Background: Hypertension (HTN) is the most important modifiable risk factor for the development of cardiovascular events (CVEs). Patients with axSpA are also associated with an increased risk of future CVE. Objectives: To ascertain whether baseline early-stage HTN is a predictor of future CVE in addition to inflammation in patients with axial spondyloarthritis (axSpA). Design: A retrospective cohort study. Methods: Patients with axSpA were recruited from 2001 to 2017. Patients with at least 2 years of follow-up and without prior CVE were divided into three groups according to the calculated mean blood pressure (BP) over the first 2-year follow-up period (adjusted mean BP) (⩾140/90, 130–139/80–89, and <130/80 mm Hg). They were followed from baseline until the end of 2020 or the occurrence of a first CVE. Multivariate Cox regression analyses adjusting for baseline and time-varying variables were used to assess the relationship between mean BP and CVE. Results: Out of the 437 patients fulfilling the inclusion criteria, 49 (11.2%) and 132 (30.2%) had an adjusted mean BP ⩾ 140/90 and 130–139/80–89 mm Hg, respectively, and 256 (58.6%) were pre-HTN. After a median follow-up of 12 (7–18) years, 56 (12.8%) CVEs were documented. The incidence rates were 21.4, 14.2, and 5.9 per 1000 patient-years for the three groups, respectively. Baseline adjusted mean BP of 130–139/80–89 mm Hg was independently associated with the occurrence of CVE after adjusting for the baseline covariates as well as time-varying high inflammatory burden. Conclusion: Baseline-defined early-stage HTN carries excessive risk of developing CVE which may be due to untreated inflammatory burden. Early antihypertensive therapy should target this BP level to minimize their future risk of CVE.

Background Hypertension (HT) is one of the modifiable risk factors for the development of CV event (CVE) [1,2]. The American College of Cardiology/American Heart Association (ACC/AHA) recommended a new definition for arterial HT in adults since 2017 [3]. Whether this new definition of HT is associated with increased CV risk in patients with axSpA remains unknown. Objectives To ascertain whether stage 1 hypertension at baseline is a predictor of future cardiovascular event (CVE) in patients with axial spondyloarthritis (axSpA). Methods We conducted a retrospective cohort study in axSpA patients who were recruited from 2001-2017. Patients with at least 2 years of follow-up and without prior CVE were divided into three groups according to the calculated mean BP over the first 2-year period (adjusted mean BP) (≥140/90mm Hg, 130-139/80-89mm Hg and <130/80mm Hg). They were followed from baseline until the end of 2020 or occurrence of a first CVE. Multivariate Cox regression analyses adjusting for baseline and time-varying variables were used to assess the relationship between mean BP and with CVE. Results Out of the 458 patients fulfilling the inclusion criteria, 56 (12.2%) and 141 (30.8%) had an adjusted mean BP ≥140/90mm Hg and 130–139/80–89mm Hg respectively, and 261 (57.0%) were normotensives. After a median follow-up of 12 [7-18] years, 56 (12.2%) CVE were documented. The incidence rates were 21.4, 14.2 and 5.9 per 1000 patient-years for the three groups respectively. A adjusted mean BP of 130–139/80–89 mm Hg was independently associated with the occurrence of CVE after adjusting for the baseline covariates (Figure 1) as well as time-varying inflammatory burden (Table 1). This association was not significant after adjustment for time-varying traditional CV risk factors. Conclusion Stage I hypertension at baseline is associated with increased risk of developing CVE in axSpA patients. This association may be mediated by other traditional CV risk factor.s. References [1]Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937-52.[2]Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224-60.[3]Whelton PK, Carey RM, Aronow WS, Casey DE, Jr., Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e484-e594. Acknowledgements I would acknowledge all the supports from our teammates. Disclosure of Interests None Declared.Figure 1Kaplan-Meier analysis for CVE-free cumulative survival among the three patient groups (green line: ≥140/90mm Hg, red line: 130–139/80–89 mm Hg, blue line <130/80mm Hg).Table 1Multivariable Cox regression analysis of the 3 BP groups stratified by age group after excluding patients who are older than 60 years.Model 1Model 2Model 3Time-dependent HR (95%CI)p-valueTime-dependent HR (95%CI)P-valueTime-dependent HR (95%CI)P-value<130/80RefRefRefRefRefRef130-139/80-892.60 (1.07, 6.31)0.035*1.90 (0.98, 3.69)0.0572.16 (0.87, 5.35)0.098≥140/904.39 (1.66, 11.63)0.003*2.15 (0.98, 4.69)0.0553.52 (1.28, 9.67)0.015*Age groupAge<30RefRefRefRefRefRef30≤Age<402.46 (0.47, 12.80)0.2841.70 (0.56, 5.13)0.3452.55 (0.49, 13.29)0.26640≤Age<508.04 (1.81, 35.62)0.006*4.69 (1.73, 12.70)0.002*7.12 (1.58, 32.15)0.011*50≤Age<6011.40 (2.36, 55.19)0.002*7.91 (2.69, 23.29)<.001*8.65 (1.70, 43.86)0.009*ESR ≥202.27 (1.07, 4.82)0.033*2.07 (0.97, 4.44)0.061LP ever1.78 (0.80, 3.98)0.1601.33 (0.47, 3.79)0.595DM ever1.62 (0.91, 2.87)0.0992.19 (1.09, 4.40)0.029*

