAKE 1 and KEEPsAKE 2 randomized controlled trials

In the KEEPsAKE 1 (NCT03675308) and KEEPsAKE 2 (NCT03671148) phase 3 trials, risankizumab demonstrated greater efficacy compared with placebo in patients with active psoriatic arthritis (PsA). This post hoc integrated analysis evaluated achieving the following efficacy outcomes at weeks 24 and 52 by baseline demographics and clinical characteristics: ≥20%/50%/70% improvement in American College of Rheumatology response criteria (ACR20/50/70), ≥90% improvement in Psoriasis Area and Severity Index, minimal disease activity status, Low Disease Activity status (Disease Activity in Psoriatic Arthritis), and minimal clinically important difference in pain. Baseline demographics and clinical characteristics were similar between risankizumab (n = 707) and placebo (n = 700) groups. Numerically higher ACR20 response rates at week 24 (primary endpoint) were observed among the risankizumab (46.3%−60.1%) vs. placebo (15.5%−36.2%) cohorts, regardless of subgroups. At week 52, consistent proportions of patients randomized to risankizumab achieved ACR20 (48.6%−75.8%) while those initially randomized to placebo and switched to risankizumab experienced an improvement from week 24 (43.7%−63.9%), regardless of subgroups. Similar trends were observed for other efficacy measures assessing rigorous skin response criteria, composite measures of overall disease activity, and PsA-related symptoms. Risankizumab treatment was efficacious among patients with varying demographic and psoriatic disease characteristics through 52 weeks.

Correlation of changes in inflammatory and collagen biomarkers with durable guselkumab efficacy through 2 years in participants with active psoriatic arthritis: results from a phase III randomized controlled trial.

Guselkumab (human monoclonal antibody) selectively inhibits the interleukin (IL)-23p19 subunit. Assess the longer-term pharmacodynamic effects of guselkumab and explore associations between such effects and clinical responses in patients with active psoriatic arthritis (PsA). DISCOVER-2 randomized 739 biologic-naïve patients with active PsA (swollen/tender joint counts each ⩾5, C-reactive protein (CRP) ⩾0.6 mg/dL) to guselkumab (100 mg every 4 weeks (Q4W) or at Weeks 0, 4, and then Q8W) or placebo. Guselkumab-randomized participants with available serum biomarker data (randomly selected to reflect demographic and disease characteristics of the DISCOVER-2 population) comprised inflammatory (N = 100) and collagen (N = 178) biomarker cohorts. Pharmacodynamic effects of guselkumab through 2 years on inflammatory and collagen biomarker levels (general linear model) and associations between biomarkers and improvements in composite measures of joint, skin, and overall disease activity (Spearman linear regression) through 2 years were assessed. The relationship between the pharmacodynamic effects of guselkumab and achieving ⩾50% improvement in the American College of Rheumatology response criteria (ACR50) was assessed using a general linear model. With guselkumab, pharmacodynamic effects on inflammatory (CRP, IL-6, serum amyloid A (SAA), IL-17A, IL-17F, IL-22, and beta-defensin 2 (BD-2)) and collagen (matrix metalloproteinase-degradation type I, III, IV, and VI collagen (C1M, C3M, C4M, and C6M)) biomarker levels were sustained or enhanced through Week 100. Throughout follow-up timepoints (Week 24/52/100), decreases in CRP, IL-6, C1M, and C6M levels correlated (r = 0.26-0.30; p < 0.05) with improved joint disease activity (Disease Activity in Psoriatic Arthritis); decreases in IL-17A, IL-17F, IL-22, and BD-2 levels correlated (r = 0.34-0.58; p < 0.05) with improved skin disease (Psoriasis Area and Severity Index); and decreases in C1M, C3M, C4M, and C6M correlated (r = 0.27-0.31; p < 0.05) with improved overall disease activity (Psoriatic Arthritis Disease Activity Score). Significantly (p < 0.05) greater reductions from baseline at Week 100 in CRP, IL-6, SAA, and C1M levels were observed in participants improving from Week 24 ACR50 nonresponse to Week 100 ACR50 response and were accompanied by a significant decrease in C1M from Week 24 to Week 100 versus nonresponders at both Weeks 24 and 100. In biologic-naïve participants with active PsA, guselkumab elicited substantial and enduring reductions in biomarkers that were associated with durable improvements in joint, skin, and overall disease activity through 2 years of DISCOVER-2. NCT03158285 (clinicaltrials.gov identifier).

