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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., (© 2021, American College of Rheumatology.)

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., (© 2019, American College of Rheumatology.)

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., (© 2019, American College of Rheumatology.)

Objective: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group is developing a Core Outcome Measurement Set for PsA clinical trials [randomized controlled trials (RCT) and longitudinal observational studies (LOS)] using the OMERACT Filter 2.1 instrument selection algorithm. Our objective was to assess the Psoriatic Arthritis Impact of Disease questionnaire (PsAID12) for the measurement of the core domain PsA-specific health-related quality of life (HRQOL)., Methods: PsAID12 measurement property evidence gathered in a systematic literature review, and additional analyses conducted in LOS, were used to inform a consensus process. Analyses that had not been published were independently reviewed by the OMERACT technical advisory group. Data and process were presented, discussed in breakout groups, and voted on at the OMERACT conference (Terrigal, Australia, May 2018)., Results: PsAID12 fulfilled the green (good to go) OMERACT standards for domain match, feasibility, reliability, and construct/longitudinal construct validity. Discrimination and thresholds of meaning were amber (caution but good enough to go forward). The overall working group recommendation was amber/provisional endorsement of PsAID12 for measuring PsA-specific HRQOL in RCT and LOS. Of 96 participants who voted at the PsA OMERACT workshop, 87.5% (84) voted "yes" to endorse this recommendation; 14 of the 96 were patient research partners (PRP) and 93% of them (13) voted "yes"; 82 participants were not PRP and 87% of them (71) voted "yes.", Conclusion: At OMERACT 2018, PsAID12 was the first patient-reported outcome measure provisionally endorsed as a core outcome measure for disease-specific HRQOL in PsA clinical trials. PsAID12 discrimination and improvement thresholds will be studied in future RCT.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Working Group reported at the 2018 GRAPPA annual meeting on the outcome of the OMERACT 2018 Conference in Terrigal, Australia. The working group presented the endorsement of the 66/68 joint count for the assessment of peripheral arthritis and the provisional endorsement of the PsA Impact of Disease 12 questionnaire for the assessment of PsA-specific health-related quality of life in PsA randomized controlled trials and observational studies. In this report, the group presents its plan to seek OMERACT endorsement for outcome measures that address the domains of MSK disease activity for enthesitis and dactylitis, physical function, fatigue, and structural damage following the OMERACT Filter 2.1 methodology.

Background: An updated psoriatic arthritis (PsA) core outcome set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016., Objectives: To synthesize the evidence on measurement properties of patient reported outcome measures (PROMs) for PsA and thereby contribute to development of a PsA core outcome measurement set (COMS) as described by the OMERACT Filter 2.0., Methods: A systematic literature search was performed in EMBASE, MEDLINE and PsycINFO on Jan 1, 2017 to identify full-text articles with an aim of assessing the measurement properties of PROMs in PsA. Two independent reviewers rated the quality of studies using the COnsensus based standards for the Selection of health Measurement INstruments (COSMIN) checklist, and performed a qualitative evidence synthesis., Results: Fifty-five studies were included in the systematic review. Forty-four instruments and a total of 89 scales were analyzed. PROMs measuring COS domains with at least fair quality evidence for good validity and reliability (and no evidence for poor properties) included the Stockerau Activity Score for PsA (German), Psoriasis Symptom Inventory, visual analogue scale for Patient Global, 36 Item Short Form Health Survey Physical Function subscale, Health Assessment Questionnaire Disability Index, Bath Ankylosing Spondylitis Functional Index, PsA Impact of Disease questionnaire, PsA Quality of Life questionnaire, VITACORA-19, Functional Assessment of Chronic Illness Therapy Fatigue scale and Social Role Participation Questionnaire., Conclusions: At least one PROM with some evidence for aspects of validity and reliability was available for six of the eight mandatory domains of the PsA COS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS)., Methods: At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants., Results: We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda., Conclusion: The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

