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ObjectivesVitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance.MethodsThe Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (

ObjectivesTo assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications.MethodsThis observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ⩽15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication.ResultsA total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)].ConclusionCHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.

Objectives To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of IL-17F in addition to IL-17A, vs other biologic and targeted synthetic DMARDs (b/tsDMARDs) for PsA using network meta-analysis (NMA). Methods A systematic literature review (most recent update conducted on 1 January 2023) identified randomized controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12–24 for b/tsDMARD-naïve and TNF inhibitor (TNFi)-experienced patients. Safety at Weeks 12–24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank. Results The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-experienced patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th and 3rd for ACR response ACR20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index 90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-experienced patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events. Conclusion Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA. [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were to investigate the incidence of demyelinating disease (DD) among SpA patients and to identify risk factors that predict DD in this patient population. Methods Axial SpA (axSpA) and PsA patients were identified from a longitudinal cohort database. Each group was analysed according to the presence or absence of DD. Incidence rates (IRs) of DD were obtained, with competing risk analysis. Cox regression analysis (with Fine and Gray's method) was used to evaluate predictors of DD development. Results Among 2260 patients with follow-up data, we identified 18 DD events, corresponding to an average IR of 31 per 100 000 persons per year for SpA. The IR of DD at 20 years was higher in axSpA than in PsA (1.30% vs 0.13%, P  = 0.01). The risk factors retained in the best predictive model for DD development included ever- (vs never-) smoking [hazard ratio (HR) 2.918, 95% CI 1.037–8.214, P  = 0.0426], axSpA (vs PsA) (HR 8.790, 95% CI 1.242–62.182, P  = 0.0294) and presence (vs absence) of IBD (HR 5.698, 95% CI 2.083–15.589, P  = 0.0007). History of TNF-α inhibitor therapy was not a predictor of DD. Conclusion The overall incidence of DD in this SpA cohort was low. Incident DD was higher in axSpA than in PsA. A diagnosis of axSpA, the presence of IBD, and ever-smoking predicted the development of DD. History of TNF-α inhibitor use was not found to be a predictor of DD in this cohort. [ABSTRACT FROM AUTHOR]

ObjectivesTo describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use.MethodsPatients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time.ResultsWe studied 1700 patients with a mean (s.d.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis.ConclusionGCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.

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]

Objectives To examine which composite measures are most sensitive to change when measuring psoriatic arthritis (PsA) disease activity, analyses compared the responsiveness of composite measures used in a 48-week randomized, controlled trial of MTX and etanercept in patients with PsA. Methods The trial randomised 851 patients to receive weekly: MTX (20 mg/week), etanercept (50 mg/week) or MTX plus etanercept. Dichotomous composite measures examined included ACR 20/50/70 responses, minimal disease activity (MDA) and very low disease activity (VLDA). Continuous composite measures examined included Disease Activity Score (28 joints) using CRP (DAS28-CRP), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS). Results At week 24, etanercept-treated groups were significantly more effective than MTX monotherapy to achieve ACR 20 (primary end point) and MDA (key secondary end point). When examining score changes from baseline at week 24 across the five continuous composite measures, PASDAS demonstrated relatively greater changes in the etanercept-treated groups compared with MTX monotherapy and had the largest effect size and standardized response. Joint count changes drove overall score changes at week 24 from baseline in all the continuous composite measures except for PASDAS, which was driven by the Physician and Patient Global Assessments. Conclusion PASDAS was the most sensitive continuous composite measure examined with results that mirrored the protocol-defined primary and key secondary outcomes. Composite measures with multiple domains, such as PASDAS, may better quantify change in PsA disease burden. Trail registration https://ClinicalTrials.gov , number NCT02376790. [ABSTRACT FROM AUTHOR]