Central Sensitization in Psoriatic Arthritis: Relationship With Composite Measures of Disease Activity, Functional Disability, and Health-Related Quality of Life.

To investigate the prevalence of central sensitization (CS) in patients with psoriatic arthritis (PsA) and its association with disease activity and patient-reported outcome measures. This cross-sectional study included adults with PsA without coexisting fibromyalgia (FM). Patients underwent a clinimetric assessment to collect variables regarding disease activity, quality of life (QOL), functional ability, impact of disease, and CS. Spearman ρ was used to examine the relationship between CS Inventory (CSI) scores and other variables. A multivariate analysis was performed to determine the independent contribution of each variable to the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) score. One hundred fifty-seven patients were enrolled. Of them, 45.2% scored a CSI ≥ 40, indicating a high probability of CS. Significant correlations were found between CSI and disease activity, as evaluated by Disease Activity in Psoriatic Arthritis score and Psoriatic Arthritis Disease Activity Score (ρ 0.587 and ρ 0.573, respectively), between CSI and the Health Assessment Questionnaire (ρ 0.607), and between CSI and the 36-item Short Form Health Survey physical component summary and mental component summary scores (ρ -0.405 and ρ -0.483, respectively). In multivariate analysis, CSI score was the principal independent variable (P < 0.001) contributing to PsAID-12 score. Patients with PsA with symptoms of CS had higher disease activity, worse functional ability, and worse QOL. The presence of CS is the major contributor in the impact of disease.

Construct validity and responsiveness of feasible composite disease activity measures for use in daily clinical practice in patients with psoriatic arthritis

ObjectiveThere is a need for a widely accepted comprehensive disease activity measure for use in daily practice in patients with psoriatic arthritis (PsA). For this reason, the 3-item Visual Analogue...

The Psoriatic Arthritis 5-Thermometer Scales (PsA-5Ts): Measurement Properties of a New Multidimensional Composite Tool for the Quick Assessment of the Overall Health Status in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a heterogeneous condition that is difficult to assess. The goal of this research was to evaluate the clinimetric properties of the Psoriatic Arthritis 5-Thermometer Scales (PsA-5Ts), a new patient-reported outcome (PRO) to measure the overall health status in PsA patients. The PsA-5Ts were compared to composite measures of disease activity (DAPSA, PASDAS, CPDAI) and PROs (PsAID-12 and SF-36). The convergent validity was assessed through the Spearman's correlation coefficient and the discriminant validity through the receiver operating characteristic (ROC) curve analysis, applying the Minimal Disease Activity (MDA) as an external criterion. The cross-sectional assessment included 155 patients. Significant high correlations were observed when comparing PsA-5Ts to composite indices of disease activity and PROs (all at significance levels of p < 0.0001). The PsA-5Ts subscales were highly significantly different in terms of MDA status (all at p < 0.0001). The PsA-5Ts had good discriminant validity like that of the DAPSA, CPDAI, PASDAS, and PsAID-12, and better than that of the SF-36, with an area under the ROC curve of 0.944 (65% CI 0.895-0.974). The PsA-5Ts are an easy-to-use PRO that can be integrated with disease activity indices in the assessment of PsA in daily clinical practice.

