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Objective: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib. Methods: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL‐23) pathway (IL‐17A, β‐defensin [BD‐2], and IL‐19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed. Results: IL‐17A, BD‐2, and IL‐19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL‐17A, BD‐2, IL‐19, C‐X‐C motif ligand 9 (CXCL9), CXCL10, C‐reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL‐23 pathway–associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib‐treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL‐17A (odds ratio 15.76) and BD‐2 levels (odds ratio 15.41) versus low baseline IL‐17A and BD‐2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib. Conclusion: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL‐23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the immunologic profile associated with disease flares in patients with systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following a flare. Methods: Multiparameter flow cytometry was used to examine 47 immune populations within the peripheral blood of 16 healthy controls, 25 patients with clinically quiescent SLE, and 46 patients with SLE experiencing a flare at baseline and at 6‐ and 12‐month follow‐up visits. Unsupervised clustering was used to identify patients with similar immune profiles and to track changes over time. Parametric or nonparametric statistics were used when appropriate to assess the association of cellular phenotypes with clinical and laboratory parameters. Results: Five clusters of patients were identified that variably contained patients with active and quiescent SLE, and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age‐associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow‐up. In contrast, patients who had increased T helper (Th) cells in the absence of B cell changes, or who had increased Th1 cells and innate immune populations, mostly developed quiescent SLE on follow‐up. A significant proportion of patients with SLE had depletion of many immune populations at flare and only showed increases in these populations post‐flare. Conclusion: Cellular phenotyping of patients with SLE reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment. [ABSTRACT FROM AUTHOR]

Objective. To address suboptimal cardiovascular risk prediction in patients with psoriatic disease (PsD), we developed and internally validated a five-year disease-specific cardiovascular risk prediction model. Methods. We analyzed data from a prospective cohort of participants with PsD without a history of cardiovascular events. Traditional cardiovascular risk factors and PsD-related measures of disease activity were considered as potential predictors. The study outcome included nonfatal and fatal cardiovascular events. A base prediction model included 10 traditional cardiovascular risk factors. Eight PsD-related factors were assessed by adding them to the base model to create expanded models, which were controlled for PsD therapies. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression with 10-fold cross-validation. Model performance was assessed using measures of discrimination and calibration and measures of sensitivity and specificity. Results. Between 1992 and 2020, 85 of 1,336 participants developed cardiovascular events. Discrimination of the base model (with traditional cardiovascular risk factors alone) was excellent, with an area under the receiver operator characteristic curve (AUC) of 85.5 (95% confidence interval [CI] 81.9–89.1). Optimal models did not select any of the tested disease-specific factors. In a sensitivity analysis, which excluded lipid lowering and antihypertensive treatments, the number of damaged joints was selected in the expanded model. However, this model did not improve risk discrimination compared to the base model (AUC 85.5, 95% CI 82.0–89.1). Conclusion. Traditional cardiovascular risk factors alone are effective in predicting cardiovascular risk in patients with PsD. A risk score based on these factors performed well, indicating excellent discrimination and calibration. [ABSTRACT FROM AUTHOR]

Objective: Psoriatic arthritis (PsA) is an immune‐mediated inflammatory arthritis, associated with psoriasis, that significantly increases morbidity and mortality risk. We currently lack the means of predicting which patients with psoriasis will develop PsA, and a large number of patients remain undiagnosed. Regulation of gene expression through DNA methylation can potentially trigger and maintain PsA pathophysiological processes. We aimed to identify DNA methylation markers that can predict which patients with psoriasis will develop PsA prior to the onset of musculoskeletal symptoms. Methods: Genome‐wide DNA methylation was assessed in blood samples from patients with psoriasis who went on to develop arthritis (converters) and patients with psoriasis who did not (biologic naive, matched for age, sex, psoriasis duration, and duration of follow‐up). Methylation differences between converters and nonconverters were identified by a multivariate linear regression model including clinical covariates (age, sex, body mass index, smoking). Predictive performance of methylation markers was assessed by developing support vector machine classification models with and without the addition of clinical variables. Results: We identified a set of 36 highly relevant methylation markers (false discovery rate: adjusted P < 0.05 and a minimum change in methylation of 0.05) across 15 genes and several intergenic regions. A classification model relying on these markers identified converters and nonconverters with an area under the receiver operating characteristic curve of 0.9644. Conclusion: This study shows that DNA methylation patterns at an early stage of psoriatic disease can distinguish between patients who will develop PsA from those who will not during the same follow‐up. [ABSTRACT FROM AUTHOR]

Objective: The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow‐up. Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. Results: Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39). Conclusion: Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five‐year mortality. [ABSTRACT FROM AUTHOR]

Objective: To analyze the trends in biologics use at a specialized center over a period of 20 years. Methods: We performed a retrospective analysis of 571 patients diagnosed with psoriatic arthritis enrolled in the Toronto cohort who initiated biologic therapy between January 1, 2000, and July 7, 2020. The probability of drug persistence over time was estimated nonparametrically. The time to discontinuation of first and second treatment was analyzed using Cox regression models, whereas a semiparametric failure time model with a gamma frailty was used to analyze the discontinuation of treatment over successive administrations of biologic therapy. Results: The highest 3‐year persistence probability was observed with certolizumab when used as first biologic treatment, while interleukin‐17 inhibitors had the lowest probability. However, when used as second medication, certolizumab had the lowest drug survival even when accounting for selection bias. Depression and/or anxiety were associated with a higher rate of drug discontinuation due to all causes (relative risk [RR] 1.68, P = 0.01), while having higher education was associated with lower rates (RR 0.65, P = 0.03). In the analysis accommodating multiple courses of biologics, a higher tender joint count was associated with a higher rate of discontinuation due to all causes (RR 1.02, P = 0.01). Older age at the start of first treatment was associated with a higher rate of discontinuation due to side effects (RR 1.03, P = 0.01), while obesity had a protective role (RR 0.56, P = 0.05). Conclusion: Persistence in taking biologics depends on whether the biologic was used as first or second treatment. Depression and anxiety, higher tender joint count, and older age lead to drug discontinuation. [ABSTRACT FROM AUTHOR]

Objective: To estimate direct and indirect costs associated with neuropsychiatric (NP) events in the Systemic Lupus International Collaborating Clinics inception cohort. Methods: NP events were documented annually using American College of Rheumatology definitions for NP events and attributed to systemic lupus erythematosus (SLE) or non‐SLE causes. Patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). Change in NP status was characterized by interstate transition rates using multistate modeling. Annual direct costs and indirect costs were based on health care use and impaired productivity over the preceding year. Annual costs associated with NP states and NP events were calculated by averaging all observations in each state and adjusted through random‐effects regressions. Five‐ and 10‐year costs for NP states were predicted by multiplying adjusted annual costs per state by expected state duration, forecasted using multistate modeling. Results: A total of 1,697 patients (49% White race/ethnicity) were followed for a mean of 9.6 years. NP events (n = 1,971) occurred in 956 patients, 32% attributed to SLE. For SLE and non‐SLE NP events, predicted annual, 5‐, and 10‐year direct costs and indirect costs were higher in new/ongoing versus no events. Direct costs were 1.5‐fold higher and indirect costs 1.3‐fold higher in new/ongoing versus no events. Indirect costs exceeded direct costs 3.0 to 5.2 fold. Among frequent SLE NP events, new/ongoing seizure disorder and cerebrovascular disease accounted for the largest increases in annual direct costs. For non‐SLE NP events, new/ongoing polyneuropathy accounted for the largest increase in annual direct costs, and new/ongoing headache and mood disorder for the largest increases in indirect costs. Conclusion: Patients with new/ongoing SLE or non‐SLE NP events incurred higher direct and indirect costs. [ABSTRACT FROM AUTHOR]