Background Patients with systemic lupus erythematosus (SLE) are at increased risk of severe COVID-19 due to the underlying disease, comorbidities and use of immunosuppressants (IS). An alternative option would be to adopt telemedicine (TM) to maintain medical care while minimizing exposure. Despite being widely adopted during the pandemic, the evidence supporting the use of TM in rheumatology has been limited. Objectives We primarily aimed to evaluate the effectiveness to maintain disease activity control using TM delivered care compared to conventional in-person follow-up in patients with lupus nephritis (LN). The secondary objectives were to compare the patient reported outcomes, safety and cost-of-illness from the patient’s perspective between the 2 modes of health care delivery. Methods This was a 1-year, single-center, RCT conducted at a regional hospital in Hong Kong. From May 2020, consecutive adult patients with a SLE according to the 2019 EULAR/ACR classification criteria followed up at the LN clinic were invited to participate in the study. Participants were randomized 1:1 to either TM (TM group) or standard FU (SF group). Patients randomized to receive TM FU were scheduled for a video consultation via a commerical software ZOOM. Patients in the SF group received standard in-person outpatient care. SLE disease activity at each consultation was assessed by SLEDAI-2k and physician global assessment (PGA). Results A total of 144 patients with LN were randomized and 3 patients self-withdrew from the study. The mean age was 44.5±11.4 years and the median time from diagnosis to randomization was 168 months (range: 1-528). Most of the patients had class III, IV or V LN (87.2%) and were on prednisolone (89.4%, median dose 5mg daily). Many of them (68.1%) were on IS. While 66.0% of the patients were in lupus low disease activity state (LLDAS), none had disease remission. There were no baseline differences, including demographics, SLEDAI-2k (TM: 3.8±2.3, SF: 3.2±2.2, p =0.13, PGA (TM: 6.2±6.5, SF: 4.6±5.9, p =0.13) and SLE damage index (TM: 1.1±1.3, SF: 0.8±1.1, p =0.10), between the 2 groups. At one year, 80.0% and 80.2% of the patients in the TM group and SF group were in LLDAS or remission respectively. SLE disease activity indices including SLEDAI-2k, PGA, proteinuria amount and serum anti-ds-DNA level remained similar between the 2 groups. Within the study period, 28 (40%) patients in the TM group and 21 (29.6%) patients in the SF group had disease flare ( p =0.20). There were no differences in the SF-36, lupusQoL and HADS scores between the 2 groups at the end of the study. The overall patient satisfaction score was higher in the TM group with a significantly shorter waiting time before seeing doctors. At the end of the study, 67.9% of the overall participants agreed to (versus 15.0% who did not agree to) use TM as a mode of future FU. The mean indirect costs of illness (HKD26,681 vs HKD12,016, p =0.20) and the out-of-pocket costs for health care services were similar between the 2 groups (TM: HKD13,547 vs SF: HKD12,297, p =0.83) in one year. The total number of FU was similar (TM: 6.0±2.0, SF: 5.7±1.7, p =0.40). However, significantly more patients in the TM group (29/70, 41.4% vs 4/71, 5.6%; p <0.01) requested change mode of FU. The proportion of patients requiring hospitalization during the study period was also higher in the TM group (TM: 23/70, 32.9% vs 11/71, 15.5%; p =0.02). After adjusting for age and prednisolone dosage, not being in LLDAS at baseline was the predictor of hospitalization (OR 3.4, 95%CI 1.20-9.65). None of the participants was tested positive for COVID-19. Conclusion TM FU resulted in similar 1-year disease activity control and better satisfaction in patients with LN compared to standard care. However, a significant proportion of patients cared by TM required in-person visits or were hospitalized. The results of the study suggest that TM delivered care could help minimizing exposure to COVID-19, but it needs to be complemented by physical visits, particularly in those with unstable disease. Acknowledgements We would also like to thank the University of Central Lancashire & East Lancashire Hospitals NHS Trust for granting us permission to use the LupusQoL questionnaire. Disclosure of Interests None declared

