Utility of multi-biomarker panel on discriminating disease activity in patients with psoriatic arthritis.

OBJECTIVE: To investigate the correlation of serum protein biomarkers and disease activity in patients with PsA. METHODS: 176 patients fulfilled the CASPAR (ClASsification criteria for Psoriatic ARthritis) were recruited in this cross-sectional study. The level of 48 protein biomarkers, cartilage and bone turn-over markers were assessed. The patients were randomly divided into a derivation-cohort and a validation-cohort at a ratio of 7:3. Patients were further categorized based on their disease activity states using cDAPSA (remission/low disease activity and moderate/high disease activity). Least absolute shrinkage and selection operator (LASSO) was used to select biomarkers which were associated with moderate/high disease activity in the derivation cohort. Receiver operating characteristic (ROC) curve, GiViTI calibration belt were used to assess the performance of the model in both cohorts. RESULTS: The cohort [age: 55.5 (44.0-62.75) years, male: 80 (45.5 %)] had moderate disease activity [DAPSA: 15.9 (8.3-26.9); PASI: 3.2 (0.5-6.8)]. 101 PsA patients (57.4 %) had clinical DAPSA moderate/high disease activity. Biomarker levels associated with moderate/high disease activity included SAA (Serum amyloid A), IL-8 (Interleukin 8), IP10 (Interferon gamma-induced protein 10)/CXCL10, M-CSF (Macrophage colony-stimulating factor), SCGF-ß (Stem cell growth factor), SDF-1α (Stromal cell-derived factor 1α)/CXCL12. The model's equation including the 6 biomarker levels was applied to the validation-cohort. The area under the ROC curve (AUC) for discriminating moderate/high disease activity was 0.802 and 0.835 for the derivation-and-validation-cohorts, respectively. The multi-biomarkers panel model had higher-AUC when compared with that of C-reactive protein (CRP) (AUC = 0.727, p = 0.022). The P-values of calibration charts in the two sets were 0.902 and 0.123. CONCLUSIONS: The multi-biomarkers panel demonstrated the ability to discriminate patients with moderate/high disease activity from those with low disease activity/remission.

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

OBJECTIVES: To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). METHODS: This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. RESULTS: Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. CONCLUSION: Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

Management of bone health in idiopathic inflammatory myopathies: A two-center audit in the United Kingdom and Hong Kong.

BACKGROUND: Patients with inflammatory idiopathic myopathies (IIM) face elevated risks of osteoporosis and fragility fracture. AIM: To evaluate current practice relating to bone health in adult patients with IIM in the United Kingdom and Hong Kong (HK). METHODS: Patients were identified from IIM patient lists. Demographics, osteoporosis risk factors, DXA scans, and bone protection treatment were recorded. Adherence to regional standards was evaluated for each center. Following this, in the United Kingdom, up-to-date DXA scans were performed. RESULTS: Of 136 patients identified, 51 met selection criteria (UK, n = 20, HK, n = 31). Mean age in the United Kingdom was 59 (IQR 54-66); in Hong Kong, 65 (IQR 52.5-70). Most were female (UK 70%; HK 77%), current or previous steroid treatment was common (UK 90%; HK 100%) and some had experienced fragility fracture (UK 15%; HK 9%). The mean daily dose of prednisolone that patients were prescribed during the study was 12.5 mg (UK) and 14.3 mg (HK). Some patients had had a DXA scan (UK 50%; HK 35%) though several were outdated. Among those with BMD measured (UK, n = 20; HK, n = 11), osteopenia prevalence was 35% (UK) and 36% (HK) while osteoporosis was 5% (UK) and 36% (HK). Notably, 25% (UK) and 64% (HK) exceeded treatment thresholds. Treatments included anti-osteoporotic agents (UK 55%; HK 15%), Vitamin D/calcium supplements (UK 95%; HK 52%), or no treatment (UK 5%, HK 15%). CONCLUSION: Poor compliance with guidelines exists in both centers, particularly around investigation and monitoring of bone health for IIM patients. Integrated care models and increased resource allocation to bone health are imperative to improve management of this aspect of IIM.

Impact of inflammation and anti-inflammatory therapies on the incidence of major cardiovascular events in patients with ankylosing spondylitis: A population-based study.