Using the derived 28-joint disease activity score patient-reported components (DAS28-P) index as a discriminatory measure of response to disease-modifying anti-rheumatic drug therapy in early rheumatoid arthritis

BackgroundThe 28-joint disease activity score (DAS28) is a widely used measure to assess disease activity in rheumatoid arthritis (RA). The DAS28-P index, a derived proportion of the patient-reported components (joint tenderness and patient global assessment) within the DAS28, has been utilized as a discriminatory measure of non-inflammatory pain mechanisms in RA. This study aimed to evaluate the use of the DAS28-P index as a predictor of treatment response in early RA.MethodsPatients with early RA enrolled in a supplemental fish oil clinical trial received a combination of disease-modifying anti-rheumatic drugs (DMARDs) according to a ‘treat-to-target’ protocol. First, consecutive measures of the DAS28-P index, derived from the DAS28-erythrocyte sedimentation rate (DAS28-ESR), at each visit over a 1-year period were estimated for each patient. Then, distinct subgroups of treatment responders based on the trajectories of the DAS28-P indices were identified using bivariate k-means cluster analysis. Data on baseline predictors as well as longitudinal outcomes of disease impact and DMARD use over a 1-year period and radiographic progression over a 3-year period were collected and analyzed using a random intercept, population-averaged generalized estimating equation model.Results121 patients were included (74% female; mean age of 57; median of 16 weeks of active disease) and a 3-cluster model was identified—the ‘Responders’ group (n = 58; 48%), the ‘Partial Responders’ group (n = 32; 26%), and the ‘Non-Responders’ group (n = 31; 26%). The ‘Partial Responders’ group had consistently higher proportions of the DAS28-P index throughout the study period and had minimal radiographic progression over time, with the lowest joint erosion score of 0.9 [95% confidence interval (CI) 0.2, 1.6], observed at the 3-year follow-up. At 52 weeks, the methotrexate dose was higher for both ‘Partial Responders’ and ‘Non-Responders’ groups (18.5 mg [95% CI 15.5, 21.5] and 18.6 mg [95% CI 15.3, 21.8] respectively), when compared with the ‘Responders’ group (12.8 mg [95% CI 14.7, 20.9]).ConclusionsPersistently high DAS28-P index scores are useful to distinguish poor patient global assessment and excessive treatment escalation in early RA, suggestive of underlying non-inflammatory pain contributing to higher disease activity score. Early identification of patients with discordant subjective and objective components of composite disease activity measures may allow better tailoring of treatment in RA.

The role of ultrasonographic synovial assessment in rheumatoid arthritis patients with concomitant fibromyalgia.

This study aimed to compare the prevalence and musculoskeletal ultrasonography (US) findings of rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) according to the 1990 American College of Rheumatology (ACR) FM classification criteria or the 2016 ACR FM diagnostic criteria. This cross-sectional study included 63 patients (17 males, 46 females; mean age: 48.2±7.1 years; range, 18 to 62 years) with RA. Medical history and laboratory data were obtained from electronic records. Clinical examination, composite disease activity measures, functional status, and the German 7-joint ultrasound score were assessed to evaluate disease activity and synovial inflammation. The patients were divided into three groups: patients who met only the 2016 ACR criteria, patients who met only the 1990 ACR criteria, and patients who met both criteria. In patients with RA, concomitant FM prevalence was 34.9% according to the 2016 ACR FM diagnostic criteria versus 23.8% according to the 1990 ACR FM classification criteria. Rheumatoid arthritis patients with FM had high tender joint count and disease activity scores, while musculoskeletal US findings were similar. Patients who met only the 2016 ACR FM diagnostic criteria had significantly higher gray-scale US and power Doppler US synovitis scores than patients who satisfied only ACR 1990 FM classification criteria (p=0.03 and p=0.02, respectively). Synovial inflammation is a prominent sign in RA patients diagnosed with FM according to the 2016 ACR FM diagnostic criteria. The higher disease activity seen in the presence of FM in RA patients is associated with FM rather than synovitis.