Objective: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. Methods: We conducted a 3‐part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. Results: Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life‐course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. Conclusion: We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine whether the presence of depression or anxiety is associated with the achievement of sustained minimal disease activity (MDA) in patients with psoriatic arthritis (PsA). Methods: Adult patients satisfying classification criteria for PsA prospectively followed from 2008 to 2017 were included. A standard protocol including physician assessment and patient‐reported outcomes determined whether patients achieved sustained MDA, which was defined as meeting MDA criteria for ≥2 consecutive visits. The presence of depression/anxiety was determined using 3 definitions: 1) a score of ≤38 on the mental component summary of the Medical Outcomes Study Short Form 36 (SF‐36) health survey, 2) a score of ≤56 on the mental health domain of the SF‐36 health survey, and 3) a rheumatologist's report of a diagnosis or treatment for depression/anxiety. A discrete time‐to‐event analysis was conducted based on a proportional odds model to identify factors associated with achieving sustained MDA. Results: A total of 743 patients were included in the study. The number of patients identified as having depression/anxiety at baseline included 331 patients (44.54%) according to definition 1, 364 patients (48.99%) according to definition 2, and 211 patients (28.4%) according to definition 3. A total of 337 patients (45.36%) did not achieve sustained MDA. The presence of depression/anxiety was associated with reduced probability of achieving sustained MDA, with odds ratio (OR) 0.30 (P < 0.0001), OR 0.34 (P < 0.0001), and OR 0.47 (P < 0.0001) for definitions 1, 2, and 3, respectively. Other variables associated with a reduced probability of achieving sustained MDA included the Charlson comorbidity index and fibromyalgia. Conclusion: Symptoms of anxiety/depression reduce the probability of achieving sustained MDA in PsA. Comprehensive management of PsA should include measures for addressing these comorbidities. [ABSTRACT FROM AUTHOR]

Objective: The existing guidelines for lupus nephritis (LN) recommend initial prednisone doses of 0.3–1.0 mg/kg/day. However, recent studies reported noninferior outcomes with lower doses. The aim of this study was to compare the complete renal response rates in LN patients treated with prednisone ≤30 mg/day or ≥40 mg/day. Methods: Patients with new‐onset LN and standard immunosuppressive treatment were followed for at least 12 months, divided into medium (≤30 mg/day) and high prednisone groups (≥40 mg/day) and matched (propensity score) based on the baseline differences. Complete renal response was defined as proteinuria <0.5 gm/day and no worsening in renal function. Glucocorticoid‐related damage was also assessed. Results: High‐dose prednisone patients (n = 103; mean ± SD dose 48.6 ± 12.3 mg/day) achieved better rates of complete response compared to the medium group (n = 103; mean ± SD dose 24.2 ± 4.6 mg/day) (61.8% versus 38.2%; P = 0.024) at 12 months. The difference in response rates was reproduced for several subgroups (concomitant immunosuppressive treatment, proliferative/nonproliferative LN). Complete remission rates were higher at 2 years (67.8% versus 39%; P = 0.002) and 3 years (64.9% versus 49.1%; P = 0.025) after LN diagnosis. Cumulative glucocorticoid dose was comparable at 2 and 3 years. Glucocorticoid‐related damage was accelerated in both groups for the same period. Conclusion: Higher initial prednisone doses (median 45 mg/day) achieved significantly better rates of complete renal response at 12 months in new‐onset LN. Cumulative glucocorticoid dose and damage accrual were not different at 2 and 3 years after LN. Damage was more prominent in the late phases of LN in both groups, underlining the importance of rapid tapering and the need to implement alternative strategies. [ABSTRACT FROM AUTHOR]

Objective: To assess the incidence and risk factors for heart failure in patients with psoriatic disease and to describe their electrocardiographic and echocardiographic findings.Methods: A cohort analysis was conducted involving patients with psoriatic disease followed prospectively from 1978 to 2018. Participants were assessed according to a standard protocol every 6 to 12 months. The primary outcome was the time to first event of heart failure, further classified into ischemic and nonischemic heart failure (secondary outcomes). The association between cardiovascular risk factors, measures of disease activity, and heart failure events was assessed using Cox proportional hazards regression. Electrocardiographic and echocardiographic findings associated with heart failure events were described.Results: A total of 1,994 patients with psoriatic disease were analyzed, with 64 incident heart failure events (38 ischemic, 26 nonischemic). The incidence rate of first heart failure event was 2.85 per 1,000 patient-years. In all events, the most common electrocardiographic findings were atrial fibrillation (22%) and bundle branch blocks (29%). Echocardiogram revealed 37% reduced ejection fraction and 63% preserved ejection fraction. In multivariable analysis, independent risk factors for all heart failure events were ischemic heart disease, adjusted mean tender joint count, adjusted mean swollen joint count, adjusted mean erythrocyte sedimentation rate, adjusted mean C-reactive protein level, and physical function (by Health Assessment Questionnaire) (all P < 0.05). Minimal disease activity state was protective for all heart failure (P < 0.05).Conclusion: Increased risk of heart failure is associated with a combination of known cardiovascular risk factors and measures of disease activity, particularly in nonischemic heart failure. The effect of inflammation on heart failure may be partially independent of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Objective: In patients with psoriatic disease (PsD), we determined whether cardiac troponin I (cTnI) and N‐terminal pro–brain natriuretic peptide (NT‐proBNP) were associated with carotid plaque burden and the development of cardiovascular events independent of the Framingham Risk Score (FRS). Methods: Among 1,000 patients with PsD, carotid total plaque area (TPA) was measured in 358 participants at baseline. Cardiac troponin I and NT‐proBNP were measured using automated clinical assays. The association between cardiac biomarkers and carotid atherosclerosis was assessed by multivariable regression after adjusting for cardiovascular risk factors. Improvement in the prediction of cardiovascular events beyond the FRS was tested using measures of risk discrimination and reclassification. Results: In univariate analyses, cTnI (β coefficient 0.52 [95% confidence interval (95% CI) 0.3, 0.74], P < 0.001) and NT‐proBNP (β coefficient 0.24 [95% CI 0.1, 0.39], P < 0.001) were associated with TPA. After adjusting for cardiovascular risk factors, the association remained statistically significant for cTnI (adjusted β coefficient 0.21 [95% CI 0, 0.41], P = 0.047) but not for NT‐proBNP (P = 0.21). Among the 1,000 patients with PsD assessed for cardiovascular risk prediction, 64 patients had incident cardiovascular events. When comparing a base model (with the FRS alone) to expanded models (with the FRS plus cardiac biomarkers), there was no improvement in predictive performance. Conclusion: In patients with PsD, cTnI may reflect the burden of atherosclerosis, independent of traditional cardiovascular risk factors. Cardiac troponin I and NT‐proBNP are associated with incident cardiovascular events independent of the FRS, but further study of their role in cardiovascular risk stratification is warranted. [ABSTRACT FROM AUTHOR]