OBJECTIVE: To examine the independent effect of inflammatory burden and various treatments on the risk of incident major adverse cardiovascular events (MACE) in ankylosing spondylitis (AS) patients. METHODS: AS patients were retrospectively selected from a territory-wide database between 2006 and 2015, and were followed until the end of 2018. The primary outcome was the first occurrence of MACE. Multivariate time-varying Cox proportional hazard models were used to determine the associations between inflammatory burden (measured by c-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and different therapies with incident MACE, after adjusting for traditional cardiovascular (CV) risk factors. RESULTS: A total of 3827 patients with AS (mean age: 45.2 ± 15.0 years, male: 2911 [76.1 %]) were recruited. After a follow-up of 23,275 person-years, 135 patients (3.5 %) developed a first MACE. Univariate analyses showed that elevated ESR and CRP levels, and the use of glucocorticoids were associated with a significantly higher risk of MACE, while the use of sulfasalazine (SLZ), biologic DMARDs and non-cyclooxygenase-2 inhibitors (non-COX-IIi) were associated with reduced risk of MACE. After adjusting for CV risk factors in the multivariable models, only ESR (HR: 1.02; ESR ≥30 mm/h, HR:1.94) and CRP level (HR: 1.14; CRP >3 mg/dl HR:5.43) remained significantly associated with increased risk of MACE, while SLZ use (HR: 0.41-0.52) was protective against MACE. CONCLUSION: High inflammatory burden was an independent predictor associated with an increased risk of MACE, while the use of SLZ might reduce risk of incident MACE in patients with AS.

Mitochondrial defects in sporadic inclusion body myositis-causes and consequences.

Sporadic inclusion body myositis (sIBM) is a distinct subcategory of Idiopathic Inflammatory Myopathies (IIM), characterized by unique pathological features such as muscle inflammation, rimmed vacuoles, and protein aggregation within the myofibers. Although hyperactivation of the immune system is widely believed as the primary cause of IIM, it is debated whether non-immune tissue dysfunction might contribute to the disease's onset as patients with sIBM are refractory to conventional immunosuppressant treatment. Moreover, the findings that mitochondrial dysfunction can elicit non-apoptotic programmed cell death and the subsequent immune response further support this hypothesis. Notably, abnormal mitochondrial structure and activities are more prominent in the muscle of sIBM than in other types of IIM, suggesting the presence of defective mitochondria might represent an overlooked contributor to the disease onset. The large-scale mitochondrial DNA deletion, aberrant protein aggregation, and slowed organelle turnover have provided mechanistic insights into the genesis of impaired mitochondria in sIBM. This article reviews the disease hallmarks of sIBM, the plausible contributors of mitochondrial damage in the sIBM muscle, and the immunological responses associated with mitochondrial perturbations. Additionally, the potential application of mitochondrial-targeted chemicals as a new treatment strategy to sIBM is explored and discussed.

Incidence and risk factors of major cardiovascular events in rheumatoid arthritis and psoriatic arthritis: A population-based cohort study.

OBJECTIVE: To evaluate the incidence and risk factors of major adverse cardiovascular events (MACE) in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. METHODS: A population-based retrospective cohort of RA and PsA patients was identified in a citywide database. All patients recruited from Jan 2006 to Dec 2015 were followed until the end of 2018. The outcome was the occurrence of a first MACE. Covariates of interest included traditional cardiovascular (CV) risk factors, inflammatory markers and pharmacotherapies. The independent predictors of MACE were identified by the time-dependent cox proportional hazard models. RESULTS: A total of 13,905 patients (12,233 RA and 1,672 PsA) were recruited. After a total of 119,571 patient-years of follow-up, 934 (6.7%) patients developed a first MACE. RA and PsA patients had similar adjusted incidence (incidence rate ratio 0.96, 95 % CI 0.75-1.22, p = 0.767). After adjusting for traditional CV risk factors, the time-varying erythrocyte sedimentation (ESR) rate and C-reactive protein (CRP) levels, and the use of glucocorticoids were independently associated with higher risk of MACE in both the RA and PsA cohorts. In RA, the use of methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) were associated with fewer MACE. The use of biologic disease modifying anti-rheumatic drugs was not associated with MACE in both RA and PsA. CONCLUSION: The incidence of MACE was similar in RA and PsA. Systemic inflammation and glucocorticoid use independently increased the risk of MACE in inflammatory arthritis, while methotrexate and NSAIDs use were protective against the development of MACE in RA.

Moderate and high disease activity levels increase the risk of subclinical atherosclerosis progression in early rheumatoid arthritis: a 5-year prospective study.