Background and Aims: We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients., Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality., Results: We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point)., Conclusions: Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To examine the frequency, characteristics, and outcome of mood disorders, as well as clinical and autoantibody associations, in a multiethnic/racial, prospective inception cohort of patients with systemic lupus erythematosus (SLE)., Methods: Patients were assessed annually for mood disorders (4 types, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 18 other neuropsychiatric events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 subscales, mental and physical component summary scores were collected. Time to event, linear and ordinal regressions, and multi-state models were used as appropriate., Results: Among the 1,827 patients with SLE, 88.9% were female, and 48.9% were Caucasian. The mean ± SD age of the patients was 35.1 ± 13.3 years, disease duration was 5.6 ± 4.8 months, and the length of followup was 4.7 ± 3.5 years. During the course of the study, 863 (47.2%) of the 1,827 patients had 1,627 neuropsychiatric events. Mood disorders occurred in 232 (12.7%) of 1,827 patients, and 98 (38.3%) of 256 mood disorder events were attributed to SLE. The estimated cumulative incidence of any mood disorder after 10 years was 17.7% (95% confidence interval 15.1, 20.2%). A greater risk of mood disorder was associated with concurrent neuropsychiatric events (P ≤ 0.01), and a lower risk was associated with Asian race/ethnicity (P = 0.01) and treatment with immunosuppressive drugs (P = 0.003). Mood disorders were associated with lower mental health and mental component summary scores but not with the SLEDAI-2K, SDI, or lupus autoantibodies. Among the 232 patients with depression, 168 (72.4%) were treated with antidepressants. One hundred twenty-six (49.2%) of 256 mood disorders resolved in 117 (50.4%) of 232 patients., Conclusion: Mood disorders, the second most frequent neuropsychiatric event in patients with SLE, have a negative impact on health-related quality of life and improve over time. The lack of association with global SLE disease activity, cumulative organ damage, and lupus autoantibodies emphasizes the multifactorial etiology of mood disorders and a role for non-lupus-specific therapies., (© 2015, American College of Rheumatology.)

Objective: To assess the added effect of comorbidity on quality of life (QOL) in psoriatic arthritis (PsA)., Methods: Between 2006 and 2012, 631 patients were recruited from the University of Toronto PsA Clinic. Using the clinical database, we ascertained the frequency of 15 comorbidities. The Medical Outcomes Study Short Form-36 (SF-36) physical (PCS) and mental component (MCS) summary scales were used to assess QOL. Linear regression analyses were conducted to estimate the magnitude of the association between number and type of comorbidities and PCS and MCS scores, after adjustment for disease-related and sociodemographic variables., Results: Prevalence of comorbidity was high, with 42% of patients having 3 or more comorbid conditions. After adjustment for inflammatory disease-related and sociodemographic factors, a history of 3 or more comorbid conditions accounted for only 2% and 1% of the R(2) value explained in PCS and MCS scores, respectively. In terms of added burden, type of comorbid condition was more significant than number of comorbidities. After adjustment for disease-related and sociodemographic factors, fibromyalgia (FM), neurological disorders, and obesity jointly accounted for 6% of R(2) value explained in PCS scores, while FM and depression/anxiety jointly accounted for about 9% of the R(2) explained in MCS scores. The point decrease in PCS and MCS scores associated with each of these disorders was clinically significant. The 11 other comorbid conditions failed to achieve statistical significance in the models., Conclusion: The added effect of comorbidity on patient-reported physical and mental health in PsA was more related to type of comorbidity than number of comorbidities.