Objective: To determine bone mineral density (BMD) in psoriatic arthritis (PsA) patients, factors associated with undergoing BMD testing, and the effect of PsA clinical activity on BMD. Methods: Patients attending the University of Toronto PsA Clinic with BMD testing results from cohort inception to January 2019 were included. Descriptive statistics summarized lumbar spine, femoral neck, and total hip T scores. Cox proportional hazards regression identified predictors for BMD testing. Logistic regression analysis determined odds of having normal (T score −1.0 or more) versus osteoporotic‐range BMD (T score −2.5 or less). A multistate model determined factors associated with BMD state changes over time. Results: Of the 1,479 patients, 214 had BMD tests performed. The mean ± SD T scores at the lumbar spine, femoral neck, and total hip were −0.30 ± 0.32, −1.10 ± 1.04, and −0.45 ± 0.42, respectively. Osteopenia and osteoporosis occurred in 45.27% and 12.94% of patients. Increasing age, menopause, elevated acute‐phase reactants, and biologics, methotrexate, and systemic glucocorticoids use were associated with a higher chance of undergoing BMD testing. Increased body mass index (BMI) and biologics use were associated with a lower chance of having osteoporotic‐range BMD test results. In multistate analysis, polyarthritis may portend lower BMD results over time, although this did not achieve statistical significance due to low patient numbers. Conclusion: The prevalence of osteopenia and osteoporosis in the PsA cohort was similar to that of the general population. Clinicians are using osteoporosis risk factors and PsA disease severity markers to select patients for BMD testing. Polyarticular disease may portend worse BMD test results. Biologic use and increased BMI appear to have a protective effect. [ABSTRACT FROM AUTHOR]

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC‐FI values with future hospitalizations in the SLICC inception cohort. Methods: Baseline SLICC‐FI scores were calculated. The number and duration of inpatient hospitalizations during follow‐up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC‐FI values and the rate of hospitalizations per patient‐year of follow‐up. Linear regression was used to estimate the association of baseline SLICC‐FI scores with the proportion of follow‐up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics. Results: The 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5) at baseline. Mean ± SD baseline SLICC‐FI was 0.17 ± 0.08. During mean ± SD follow‐up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC‐FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow‐up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13–1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC‐FI values predicted a greater proportion of follow‐up time spent hospitalized (relative rate 1.09 [95% CI 1.02–1.16]). Conclusion: The SLICC‐FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC‐FI as a valid health measure in SLE. [ABSTRACT FROM AUTHOR]

Objective: To determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE). Methods: Upon enrollment and annually thereafter, NP events attributed to SLE and non‐SLE causes and physician‐determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time‐to‐event analysis using a multistate modeling structure. Results: NP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE‐associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P = 0.028), concurrent non‐SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non‐SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non‐SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non‐SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001). Conclusion: In a large and long‐term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution. [ABSTRACT FROM AUTHOR]

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 systemic lupus erythematosus (SLE) classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria and compared its performance to the revised ACR 1997, the unweighted SLICC 2012, and the newly reported European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria sets.Methods: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were reemployed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules.Results: The weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis.Conclusion: The 2 new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a data set originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived and whether the goal is to prioritize sensitivity or specificity. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K Glucocorticoids (SLEDAI-2KG) indices in identifying responders to standard of care therapy.Methods: Data from adult patients seen between 1995 and 2018 at the University of Toronto Lupus Clinic were analyzed. Patients with active disease (SLEDAI-2K score ≥6) and receiving prednisone ≥5 mg/day, and with a follow-up visit at 9 months, were studied. Response to standard of care therapy at first follow-up visit was assessed using the SLEDAI-2K and SLEDAI-2KG. The performances of the SLEDAI-2K and SLEDAI-2KG were compared using a cutoff point of 4.Results: In a cohort of 188, the majority of patients were female (86.0%) and White (47.9%). Of 188 patients, 145 (77.1%) were responders and had a decrease in SLEDAI-2K score of ≥4. The SLEDAI-2KG identified 142 (97.9%) responders among the SLEDAI-2K responders. More importantly, the SLEDAI-2KG identified 11 (25.6%) additional responders among SLEDAI-2K nonresponders (n = 43). This resulted from the ability of the SLEDAI-2KG to account for the decrease in glucocorticoids dose.Conclusion: The SLEDAI-2KG provides a novel concept for the assessment of lupus disease activity while accounting for glucocorticoids dosage to reflect on disease activity overall at a particular visit. The SLEDAI-2KG accounts for the disease activity for each descriptor while also accounting for the current glucocorticoids dosage. The SLEDAI-2KG adds 1 additional variable (glucocorticoids dosage) to the SLEDAI-2K, which could alter response rates in drug trials and observational studies. [ABSTRACT FROM AUTHOR]

Objectives: Patients with systemic lupus erythematosus (SLE) are usually treated with glucocorticosteroids even during periods of clinically quiescent disease. A recent study showed that abrupt glucocorticoid withdrawal was associated with an increased likelihood of flare in the next 12 months. The aim of the present study was to assess clinical flare rates and damage accrual in patients who tapered glucocorticosteroids gradually. Methods: Patients from the Toronto Lupus Clinic with 2 consecutive years of clinically quiescent disease were retrieved from the database. Individuals who maintained a low prednisone dose (5 mg/day) comprised the maintenance group, whereas patients who gradually tapered prednisone within these two years comprised the withdrawal group. All individuals were followed for 2 years after prednisone discontinuation or the corresponding date for the maintenance group. Propensity score matching was implemented to adjust for certain baseline differences. Outcomes included clinical flares and damage accrual. Results: Of 270 eligible patients, 204 were matched (102 in each group). Flare rate (any increase in clinical SLE Disease Activity Index 2000) was lower in the withdrawal group both at 12 (17.6% versus 29.4%; P = 0.023) and 24 months (33.3% versus 50%; P = 0.01). Moderate to severe flares (requiring systemic treatment escalation) were not different at 12 months (10.8% versus 13.7%; P = 0.467) but were less frequent at 24 months (14.7% versus 27.5%; P = 0.024). Damage accrual was less frequent in the withdrawal group (6.9% versus 17.6%; P = 0.022). No predictors for clinical flares were identified. Conclusion: Gradual glucocorticoid withdrawal is safe in clinically quiescent SLE and is associated with fewer clinical flares and less damage accrual at 24 months. [ABSTRACT FROM AUTHOR]