OP0224 CONTINUOUS COMPOSITE MEASURES FOR ROUTINE CARE IN PSORIATIC ARTHRITIS: THRESHOLDS OF MEANING AND CLINICALLY IMPORTANT DIFFERENCE ESTIMATES FOR THE 3 AND 4 VAS SCALES FROM A UK MULTICENTRE STUDY

Background:There is a recognised need for a continuous composite measure of disease activity for the assessment of Psoriatic Arthritis (PsA) in routine clinical settings to allow objective assessment of response and implementation of treat to target.1 Longer multidimensional measures are considered less feasible in routine care and a number of shorter measures have been proposed including, the Disease Activity Score for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), the 3 Visual Analogue Scale (VAS) (comprising physician global VAS, patient global VAS and patient skin VAS) or 4 VAS (comprising physician global VAS, patient pain VAS, joint VAS and patient skin VAS). Testing of these measures in clinical trial datasets has been suggested but thresholds of meaning have not been established.2Objectives:To estimate clinically relevant thresholds of disease activity and improvement for composite measures for routine clinical practice in PsA.Methods:Clinical and patient reported outcome measures were assessed in patients fulfilling CASPAR criteria for PsA at three consecutive follow up visits in a UK multicentre observational study. Participants underwent clinical assessment and completed patient reported measures including health anchor questions. Estimates for Minimal Detectible Change (MDC) were derived using 1.96*2*Standard Error of the Mean (SEM). Minimal Clinically Important Difference (MCID) for improvement were derived using the health anchor method and two distribution methods (Table 1). Thresholds for low, moderate and high disease activity were triangulated from established cut-off values for the patient global VAS, PASDAS and DAPSA.Table 1.Minimal Clinically Important Difference (MCID) and Minimal detectable change (MDC)ANCHOR (MEDIAN)DISTRIBUTION#1DISTRIBUTION #2MDCCPDAI0.51.491.54.16GRACE0.260.60.772.18PASDAS1.220.640.761.58DAS280.20.850.621.463VAS1.131.160.913.124VAS1.110.960.942.45DAPSA7.259.0910.4035.63Disease Activity Score for Psoriatic Arthritis (DAPSA); Psoriatic Arthritis Disease Activity Score (PASDAS); Composite Psoriatic Arthritis Disease Activity Index (CPDAI); Disease Activity Score 28 (DAS28).Distribution #1: Baseline standard deviation (sd) * √ 1 – Cronbach’s alphaDistribution #2: 0.5 * baseline sdMinimal detectable change (MDC): 1.96*2*SEM where SEM = baseline sd √1 - ICCResults:139 subjects were recruited (59 male, 80 female, mean (range) age (years) 52.7 (19 – 83), mean (range) duration of psoriasis (years) 21.9 (2 – 71), mean (range) duration of psoriatic arthritis (years) 6.1 (0 – 41). Cut-off values for low, moderate and high disease activity were 1.3, 2.4, and 4.8 for the 3 Vas and 1.6, 2.8 and 5.0 for the 4 VAS (Figure 1). Estimates for the MCID and MDC for the continuous composite measures and are reported in Table 1.Conclusion:We report estimates of clinically relevant improvements for continuous composite measures in PsA and estimates of low, moderate and high disease activity for the 3 and 4 VAS scales. The thresholds of meaning can now be tested in independent observational and clinical trial datasets.

OP0089 DO PAIN CATASTROPHIZING REDUCE THE LIKELIHOOD OF REMISSION IN PATIENTS WITH CHRONIC INFLAMMATORY JOINT DISORDERS?