Objective: Neuropsychiatric (NP) manifestations attributable to active disease affect up to 30% of individuals with systemic lupus erythematosus (SLE). The short-term impact of NP events includes increased organ damage, fatigue, and mortality, and lower health-related quality of life. We investigated the impact of NP events attributable to active SLE at presentation on long-term disease activity, organ damage, and health-related quality of life., Methods: Seventy-two NP cases and 144 matched controls from the University of Toronto Lupus Cohort, enrolled between 1970 and 2005, were included in the study. NP cases had at least 1 NP event attributable to active SLE at the first clinic visit. Controls did not have NP events at the first clinic visit and were matched to cases on age, sex, disease duration, and decade. Paired case-control analyses were performed on measures of disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000), disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and health-related quality of life (Short Form 36) at 1 year, 3 years, and 5 years after the first clinic visit., Results: NP cases showed greater disease activity than controls at the first clinic visit (P < 0.0001) and greater cumulative organ damage at 1-year followup (P = 0.01). No statistically significant differences were found on 3-year or 5-year outcomes. Mean scores showed a decreasing trend of disease activity, increasing organ damage, and persistently low quality of life for both cases and controls., Conclusion: This study shows that early NP events due to active SLE are not major contributors to long-term disease activity, accumulation of damage, or health-related quality of life. The long-term prognosis and patterns of disease in SLE patients with early NP events are similar to those of SLE patients without these events., (Copyright © 2012 by the American College of Rheumatology.)

Objective: PsA is an inflammatory arthritis present in ∼30% of people with psoriasis (PsC). Both conditions have a significant impact on quality of life (QoL). Our objective was to test the hypothesis that people with PsA have poorer QoL than patients with PsC because of the added burden of arthritis, age and comorbidities., Methods: Consecutive patients with PsA (CASPAR criteria) and PsC were approached to participate in this study. Patients with PsC were examined by a rheumatologist using a standardized protocol to exclude PsA. Patients completed the HAQ, Medical Outcome Study 36-item Short Form Health Survey, Dermatology Life Quality Index (DLQI), EuroQoL 5 domains (EQ-5D) and Fatigue Severity Scale (FSS). Mean scores were compared and multivariate analyses were conducted to compare the QoL measures between the two patient groups., Results: Two hundred and one patients with PsC and 201 patients with PsA were studied. A significant decrease in QoL for patients with PsA compared with those with PsC was identified by all questionnaires except for the DLQI. This skin-specific questionnaire revealed a lower QoL in patients with PsC. Multivariate analyses for each QoL measure confirmed the results of these analyses. After adjusting for age, sex, duration of PsC, comorbidities, DMARDs and biologic therapy, HAQ and DLQI were independently associated with PsA in a logistic regression., Conclusion: Patients with PsA have a poorer QoL compared with those with PsC as measured by all questionnaires except the DLQI.

Objective: To assess whether the Lupus Quality of Life (LupusQoL) questionnaire contributed additional information not obtained using the Medical Outcomes Study Short-Form 36 questionnaire (SF-36) in a cohort of patients with systemic lupus erythematosus (SLE)., Methods: Forty-one patients seen at a single center were followed at monthly intervals for 12 months. The LupusQoL and the SF-36 questionnaires were coadministered monthly. Disease activity was determined by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) every 30 days. We determined the correlation of the 4 comparable domains of both questionnaires. For the 4 noncomparable domains of the LupusQoL we determined the correlation between each domain with the Physical Component Summary scores (PCS) and the Mental Component Summary scores (MCS) of the SF-36. The effect size (ES) and the standardized response mean (SRM) were used to compare the responsiveness of both questionnaires when a clinically significant change in disease activity occurred as determined by SLEDAI-2K., Results: Three hundred seventy-six patient visits were recorded. There was a strong correlation between comparable domains in both questionnaires. For the 4 noncomparable domains of the LupusQoL, there was a correlation with the MCS and PCS of SF-36. The mean scores for comparable domains in both questionnaires were similar. Both questionnaires displayed responsiveness, as determined by ES and SRM among patients who flared and improved, but not among patients in remission, when compared to the previous visit., Conclusion: LupusQoL and SF-36 were equivalent in assessing quality of life over time in this group of patients. Both questionnaires are responsive measures of quality of life in patients with SLE flares and improvement.