Objective: To describe the radiographic phenotype of axial spondyloarthritis (SpA) according to the presence of HLA-B27.Methods: An international collaboration compared the radiographic phenotype of axial SpA according to HLA-B27 status. Patients with ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA) were collected. Radiographs were read centrally, blinded to clinical details. The symmetry of the sacroiliac joints and lumbar syndesmophytes and the morphology of syndesmophytes (typical marginal versus atypical chunky), together with the modified Stoke Ankylosing Spondylitis Spine Score and the Psoriatic Arthritis Spondylitis Radiographic Index, were recorded.Results: A total of 244 patients with PsA and 198 patients with AS were included. In PsA, 60 patients (25%) were HLA-B27 positive while in AS, 148 patients (75%) were HLA-B27 positive. Patients with HLA-B27 were younger and more often male and had a longer duration of disease. In multivariable logistic regression, HLA-B27 was significantly associated with syndesmophyte symmetry (odds ratio [OR] 3.02 [95% confidence interval (95% CI) 1.38, 6.61]) and marginal syndesmophytes (OR 1.97 [95% CI 1.16, 3.36]) but not with sacroiliac symmetry. Mean radiographic scores were higher for patients with HLA-B27.Conclusion: Patients with axial SpA who are positive for HLA-B27 have more severe radiographic damage, more marginal syndesmophytes, and more frequent syndesmophyte symmetry compared to patients who are negative for HLA-B27. [ABSTRACT FROM AUTHOR]

Objective: Information about the prediagnosis period in psoriatic arthritis (PsA) is limited. The present study was undertaken to compare health care utilization related to musculoskeletal issues during a 5-year period prior to the diagnosis of PsA versus that of subjects with no prior inflammatory arthritis within a primary care setting.Methods: We conducted a population-based, matched cohort study using electronic medical records and administrative data in Ontario, Canada. Age- and sex-matched cohorts of PsA patients and comparators from the same family physicians were assembled. Comparators were not allowed to have prior spondyloarthritis, ankylosing spondylitis, or rheumatoid arthritis billing code diagnoses. The study outcomes included health care utilization and costs related to nonspecific musculoskeletal issues during a 5-year period prior to the index date.Results: We studied 462 PsA patients and 2,310 matched comparators. The odds ratio (OR) related to visiting a primary care physician for nonspecific musculoskeletal issues in patients with PsA was 2.14 (95% confidence interval 1.73-2.64) in the year immediately preceding the index date and was similarly elevated up to 5 years prior. The OR related to using other musculoskeletal-related health care services, including musculoskeletal specialists visits, joint injections, joint imaging, and emergency department visits, was higher in PsA as early as 5 years preceding the index date. Total and musculoskeletal-related health care costs prior to the index date were higher for patients with PsA versus comparators.Conclusion: A prodromal PsA phase characterized by nonspecific musculoskeletal symptoms may exist. Further study is needed to determine if this represents a window for earlier diagnosis of PsA. [ABSTRACT FROM AUTHOR]

Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling. Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten‐year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model. Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow‐up was 8.9 years (range 0.6–18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10‐year cumulative costs were higher for those with higher SDI scores at the beginning of the 10‐year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0. Conclusion: Patients with the highest SDI scores incur 10‐year cumulative costs that are ~9‐fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost‐effectiveness of novel therapies. [ABSTRACT FROM AUTHOR]

Objective: To assess performance of psoriatic arthritis (PsA) composite indices and evaluate guselkumab's effect on achieving low disease activity or remission. Methods: In this phase II trial, patients with active PsA (≥3 tender and ≥3 swollen joints, C‐reactive protein level ≥0.3 mg/dl, ≥3% body surface‐area with psoriasis involvement) were randomized 2:1 to subcutaneous guselkumab 100 mg (n = 100) or placebo (n = 49) at week 0, week 4, and every 8 weeks through week 44. At week 16, patients with <5% improvement in swollen and tender joints could early escape to open‐label ustekinumab. Patients continuing placebo crossed over to receive guselkumab 100 mg at weeks 24, 28, 36, and 44 (placebo to guselkumab). PsA composite indices (Psoriatic Arthritis Disease Activity Score [PASDAS], Group for Research and Assessment of Psoriasis and Psoriatic Arthritis composite score [GRACE], modified Composite Psoriatic Disease Activity Index [mCPDAI], and Disease Activity in Psoriatic Arthritis [DAPSA]) were analyzed as secondary outcomes (last observation carried forward for missing/post–early escape data through week 24; observed data post–week 24). Instrument performance was assessed. Results: Baseline PASDAS, GRACE, mCPDAI, and DAPSA scores indicated moderate‐to‐high disease activity. At week 24, mean changes in each of these composite indices showed significant improvement with guselkumab (–2.50, –2.73, –3.8, and –23.08, respectively) versus placebo (–0.49, 0.35, –0.8, and –4.98, respectively; P < 0.001 for all). Significantly more guselkumab‐treated patients achieved low/very low/remitted disease activity states according to PASDAS (very low + low 35% versus 4%; P < 0.001), GRACE (30% versus 2%; P < 0.001), mCPDAI (46% versus 10%; P < 0.001), and DAPSA (remission + low 40% versus 12%; P < 0.001). A total of 12% of guselkumab‐treated versus no placebo‐treated patients achieved DAPSA remission (P < 0.01). The PASDAS and GRACE instruments were more sensitive than the mCPDAI and DAPSA tools in detecting treatment effect. Residual skin disease and enthesitis were marginally more prominent in patients achieving DAPSA low disease activity versus other indices. Conclusion: Guselkumab demonstrated efficacy in achieving low disease activity/remission based on all PsA composite indices assessed. Composite index use in PsA trials and the clinic requires careful consideration to optimize feasibility and instrument performance. [ABSTRACT FROM AUTHOR]

Objective: In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE. Methods: A large 33‐center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient‐years, and univariable and multivariable relative risk regression models. Results: Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow‐up visit after enrollment, for a total of 13,666 patient‐years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient‐years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32–0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55–10.30]) and a body mass index of >40 kg/m2 (HR 2.74 [95% CI 1.04–7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17–9.27], P < 0.001). Conclusion: The prevalence of AVEs and the rate of AVE accrual demonstrated in the present study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors. [ABSTRACT FROM AUTHOR]

Objective: Psoriatic arthritis (PsA) requires long‐term treatment, yet safety concerns and monitoring requirements make maintenance a challenge. This analysis of pooled Psoriatic Arthritis Long‐term Assessment of Clinical Efficacy (PALACE) 1, 2, and 3 data describes 3‐year apremilast safety and tolerability in PsA. Methods: Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg twice daily, or apremilast 20 mg twice daily. Placebo patients were re‐randomized to apremilast 30 mg twice daily or 20 mg twice daily at week 16 (early escape) or 24. Double‐blind treatment continued to week 52; patients could continue apremilast during an open‐label, long‐term treatment phase. Results: In total, 1493 patients received at least one dose of study medication and were included in the safety population (placebo: n = 495; apremilast 30 mg: n = 497; apremilast 20 mg: n = 501). Among patients receiving apremilast, 53.2% (767/1441) completed 3 years of treatment. Greater rates of adverse events (AEs) were reported with apremilast (61.1%; exposure‐adjusted incidence rate [EAIR]/100 patient‐years, 265.1) versus placebo (47.5%; EAIR/100 patient‐years, 200.7) in the placebo‐controlled period. During weeks 0 to ≤52, the most common AEs occurring in apremilast‐exposed patients were diarrhea (13.9%; EAIR/100 patient‐years, 18.6), nausea (12.3%; EAIR/100 patient‐years, 16.0), headache (9.4%; EAIR/100 patient‐years, 12.1), upper respiratory tract infection (9.1%; EAIR/100 patient‐years, 11.5), and nasopharyngitis (6.2%; EAIR/100 patient‐years, 7.7). Most AEs were mild/moderate with apremilast exposure ≤156 weeks. Rates of depression remained low (EAIR/100 patient‐years, 1.8). Major adverse cardiac events (EAIR/100 patient‐years, 0.5), malignancies (EAIR/100 patient‐years, 0.9), and serious opportunistic infections (EAIR/100 patient‐years, 0.0) were infrequent over the 3‐year exposure period. Discontinuation rates due to AEs were low (<7.5%) across all apremilast‐exposure periods. Incidences of clinically meaningful abnormalities in postbaseline laboratory values was low; most values returned to baseline levels with continued treatment and without intervention. Conclusion: Apremilast demonstrated a favorable safety profile and was well tolerated up to 156 weeks. [ABSTRACT FROM AUTHOR]