Background: Axial spondyloarthritis (axSpA) patients are at higher risk of cardiovascular (CV) disease (CVD) than the general population, partly due to consequences of inflammation or its treatment. But relationship between inflammation in axSpA and cardiovascular events (CVE) is unknown. Objectives: To examine whether inflammatory burden over time can predict CVE independent of baseline CV risk factors in axSpA patients. Design: A cohort analysis was performed in patients who had been recruited since January 2001. The primary outcome was a first CVE occurring between January 2001 and December 2020. Methods: Three CVD risk scores were computed at baseline. The performance of the original and modified (*1.5 multiplication factor) CV risk algorithms were assessed. Time-varying Cox proportional hazard models and Kaplan–Meier survival analysis were used to assess whether inflammatory burden (Bath ankylosing spondylitis disease activity index [BASDAI] and inflammatory markers), nonsteroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs) can predict the development of first CVE. Results: 463 patients (35 [26–45] years, male: 360 [77.8%]) were recruited. After a median follow-up of 12 (7–19) years, 61 patients (13.2%) experienced a first CVE. Traditional/modified CV risk scores underestimated CV risk. Erythrocyte sedimentation rate (ESR) ⩾ 20 mm/h was associated with a significantly higher risk of CVE during follow-up (HR: 2.07, 95%CI [1.10, 3.98], p = 0.008). Active disease as indicated by a rising BASDAI also showed positive trend towards a higher risk of developing CVE over time. After adjusting for CV risk scores in the multivariable models, high ESR level (ESR ⩾ 20 mm/h) over time remained significantly associated with a higher risk of developing CV events. Conclusion: Increased inflammatory burden as reflected by elevated ESR levels (ESR ⩾ 20) was associated with increased risk of CVE, while the use of NSAIDs and DMARDs were not.

BackgroundAxial spondyloarthritis (axSpA) patients have increased risks of developing cardiovascular diseases (CVD) compared to the general population. Hypertension (HT) as the most common CV risk factor in these patients. Whether chronic, low-grade inflammation predispose to the development of incident hypertension in axSpA remained uncertain.ObjectivesTo examine the association between markers of systemic inflammation and incident hypertension in axSpA patients.MethodsA cohort analysis was performed in patients with axSpA who had been followed since January 2001. Patients diagnosed with hypertension and/or on anti-hypertensives at baseline were excluded. The primary outcome was first diagnosis of HT occurring between January 2001 and December 2020. Three different CVD risk scores including Framingham risk score (FRS), QRISK3 and SCORE were computed at baseline. Baseline demographic data and clinical inflammatory and disease activity parameters were assessed using Cox proportional hazard regression. The association between disease activity measures, inflammatory markers, medications, and the occurrence of incident HT was assessed using time-varying Cox proportional hazard models after adjusting for baseline CVD risk scores.Results413 patients [34(25-43) years, male: 319 (77.2%)] were recruited. After a median follow up of 12 (6-17) years, 58 patients (14%) developed incident HT (IHT+group). In baseline multivariable Cox regression analysis, ESR and CV risk scores were significantly associated with developing IHT (p<0.05) (Table 1). Using time-varying multivariate analysis, higher inflammatory burden (ESR≥20) was significantly associated with developing IHT after adjusting for FRS and SCORE respectively. Use of csDMARDs was significantly linked to develop IHT after adjusting for baseline FRS, while a trend suggesting that csDMARDs was associated with an increased risk of IHT after adjusting for baseline SCORE was observed (Table 2).Table 1.Multivariable analysis with Cox proportional hazard regression for the baseline predictors of incident HT.Model 1Model 2HR (95%CI)p-valueHR (95%CI)P-valueBASDAI≥51.44 (0.78, 2.67)0.2441.39 (0.75, 2.59)0.3ESR1.01 (1.00, 1.02)0.003*1.01 (1.00, 1.02)0.003*BASFI1.03 (1.00, 1.02)0.6161.03 (0.92, 1.16)0.572Baseline disease duration1.04 (1.00, 1.08)0.1021.03 (0.98, 1.08)0.215Symptom duration1.01 (0.98, 1.05)0.5131.02 (0.98, 1.05)0.386FRS1.05 (1.03, 1.08)SCORE1.23 (1.12, 1.36)Table 1b.Model 1Model 2HR (95%CI)p-valueHR (95%CI)P-valueBASDAI≥61.53 (0.84, 2.78)0.1661.47 (0.81, 2.69)0.209ESR1.01 (1.00, 1.02)0.003*1.01 (1.00, 1.02)0.003*BASFI1.03 (0.92, 1,15)0.6461.03 (0.92, 1.16)0.599Baseline disease duration1.04 (1.00, 1.08)0.1211.03 (0.98, 1.07)0.244Symptom duration1.01 (0.98, 1.05)0.5301.02 (0.98, 1.05)0.391FRS1.05 (1.03, 1.08)SCORE1.23 (1.11, 1.35)ConclusionHigher baseline and time-varying inflammatory burden predict the development of IHT in addition to traditional CV risk scores in axSpA patients. While exposure to csDMARDs may be associated with the development of IHT, NSAIDs and biologic DMARDs use were not associated with the development of IHT.References[1]Exarchou, S., et al., Mortality in ankylosing spondylitis: results from a nationwide population-based study. Ann Rheum Dis, 2016. 75(8): p. 1466-72.Table 2.Multivariable analysis with Cox proportional hazard regression for the time-dependent predictors of incident HT.Table 2a.Model 1Model 2Time-dependent HR (95%CI)p-valueTime-dependent HR (95%CI)P-valueESR1.01 (1.00, 1.03)0.0851.01 (1.00, 1.03)0.074csDMARDs2.24 (1.04, 4.82)0.04*2.16 (1.00, 4.68)0.05FRS1.05 (1.01, 1.08)0.008*SCORE1.24 (1.09 1.41)0.001*Table 2b.Model 1Model 2Time-dependent HR (95%CI)P-valueTime-dependent HR (95%CI)P-valueESR≥202.22 (1.05, 4.72)0.038*2.27 (1.06,4.82)0.034*csDMARDs2.17 (1.01, 4.64)0.047*2.09 (0.97, 4.50)0.059FRS1.05 (1.01, 1.08)0.01*SCORE1.23 (1.08, 1.41)0.002*Disclosure of InterestsNone declared