Objective: To compare health-related quality of life (HRQOL) of patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) with and without previous thrombovascular events (TE)., Methods: The Medical Outcomes Study Short-Form 36 (SF-36) was used to assess HRQOL in 5 patient groups: (1) primary APS (PAPS; n = 35); (2) APS associated to SLE (SAPS; n = 37); (3) SLE+TE without persistent positive antiphospholipid antibody (SLE+TE-aPL; n = 75); (4) SLE-TE+aPL (n = 71); and (5) SLE-TE-aPL (n = 608)., Results: The data on both mental component summary and physical component summary (PCS) scores showed an impaired quality of life in all patient groups. Patients in the SLE+TE-aPL group had a lower PCS score compared to patients in the SLE-TE+aPL group., Conclusion: The combination of SLE and TE has a more negative influence on reported HRQOL, compared to having SLE or APS alone.

Objective: To determine whether quality of life in patients with systemic lupus erythematosus (SLE) measured by the Short Form 36 (SF-36) changes over time and which patient- and disease-related factors influence such change., Methods: SLE patients who had > or =6 SF-36 evaluations during followup were identified from a database. Outcomes were slopes of scores of the 8 SF-36 domains as well as the physical and mental component scores. Based on the direction of the slope, patients were designated as unchanged, improved, or worsened. Linear regression models were used to test the contribution of risk factors to slopes. Nonparametric tests were used to evaluate risk factors between patterns of clinical change., Results: A total of 146 patients had > or =6 SF-36 evaluations in 1,047 visits over a mean +/- SD period of 8.2 +/- 1.1 years. During the interval, the majority of patients showed no change in the SF-36 domains and only a small minority demonstrated improvement. Physical and mental component scores were unchanged in 84.3% and 87.7% of patients whereas 4.1% and 7.5% improved, respectively. According to slopes of the domains and summary scores, only physical functioning demonstrated a significant decrease over time. There were no lupus disease features associated with decline in physical functioning except for the presence of fibromyalgia., Conclusion: The SF-36 in SLE patients with established disease changed little over an 8-year period. Changes in the SF-36 were not affected by disease activity, steroids, or damage accumulation during the interval, but were affected by the presence of fibromyalgia.

ObjectiveTo 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).MethodsFor 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.ResultsIn 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.ConclusionThe 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.

ObjectiveTo 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).MethodsA 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.ResultsCerVEs 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.ConclusionCerVEs, 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.

ObjectiveTo determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort.MethodsPatients in the Systemic Lupus International Collaborating Clinics inception cohort (≤15 months of SLE diagnosis) were assessed annually for estimated glomerular filtration rate (eGFR), proteinuria and end-stage renal disease (ESRD). Health-related quality of life was measured by the Short Form (36 questions) health survey questionnaire (SF-36) subscales, mental and physical component summary scores.ResultsThere were 1827 patients, 89% females, mean (s.d.) age 35.1 (13.3) years. The mean (s.d.) SLE duration at enrolment was 0.5 (0.3) years and follow-up 4.6 (3.4) years. LN occurred in 700 (38.3%) patients: 566/700 (80.9%) at enrolment and 134/700 (19.1%) during follow-up. Patients with nephritis were younger, more frequently men and of African, Asian and Hispanic race/ethnicity. The estimated overall 10-year incidence of ESRD was 4.3% (95% CI: 2.8%, 5.8%), and with nephritis was 10.1% (95% CI: 6.6%, 13.6%). Patients with nephritis had a higher risk of death (HR = 2.98, 95% CI: 1.48, 5.99; P = 0.002) and those with eGFR