Objective: The present study was undertaken to evaluate the probability of achieving the Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) treatment targets of remission or low disease activity (LDA) with apremilast based on disease activity categories and corresponding responses in arthritis and other domains of psoriatic arthritis (PsA) not included in the cDAPSA.Methods: Pooled analyses from the Psoriatic Arthritis Long-term Assessment of Clinical Efficacy studies 1, 2, and 3 were performed. Probability analyses assessing the likelihood of achieving cDAPSA treatment targets by week 52 were performed using multiple imputation for discontinuations and missing values. Longitudinal analyses were performed in patients grouped by cDAPSA category at week 52.Results: Among 494 patients in the probability analyses, 46.9% with moderate disease activity and 24.9% with high disease activity at baseline achieved treatment targets (remission or LDA) by week 52. For patients with moderate disease activity at baseline, small improvements (cDAPSA reductions ≥30%) by week 16 were associated with achieving targets. Patients achieving remission or LDA by week 16 had high probabilities of remaining at treatment targets at week 52. Of 375 patients with cDAPSA components available at week 52, achieving targets with apremilast was associated with continuous disease activity improvements and no or mild arthritis and other PsA manifestations.Conclusion: The probability of achieving treatment targets (remission or LDA) at week 52 was greater for patients with moderate versus high disease activity at baseline. At a mean level, partial improvements by week 16 were associated with achieving treatment targets. Patients receiving apremilast who achieved cDAPSA targets by week 52 also had no or mild arthritis or other PsA manifestations. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to report the incidence of uveitis in secukinumab‐treated patients with ankylosing spondylitis (AS) in a pooled analysis of three phase 3 trials (MEASURE 1‐3 [ClinicalTrials.gov identifiers NCT01358175, NCT01649375, NCT02008916]). Methods: Analysis included pooled patient‐level data from all patients (N = 794) who received any dose (one or more) of secukinumab up to the last patient attending the week 156 study visit in MEASURE 1 and up to the week 156 visit in MEASURE 2 and the week 104 visit in MEASURE 3 for each patient. Postmarketing data were from the periodic safety update report. Incidence of uveitis is reported as the exposure‐adjusted incidence rate (EAIR) per 100 patient‐years of secukinumab exposure. Results: Overall, 135 (17%) patients reported preexisting (but not active or ongoing) uveitis at baseline, and 589 (74.2%) patients were HLA antigen B27 positive. The EAIR for uveitis was 1.4 per 100 patient‐years over the entire treatment period. Among all cases of uveitis (n = 26), 14 (54%) were flares. The exposure‐adjusted reporting rate of uveitis in the postmarketing data (which included patients across the three approved indications of psoriasis, psoriatic arthritis, and AS) was 0.03 per 100 patient‐years based on cumulative secukinumab exposure of 96 054 patient‐years. Conclusion: The incidence rate of uveitis in secukinumab‐treated patients with active AS does not suggest an increased risk with secukinumab treatment. [ABSTRACT FROM AUTHOR]

Objective: The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure of psoriatic arthritis (PsA) disease activity. The length of its patient-reported components raises concern about questionnaire burden. The PASDAS includes the Medical Outcomes Study Short Form 36 (SF-36) health survey. We undertook this study to investigate the agreement between the PASDAS and a modified PASDAS (mPASDAS), which substituted the SF-36 with the shortened SF-12.Methods: A total of 100 patients who fulfilled the criteria of the Classification of Psoriatic Arthritis Study Group for PsA were consecutively recruited. All of the PASDAS-required variables were collected. The 12 item responses for SF-12 were extracted from the SF-36 questionnaire. The PASDAS and the mPASDAS were calculated using the SF-36 and SF-12 scores, respectively. A Bland-Altman plot of the mean differences in PASDAS and mPASDAS scores was generated to evaluate agreement. Construct validity was assessed by examining correlations of the PASDAS and the mPASDAS with the Health Assessment Questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue subscale, the EuroQol 5-domain instrument (health-related quality of life), and pain scores (range 0-10, visual analog scale). The kappa statistic was used to measure agreement between disease activity states as determined by the PASDAS and mPASDAS.Results: The mean ± SD PASDAS and mPASDAS was 3.29 ± 1.39 and 3.24 ± 1.27, respectively. The correlation between the 2 scores was 0.998 (P < 0.0001), and the mean difference was -0.05 (95% confidence interval [95% CI] -0.07, -0.03). Construct validity was found, with nearly identical correlations of the PASDAS and mPASDAS with each of the external health measures. The misclassification rate with the mPASDAS was only 6%. The weighted κ = 0.90 (95% CI 0.82, 0.97).Conclusion: The mPASDAS may replace the PASDAS in disease activity assessment given the excellent agreement, validity, and low misclassification rate. [ABSTRACT FROM AUTHOR]

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort. Methods: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health‐related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow‐up, adjusting for relevant demographic and clinical characteristics. Results: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9–1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow‐up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow‐up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13–1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents. Conclusion: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow‐up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF‐36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF‐36 summary scores for peripheral neuropathy and mononeuropathy. Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health‐related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution. [ABSTRACT FROM AUTHOR]

Objective: The risk of cardiovascular disease (CVD) is higher in patients with psoriatic arthritis (PsA) compared to the general population. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Because tofacitinib increases circulating lipid levels in some patients, we evaluated CVD risk factors and major adverse cardiovascular events (MACE) in patients with active PsA receiving tofacitinib 5 or 10 mg twice daily plus conventional synthetic disease-modifying antirheumatic drugs.Methods: Data were pooled from 2 phase III studies (Efficacy and Safety of Tofacitinib in Psoriatic Arthritis [OPAL Broaden] and Tofacitinib in Patients with Psoriatic Arthritis With Inadequate Response to TNF Inhibitors [OPAL Beyond]) and 1 ongoing long-term extension (Open-Label Extension Study of Tofacitinib in Psoriatic Arthritis [OPAL Balance], data cutoff January 2017; database not locked). Outcomes included fasting lipid levels, blood pressure, hypertension-related adverse events (AEs; including hypertension, high blood pressure, and increased blood pressure), and MACE.Results: Overall, 783 tofacitinib-treated patients were included. Percentage increases from baseline in low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) levels ranged from 9% to 14% for tofacitinib 5 mg and 10 mg at 3 and 6 months; no meaningful changes in LDL-c:HDL-c or total cholesterol:HDL-c ratios were observed. Blood pressure remained stable for 24 months. Fifty-eight patients (7.4%) had hypertension-related AEs; none were fatal (incidence rate [IR] per 100 patient-years 4.81 [95% confidence interval (95% CI) 3.65-6.22]). Five patients (0.6%) had MACE (IR 0.24 [95% CI 0.05-0.70]); 2 were fatal.Conclusion: Serum lipid level increases at month 3 following tofacitinib treatment in PsA were consistent with observations in rheumatoid arthritis and psoriasis. The IR of hypertension-related AEs and MACE was low; long-term follow-up is ongoing. [ABSTRACT FROM AUTHOR]