Background:Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA) may have a devastating impact on patients’ lives, including chronic and relapsing pain. One factor contributing to bio-psycho-social model of pain in these diseases, is pain catastrophizing (PC) defined as tendency to report pain experience in exaggerated terms, to ruminate more or to feel helpless about it. In one RA study PC has been shown to be associated with patient reported outcomes e.g. reduced likelihood of remission using composite measures.[1]Objectives:Main objective of this study was to explore if pain catastrophizing score is associated with remission rates in the chronic inflammatory joint disorders RA, PsA and ax-SpA.Methods:Patients were recruited during routine assessment at an outpatient clinic in Norway. Variables collected included demographics, treatment, disease duration, global pain VAS, pain catastrophizing score (PCS), and disease activity scores: DAS28-CRP for RA, BASDAI for ax-SpA and DAPSA for PsA. Cut off definitions of remission was for DAS28 &lt;2.6, for BASDAI &lt;4.0 and for DAPSA ≤4.0. Two questions from Coping Strategies Questionnaire as recommended by Jensen et al [2] were used to describe PC, range PC total score (PCS) 0–6. Patients with PCS ≥ 4 were defined as high pain catastrophizers. Statistics included Chi-Square test and adjusted logistic regression (enter procedure).Results:For RA (N=580), PsA (N=394) and ax-SpA (N=225) mean age (SD) was 61.5 (13.1), 54.4 (12.9) and 47.5 (12.9) years, mean disease duration 12.6 (10.9), 10.2 (8.4) and 12.2 (10.7) years and percentage of women 66.7%, 47.0% and 38.4%. Mean (SD) DAS28-CRP in RA was 2.3 (1.0), BASDAI for ax-SpA 3.7 (2.3) and DAPSA for PsA 10.8 (8.5). Mean (SD) global pain (VAS 0-100mm) was for RA 32.0 (25.6), for PsA 35.5 (25.4) and for ax-SpA 39.4 (25.4) mm. Conventional synthetic DMARDs were used by 65.0% of RA patients, 54.8% by PsA and 9.8% in ax-SpA and for biologic DMARDs the corresponding numbers were 36.7%, 43.9%, 65.9%, respectively.Percentage of patients in remission was significantly lower in high pain catastrophizers compared with low pain catastrophizers in RA (34.1% vs 70.3%, p&lt;0.01) and ax-SpA patients (17.9% vs 64.5%, p&lt;0.01) but not in PsA (10.3% vs 26.7%, p=0.06).In analysis adjusting for age, gender, disease duration and global pain (Tab. 1), PC was independently associated with lower remission rate in RA (OR 0.79 (95% CI 0.63, 0.99), p=0.04) and in ax-SpA (OR 0.65 (95% CI 0.46, 0.93), p=0.02) but not in PsA (OR 0.83 (95% CI 0.55, 1.25), p=0.37)Conclusion:Our data indicates that high level of patient’s PC may reduce likelihood of achieving remission in RA and ax-SpA. Interestingly, this was not shown in PsA patients. Further studies are needed to reveal the importance of PC and its influence on composite disease activity measures used to define disease status e.g. remission.Table 1.Variables and their associations with remission rates in RA, PsA, ax-SpA in logistic regression analysis.RA remissionPsA remissionax-SpA remissionOR (95%CI)pOR (95%CI)pOR (95%CI)pPCS0.79 (0.63, 0.99)0.040.83 (0.55, 1.25)0.370.65 (0.46, 0.93)0.02Age0.99 (0.97, 1.01)0.171.00 (0.96, 1.04)0.850.98 (0.94, 1.02)0.27Gender0.87 (0.52, 1.45)0.590.37 (0.15, 0.93)0.030.92 (0.40, 2.14)0.85Disease duration1.03 (1.00, 1.05)0.030.95 (0.90, 1.00)0.061.04 (0.99, 1.09)0.09Global pain (VAS)0.96 (0.95, 0.97)&lt;0.010.85 (0.81, 0.89)&lt;0.010.90 (0.88, 0.92)&lt;0.01

O13 Which composite measure best reflects disease activity and predicts treatment change in psoriatic arthritis?