Objectives Evaluate effects of long-term bimekizumab treatment on patient-reported outcome (PRO) measures, symptoms and the impact of PsA on patients. Methods Patients with active PsA were enrolled into BE ACTIVE, a 48-week randomised controlled trial (NCT02969525). After Week 48, patients could enter a 104-week open-label extension (NCT03347110), receiving bimekizumab 160 mg every four weeks. PRO measures assessed included arthritis pain visual analogue scale (VAS), PsA Impact of Disease (PsAID)-9, 36-Item Short Form Survey (SF-36) and HAQ-Disability Index (HAQ-DI). Results were analysed as mean (S.E.M.) changes from baseline (CfB) from Week 0 to the end of the open-label extension (3 years) and as percentage of patients reaching patient-acceptable symptom state (PASS) for global impact (PsAID-9 total score ≤4) and normal function (HAQ-DI total score <0.5). Non-responder imputation was applied to missing binary outcomes. Results In 206 patients (mean age 49.3 years, 51.0% male), completion rate was high; 161 (78.2%) patients completed Week 152. Bimekizumab treatment was associated with long-term sustained improvements in pain [arthritis pain VAS CfB; Week 48: −29.9 (1.9); Week 152: −32.0 (1.9)] and fatigue [PsAID-9 fatigue CfB; −2.4 (0.2); −2.7 (0.2)]. High percentages of patients achieved acceptable symptom state (PsAID-9 PASS: 75.2%; 65.0%) and normalised function (HAQ-DI <0.5: 49.0%; 46.1%). Improvements in patient global assessment and SF-36 Physical Component Summary were also sustained. Conclusions Bimekizumab treatment was associated with long-term sustained improvements in pain and fatigue, reducing overall impact of PsA on patients. Physical function and quality of life improved up to 3 years. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT02969525, NCT03347110. [ABSTRACT FROM AUTHOR]

Introduction: In DISCOVER-2, guselkumab, an interleukin-23 p19 subunit inhibitor, was efficacious in biologic-naïve psoriatic arthritis (PsA) patients. We report the effect of guselkumab on health-related quality of life (HRQoL) using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and Visual Analog Scale (EQ-VAS) through Week 52.Methods: Adults with active PsA were randomized to guselkumab 100 mg every 4 weeks (Q4W) or Weeks 0, 4, then every 8 weeks (Q8W), or placebo (crossover to guselkumab Q4W at Week 24). Least squares (LS) mean changes in EQ-5D-5L Index (0-1, US-based value set) and EQ-VAS (0-100) from baseline through Week 52 were assessed. Proportions of patients achieving minimally important differences (MIDs) were assessed through Week 52. Associations between patient clinical features and EQ-5D-5L Index and EQ-VAS scores were examined cross-sectionally with pooled data through Week 24.Results: The analysis included 738 patients (Q4W n = 245; Q8W n = 248; placebo n = 245). At Week 24, LS mean changes from baseline in the Q4W, Q8W, and placebo groups were 0.12, 0.12, and 0.05, respectively, for EQ-5D-5L Index, and 18.2, 18.4, and 6.8, respectively, for EQ-VAS. At Week 52, improvement was maintained in the guselkumab groups and increased in the placebo crossover group. EQ-5D-5L Index MID was achieved by 56.0% in each guselkumab group at Week 24 and 66.2% in Q4W, 68.5% in Q8W, and 66.1% in placebo crossover group at Week 52. Higher C-reactive protein level, Psoriasis Area and Severity Index score, fatigue, and pain were correlated with worse EQ-5D-5L Index and EQ-VAS, based on pooled data through Week 24. Higher tender joint count was correlated with worse EQ-5D-5L, while higher swollen joint count was correlated with worse EQ-VAS.Conclusions: Guselkumab improved HRQoL through 52 weeks in patients with active PsA. Impairment in HRQoL was correlated with increased inflammation, fatigue, pain, and measures of skin and joint symptom severity.Clinicaltrials: GOV: NCT03158285. [ABSTRACT FROM AUTHOR]