OBJECTIVES: To elucidate the association between different disease activity levels over time on long-term vascular outcomes in patients with early rheumatoid arthritis (ERA). METHODS: This was a 5-year prospective study. Patients with consecutive ERA without overt cardiovascular disease (CVD) were recruited to receive 1 year of tight-control treatment followed by standard-of-care management. High-resolution carotid ultrasound was assessed at baseline and year 5. The primary outcome was subclinical atherosclerosis progression (AP+), defined as the occurrence of incident plaque, increased region harbouring plaques and/or maximum carotid intima-media thickness progression ≥0.9 mm at year 5. Inflammatory burden during the follow-up period was represented by the cumulative average Disease Activity Score 28-erythrocyte sedimentation rate (ca-DAS28-ESR). Persistent low disease activity (LDA) or remission state was defined as ca-DAS28-ESR≤3.2. RESULTS: One-hundred and four patients with ERA (age: 52±11 years, 81 (77.9%) female) were included in this analysis. Fifty-two (50%) patients achieved persistent LDA or remission and 42 patients (40.4%) had AP+. Patients in the AP+ group were older and had more traditional cardiovascular risk factors at baseline. Multivariate logistic regression analysis revealed that patients with persistent moderate or high disease activity (ca-DAS28-ESR>3.2) had a significantly increased risk of AP+ (OR 5.05, 95% CI 1.53, 16.64, p=0.008) compared with those who achieved persistent remission. The risk of AP+ was similar in patients who achieved persistent LDA and remission. CONCLUSIONS: Achieving persistent LDA or remission may prevent progression of atherosclerosis in ERA. A treat-to-target approach aiming at sustained LDA or remission may reduce the risk of CVD by preventing AP+.

Safety of the JAK and TNF inhibitors in rheumatoid arthritis: real world data from the Hong Kong Biologics Registry.

OBJECTIVES: To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using Janus kinase (JAKis) and TNF (TNFis) inhibitors. METHOD: A retrospective analysis of data from the Hong Kong Biologics Registry 2008-2021 was performed. RA patients who had ever used JAKis or TNFis were included. The incidence of MACEs, cancer and infections were compared between the two groups, with adjustment for confounding factors. RESULTS: A total of 2471 courses of JAKis (n = 551) and TNFis (n = 1920) were used in 1732 RA patients (83.7% women, age 53.8 [12.5] years; follow-up 6431 patient-years). JAKi users had significantly older age, more atherosclerotic risk factors and higher frequency of past malignancies. A total of 15 and 40 MACEs developed in the JAKi and TNFi users, respectively (incidence 1.34 vs 0.75 per 100 patient-years; P = 0.22). There was no significant difference in the incidence of cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; P = 0.25). The adjusted hazard ratios of MACE and cancer in the JAKi users were 1.36 (95% CI: 0.62, 2.96) (P = 0.44) and 0.87 (95% CI: 0.39, 1.95) (P = 0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; P = 0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; P < 0.001). CONCLUSIONS: In a real-life setting, there is no increase in MACEs or cancers in users of JAKis compared with TNFis. However, the incidence of non-serious infections, including herpes zoster, was increased in users of JAKis.

Clinical heterogeneity and prognostic factors of anti-synthetase syndrome: a multi-centered retrospective cohort study.

OBJECTIVE: Anti-synthetase syndrome (ASyS) patients have heterogeneous clinical manifestations with different initial presentations, complications, and outcomes. This study aimed to assess the clinical characteristics and complications in patients with ASyS, and to identify factors that were associated with the survival of ASyS patients. METHODS: This was a retrospective multicentre longitudinal study. Patients fulfilling either the Connor's criteria or Solomon's criteria for ASyS were recruited. Electronic health records were reviewed until October 2022. Multivariate Cox-regression analysis was used to determine the independent prognostic factors. Auto-antibodies were checked by commercial immunoassays. RESULTS: A total of 205 patients (anti-Jo-1 49.3%, anti-PL-7 19.0%, anti-EJ 11.2%, anti-PL-12 10.2% and anti-OJ 3.4%) were included. The median follow-up time was 4 years. The time from symptoms onset to diagnosis was significantly longer for non-anti-Jo1 patients (median 5 vs 3 months). Common initial presentations included myositis (56.1%), arthritis (54.6%), and interstitial lung disease (ILD) (54.1%). Patients with anti-Jo-1 had significantly higher muscle enzyme levels and more arthritis. All patients with anti-EJ would develop ILD on follow-up and malignancy was noted in 28.6% of the anti-OJ positive patients. 15.6% of the patients died and pulmonary diseases (ILD or pneumonia) were the major causes. Age at diagnosis, malignancy and rapidly progressive-ILD were independently associated with mortality, while joint manifestation was a protective factor. CONCLUSION: In view of the heterogeneity of clinical presentation of ASyS, high index of suspicion and early checking of specific autoantibodies might help prompt diagnosis of ASyS and detection of related complications.

Role of inflammatory burden and treatment on joint space width in psoriatic arthritis-a high-resolution peripheral quantitative computed tomography study.