Abstract Background/Aims Multiple composite measures of disease activity are available and used in psoriatic arthritis (PsA) research; however, poor agreement remains amongst clinicians on the optimal measure of disease activity. Research to date has focused on polyarticular PsA, despite oligoarticular disease accounting for around half of cases in clinical practice. We aim to compare the ability of Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), Disease Activity score for PSoriatic Arthritis (DAPSA), GRAppa Composite scorE (GRACE) and Disease Activity Score 28 CRP (DAS28-CRP) to assess disease activity and predict treatment change, amongst usual care patients with oligoarticular and polyarticular psoriatic disease. Methods The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise (GRACE) dataset was utilised. Oligoarthritis was defined as &amp;lt; 5 active joints. Reference measures were clinician and patient opinions on disease control and whether treatment was escalated. Patients with baseline data for all composite measures were included. The ability of each composite measure to predict treatment change and capture disease activity was compared using the Mann-Whitney U test. Results Data were available for 271 patients (152 oligoarthritis, 119 polyarthritis). The mean age, duration of PsA and psoriasis were similar for both groups. A higher proportion of oligoarticular patients were male. Patients with polyarticular disease had higher disease activity in skin, enthesitis and dactylitis. Using both patient and physician definitions of disease control, all composite measures were able to differentiate between patients with active and quiescent disease, regardless of disease subtype (p &amp;lt; 0.05). PASDAS demonstrated the largest differentiation in score. Differences between active and inactive disease scores were more pronounced in oligoarticular disease. PASDAS demonstrated the greatest ability to predict treatment change in both oligoarticular and polyarticular disease. Interestingly, DAPSA could not predict treatment change in polyarticular patients, p = 0.074 (Table 1). Conclusion This is the first study to compare composite measures, in oligoarticular and polyarticular PsA in a multinational cohort. All composite measures of disease activity were able to differentiate between active and inactive disease in both subtypes. PASDAS demonstrated the largest discrimination in both polyarticular and oligoarticular disease, suggesting greatest clinical and research utility. Disclosure L. Tucker: None. P. Helliwell: None. L. Coates: None.

Relationships between psoriatic arthritis composite measures of disease activity with patient-reported outcomes in phase 3 studies of tofacitinib

BackgroundIn psoriatic arthritis (PsA), further understanding of the relationships between clinical measures and patient-reported outcomes (PROs) is needed. This post hoc analysis evaluated associations between minimal disease activity (MDA) as a continuous outcome (termed ScoreMDA) or Psoriatic Arthritis Disease Activity Score (PASDAS) with selected PROs not included in the composite measures.MethodsData from two phase 3 studies of tofacitinib in PsA (OPAL Broaden [NCT01877668; N = 422]; OPAL Beyond [NCT01882439; N = 394]) were included. MDA (binary outcome) was defined as meeting ≥5/7 criteria. For ScoreMDA, each criterion was assigned a value (1 = true; 0 = false; score range, 0–7; scores ≥5 indicated MDA). For PASDAS (score range, 0–10), higher scores indicated worse disease activity. PROs analyzed included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Patient’s Assessment of Arthritis Pain visual analog scale (Pain VAS), and EuroQoL-Five Dimensions-Three Level Health Questionnaire visual analog scale (EQ-5D-3L VAS) and utility index. Relationships were evaluated using repeated measures regression models.ResultsSimilar, approximately linear relationships were confirmed between PASDAS or ScoreMDA and PROs in both studies. In OPAL Broaden and OPAL Beyond, a one-point difference in PASDAS was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (− 6.7 mm, − 6.9 mm), Pain VAS (9.9 mm, 10.7 mm), and FACIT-F (− 2.8, − 3.3). A one-point difference in ScoreMDA was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (5.0 mm, 5.5 mm) and FACIT-F (1.9, 2.7) in OPAL Broaden and OPAL Beyond, respectively.ConclusionsLinear associations between PASDAS or ScoreMDA and PROs provide interpretable and quantifiable metrics between composite clinical measures and PROs, highlighting the importance of these measures in understanding the relevance of treat-to-target goals in PsA.Trial registrationClinicalTrials.gov, NCT01877668. Registered on June 12, 2013. ClinicalTrials.gov, NCT01882439. Registered on June 18, 2013

Patient-reported wellbeing and clinical disease measures over time captured by multivariate trajectories of disease activity in individuals with juvenile idiopathic arthritis in the UK: a multicentre prospective longitudinal study.

SummaryBackgroundJuvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use of composite disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score (cJADAS). However, clusters of children and young people might experience different global patterns in their signs and symptoms of disease, which might run in parallel or diverge over time. We aimed to identify such clusters in the 3 years after a diagnosis of JIA. The identification of these clusters would allow for a greater understanding of disease progression in JIA, including how physician-reported and patient-reported outcomes relate to each other over the JIA disease course.MethodsIn this multicentre prospective longitudinal study, we included children and young people recruited before Jan 1, 2015, to the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort. Participants without a cJADAS score were excluded. To assess groups of children and young people with similar disease patterns in active joint count, physician's global assessment, and patient or parental global evaluation, we used latent profile analysis at initial presentation to paediatric rheumatology and multivariate group-based trajectory models for the following 3 years. Optimal models were selected on the basis of a combination of model fit, clinical plausibility, and model parsimony.FindingBetween Jan 1, 2001, and Dec 31, 2014, 1423 children and young people with JIA were recruited to CAPS, 239 of whom were excluded, resulting in a final study population of 1184 children and young people. We identified five clusters at baseline and six trajectory groups using longitudinal follow-up data. Disease course was not well predicted from clusters at baseline; however, in both cross-sectional and longitudinal analyses, substantial proportions of children and young people had high patient or parent global scores despite low or improving joint counts and physician global scores. Participants in these groups were older, and a higher proportion of them had enthesitis-related JIA and lower socioeconomic status, compared with those in other groups.InterpretationAlmost one in four children and young people with JIA in our study reported persistent, high patient or parent global scores despite having low or improving active joint counts and physician's global scores. Distinct patient subgroups defined by disease manifestation or trajectories of progression could help to better personalise health-care services and treatment plans for individuals with JIA.FundingMedical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and National Institute for Health Research.

Predicting the treatment response of certolizumab for individual adult patients with rheumatoid arthritis: protocol for an individual participant data meta-analysis

BackgroundA model that can predict treatment response for a patient with specific baseline characteristics would help decision-making in personalized medicine. The aim of the study is to develop such a model in the treatment of rheumatoid arthritis (RA) patients who receive certolizumab (CTZ) plus methotrexate (MTX) therapy, using individual participant data meta-analysis (IPD-MA).MethodsWe will search Cochrane CENTRAL, PubMed, and Scopus as well as clinical trial registries, drug regulatory agency reports, and the pharmaceutical company websites from their inception onwards to obtain randomized controlled trials (RCTs) investigating CTZ plus MTX compared with MTX alone in treating RA. We will request the individual-level data of these trials from an independent platform (http://vivli.org). The primary outcome is efficacy defined as achieving either remission (based on ACR-EULAR Boolean or index-based remission definition) or low disease activity (based on either of the validated composite disease activity measures). The secondary outcomes include ACR50 (50% improvement based on ACR core set variables) and adverse events. We will use a two-stage approach to develop the prediction model. First, we will construct a risk model for the outcomes via logistic regression to estimate the baseline risk scores. We will include baseline demographic, clinical, and biochemical features as covariates for this model. Next, we will develop a meta-regression model for treatment effects, in which the stage 1 risk score will be used both as a prognostic factor and as an effect modifier. We will calculate the probability of having the outcome for a new patient based on the model, which will allow estimation of the absolute and relative treatment effect. We will use R for our analyses, except for the second stage which will be performed in a Bayesian setting using R2Jags.DiscussionThis is a study protocol for developing a model to predict treatment response for RA patients receiving CTZ plus MTX in comparison with MTX alone, using a two-stage approach based on IPD-MA. The study will use a new modeling approach, which aims at retaining the statistical power. The model may help clinicians individualize treatment for particular patients.Systematic review registrationPROSPERO registration number pending (ID#157595).

