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Objectives: To compare isolated axial psoriatic arthritis (PsA), axial PsA with peripheral involvement and isolated axial ankylosing spondylitis (AS) with psoriasis. To evaluate predictors for developing peripheral disease from isolated axial PsA over time.Methods: Two PsA and AS cohorts identified patients with PsA with axial disease and isolated axial patients with AS with psoriasis. Logistic regression compared isolated axial PsA to axial PsA with peripheral involvement and isolated axial AS with psoriasis. Cox proportional hazards model evaluated predictors for developing peripheral disease from isolated axial PsA.Results: Of 1576 patients with PsA, 2.03% had isolated axial disease and 29.38% had axial and peripheral disease. human leucocyte antigen HLA-B*27 positivity (OR 25.00, 95% CI 3.03 to 206.11) and lower Health Assessment Questionnaire scores (OR 0.004, 95% CI 0.00 to 0.28) were associated with isolated axial disease. HLA-B*27 also predicted peripheral disease development over time (HR 7.54, 95% CI 1.79 to 31.77). Of 1688 patients with AS, 4.86% had isolated axial disease with psoriasis. Isolated axial patients with PsA were older at diagnosis (OR 1.06, 95% CI 1.01 to 1.13), more likely to have nail lesions (OR 12.37, 95% CI 2.22 to 69.07) and less likely to have inflammatory back pain (OR 0.12, 95% CI 0.02 to 0.61) compared with patients with isolated axial AS with psoriasis.Conclusions: Isolated axial PsA and AS with psoriasis are uncommon. HLA-B*27 positivity is associated with isolated axial PsA and may identify those who develop peripheral disease over time. Isolated axial PsA is associated with better functional status. Isolated axial PsA appears clinically distinct from isolated axial AS with psoriasis. [ABSTRACT FROM AUTHOR]

Objective: To determine the independent impact of different definitions of remission and low disease activity (LDA) on damage accrual.Methods: Patients with ≥2 annual assessments from a longitudinal multinational inception lupus cohort were studied. Five mutually exclusive disease activity states were defined: remission off-treatment: clinical Systemic Lupus Erythematosus Disease Activity Index (cSLEDAI)-2K=0, without prednisone or immunosuppressants; remission on-treatment: cSLEDAI-2K score=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; low disease activity Toronto cohort (LDA-TC): cSLEDAI-2K score of ≤2, without prednisone or immunosuppressants; modified lupus low disease activity (mLLDAS): Systemic Lupus Erythematosus Disease Activity Index-2K score of 4 with no activity in major organ/systems, no new disease activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants; active: all remaining visits. Only the most stringent definition was used per visit. Antimalarials were allowed in all. The proportion of time that patients were in a specific state at each visit since cohort entry was determined. Damage accrual was ascertained with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Univariable and multivariable generalised estimated equation negative binomial regression models were used. Time-dependent covariates were determined at the same annual visit as the disease activity state but the SDI at the subsequent visit.Results: There were 1652 patients, 1464 (88.6%) female, mean age at diagnosis 34.2 (SD 13.4) years and mean follow-up time of 7.7 (SD 4.8) years. Being in remission off-treatment, remission on-treatment, LDA-TC and mLLDAS (per 25% increase) were each associated with a lower probability of damage accrual (remission off-treatment: incidence rate ratio (IRR)=0.75, 95% CI 0.70 to 0.81; remission on-treatment: IRR=0.68, 95% CI 0.62 to 0.75; LDA: IRR=0.79, 95% CI 0.68 to 0.92; and mLLDAS: IRR=0.76, 95% CI 0.65 to 0.89)).Conclusions: Remission on-treatment and off-treatment, LDA-TC and mLLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers. [ABSTRACT FROM AUTHOR]