Objective: To evaluate the effects and side effects of both inactivated and mRNA COVID-19 vaccines in patients with systemic lupus erythematosus (SLE). Methods: This was a prospective, single-center, observational study. Patients with SLE planning to receive COVID-19 vaccines were recruited and matched 1:1 with healthy controls. The immunogenicity of the COVID-19 vaccines was assessed by a surrogate neutralization assay at 28days after the second dose. The main outcome was the antibody response comparing SLE patients and controls. Other outcomes included reactogenicity, disease activity and predictors of antibody responses in patients with SLE. Results: Sixty-five SLE patients received 2 doses of COVID-19 vaccines (Comirnaty: 38; CoronaVac: 27) were recruited. Many of them were on systemic glucocorticoids (76%) and immunosuppressants (55%). At day 28 after the second dose of vaccines, 92% (Comirnaty: 100% vs CoronaVac: 82%, p =0.01) of the patients had positive neutralizing antibody. However, compared to the age, gender, vaccine type matched controls, the level of neutralizing antibody was significantly lower (p < 0.001). The self-reported adverse reactions after vaccines in lupus patients were common but mild, and were more frequent in the Comirnaty group. There was no significant change in lupus disease activity up to 28days after vaccination. The independent predictors of neutralizing antibody level included the dosage of systemic glucocorticoids, use of mycophenolate and type of vaccines. Conclusions: COVID-19 vaccines produced satisfactory but impaired humoral response in SLE patients compared to controls which was dependent on the immunosuppressive medications use and type of vaccines received. There was no new short-term safety signal noted. Booster dose is encouraged.

Background Whether calprotectin could play a role in augmenting cardiovascular (CV) risk in patients with psoriatic arthritis (PsA) remains uncertain. The aim of this study is to elucidate the association between serum calprotectin level and subclinical atherosclerosis in patient with PsA. Method Seventy-eight PsA patients (age: 52 ± 10 years, 41 [52.6%] male) without CV disease were recruited into this cross-sectional study. Carotid intima-media thickness (cIMT) and the presence of plaque were determined by high-resolution ultrasound. Calprotectin levels in serum were quantified by enzyme-linked immunosorbent assay. The variables associated with the presence of carotid plaque (CP) were selected from the least absolute shrinkage and selection operator (LASSO) regression analysis. Results 29/78 (37.2%) of patient had carotid plaque (CP+ group). Serum calprotectin level was significantly higher in the CP+ group (CP− group: 564.6 [329.3–910.5] ng/ml; CP+ group: 721.3 [329.3–910.5] ng/ml, P = 0.005). Serum calprotectin level correlated with PsA disease duration (rho = 0.280, P = 0.013) and mean cIMT (rho = 0.249, P = 0.038). Using LASSO regression analysis, the levels of Ln-calprotectin (OR: 3.38, 95% CI [1.37, 9.47]; P = 0.026) and PsA disease duration (OR: 1.09, 95% CI [1.01, 1.18]; P = 0.013) were screened out from a total of 19 variables. The model in predicting the presence of CP was constructed by Ln-calprotectin and PsA disease duration with an area under the receiver-operating characteristic (ROC) curve of 0.744, (95 CI% [0.59, 0.80], P = 0.037). Conclusion Serum calprotectin level is associated with the presence of CP in PsA. Further studies are required to confirm whether this pathway is associated with CV events in PsA.

OBJECTIVE:To determine causal associations between genetically predicted TNF-α, IL-12p70 and IL-17 levels and risk of PsA.METHODS:The publicly available summary-level findings from genome-wide association studies (GWAS) was used to identify loci influencing normal physiological concentrations of TNF-α, IL-12p70 and IL-17 (n = 8293) among healthy individuals as exposure and a GWAS for PsA from the UK Biobank (PsA = 900, control = 462 033) as the outcome. A two-sample Mendelian randomization (MR) analysis was performed using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods. Sensitivity analysis and MR-Egger regression analysis were performed to evaluate the heterogeneity and pleiotropic effects of each variant.RESULTS:Single-nucleotide polymorphisms (SNPs) at genome-wide significance from GWASs on TNF-α, IL-12p70 and IL-17 were identified as the instrumental variables. The IVW method indicated a causal association between increased IL-17 level and risk of PsA (β = -0.00186 per allele, s.e. = 0.00043, P = 0.002). Results were consistent in the weighted median method (β = -0.00145 per allele, s.e. = 0.00059, P = 0.014) although the MR-Egger method suggested a non-significant association (β = -0.00133 per allele, s.e. = 0.00087; P = 0.087). Single SNP MR results revealed that the C allele of rs117556572 was robustly associated with risk of PsA (β = 0.00210, s.e. = 0.00069, P = 0.002). However, no evidence for a causal effect was observed between TNF-α, IL-12p70, decreased IL-17 levels and risk of PsA.CONCLUSION:Our findings provide preliminary evidence that genetic variants predisposing to higher physiological IL-17 level are associated with decreased risk of PsA.