Objective: Psoriatic arthritis (PsA) substantially impairs quality of life. Clinical trials generally focus on polyarticular PsA, but less is known about the assessment and management of oligoarticular and moderate PsA. An online survey was conducted to determine Canadian rheumatologists' perspectives on the definition and treatment of oligoarticular and moderate PsA.Methods: Regional and national experts treating patients with PsA were asked to complete an online survey to assess their approach to identifying and managing patients with PsA. Survey questions were developed based on guidance from a committee of Canadian rheumatologists.Results: Sixty-four of 78 rheumatologists responded, representing 6 major Canadian provinces. Nearly half of respondents were in practice > 20 years. The majority of rheumatologists reported using swollen joint count (SJC) to describe moderate PsA (86.4%) and oligoarticular PsA (96.7%), and considered location of inflammation in PsA assessments. SJC cutoff scores for reporting moderate PsA varied among rheumatologists, suggesting lack of an agreed-upon definition for moderate PsA. Sixty-eight percent of rheumatologists identified access to treatment as the greatest challenge with oligoarticular PsA.Conclusion: According to the surveyed rheumatologists, SJC remains a key assessment variable when defining oligoarticular and moderate PsA. Although the number of joints is considered when determining the effect of PsA on patients, joint location and functional impairment are also considered when describing the disease as moderate. Access to treatment for patients with < 5 affected joints is challenging. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of secukinumab with that of placebo across the updated Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and Outcome Measures in Rheumatology (GRAPPA-OMERACT) individual psoriatic arthritis (PsA) core domains using pooled data from 4 phase III PsA studies and 1 phase III ankylosing spondylitis (AS) study.Methods: Data were pooled from 2049 patients with PsA participating in 4 on-label phase III PsA studies (FUTURE 2-5), and the efficacy of each GRAPPA-OMERACT PsA core domain (musculoskeletal disease activity, skin disease activity, pain, patient's global assessment, physical function, health-related quality of life, fatigue, and systemic inflammation) was assessed using multiple measures and definitions specific to each domain. The MEASURE 2 study, a phase III clinical trial in patients with AS, was used to assess improvement in spine symptoms at Week 16.Results: Treatment with secukinumab demonstrated robust and consistent efficacy across all GRAPPA-OMERACT PsA core domains, with secukinumab 300 mg showing the greatest response rates across most PsA core domains compared with placebo at Week 16. Notably, among patients treated with secukinumab 300 mg, 34.3% and 19.5% achieved complete resolution of swollen and tender joint counts, respectively; 53.2% and 61.5% achieved complete resolution of enthesitis and dactylitis, respectively; and 33.2% achieved 100% improvement in Psoriasis Area and Severity Index (all p < 0.05 vs placebo); similar improvements were shown for all other core domains.Conclusion: This analysis suggests that secukinumab can benefit people with PsA across the clinical phenotypic spectrum commonly encountered in this disease. [ABSTRACT FROM AUTHOR]

Objectives: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients.Methods: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states.Results: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001).Conclusions: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE. [ABSTRACT FROM AUTHOR]

Objective: The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis (PsA). We aimed to validate a cutoff value of PASDAS that defines minimal disease activity (MDA) state, as well as to validate previously defined PASDAS cutoffs for low and high disease activity.Methods: Patients were prospectively recruited from the University of Toronto PsA clinic according to a standard protocol, and variables necessary to complete the PASDAS and the MDA were collected. Receiver-operating characteristic (ROC) curve analysis determined the optimal PASDAS cutoff discriminating patients in MDA state from those not in MDA. Previously proposed PASDAS disease activity cutoff scores were validated by determining the proportion of patients requiring treatment escalation, a surrogate of active disease, in each of low, moderate, and high disease activity groups.Results: One hundred seventy-eight patients [53.9% male, mean PASDAS 3.29 (SD 1.29), 47.8% in MDA] were recruited. ROC curve analysis identified a PASDAS score of 3.2 as the point that maximized the sensitivity and specificity for MDA based on 5 of 7 criteria (sensitivity 88%, specificity 92%, area under the curve 0.96). For MDA based on meeting 6 of 7 and 7 of 7 criteria, PASDAS scores of 2.6 and 2.1 maximized sensitivity and specificity, respectively. An increasing proportion of patients from low to moderate to high disease activity groups required treatment escalation, increasing from 8.1% to 42% to 67%, respectively.Conclusion: A PASDAS score < 3.2 reflects MDA. This study has externally validated PASDAS cutoff scores previously proposed to differentiate between low, moderate, and high disease activity. [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]