Objectives: A perception derived from cross-sectional studies of small systemic lupus erythematosus (SLE) cohorts is that there is a marked discrepancy between antinuclear antibody (ANA) assays, which impacts on clinicians' approach to diagnosis and follow-up. We compared three ANA assays in a longitudinal analysis of a large international incident SLE cohort retested regularly and followed for 5 years.Methods: Demographic, clinical and serological data was from 805 SLE patients at enrolment, year 3 and 5. Two HEp-2 indirect immunofluorescence assays (IFA1, IFA2), an ANA ELISA, and SLE-related autoantibodies were performed in one laboratory. Frequencies of positivity, titres or absorbance units (AU), and IFA patterns were compared using McNemar, Wilcoxon and kappa statistics, respectively.Results: At enrolment, ANA positivity (≥1:80) was 96.1% by IFA1 (median titre 1:1280 (IQR 1:640-1:5120)), 98.3% by IFA2 (1:2560 (IQR 1:640-1:5120)) and 96.6% by ELISA (176.3 AU (IQR 106.4 AU-203.5 AU)). At least one ANA assay was positive for 99.6% of patients at enrolment. At year 5, ANA positivity by IFAs (IFA1 95.2%; IFA2 98.9%) remained high, while there was a decrease in ELISA positivity (91.3%, p<0.001). Overall, there was >91% agreement in ANA positivity at all time points and ≥71% agreement in IFA patterns between IFA1 and IFA2.Conclusion: In recent-onset SLE, three ANA assays demonstrated commutability with a high proportion of positivity and titres or AU. However, over 5 years follow-up, there was modest variation in ANA assay performance. In clinical situations where the SLE diagnosis is being considered, a negative test by either the ELISA or HEp-2 IFA may require reflex testing. [ABSTRACT FROM AUTHOR]

Objective: In patients with psoriatic disease (PsD), we sought serum metabolites associated with cardiovascular (CV) events and investigated whether they could improve CV risk prediction beyond traditional risk factors and the Framingham Risk Score (FRS).Methods: Nuclear magnetic resonance metabolomics identified biomarkers for incident CV events in patients with PsD. The association of each metabolite with incident CV events was analysed using Cox proportional hazards regression models first adjusted for age and sex, and subsequently for traditional CV risk factors. Variable selection was performed using penalisation with boosting after adjusting for age and sex, and the FRS.Results: Among 977 patients with PsD, 70 patients had incident CV events. In Cox regression models adjusted for CV risk factors, alanine, tyrosine, degree of unsaturation of fatty acids and high-density lipoprotein particles were associated with decreased CV risk. Glycoprotein acetyls, apolipoprotein B and cholesterol remnants were associated with increased CV risk. The age-adjusted and sex-adjusted expanded model with 13 metabolites significantly improved prediction of CV events beyond the model with age and sex alone, with an area under the receiver operator characteristic curve (AUC) of 79.9 versus 72.6, respectively (p=0.02). Compared with the FRS alone (AUC=73.9), the FRS-adjusted expanded model with 11 metabolites (AUC=75.0, p=0.72) did not improve CV risk discrimination.Conclusions: We identify novel metabolites associated with the development of CV events in patients with PsD. Further study of their underlying causal role may clarify important pathways leading to CV events in this population. [ABSTRACT FROM AUTHOR]

Background/objectives: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria.Methods: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE.Results: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement.Conclusions: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set. [ABSTRACT FROM AUTHOR]

Objective: To determine the ominosity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Systemic Lupus Erythematosus Classification Criteria by determining its predictive role for disease severity in the first 5 years following diagnosis.Methods: 867 patients with systemic lupus erythematosus (SLE) from the Toronto Lupus Clinic were included (all first 12 months after SLE diagnosis). The EULAR/ACR criteria score was calculated based on baseline information. To determine disease severity in the first 5 years after diagnosis, adjusted mean SLE Disease Activity Index 2000 (AMS), flares, remission and immunosuppressive treatment were used as outcomes. The Systemic Lupus International Collaborating Clinics (SLICC) registry comprised the validation cohort.Results: Based on receiver operating characteristic analysis, a EULAR/ACR score of 20 was used as a threshold to compare outcomes between groups. In the first 5 years of disease course, patients with a score of ≥20 had higher AMS scores (p<0.001) and were more likely to ever experience a flare (p<0.001). These patients had lower probabilities of achieving remission and higher requirements for immunosuppressives. Results were confirmed in the SLICC validation cohort. Patients with a score of ≥20 had higher AMS during the first 5 years of disease (5.4 vs 3.1% and ≥20 vs <20 respectively, p≤0.001). The score correlated with AMS (r=0.43, p≤0.001) in the same time frame.Conclusion: A EULAR/ACR score of ≥20 is an indicator of ominosity in SLE. Patients with a score of ≥20 were characterised by a more active disease course throughout the first 5 years. These criteria provide prognostic information regarding disease severity in the first 5 years following diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria.Methods: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated.Results: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%).Conclusions: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups. [ABSTRACT FROM AUTHOR]