Background: Patients with lupus nephritis (LN) might be more susceptible to COVID-19 due to the underlying disease, co-morbidities and use of immunosuppressants. We hypothesized that telemedicine (TM) could be a well-accepted mode of health-care delivery minimizing the risk of exposure to the severe acute respiratory syndrome coronavirus 2 ( SARS - CoV - 2 ), while maintaining disease control in these patients. Objectives: To evaluate the short-term patient satisfaction, compliance, disease control and infection risk of TM compared with standard in-person follow-up (FU) for patients with LN during COVID-19. Methods: This was a single-center randomized-controlled study. Consecutive patients followed at the LN clinic were randomized to either TM (TM group) or standard FU (SF group) in a 1:1 ratio. Patients in the TM group received scheduled follow-ups via videoconferencing. SF group patients continued conventional in-person outpatient care. The 6-month data were compared. Results: From June to December 2020, 122 patients were randomized (TM: 60, SF: 62) and had attended at least 2 FU visits. There were no baseline differences, including SLEDAI-2k and proportion of patients in lupus low disease activity state (LLDAS), between the 2 groups except a higher physician global assessment score (PGA) in the TM group (mean 0.67±0.69 vs 0.45±0.60, p=0.003) (Table 1). The mean FU duration was 19.8±4.5 weeks. When comparing the most recent visit, the mean waiting time between entering the clinic waiting room (virtual or real) and seeing a rheumatologist (virtual or in-person) was significantly shorter in the TM group (22.5±28.6 vs 68.9±40.7 minutes, p< 0.001) (Figure 1A). The mean overall patient satisfaction score was higher in the TM group (mean 2.19±0.61 vs 1.89±0.78, p=0.042). The results of the post-consultation satisfaction questionnaire are shown in Figure 1B. The number of visits was similar in the two groups (TM: 3.1±1.3 vs SF: 3.0±1.2, p=0.981). However, there was a trend suggesting that alternative mode of FU was requested more frequently in the TM group than the SF group (TM: 12/60, 20.0% and SF: 5/62, 8.1%; p=0.057). More patients in the TM group had hospitalization (15/60, 25.0% vs 7/62, 11.3%; p=0.049) within the FU period, which was no longer statistically significant after adjusting for the baseline PGA. The proportions of patients remained in LLDAS were similar in the 2 groups (TM: 75.0% vs SF: 74.2%, p=0.919). None of the patients had COVID-19. Conclusion: TM resulted in better patient satisfaction and could achieve similar disease control in patients with LN in the short-term when compared to standard care. Table 1. Baseline clinical data of the recruited patients and comparison between the telemedicine/standard follow-up groups Overall (n=122) Telemedicine group (n=60) Standard follow-up group (n=62) P-value Age in years 44.4±11.5 44.1±11.7 44.7±11.5 0.779 Gender: Female 111 (91.0) 55 (91.7) 56 (90.3) 0.796 Disease duration in years 15.1±9.0 16.2±8.7 14.0±9.1 0.115 Nephritis class III, IV or V 108 (88.5) 54 (90.0) 54 (87.1) 0.427 24 hour urine proteinuria in gram 0.51±0.63 0.53±0.60 0.50±0.65 0.712 Current use of prednisolone 112 (91.8) 57 (95.0) 55 (88.7) 0.323 Daily prednisolone dose in mg 5.51±4.21 5.69±4.17 5.34±4.29 0.570 Use of immunosuppressant 90 (73.8) 46 (76.7) 44 (71.0) 0.474 SLEDAI-2K 3.65±2.33 4.00±2.34 3.30±2.29 0.097 PGA 0.56±0.65 0.67±0.69 0.45±0.60 0.003 LLDAS 78 (63.9) 36 (60.0) 42(67.7) 0.251 Remission 0 (0) 0 (0) 0 (0) n/a Presence of comorbidity 87 (71.3) 40 (66.7) 47 (75.8) 0.264 SDI 0.93±1.15 1.08±1.28 0.78±0.98 0.243 HAQ-DI 0.23±0.46 0.25±0.47 0.21±0.44 0.571 HADS: Anxiety scale Depression scale 6.07±4.12 5.72±4.31 6.20±4.19 5.73±3.93 5.93±4.09 5.70±4.68 0.720 0.724 Data are reported as mean ± SD or number (%). LLDAS: lupus low disease activity state; SDI: Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index; HAQ-DI: Health Assessment Questionnaire Disability Index; and HADS: Hospital Anxiety and Depression Scale. Disclosure of Interests: Ho SO: None declared, Evelyn Chow: None declared, Tena K. Li: None declared, Sze-Lok Lau: None declared, Isaac T. Cheng: None declared, Cheuk-Chun Szeto: None declared, Lai-Shan Tam Grant/research support from: Grants from Novartis and Pfizer.