Objective: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta‐regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi‐criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. Results: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE‐specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research. Video Abstract [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence and incidence of psoriasis and psoriatic arthritis (PsA) over time in Ontario, Canada. Methods: We performed a population‐based study of Ontario health administrative data, using validated case definitions for psoriasis and PsA. We computed the crude and age‐ and sex‐standardized cumulative prevalence and incidence of psoriasis from 2000 to 2015. Results: Among the 10,774,802 individuals ages ≥20 years residing in Ontario in 2015, we identified 273,238 patients with psoriasis and 18,655 patients with PsA, equating to cumulative prevalence estimates of 2.54% and 0.17%, respectively. Correcting the prevalence estimates for imperfect sensitivity and specificity resulted in similar estimates. The male:female ratio was approximately 1.0 for both conditions. For psoriasis, the age‐ and sex‐standardized cumulative prevalence increased from 1.74% in 2000 to 2.32% in 2015. For PsA, the age‐ and sex‐standardized cumulative prevalence increased from 0.09% in 2008 to 0.15% in 2015. Between 2008 and 2015, annual incidence rates for psoriasis decreased, whereas those for PsA remained relatively stable. Conclusion: The prevalence and incidence of psoriasis and PsA in Ontario are similar to those observed in Europe and the US. The steady increase in the prevalence of psoriasis and PsA over the past decade may be due to a combination of population aging, population growth, and increasing life expectancy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the properties of a frailty index (FI), constructed using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, as a novel health measure in systemic lupus erythematosus (SLE). Methods: For this secondary analysis, the baseline visit was defined as the first study visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health‐related quality of life (Short‐Form 36 [SF‐36] scores) were assessed. The SLICC‐FI was constructed using baseline data. The SLICC‐FI comprises 48 health deficits, including items related to organ damage, disease activity, comorbidities, and functional status. Content, construct, and criterion validity of the SLICC‐FI were assessed. Multivariable Cox regression was used to estimate the association between baseline SLICC‐FI values and mortality risk, adjusting for demographic and clinical factors. Results: In the baseline data set of 1,683 patients with SLE, 89% were female, the mean ± SD age was 35.7 ± 13.4 years, and the mean ± SD disease duration was 18.8 ± 15.7 months. At baseline, the mean ± SD SLICC‐FI score was 0.17 ± 0.08 (range 0–0.51). Baseline SLICC‐FI values exhibited the expected measurement properties and were weakly correlated with baseline SDI scores (r = 0.26, P < 0.0001). Higher baseline SLICC‐FI values (per 0.05 increment) were associated with increased mortality risk (hazard ratio 1.59, 95% confidence interval 1.35–1.87), after adjusting for age, sex, steroid use, ethnicity/region, and baseline SDI scores. Conclusion: The SLICC‐FI demonstrates internal validity as a health measure in SLE and might be used to predict future mortality risk. The SLICC‐FI is potentially valuable for quantifying vulnerability among patients with SLE, and adds to existing prognostic scores. [ABSTRACT FROM AUTHOR]

Objective: To examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA). Methods: In this double‐blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed. Results: Patients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between‐group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen. Conclusion: Etanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow‐up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept. [ABSTRACT FROM AUTHOR]

Objective: The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort.Methods: Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis.Results: A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP-positive group did not differ from the ANA-positive or anticellular antibody-negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti-U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative.Conclusion: In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody-negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA. [ABSTRACT FROM AUTHOR]

Objective: A recent study conducted by our clinical group demonstrated that low disease activity (LDA), defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤2, maintained for 12 months, confers the same risk for damage accrual as complete remission after 2 years. The aim of the present study was to assess the validity of these findings in the long term (10 years).Methods: Patients in the inception cohort of the Toronto Lupus Clinic, who had a minimum follow-up of 10 years and no interval >18 months between consecutive visits, were included in the analysis. Prolonged clinical remission was defined based on a SLEDAI-2K score of 0 (serology excluded), achieved within the first 5 years of enrollment and maintained for ≥10 years. Prolonged LDA was defined as SLEDAI-2K score ≤2 (serology excluded) with the same time frame restrictions.Results: Of 267 patients, 27 (10.1%) achieved prolonged clinical remission and 48 (18%) attained prolonged LDA. There were no differences regarding demographic, clinical, and immunologic variables at any time. The mean prednisone dose at enrollment was higher in patients in whom remission was achieved, while patients with prolonged LDA were taking antimalarials more frequently, both at enrollment and after the 10-year time period. Cumulative damage and flare rate after 10 years, and mortality throughout follow-up were comparable. SLE in patients in the prolonged LDA group was in complete remission for 76% of the follow-up time.Conclusion: Prolonged clinical remission and LDA were demonstrated in 10.1% and 18% of our patients, respectively, and comparable outcomes were demonstrated in the long term, rendering sustained LDA an acceptable treat-to-target outcome in SLE. [ABSTRACT FROM AUTHOR]

Objective: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF).Methods: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations.Results: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment.Conclusion: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE).Methods: A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate.Results: CerVEs were the fourth most frequent NP event: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NP events attributed to SLE, non-SLE-attributed NP events, African ancestry (at US SLICC sites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF-36 summary and subscale scores following a CerVE.Conclusion: CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician-reported outcomes, patients reported a sustained reduction in health-related quality of life following a CerVE. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the long-term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling.Methods: Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration.Results: A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten-year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) <30 ml/minute ($310,579 2015 Canadian dollars versus $19,987 if no LN and estimated GFR >60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria <0.25 gm/day).Conclusion: Patients with estimated GFR <30 ml/minute incurred 10-year costs 15-fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies. [ABSTRACT FROM AUTHOR]