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Working Group reported at the 2018 GRAPPA annual meeting on the outcome of the OMERACT 2018 Conference in Terrigal, Australia. The working group presented the endorsement of the 66/68 joint count for the assessment of peripheral arthritis and the provisional endorsement of the PsA Impact of Disease 12 questionnaire for the assessment of PsA-specific health-related quality of life in PsA randomized controlled trials and observational studies. In this report, the group presents its plan to seek OMERACT endorsement for outcome measures that address the domains of MSK disease activity for enthesitis and dactylitis, physical function, fatigue, and structural damage following the OMERACT Filter 2.1 methodology. [ABSTRACT FROM AUTHOR]

Objective To report patient-reported outcomes of patients with PsA treated with ixekizumab up to 52 weeks. Methods In SPIRIT-P1, biologic-naïve patients with active PsA were randomized to ixekizumab 80 mg every 4 weeks (IXEQ4W; N = 107) or every 2 weeks (IXEQ2W; N = 103) following a 160 mg starting dose, adalimumab 40 mg every 2 weeks (ADA; N = 101) or placebo (PBO; N = 106) during the initial 24-week double-blind treatment period. At week 24 (week 16 for inadequate responders), ADA (8-week washout before starting ixekizumab) and PBO patients were re-randomized to IXEQ2W or IXEQ4W. Patients receiving ixekizumab at week 24 received the same dose during the extension period (EP) to week 52. Patients completed measures including the Dermatology Life Quality Index (DLQI), Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2, European Quality of Life 5 Dimensions Visual Analogue Scale and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem. Results The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in DLQI at week 24; 22% (PBO), 53% (IXEQ4W), 63% (IXEQ2W) and 54% (ADA) of patients reported DLQI scores of 0/1. The IXEQ4W, IXEQ2W and ADA groups reported significant improvements in Itch Numeric Rating Scale, 36-Item Short Form Health Survey version 2 physical component summary and some domain scores, and European Quality of Life 5 Dimensions Visual Analogue Scale at weeks 12 and 24; and in three of four Work Productivity and Activity Impairment Questionnaire-Specific Health Problem domains at week 24. Results are also presented through week 52 for the EP. Conclusion In biologic-naïve patients with active PsA, ixekizumab significantly improved skin symptoms, health-related quality of life and work productivity. Trial Registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239; EU Clinical Trials Register, https://www.clinicaltrialsregister.eu, EudraCT2011-002326-49 [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA).Methods: This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24.Results: Abatacept significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p<0.001). Although abatacept numerically increased Health Assessment Questionnaire-Disability Index response rates (reduction from baseline ≥0.35) at week 24, this was not statistically significant (31.0% vs 23.7%; p=0.097). The benefits of abatacept were seen in ACR20 responses regardless of tumour necrosis factor inhibitor exposure and in other musculoskeletal manifestations, but significance could not be attributed due to ranking below Health Assessment Questionnaire-Disability Index response in hierarchical testing. However, the benefit on psoriasis lesions was modest. Efficacy was maintained or improved up to week 52. Abatacept was well tolerated with no new safety signals.Conclusions: Abatacept treatment of PsA in this phase III study achieved its primary end point, ACR20 response, showed beneficial trends overall in musculoskeletal manifestations and was well tolerated. There was only a modest impact on psoriasis lesions.Trial Registration Number: ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb). [ABSTRACT FROM AUTHOR]