Aims: Psoriatic arthritis (PsA) is associated with accelerated atherosclerosis due to underlying inflammation. Whether inflammatory burden and drugs used to suppress inflammation over time are associated with cardiovascular (CV) events remained unclear. This study aims to examine the time-varying effect of C-reactive protein (CRP) levels and the use of drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs, on the risk of CV events independent of traditional CV risk factors in PsA patients. Methods: A retrospective cohort analysis was performed in patients with PsA who were recruited from 2008 to 2015 and followed until the end of 2019. The outcome was occurrence of a first CV event. Framingham risk score (FRS) was used to quantify the traditional CV risk. Cox proportional hazard models with time-varying CRP levels and drugs used were analysed to identify the risk factors for CV events in PsA patients. Results: Two hundred patients with PsA [median age: 47.5 (40.0–56.0); male: 119 (59.5%)] were recruited. After a mean follow-up of 8.8 ± 3.8 years, 30 (15%) patients developed a first CV event. The multivariable Cox regression model showed that time-varying CRP level [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00–1.04] and NSAIDs exposure (HR 0.38, 95% CI 0.15–0.96) were significantly associated with CV events after adjusting for baseline FRS (HR 5.06, 95% CI 1.84–13.92). Conclusion: Increased inflammatory burden as reflected by elevated CRP level was associated with increased risk of CV events, while the risk was significantly reduced with NSAIDs use in PsA patients.

Aims Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. Methods A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture. Results All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively. Conclusion Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies. Cite this article: Bone Joint Res 2021;10(1):41–50.

ObjectiveTo evaluate the effects of denosumab on erosion healing at 2–4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease.MethodsThis was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2–4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined.ResultsAt 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months.ConclusionAlthough no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months.Trial registration numberNCT03239080.

Background:It is important to weigh the potential risk of exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during a doctor visits against the risk of missing disease controls in patients with lupus nephritis during the COVID-19. Telemedicine (TM) follow-up is a reasonable option. Despite the recent exponential increase in application worldwide, there is no study examining the clinical factors associated with the patients‘ choice of TM use in lupus nephritis.Objectives:In this study, we aimed to examine the clinical variables associated with a higher preference for TM follow-up in patients with lupus nephritis.Methods:Consecutive patients followed at the lupus nephritis clinic were contacted for their preferred mode of follow-up. The demographic, socioeconomic and clinical data of the first 140 patients opted for TM and 140 patients preferred to continue standard in-person follow-up were collected and compared.Results:The mean age of the 280 recruited patients was 45.6 ± 11.8 years. The mean disease duration was 15.0 ± 9.2 years. The majority of them had lupus nephritis class III, IV or V (88.2%) and were on prednisolone (90%). Three quarters of the patients (67.1%) were on immunosuppressants. The mean SLEDAI-2k was 4.06 ± 2.54, physician global assessment (PGA) 0.46 ± 0.62 and SLICC/ACR damage index 1.11 ± 1.36. A significant proportion of the patients (72.1%) had one or more comorbidities. It was found that patients with higher PGA and family monthly income (> USD3,800) preferred TM, while fulltime employees preferred in-person follow-up (Table 1). These predictors remained significant after controlling for age in the multivariate analysis with odd ratios for PGA 1.05 (95% CI 1.01-1.09), family income >USD3,800 1.90 (95% CI 1.24-3.79) and fulltime employment 0.53 (95% CI 0.32-0.88). PGA was noted to be positively correlated with the perceptions that TM reduces (r=0.13, p=0.036) and routine visit increases (r=0.12, p=0.04) the risk of COVID-19 during the outbreak.Conclusion:When choosing the mode of care delivery between TM and clinic visit, the patient’s disease activity as well as employment and economic status appeared to be important.Table 1.Demographic, socio-economic and disease data of the recruited lupus nephritis patients with comparison between the telemedicine/standard follow-up groupsOverall (n=280)Telemedicine group (n=140)Standard follow-up group (n=140)P-valueAge in years45.6±11.844.6±11.446.6±12.10.159Gender: Female256 (91.4)127 (90.7)129 (92.1)0.669Ever presence of rash170 (60.8)87 (62.1)82 (58.6)0.527Ever presence of joint pain174 (62.1)92 (65.7)82 (58.6)0.247Disease duration in months15.8±9.515.0±9.316.5±9.60.17624 hour urine proteinuria in gram0.45±0.600.50±0.630.40±0.570.176Daily prednisolone dose in mg8.82±6.15.28±4.466.35±7.370.143Use of immunosuppressant188 (67.1)96 (68.6)92 (65.7)0.611SLEDAI-2K3.39±2.353.51±2.283.26±2.410.366PGA0.46±0.620.54±0.630.38±0.590.025LLDAS196 (70)92 (0.66)104 (74.3)0.160Presence of comorbidity202 (72.1)100 (71.4)102 (72.9)0.790SDI0.97±1.230.95±1.211.00±1.260.732HAQ-DI0.20±0.400.23±0.450.18±0.340.300HADS: Anxiety scale5.93±3.985.86±4.066.00±3.910.776 Depression scale5.57±3.915.56±4.255.59±3.540.954Education level: tertiary or above122 (43.6)63 (45.0)59 (42.1)0.746Fulltime employment127 (45.4)56 (40.0)71 (50.7)0.041Occupation: professionals36 (12.9)22 (15.7)14 (10.0)0.181Monthly family income > USD3,80084 (30.0)51 (36.4)33 (23.6)0.028Data are reported as mean ± SD or number (%). HAQ-DI: Health Assessment Questionnaire Disability Index; HADS: Hospital Anxiety and Depression Scale; PGA: physician global assessment; LLDAS: lupus low disease activity state and SDI: Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index.Disclosure of Interests:Ho SO: None declared, Evelyn Chow: None declared, Tena K. Li: None declared, Isaac T. Cheng: None declared, Sze-Lok Lau: None declared, Cheuk-Chun Szeto: None declared, Lai-Shan Tam Grant/research support from: Grants from Novartis and Pfizer