Background: The 2017 American College of Cardiology/American Heart Association guidelines defined hypertension at ≥130/80 mm Hg. Studies on patients with connective tissue diseases were not considered. Our aim was to assess the impact of this definition on atherosclerotic vascular events (AVEs) in systemic lupus erythematosus.Patients Methods: Individuals from the Toronto Lupus Clinic with at least 2 years of follow-up and no prior AVE were divided in three groups according to their mean blood pressure (BP) over that period (≥140/90 mm Hg, 130-139/80-89 mm Hg and <130/80 mm Hg). They were followed until the first occurrence of an AVE (fatal or non-fatal coronary artery disease, cerebrovascular event and peripheral vascular disease) or last visit. Groups were compared as per the baseline atherosclerotic risk factors. A multivariable time-dependent analysis was performed to adjust for the presence of other risk factors.Results: Of 1532 patients satisfying the inclusion criteria, 155 (10.1%) had a BP ≥140/90 mm Hg, 316 (20.6%) 130-139/80-89 mm Hg and 1061 (69.3%) were normotensives. After a mean follow-up of 10.8 years, 124 AVEs were documented. The incidence rates were 18.9, 11.5 and 4.5 per 1000 patient-years for the three groups, respectively (p=0.0007 between the 130-139/80-89 mm Hg group and the normotensives). A mean BP of 130-139/80-89 mm Hg over the first 2 years was independently associated with the occurrence of AVEs (HR 1.73, 95% CI 1.13 to 2.65, p=0.011).Conclusion: Patients with lupus with a sustained mean BP of 130-139/80-89 mm Hg over 2 years had a significantly higher incidence of AVEs compared with normotensive individuals. This BP level should be the target for antihypertensive therapy to minimise their cardiovascular risk. [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: 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 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 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 seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (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 reflect current thinking about SLE and provide an improved foundation for SLE research. [ABSTRACT FROM AUTHOR]

Background: Survival in systemic lupus erythematosus (SLE) has improved substantially in the last 50 years. The aim of the present study was to assess the evolution of the all-cause, cause-specific and age-specific standardised mortality ratios (SMRs) of patients with lupus in Ontario, Canada.Patients and Methods: Between 1971 and 2013, 1732 patients were followed in the Toronto Lupus Clinic. Causes of death were retrieved from death certificates, autopsy reports, hospital records or the records of the family physicians. They were categorised as atherosclerotic, infectious, malignancy, active lupus and others. For the calculation of the SMR (indirect standardisation method), data from the general population of Ontario, Canada were used (Statistics Canada).Results: Two hundred and forty-nine patients (205 women) died (infections 24.5%, atherosclerosis 15.7%, active lupus 13.3%, malignancy 9.6%); mean age was 53.2±16.6 years and mean disease duration 15.2±11.7 years. The all-cause SMR was substantially decreased from the 1970s (13.5, 95% CI 8.6 to 18.5) to recent years (2.2, 95% CI 1.4 to 3.1). Similar trends were observed for atherosclerosis, infections and malignancies over time. The all-cause age-specific SMR was particularly high in younger (19-39 years old) patients (SMR=12.4, 95% CI 9.7 to 15.1) as compared with individuals older than 40 years (SMR=3.1, 95% CI 2.6 to 3.6). The cause-specific SMR was also higher in younger patients, particularly for infections and malignancies.Conclusions: The all-cause and cause-specific SMR significantly decreased over time, likely reflecting the advances in the management of SLE and certain comorbidities. The all-cause and cause-specific SMR was particularly high for younger patients (<40 years old). [ABSTRACT FROM AUTHOR]