Objective: No previous study has studied the longitudinal disease course of childhood-onset systemic lupus erythematosus (cSLE). Our objectives are to assess distinguishable differences in disease activity trajectories in cSLE patients, determine baseline factors predictive of disease trajectory membership, and assess if the different disease activity trajectories are associated with different damage trajectories.Methods: This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity was modeled as a latent characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by disease activity classes were tested using a mixed model.Results: A total of 473 patients (82% females), with median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits (2,666 patient-years). We identified 5 classes of disease activity trajectories. Baseline major organ involvement, number of American College of Rheumatology criteria, and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage, while class 5 was associated with no significant damage accrual, even after 10 years.Conclusion: There are 5 distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of tumor necrosis factor inhibitors (TNFi) on subclinical cardiovascular disease in patients with psoriatic disease. Methods: We performed a 2‐stage study. In stage 1, carotid total plaque area was assessed in patients with psoriasis or psoriatic arthritis (PsA) (n = 319) by ultrasound at baseline and after 2–3 years. The annual progression rate of atherosclerosis was the outcome of interest. In stage 2, PsA patients receiving TNFi (n = 21) and age‐ and sex‐matched PsA patients not receiving any biologic agent (n = 13) underwent 18F‐fluorodeoxyglucose–positron emission tomography/computed tomography at baseline and 1 year to assess vascular inflammation, measured as target‐to‐background ratio (TBR). In both stages, multivariable regression analyses adjusted for cardiovascular risk factors and use of statins were performed. Results: In stage 1, men had significantly higher atherosclerosis progression than women (P < 0.001). TNFi was associated with reduced atherosclerosis progression in men after controlling for cardiovascular risk and use of statins (adjusted β = −2.20 [95% confidence interval −3.41, −1.00], P < 0.001). There was no association between TNFi and atherosclerosis progression in women (P = 0.74). In stage 2, patients receiving TNFi had reduced TBR at 1 year (P = 0.03). Those not receiving TNFi had no significant change in TBR (P = 0.32). The improvement in aortic vascular inflammation in the TNFi group was independent of cardiovascular risk factors (adjusted β = −0.41 [95% confidence interval −0.74, −0.08], P = 0.02). Conclusion: Our findings indicate that TNFi treatment is associated with reduced progression of carotid plaques in men and improvement in vascular inflammation in both men and women with psoriatic disease. [ABSTRACT FROM AUTHOR]

Objective: There is no widely recognized method used to assess axial disease in psoriatic arthritis (PsA). We aimed to determine the sensitivity to change of the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s), the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), the Radiographic Ankylosing Spondylitis Spine Score (RASSS), and the PsA Spondylitis Radiology Index (PASRI) in axial PsA.Methods: Radiographs of 105 patients with axial PsA were retrieved for 2 time points at least 2 years apart and subsequently anonymized. All radiographs were scored by 3 rheumatologists blinded to name and order of examination using an electronic application that allowed recording of disease manifestations specific to axial PsA and automatically calculated the BASRI-s, mSASSS, RASSS, and PASRI scores. An independent expert determined whether there was true radiographic progression from an overall impression after viewing the radiographs with knowledge of chronologic order. The sensitivity, specificity, and odds ratios for every 1-unit increase in the scores were determined to identify true change.Results: Of the patients studied, 25 (24%) showed progression, as determined by the independent expert. The respective sensitivity and specificity values for an increase in score to detect true change were as follows: 0.48 and 0.78 (BASRI-s), 0.52 and 0.84 (mSASSS), 0.44 and 0.84 (RASSS), and 0.52 and 0.74 (PASRI). Logistic regression analyses showed that an increase of 1 point in the respective scores was associated with the following odds ratios for identifying true progression: BASRI-s 3.0, mSASSS 5.27, RASSS 3.70, and PASRI 3.06.Conclusion: Available scoring systems for quantifying radiographic axial PsA have moderate sensitivity but high specificity for detecting true change. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence, prevalence, characteristics, disease associations, risk factors, and outcome of clinical enthesitis in patients with psoriatic arthritis (PsA).Methods: The study included patients with PsA followed prospectively. Enthesitis was defined as the presence of at least 1 tender enthesis at 1 of the 18 entheseal sites of the Spondyloarthritis Research Consortium of Canada enthesitis index.Results: Between 2008 and 2014, 281 of 803 patients had enthesitis, providing a prevalence of 35%. A total of 192 patients developed enthesitis during the course of followup, with an annual incidence of 0.9%. Most of the patients had 1 (48.4%) or 2 (32.2%) tender entheseal sites, and the mean ± SD number of sites per visit was 2.03 ± 1.6. The 3 most common sites were at the insertions of the Achilles tendon, plantar fascia on the calcaneus, and the lateral epicondyles (24.2%, 20.8%, and 17.2%, respectively). More active disease (higher actively inflamed joint count, tenosynovitis, and dactylitis), more pain, and less clinical damage were associated with enthesitis. Higher body mass index, more actively inflamed joints, and younger age were risk factors for developing this condition. Enthesitis resolved in most patients without changing treatment.Conclusion: Clinical enthesitis is common, with a period prevalence of 35% of PsA patients. It usually involves only 1 or 2 sites simultaneously. The most common tender sites are at the insertions of the Achilles tendon, plantar fascia, and the lateral epicondyles. More active disease and more pain are associated with enthesitis. [ABSTRACT FROM AUTHOR]

Objective To define and identify a group of systemic lupus erythematosus patients with low disease activity (LDA) and to examine whether LDA is similar to patients in remission and different from a high disease activity group (HDA) in short-term outcomes. Methods The LDA group was defined as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) <3, including only 1 clinical manifestation of rash, alopecia, mucosal ulcers, pleurisy, pericarditis, fever, thrombocytopenia, or leukopenia. The patients could be taking antimalarials. Remission was defined as no clinical manifestation from taking antimalarials alone, and the HDA group was defined as SLEDAI-2K >6. The time frame for inclusion in each group was at least 1 year. Results Of 620 patients with active disease who were seen between 1970 and 2015, 80 patients (12.9%) fulfilled the criteria for LDA, 191 (30.8%) for remission, and 349 (56.3%) for HDA. The LDA patients with and without positive serology results were similar at baseline and with prior disease characteristics. After 2 years of followup, the LDA and remission groups were similar in their adjusted mean SLEDAI-2K score, organ involvement, The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score, mortality, and therapies. After 2 and 4 years of followup, the HDA group had a higher adjusted mean SLEDAI-2K score, more major organ involvement, a higher SDI score, higher mortality, and more therapy compared to the combined LDA/remission groups. Conclusion LDA and remission groups had similar short-term outcomes, and both had better outcomes and prognosis than the HDA group. LDA may be used as an outcome measure in therapeutic trials or in treat-to-target regimens. [ABSTRACT FROM AUTHOR]

Objective To assess whether the presence of nonspecific musculoskeletal symptoms, their degree, and change over time predict the development of psoriatic arthritis (PsA) in a prospective cohort of psoriasis patients without arthritis at baseline. Methods This prospective cohort study involved patients with psoriasis who were assessed at baseline to exclude the presence of clinical PsA. The study participants were reassessed annually to determine if they had developed PsA. The presence of musculoskeletal symptoms and the patients' assessments of pain, fatigue, stiffness, physical function, and psychological distress were recorded at each visit. Cox proportional hazards models were used to assess what symptoms predicted the development of PsA. Results A total of 57 of 410 psoriasis patients developed PsA. At baseline, the presence of arthralgia in women (hazard ratio [HR] 2.59, P = 0.02), heel pain (HR 4.18, P = 0.02), high fatigue score (HR 2.36, P = 0.007), and high stiffness score (HR 2.03, P = 0.045) predicted subsequent development of PsA. In addition, an increase from baseline in fatigue score (HR 1.27, P = 0.001), pain score (HR 1.34, P < 0.001), and stiffness score (HR 1.21, P = 0.03), and a worsening in physical function score (HR 0.96, P = 0.04) predicted the development of PsA. Conclusion A preclinical phase exists in patients with PsA prior to the diagnosis of the disease. This phase is characterized by nonspecific musculoskeletal symptoms, including joint pain, fatigue, and stiffness. [ABSTRACT FROM AUTHOR]