Background: While carotid ultrasound (US) has been advocated for cardiovascular (CV) risk screening in patients with rheumatoid arthritis as various traditional scores underestimate CV risk, whether subclinical carotid atherosclerosis (SCA) is associated with coronary atherosclerosis on coronary computed tomography angiography (CCTA) in patients with psoriatic arthritis (PsA) remains uncertain. Objectives: This study aimed to identify carotid US parameters which can discriminate PsA patients with coronary artery disease (CAD) and obstructive CAD (O-CAD), and determine the utility in combination with Framingham Risk Score (FRS). Methods: Ninety-one PsA patients (56 males; age: 50±11years, disease duration: 9.4±9.2years) without overt CV diseases were recruited. Carotid intima-media thickness (cIMT), presence of plaque and total plaque area (TPA) were determined by high-resolution US. CAD was defined as the presence of any coronary plaque on CCTA. O-CAD was defined as >50% stenosis of the lumen. FRS <10% indicates low CV risk, 10-19% indicates intermediate risk while ≥20% indicates high risk (1). Results: Thirty-five (38%) patient had carotid plaque. Fifty-five (60%) patients had CAD and 9 (10%) patients had O-CAD. 53 (58%), 25 (17%) and 13 (14%) were classified as low, moderate and high CV risk according to the FRS respectively. FRS underestimated the CV risk as only 11/55 (20%) of subjects with CAD were correctly identified as having high CV risk by FRS (Figure 1). Fifteen patients out of 53 (28%) with low CV risk based on FRS were reclassified as high CV risk by the presence of carotid plaque. Nine out of these 15 (60%) had CAD and 1/15 (6.7%) had O-CAD. Concerning the carotid ultrasound parameters, cIMT (mean and maximum) and TPA were increased in both the CAD+ and O-CAD+ group compared to those without CAD or O-CAD (Table 1). Multivariate logistic regression analysis revealed that mean cIMT (OR=1.06, 95% CI:1.01-1.11, p =0.013) was an independent explanatory variables associated with CAD. Meanwhile, mean cIMT (OR=1.06, 95%CI: 1.01-1.11, p =0.013) maximum cIMT (OR=1.06, 95%CI: 1.00-1.13, p =0.043), and TPA (OR=1.55, 95%CI: 1.01-2.36, p =0.043) were independent explanatory variables associated with O-CAD after adjusting for covariates. Based on Receiver Operating Curve (ROC) analysis, an optimal cut off for FRS at 5% and mean cIMT at 0.62mm yield 63% sensitivity and 73% specificity for the presence of CAD (AUC: 0.71, p =0.001). Table 1. Relationship between carotid ultrasound parameters and the presence and extent of coronary artery disease on coronary computed tomography angiography. Coronary artery disease No (n=37) Yes (n=54) p Mean carotid IMT, mm 0.63 ± 0.12 0.69 ± 0.1 0.017 Maximum carotid IMT, mm 0.77 ± 0.17 0.84 ± 0.14 0.040 Carotid Plaque, n, % Absence 26 46.4% 30 53.6% 0.156 Presence 11 31.4% 24 68.6% Total plaque area, mm 2 0.0 [0,6] 0.0 [0, 10.8] 0.059 Obstructive coronary artery disease No (n=82) Yes (n=9) p Mean carotid IMT, mm 0.65 ± 0.12 0.76 ± 0.07 0.011 Maximum carotid IMT, mm 0.80 ± 0.16 0.93 ± 0.14 0.020 Carotid Plaque, n, % Absence 53 93.0% 4 7.0% 0.235 Presence 29 85.3% 5 14.7% Total plaque area, mm 2 0.0 [0, 7.0] 6.0 [0, 15.3] 0.103 IMT-intima media thickness; coronary computed tomography angiography. Conclusion: Increased cIMT and TPA were associated with CAD and O-CAD in PsA patients while the presence of carotid plaque alone was insufficient to discriminate patient with or without CAD. A combination of US parameters should be considered for CV risk stratification in patients with PsA. References: [1]Ford ES et al., J Am Coll Cardiol . 2004;43(10):1791-6. Disclosure of Interests: Isaac T. Cheng: None declared, Ka Tat Wong: None declared, Edmund Li: None declared, Priscilla C Wong: None declared, Billy Tin Lok Lai: None declared, Cheuk Wan Yim: None declared, Shirley King Yee Ying: None declared, Kitty Yan Kwok: None declared, Martin Li: None declared, Tena K. Li: None declared, Jack Jock Wai Lee: None declared, Alex Pui Wai Lee: None declared, Lai-Shan Tam Grant/research support from: Janssen, Pfizer, Novartis, Speakers bureau: Abbvie, Lilly, Sanofi