Objectives: We aimed to identify soluble biomarkers that differentiate psoriatic arthritis (PsA) from osteoarthritis (OA).Methods: Markers of cartilage metabolism (cartilage oligomeric matrix protein [COMP], hyaluronan), metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor [HGF], insulin, leptin) and inflammation (C-reactive protein [CRP], interleukin-1β [IL-1β], IL-6, IL-8, tumour necrosis factor alpha [TNFα], monocyte chemoattractant protein-1 [MCP-1], nerve growth factor [NGF]) were compared in serum samples from 201 patients with OA, 77 patients with PsA and 76 controls. Levels across the groups were compared using the Kruskal-Wallis test. Pairwise comparisons were made with Wilcoxon rank-sum test. Multivariate logistic regression analyses were performed to identify markers that differentiate PsA from OA. Receiver operating characteristic (ROC) curves were constructed based on multivariate models. The final model was further validated in an independent set of 73 PsA and 75 OA samples using predicted probabilities calculated with coefficients of age, sex and biomarkers.Results: Levels of the following markers were significantly different across the three groups (p<0.001)-COMP, hyaluronan, resistin, HGF, insulin, leptin, CRP, IL-6, IL-8, TNFα, MCP-1, NGF. In multivariate analysis, COMP (OR 1.24, 95% CI 1.06 to 1.46), resistin (OR 1.26, 95% CI 1.07 to 1.48), MCP-1 (OR 1.10, 95% CI 0.07 to 1.48) and NGF (OR<0.001, 95% CI <0.001 to 0.25) were found to be independently associated with PsA versus OA. The area under the ROC curve (AUROC) for this model was 0.99 compared with model with only age and sex (AUROC 0.87, p<0.001). Similar results were obtained using the validation sample.Conclusion: A panel of four biomarkers may distinguish PsA from OA. These results need further validation in prospective studies. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine the agreement between rheumatologist-judged inflammatory back pain (IBP) and criteria defining IBP in patients with psoriatic arthritis (PsA) and predictive value of IBP in identifying axial involvement in PsA.Methods: Using prospectively collected data, we investigated the agreement between rheumatologist judgement of IBP and IBP criteria (Calin, Rudwaleit and Assessment of Spondyloarthritis International Society) using the kappa coefficient. We also determined the sensitivity, specificity and likelihood ratios of the presence of back pain, rheumatologist-judged IBP and the three IBP criteria for detecting axial PsA (AxPsA). Finally, we compared the clinical and genetic markers in patients with PsA with axial radiological changes with and without back pain.Results: 171 patients (52% male, mean age 46.6 years) were identified. Ninety-six (56.13%) patients reported chronic back pain. Sixty-five (38.01%) had IBP. 54 (32%) patients had evidence of radiological change in the spine. The agreement between rheumatologist judgement of IBP and IBP criteria was highest for the Calin criteria (0.70). Positive likelihood ratio for the presence of radiological axial involvement was highest for Rudwaleit criteria (2.17). No differences between patients with AxPsA with or without back pain were found, except for higher Bath Ankylosing Spondylitis Disease Activity Index and lower prevalence of human leucocyte antigen-B*38 in those with back pain.Conclusion: Rheumatologist-judged IBP or the criteria for IBP developed for ankylosing spondylitis may not perform well when ascertaining axial involvement in PsA. [ABSTRACT FROM AUTHOR]

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field. [ABSTRACT FROM AUTHOR]

Objectives: To examine the incidence and temporal trends of psoriatic arthritis (PsA) in the general population in Denmark.Methods: Using nationwide registry data, we estimated the number of patients with incident PsA within each 1-year period between 1997 and 2011 and calculated the rate of PsA cases within gender and age subgroups. Incidence rates were presented per 100 000 person-years.Results: There was a female predominance ranging from 50.3% (1998) to 59.2% (2010), and the mean age at time of diagnosis was 47-50 years. We identified a total of 12 719 patients with PsA (prevalence=0.22%), including 9034 patients where the PsA diagnosis was made by a rheumatologist (prevalence=0.16%). Incidence rates of PsA (per 100 000 person-years) increased from 7.3 in 1997 to a peak incidence of 27.3 in 2010. Incidence rates were highest for women and patients aged 50-59 years, respectively. The use of systemic non-biologic agents, that is, methotrexate, leflunomide, ciclosporin or sulfasalazine increased over the 15-year study course and were used in 66.3% of all patients. Biologic agents (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab or ustekinumab) were used in 17.7% of patients with PsA.Conclusions: We found a clear trend of rising PsA incidence on a national level. While the cause remains unclear, our findings might be explained by increased attention by patients and physicians. [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 assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA).Methods: Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24.Results: Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7-66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05).Conclusions: In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo.Trial Registration Number: NCT01695239; EudraCT2011-002326-49; Results. [ABSTRACT FROM AUTHOR]