Objective To examine the frequency and characteristics of headaches and their association with global disease activity and health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE). Methods A disease inception cohort was assessed annually for headache (5 types) and 18 other neuropsychiatric (NP) events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 (SF-36) mental and physical component summary scores were collected. Time to first headache and associations with SF-36 scores were analyzed using Cox proportional hazards and linear regression models with generalized estimating equations. Results Among the 1,732 SLE patients enrolled, 89.3% were female and 48.3% were white. The mean ± SD age was 34.6 ± 13.4 years, duration of disease was 5.6 ± 5.2 months, and length of followup was 3.8 ± 3.1 years. At enrollment, 17.8% of patients had headache (migraine [60.7%], tension [38.6%], intractable nonspecific [7.1%], cluster [2.6%], and intracranial hypertension [1.0%]). The prevalence of headache increased to 58% after 10 years. Only 1.5% of patients had lupus headache, as identified in the SLEDAI-2K. In addition, headache was associated with other NP events attributed to either SLE or non-SLE causes. There was no association of headache with SLEDAI-2K scores (without the lupus headache variable), SDI scores, use of corticosteroids, use of antimalarials, use of immunosuppressive medications, or specific autoantibodies. SF-36 mental component scores were lower in patients with headache compared with those without headache (mean ± SD 42.5 ± 12.2 versus 47.8 ± 11.3; P < 0.001), and similar differences in physical component scores were seen (38.0 ± 11.0 in those with headache versus 42.6 ± 11.4 in those without headache; P < 0.001). In 56.1% of patients, the headaches resolved over followup. Conclusion Headache is frequent in SLE, but overall, it is not associated with global disease activity or specific autoantibodies. Although headaches are associated with a lower HRQOL, the majority of headaches resolve over time, independent of lupus-specific therapies. [ABSTRACT FROM AUTHOR]

Objective: In patients with systemic lupus erythematosus (SLE), to determine 1) the prevalence and clinical features of peripheral neuropathies (PN) and whether they were SLE related, 2) whether there are associations between other SLE features and PN. Methods: Patients who met the American College of Rheumatology case definition criteria for SLE peripheral neuropsychiatric syndromes were selected from the University of Toronto Lupus Clinic database. Demographic data and SLE-related clinical and laboratory data were extracted. Health-related quality of life was assessed using the mental and physical component summary score of the SF-36 questionnaire. In a nested case-control study, SLE patients with PN were matched by disease duration and compared with those without PN. Results: Of 1533 patients in the database, 207 (14%) had PN. Of these, 40% were non-SLE-related. Polyneuropathy was diagnosed in 56%, mononeuritis multiplex in 9%, cranial neuropathy in 13%, and mononeuropathy in 11% of patients. Asymmetric presentation was most common (59%) and distal weakness occurred in 34%. Electrophysiologic studies indicated axonal neuropathy in 70% and signs of demyelination in 20% of patients. Compared with patients without PN, those with PN had significantly more central nervous system involvement, higher SLE-disease activity index 2000 and lower SF-36-PCS. Conclusions: The prevalence of PN is relatively high in SLE and occurs more frequently in patients with central nervous system involvement and high SLE-disease activity index. There is a predilection for asymmetric and lower extremities involvement, especially peroneal and sural nerves. This manifestation of the disease has a significant impact on the patient''s quality of life. [Copyright &y& Elsevier]

Although there is still some controversy about the existence of psoriatic arthritis (PsA) as a specific form of inflammatory arthritis associated with psoriasis, epidemiological and clinical studies support the unique features of PsA. Because of lack of diagnostic or classification criteria, the disease has been thought of as uncommon. New classification criteria should facilitate case definition of PsA. Over the past several decades, it has become clear that the disease leads to serious disability and even increased mortality. Traditional medications have not been effective in preventing the progression of joint damage. New medications, including biologics, have emerged with potential to controlling the inflammation and arresting the progression of joint damage. [ABSTRACT FROM AUTHOR]

Although there is still some controversy about the existence of psoriatic arthritis as a specific form of inflammatory arthritis associated with psoriasis, epidemiological, and clinical studies support the unique features of psoriatic arthritis. Because of lack of diagnostic or classification criteria, the disease has been thought of as uncommon. Over the past several decades, it has become clear that the disease leads to serious disability and even increased mortality. Traditional medications have not been effective in preventing the progression of joint damage. New medications, including biologics, have emerged with the potential to control the inflammation and arrest the progression of joint damage. [ABSTRACT FROM AUTHOR]