Objectives Most randomized controlled trials (RCTs) in SLE have failed to reach their respective end points, with the rates of response to placebo (plus standard-of-care treatment) being unexpectedly high. The aim of this systematic review was to quantify the response to placebo in non-renal, non-neuropsychiatric lupus. Methods The PubMed database was searched (from 2000 to December 2019) for phase II/III RCTs assessing the efficacy and safety of biologics in non-renal, non-neuropsychiatric SLE. Data on the efficacy and safety of the placebo-treated patients were collected in a pre-established data retrieval form. Descriptive statistics were used. Results A total of 24 RCTs (n  = 11128 in total) were included. Placebo-treated patients (n  = 3899) were mostly females (93.5%), Caucasians (60.2%), of mean age 39.7 years, and having a mean disease duration of 7.4 years. Their mean initial SLEDAI 2000 was 10.4, whereas 60.5% had positive anti-dsDNA antibodies, 41.9% low C3 and 35.6% low C4 at randomization. Standard-of-care treatment included glucocorticosteroids in 85.9%, antimalarials in 72.8% and immunosuppressives in 48.5%. The response to placebo was 36.2% for the primary end point (as defined in each study), 39.8% for the SLE Responder Index-4 (SRI-4), 29.2% for SRI-5, 28.4% for SRI-6 and 30.9% for BILAG-based Combined Lupus Assessment response. Regarding safety, there were serious adverse events in 16.3% of patients, serious infections in 5.5% and malignancies in 0.3%, and death occurred in 0.56% of patients. Conclusion More than one-third of the placebo-treated patients achieved their respective primary end points in RCTs with biologics in non-renal, non-neuropsychiatric SLE. The response rate was higher for certain end points, such as the SRI-4, while it decreased with more stringent end points. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare patients with ankylosing spondylitis with psoriasis (ASP) and without psoriasis (AS), to axial PsA (axPsA) patients. Methods Two adult cohorts were recruited from the AS clinic: ASP and AS. These two cohorts were compared with two adult cohorts recruited from the PsA clinic: axPsA (radiographic sacroiliitis: ⩾bilateral grade 2 or unilateral grade 3 or 4); and Peripheral PsA. All patients were followed prospectively according to the same protocol. The demographic, clinical and radiographic variables were compared. Adjusted means were used to account for varying intervals between visits. A logistic regression was performed and adjusted for follow-up duration. Results There were 477 axPsA patients, 826 peripheral PsA, 675 AS and 91 ASP patients included. AS patients were younger (P < 0.001), more male and HLA-B*27 positive (76%, 72% vs 64%, P ⩽ 0.001, 82%, 75%, vs 19%, P = 0.001). They had more back pain at presentation (90%, 92% vs 19%, P = 0.001), worse axial disease activity scores (bath ankylosing spondylitis disease activity index: 4.1, 3.9 vs 3.5 P = 0.017), worse back metrology (bath ankylosing spondylitis metrology index: 2.9, 2.2 vs 1.8, P < 0.001), worse physician global assessments (2.4, 2.2 vs 2.1, P < 0.001), were treated more with biologics (29%, 21% vs 7%, P = 0.001) and had a higher grade of sacroiliitis (90%, 84% vs 51%, P < 0.001). Similar differences were detected in the comparison of ASP to axPsA and in a regression model. Conclusion AS patients, with or without psoriasis, seem to be different demographically, genetically, clinically and radiographically from axPsA patients. axPsA seems to be a distinct entity. [ABSTRACT FROM AUTHOR]

Objective LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). Methods Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. Results Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). Conclusion We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort. [ABSTRACT FROM AUTHOR]

Objectives The Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA) are composite PsA disease activity measures. We sought to identify the PASDAS and DAPSA cut-off points consistent with patient acceptable symptom state (PASS), the threshold of symptoms beyond which patients consider themselves well, and examine PASS across published PASDAS and DAPSA thresholds for low, moderate and high disease activity. Methods We used a standard protocol including physician assessment and patient-reported outcomes to prospectively record measures required to calculate PASDAS and DAPSA. We identified PASS thresholds for the PASDAS and DAPSA using receiver operating characteristics curve analyses. We assessed the frequency of reporting acceptable symptom state across disease activity thresholds for PASDAS and DAPSA scores. Results A total of 229 patients (58.5% male, mean age 55.5 years, mean disease duration 17.1 years) were recruited. The PASS threshold for the PASDAS was 3.79 [area under the curve (AUC) 0.86, sensitivity 0.75, specificity 0.82] and for the DAPSA was 11.10 (AUC 0.91, sensitivity 0.89, specificity 0.82). With the PASDAS, 90% of patients defined as having low disease activity considered their symptom state acceptable, compared with 55% and 17% among those with moderate and high disease activity, respectively. With the DAPSA, 98% of patients in disease remission considered their symptom state acceptable compared with 85, 22 and 18% among those with low, moderate and high disease activity, respectively. Conclusion We have defined PASS thresholds for PASDAS and DAPSA. The PASDAS target for low disease activity and DAPSA targets of low disease activity or remission align well with PASS. [ABSTRACT FROM AUTHOR]