Objective: To assess the incidence and risk factors of cardiovascular events in patients with psoriatic arthritis (PsA).Methods: A cohort analysis was conducted involving patients recruited and followed over the period from 1978 to 2013 in a large PsA clinic. The participants were assessed at 6 to 12-month intervals according to a standard protocol. The collected information included demographics, lifestyle habits, medical history, medications use and PsA-related outcomes. The primary outcome was a composite major cardiovascular end point comprising myocardial infarction, ischaemic stroke, revascularisation or cardiovascular death. The association between the features of disease activity and the occurrence of cardiovascular events was assessed using Cox proportional hazard models.Results: A total of 1091 patients with PsA were analysed. During the follow-up period, 104 cardiovascular events occurred. A considerable proportion of patients developed a cardiovascular event (19.8% of the patients by the age of 70 years and 30.1% of patient by the age of 80 years). No trend in the risk of developing cardiovascular events was observed over the decades from 1978 to 2013 (p=0.73). In multivariate analysis, the following variables were independent predictors of major cardiovascular events: hypertension (relative risk (RR) 1.81, p=0.015), diabetes (RR 2.72, p<0.001) and the number of dactylitic digits (RR 1.20, p<0.001). Sedimentation rate was a significant predictor only among women (RR 1.83, p=0.02).Conclusion: A significant proportion of patients with PsA develop cardiovascular events during the course of their disease. Increased cardiovascular risk is associated with a combination of traditional cardiovascular risk factors and disease activity. [ABSTRACT FROM AUTHOR]

Aim To investigate whether a higher burden of inflammation is associated with more severe atherosclerosis in patients with psoriatic arthritis (PsA). Methods Patients from a large PsA cohort were analysed. The cumulative effect of inflammation was measured by a time-adjusted arithmetic mean of all measurements from the first visit to the clinic. The following variables were considered as predictors: Psoriasis Activity and Severity Index (PASI), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, tender and swollen joint counts, C-reactive protein, Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity for PsA (DAPSA). Vascular ultrasound of the carotid arteries was performed, and total plaque area was measured. This measure represented the extent of atherosclerosis and was considered the outcome of interest. The association between inflammation over time and atherosclerosis was assessed by regression models adjusted for age, sex and cardiovascular risk factors. Results A total of 235 patients with PsA were analysed. Patients with more severe atherosclerosis were older (p<0.001), more likely to be obese (p=0.01), smokers (p=0.008) and have hypertension (p=0.001), diabetes (p<0.0001) and dyslipidaemia (p<0.0001). In a multivariate regression model adjusted for age and sex, higher ESR (p=0.009), WBC count (p=0.015) and DAPSA (p=0.04) were associated with more severe atherosclerosis. These associations were not significant after adjustment for traditional cardiovascular risk factors. No association was found between disease duration and atherosclerosis. Conclusions Exposure to an increased burden of inflammation is associated with more severe atherosclerosis in patients with PsA. This association may be mediated by traditional cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE. Methods Recently diagnosed (<15 months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards. Baseline and annual assessments recorded clinical, laboratory and therapeutic data. A longitudinal analysis of factors associated with MetS in the first 2 years of follow-up was performed using random effects logistic regression. Results We studied 1150 patients with a mean (SD) age of 34.9 (13.6) years and disease duration at enrolment of 24.2 (18.0) weeks. In those with complete data, MetS prevalence was 38.2% at enrolment, 34.8% at year 1 and 35.4% at year 2. In a multivariable random effects model that included data from all visits, prior MetS status, baseline renal disease, SLICC Damage Index >1, higher disease activity, increasing age and Hispanic or Black African race/ethnicity were independently associated with MetS over the first 2 years of follow-up in the cohort. Conclusions MetS is a persistent phenotype in a significant proportion of patients with SLE. Renal lupus, active inflammatory disease and damage are SLE-related factors that drive MetS development while antimalarial agents appear to be protective from early in the disease course. [ABSTRACT FROM AUTHOR]