OBJECTIVE PsA patients who achieved sustained minimal disease activity (sMDA) had less subclinical atherosclerosis progression. The vascular effects of achieving other potential treatment targets, including the PsA Disease Activity Score (PASDAS) and the Disease Activity in PsA (DAPSA) score, remained uncertain. This study aimed to compare the vascular effects of achieving different treatment targets in PsA patients. METHOD This is a post hoc analysis of a 2 year treat-to-target study aimed at MDA. A total of 101 consecutive PsA patients without overt cardiovascular disease were recruited. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. Low disease activity (LDA) was defined as MDA, DAPSA ≤14 or PASDAS ≤3.2. Sustained disease control was defined as achieving these targets at each visit from month 12 until month 24. RESULTS Ninety patients [52 male (57.8%), age 50 years (s.d. 11)] who completed 24 months of follow-up were included in this analysis. A total of 44%, 48% and 45% of patients achieved sustained DAPSA LDA (sDAPDA-LDA), sustained PASDAS LDA (sPASDAS-LDA) and sMDA, respectively. Patients who achieved sMDA had significantly less progression of carotid intima-media thickness than those who did not (P = 0.031). Using multivariate analysis, achieving sMDA and sPASDAS-LDA had a protective effect on plaque progression, less increase in total plaque area, reduced mean intima-media thickness and reduced augmentation index after adjusting for covariates. In contrast, no significant differences in the progression of vascular parameters were demonstrated between patients who did or did not achieve sDAPSA-LDA. CONCLUSION Achieving sMDA/sDASPAS-LDA, but not sDAPSA-LDA, was associated with a protective effect in subclinical atherosclerosis and arterial stiffness progression. A multidimensional domain of disease control might be better in minimizing cardiovascular risk in PsA.

Human cadaveric study has indicated that the metacarpal head (MCH) is intracapsular in location. We hypothesized that exposure to the intra-articular inflammatory milieu in psoriatic arthritis (PsA) will lead to bone loss in the MCH. To compare the bone structure and microstructure in the MCH between patients with PsA and healthy controls by high-resolution peripheral quantitative CT (HR-pQCT), and to ascertain factors associated with bone loss in PsA patients. Sixty-two PsA patients without joint destruction and 62 age-, gender-, and body mass index–matched healthy subjects underwent HR-pQCT imaging of the second and third MCH (MCH 2&3). The number and volume of bone erosion and enthesiophytes, as well as volumetric bone mineral density (vBMD) and microstructure at the MCH 2&3, were recorded. Correlation analysis and multivariable linear regression models were used to determine the association of demographic and disease-specific variables with compromised bone structure and microstructure in PsA. At the MCH 2&3, bone erosion (p = 0.003) and enthesiophyte (p = 0.000) volumes in PsA patients were significantly larger than healthy controls. In PsA patients, older age was associated with a larger erosion and enthesiophyte volume. Concerning the mean vBMD and microstructure at the MCH 2&3, PsA patients had significantly lower mean vBMD (average vBMD − 6.9%, trabecular vBMD − 8.8%, peri-trabecular vBMD − 7.7%, meta-trabecular vBMD − 9.8%), trabecular bone volume fraction (− 8.8%), and trabecular thickness (− 8.1%) compared with control subjects. Multivariable regression analysis revealed that older age and a higher C-reactive protein level were associated with trabecular bone loss. PsA patients had a higher burden of bone damages (erosions and enthesiophytes) and trabecular bone loss compared with healthy control at the MCH. Inflammation contributed to the deterioration in trabecular microstructure in these patients.

Objective To examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis. Methods A cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models. Results 189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42. Conclusion Higher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.

US parameters including cIMT and TPA may be considered in addition to FRS for CV risk stratification in patients with PsA.

Background Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period. Methods HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC). Results A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm 3 , P < 0.001) and enthesiophyte (0.47 ± 0.76 mm 3 , P < 0.001) volume was observed. Erosion and enthesiophyte progression were found in 37/111 (33.3%) and 50/99 (50.5%) lesions, respectively. During this 5-year period, 26 (43%) out of the 60 patients achieved sustained Disease Activity index for PSoriatic Arthritis (DAPSA) low disease activity (LDA) (SDL group, defined as achieving DAPSA-LDA at both baseline and 5 years). Fourteen (23%) out of 60 patients received a TNF inhibitor throughout the 5-year period (TNFi group). Fewer erosions progressed (12/51 [23.5%] vs 25/60 [41.7%], P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm 3 , P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte. Conclusion Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.