Objective: The phenotype of patients who remain naive of glucocorticosteroids has not been described, and the type and rate of their damage accrual remains largely unknown. The objective of this study was to compare the type, amount, rate, and nature of organ damage accrual, mortality, and atherosclerotic comorbidities in glucocorticosteroid-naive and glucocorticosteroid-exposed patients with systemic lupus erythematosus (SLE).Methods: Inception patients from the University of Toronto Lupus Clinic who had never taken glucocorticosteroids and had a minimum of 3 years of followup were compared to patients who received glucocorticosteroids within the first 6 months of SLE diagnosis and for at least 3 years. All patients had no damage at inception.Results: A total of 86 glucocorticosteroid-naive and 173 glucocorticosteroid-exposed patients were included. There were more females and whites among the glucocorticosteroid-naive patients, whereas the glucocorticosteroid-exposed patients had higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores on first examination. Overall mortality was higher in the glucocorticosteroid-exposed group, but the deaths occurred late. There was no difference in the frequency of coronary artery disease overall or at each of the time points. Damage accrual was higher in glucocorticosteroid-exposed patients overall and at 5 and 8 years. Individual damage items that were higher in glucocorticosteroid-exposed patients included ocular (cataracts) and musculoskeletal (osteoporosis with fragility fractures, and osteonecrosis) components.Conclusion: Mortality is more frequent in patients taking glucocorticosteroids for at least the first 3 years of their lupus compared to patients who are glucocorticosteroid-naive. In addition, patients taking glucocorticosteroids accumulate more damage by 5 years of disease, and damage tends to be glucocorticosteroid related, including cataracts and musculoskeletal components. [ABSTRACT FROM AUTHOR]

Objective Biomarkers that can predict the development of psoriatic arthritis (PsA) in patients with psoriasis would be useful in clinical practice. The aim of this study was to assess whether CXCL10 could be a predictive biomarker of PsA prior to its onset. Methods Psoriasis patients without arthritis were followed up prospectively and assessed annually for development of PsA by a rheumatologist. Patients in whom PsA developed were designated as converters, while those in whom PsA did not develop were termed nonconverters. Baseline serum concentrations of CXCL10 were measured by Luminex assay in 46 converters and 45 nonconverters. Results The level of CXCL10 was significantly higher in converters (median 493 pg/ml [interquartile range (IQR) 356-984]) than in nonconverters (median 371 pg/ml [IQR 263-578]; P = 0.005). In contrast, C-reactive protein (CRP) levels were not significantly different between converters and nonconverters at baseline. CXCL10 was associated with conversion status after adjustment for age, sex, duration of psoriasis, and duration of follow-up (odds ratio 1.3, 95% confidence interval 1.1-1.5, P = 0.004). In a subset of converters, the CXCL10 level was significantly higher at baseline (median 927.4 pg/ml [IQR 547.6-1,243]) than after PsA diagnosis (491.5 pg/ml [IQR 323.2-607]; P < 0.0001), while CRP levels were lower at baseline (26.6 μg/ml [IQR 16.37-62.75]) than after PsA diagnosis (36.1 μg/ml [IQR 14.74-101.7]; P = 0.003). CXCL10 gene expression was increased 17.3-fold in synovial fluid (SF) compared with blood from PsA patients ( P = 0.01) and 44.3-fold in the SF of PsA patients compared with the SF of patients with gout ( P = 0.001). Conclusion CXCL10 may be involved in PsA pathogenesis and is a candidate predictive biomarker for PsA in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Objective: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are used as an adjuvant treatment in lupus nephritis (LN) patients with proteinuria. The primary aim of this study was to discover whether ACE inhibitors/ARBs have an atheroprotective effect similar to other, at-risk, populations.Methods: A total of 144 patients (cases; mean ± SD age at onset 34 ± 12.1 years, followup 14.9 ± 8.6 years) with LN who were treated with ACE inhibitors/ARBs for at least 5 years were enrolled. The control group comprised 301 LN patients (mean ± SD age at onset 34.1 ± 13.2 years, followup 13.4 ± 7.9 years) with no such treatment. All patients were followed for the occurrence of atherosclerotic cardiovascular events (CVEs), consisting of transient ischemic attack and stroke, angina, myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), and congestive heart failure. Patients with preexisting CVEs were excluded.Results: There were no significant differences in the cumulative occurrence of CVEs (9.7% for treated versus 8.6% for nontreated patients; P = 0.708); however, hard events (stroke, myocardial infarction, CABG, and PTCA) were less frequent in treated patients (4.17% versus 5.32%). Cases were more frequently hypertensive (100% versus 52.8%; P < 0.001) and diabetic (10.4% versus 4.7%; P = 0.021), whereas controls more frequently had hypercholesterolemia (27.9% versus 18.1%; P = 0.024) and elevated triglycerides (14% versus 4.9%; P = 0.004); other variables did not differ significantly. Regression analysis failed to confirm ACE inhibitor/ARB nonuse as an important predictor of future CVEs.Conclusion: Our data do not support the hypothesis that ACE inhibitors/ARBs may be protective against atherosclerotic CVEs in LN patients. [ABSTRACT FROM AUTHOR]

Objective To study bidirectional change and predictors of change in estimated glomerular filtration rate (GFR) and proteinuria in lupus nephritis (LN) using a multistate modeling approach. Methods Patients in the Systemic Lupus International Collaborating Clinics inception cohort were classified annually into estimated GFR state 1 (>60 ml/minute), state 2 (30-60 ml/minute), or state 3 (<30 ml/minute) and estimated proteinuria state 1 (<0.25 gm/day), state 2 (0.25-3.0 gm/day), or state 3 (>3.0 gm/day), or end-stage renal disease (ESRD) or death. Using multistate modeling, relative transition rates between states indicated improvement and deterioration. Results Of 1,826 lupus patients, 700 (38.3%) developed LN. During a mean ± SD follow-up of 5.2 ± 3.5 years, the likelihood of improvement in estimated GFR and estimated proteinuria was greater than the likelihood of deterioration. After 5 years, 62% of patients initially in estimated GFR state 3 and 11% of patients initially in estimated proteinuria state 3 transitioned to ESRD. The probability of remaining in the initial states 1, 2, and 3 was 85%, 11%, and 3%, respectively, for estimated GFR and 62%, 29%, and 4%, respectively, for estimated proteinuria. Male sex predicted improvement in estimated GFR states; older age, race/ethnicity, higher estimated proteinuria state, and higher renal biopsy chronicity scores predicted deterioration. For estimated proteinuria, race/ethnicity, earlier calendar years, damage scores without renal variables, and higher renal biopsy chronicity scores predicted deterioration; male sex, presence of lupus anticoagulant, class V nephritis, and mycophenolic acid use predicted less improvement. Conclusion In LN, the expected improvement or deterioration in renal outcomes can be estimated by multistate modeling and is preceded by identifiable risk factors. New therapeutic interventions for LN should meet or exceed these expectations. [ABSTRACT FROM AUTHOR]

Objective To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). Methods GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. Results Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema. Conclusion We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves. [ABSTRACT FROM AUTHOR]