Aim To assess whether overweight and obese patients with psoriatic arthritis (PsA) are less likely to achieve sustained minimal disease activity (MDA) state compared to patients with normal weight. Methods A cohort of patients was assessed at the University of Toronto PsA clinic at 6-12-month intervals according to a standard protocol from 2003 to 2012. Patients were categorised into the following groups according to their body mass index (BMI): normal (<25), overweight (25-30), and obese (>30). Sustained MDA was defined as achieving low disease activity state in five or more of the following domains for at least 1 year: skin, enthesitis, tender and swollen joint counts, pain, patient global assessment and function. Proportional odds discrete time to event analysis was used to investigate the association between BMI category and the achievement of sustained MDA. Results Of the 557 patients included in the study, 36.2% were classified as overweight and 35.4% were obese. Overall, 66.1% of the patients achieved sustained MDA during the follow-up period. A dose-response association was found between obesity and the probability of achieving sustained MDA in the multivariate regression analysis. Patients in the higher BMI categories were less likely to achieve sustained MDA compared those in the lowest BMI category (overweight: OR 0.66 p=0.003; obese: OR 0.53 p<0.0001) after adjusting for potential confounding variables. Conclusions Overweight and obese patients with PsA are less likely to achieve sustained MDA compared to those of normal weight. [ABSTRACT FROM AUTHOR]

Aim To investigate the usefulness of carotid atherosclerosis assessment in cardiovascular risk stratification of patients with psoriatic disease compared with the Framingham Risk Score (FRS). Methods Patients with psoriatic arthritis (PsA) and psoriasis alone (PsC), who had no previous history of cardiovascular disease, chronic kidney disease or diabetes mellitus were recruited. They underwent assessment of their cardiovascular risk factors and the FRS was calculated. Based on the FRS, the participants were classified into low, intermediate and high-risk categories. Ultrasound assessment of the carotid artery was performed, and carotid intima-media thickness (cIMT) and total plaque area (TPA) were measured. Patients were stratified into three ultrasound-based risk categories (low, intermediate and high) according to the severity of atherosclerosis. The extent of reclassification from FRS-based category into US-based risk category was assessed. Results A total of 226 patients with psoriatic disease were assessed. FRS correlated moderately with TPA (r=0.36) and cIMT (r=0.37) and explained only 19% of their variability. 56.1% of the patients in the FRS-based low to intermediate risk groups were found to have carotid plaques. 55.9% of the patients from the FRS-based intermediate risk category were reclassified into an ultrasound-based high-risk category, while 47.1% of the patients in the FRS-based low-risk category were reclassified into a higher US-based risk group. The extent of reclassification into a higher risk category was particularly high among patients with PsA. Conclusions Ultrasound assessment of subclinical atherosclerosis may improve risk stratification of patients with psoriatic disease, particularly of those with PsA. [ABSTRACT FROM AUTHOR]

Objectives Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy. Methods In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16. Results At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed. Conclusions Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated. Clinical trial registration number NCT01172938. [ABSTRACT FROM AUTHOR]

Aim To determine whether tumour necrosis factor α (TNFα) blockers are more effective than methotrexate in inhibiting the progression of radiographic joint damage in patients with psoriatic arthritis (PsA). Methods A cohort analysis of patients followed prospectively in a large PsA clinic was conducted. Patients who received a TNFα blocker were compared to those treated with methotrexate. Patients who had records of at least 12 months of treatment with either medication for active peripheral PsA and had radiographic bone erosions were analysed. Radiographs of the hands and feet were performed at baseline, 1-2 years (time 1) and 3-4 years (time 2). Radiographic joint damage was scored according to the modified Steinbrocker score. The outcome of interest was the occurrence of radiographic progression. Multivariate logistic regression analysis using generalised estimating equations for repeated measures was used to compare progression in radiographic joint damage between the two treatment groups. Results 65 patients treated with TNFα blockers and 70 patients treated with methotrexate were analysed. The proportion of patients who demonstrated progression of radiographic damage score at time 1 and time 2 was higher in the methotrexate group compared to the TNFα blockers group (at time 1: 80% vs 58.9% p=0.005; at time 2: 88% vs 61% p=0.005). In the multivariate regression analysis methotrexate treatment was associated with an increase in radiographic damage compared to TNFα blockers (p=0.001). Conclusions In a clinic setting, patients with erosive PsA receiving TNFα blockers had a better radiographic outcome compared to those treated with methotrexate. [ABSTRACT FROM AUTHOR]

Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE. [ABSTRACT FROM AUTHOR]