Evaluation of Response Criteria in Rheumatoid Arthritis Treated With Biologic Disease-Modifying Antirheumatic Drugs.

Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action. Interleukin-6 inhibitors (IL-6i) block the production of acute-phase reactants (APRs), which are some of the composite measures of disease activity. We undertook this study to examine the agreement between the European League Against Rheumatism (EULAR) response based on the erythrocyte sedimentation rate (ESR) or C-reactive protein level, the Simplified Disease Activity Index 50% response measure (SDAI50), and the Clinical Disease Activity Index 50% response measure (CDAI50) in patients treated with IL-6i and other bDMARDs. We enrolled 306 patients with RA who started or switched bDMARDs. Treatment response at 6 months was analyzed. Kappa statistics were used to evaluate the agreement between different response measures. The contribution of APRs to improvement in disease activity scores was examined. The change of Health Assessment Questionnaire (HAQ) score was analyzed in IL-6i-treated patients. Good agreement was achieved between response measures, with κ >0.6 in patients treated with tumor necrosis factor inhibitors or cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein. In IL-6i-treated patients, the agreement was low between the EULAR response (ESR) and the SDAI50 or the CDAI50 (κ = 0.43 and 0.37, respectively). Under IL-6i treatment, APR improvement accounted for 56.0% of total improvement of the Disease Activity Score in 28 joints (DAS28) using the ESR. When discordance was found between the CDAI50 and EULAR response in IL-6i-treated patients, all patients were classified as EULAR-only responders; there was no HAQ improvement in EULAR-only responders. EULAR response criteria overestimate the response under IL-6i treatment because the APR improvement largely contributes to the DAS28 improvement.

Outcomes of the 2019 GRAPPA Workshop on Continuous Composite Indices for the Assessment of Psoriatic Arthritis and Membership-recommended Next Steps.

Improving the assessment of psoriatic arthritis (PsA) is a key purpose of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA). Herein, we report the proceedings of the GRAPPA composites workshop at the 2019 GRAPPA annual meeting and the membership's recommended next steps. A review of continuous composite measures was conducted in an introductory workshop, followed by 10 breakout group sessions and a final plenary session for feedback and voting. Participants included 154 members: 87 rheumatologists, 18 dermatologists, 2 rheumatologist/dermatologists, 12 patient research partners, 14 academics, 1 methodologist, and 20 industry members. Of voting members, 88.8% agreed a need exists for a continuous composite measure for routine practice, but only 62% were currently using a composite measure. Of these, 27% were using the 28-joint count Disease Activity Score (DAS), which is not a PsA-specific measure; 20% were using a PsA-specific measure such as PsA DAS (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), or Disease Activity Index for PsA (DAPSA). Members agreed that the existing measures were not feasible in their current forms (CPDAI 83%, PASDAS 82%, and DAPSA 47%) and that modification should be tested. The majority (76%) agreed that disease effect should be measured separately from disease activity. The GRAPPA membership supports the need for a continuous composite measure of disease activity for use in routine clinical care, the separate measurement of disease effect and activity, and the testing of modifications to candidate instruments rather than the development of new measures.

Assessment of the many faces of PsA: single and composite measures in PsA clinical trials.

PsA is a complex, heterogeneous disease that can place a large burden on patients’ psychological and physical well-being. The multifaceted nature of PsA poses a significant assessment challenge, both in randomized control trials and in clinical practice. In recent years, there has been much progress in the development of unidimensional and composite measures of disease activity, as well as of questionnaires that capture the patient’s perspective of the condition. Despite these advances, there remains uncertainty around which tools to implement within a research setting. This review aims to summarize the currently available clinical and patient-derived assessment tools, providing a practical and informative resource for the assessment of PsA. This review will also explore recent advancements in digital approaches to the assessment of rheumatological conditions. This will highlight the potential for digitalization in the assessment and monitoring of PsA, outlining innovative means of capturing disease activity and treatment response.