BACKGROUND: To investigate the relationship between disease-related parameters and joint space width (JSW) on high-resolution peripheral quantitative computed tomography (HR-pQCT) in psoriatic arthritis (PsA) patients. METHODS: PsA patients who underwent HR-pQCT examination of the second to fourth metacarpophalangeal joint (MCPJ 2-4) were recruited in this cross-sectional study. The joint space metrics included joint space volume (JSV), mean, minimum, and maximum JSW, JSW asymmetry, and distribution. Correlation analysis and multivariable linear regression models were used to determine the association between disease-related variables and JSW. RESULTS: Sixty-seven patients [37 (55.2%) males; median (IQR) age: 57.0 (53.0, 63.0); median disease duration: 21 (16, 28) years] were included in this analysis. Multivariable linear regression analysis demonstrated that males had larger JSV (MCPJ 2-4), mean (MCPJ 4), and maximum JSW (MCPJ 3). Longer disease duration (MCPJ 2-3) and higher ESR values (MCPJ 3) were negatively associated with mean and maximum JSW, while higher damage joint count was negatively associated with mean and minimum JSW (MCPJ 2). Use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was negatively associated with minimum JSW (MCPJ 3) while use of biologic DMARDs (bDMARDs) was positively associated with minimum JSW (MCPJ 2). CONCLUSION: Higher inflammatory burden as reflected by longer disease duration, higher ESR levels, and damage joint count was negatively associated with mean, maximum, and minimum JSW, while suppression of inflammation using bDMARDs seems to limit the decline in JSW.

Urinary Long Non-Coding RNA Levels as Biomarkers of Lupus Nephritis.

BACKGROUND: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. METHOD: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. RESULTS: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = -0.423, p = 0.018) and ANRIL levels (r = -0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = -0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = -0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). CONCLUSIONS: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis.

Time and dose-dependent effect of systemic glucocorticoids on major adverse cardiovascular event in patients with rheumatoid arthritis: a population-based study.

OBJECTIVES: Cardiovascular event (CVE) risk in rheumatoid arthritis (RA) was increased by glucocorticoids (GC) use. Whether there is a threshold dose and duration of GC use beyond which will increase CVE rate remains controversial. We studied the time-varying effect of GC and its dose on the risk of incident major adverse cardiovascular events (MACE) in patients with RA. METHODS: Patients with RA without MACE at baseline were recruited from a Hong Kong citywide database from 2006 to 2015 and followed till 2018. The primary outcome was the first occurrence of an MACE. Cox regression and inverse probability treatment weighting analyses with time-varying covariates were used to evaluate the association of GC and MACE, adjusting for demographics, traditional CV risk factors, inflammatory markers and the usage of antirheumatic drugs. RESULTS: Among 12 233 RA patients with 105 826 patient-years of follow-up and a mean follow-up duration of 8.7 years, 860 (7.0%) developed MACE. In the time-varying analyses after controlling for confounding factors, a daily prednisolone dose of ≥5 mg significantly increased the risk of MACE (erythrocyte sedimentation rate model: HR 2.02, 95% CI 1.72 to 2.37; C reactive protein model: HR 1.87, 95% CI 1.60 to 2.18), while a daily dose below 5 mg was not associated with MACE risk, compared with no GC use. In patients receiving daily prednisolone ≥5 mg, the risk of incident MACE was increased by 7% per month. CONCLUSIONS: GC was associated with a duration and dose-dependent increased risk of MACE in patients with RA. Very low dose prednisolone (<5 mg daily) did not appear to confer excessive CV risk.

Reduced bone mineral density in patients with idiopathic inflammatory myopathies: a case-control study.

Background: Patients with idiopathic inflammatory myopathies (IIMs) are at risk of reduced bone mineral density (BMD). Objectives: To compare the prevalence of reduced BMD between patients with IIMs and controls and to determine its risk factors. Design: This was a single-center case-control study. Methods: BMD was assessed by dual-energy X-ray absorptiometry. The prevalence of reduced BMD in IIM patients and age-and sex-matched non-rheumatological controls was compared. The BMD results of female IIM were also compared to age-matched female rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Independent factors associated with reduced BMD in IIM patients were identified by multivariate analyses. Results: A total of 230 patients (IIM: 65, non-rheumatological controls: 65, RA: 50, SLE: 50) were recruited. The mean age of IIM patients was 58.6 ± 11.0 years and 76.9% were females. Significantly, more IIM patients had reduced BMD (73.8% versus 43.1%, p = 0.043) and osteoporosis (29.2% versus 13.8%, p = 0.033) than non-rheumatological controls. Multivariate analysis confirmed that IIM was independently associated with reduced BMD (OR: 2.12, p = 0.048, 95% CI: 1.01-4.46). The prevalence of reduced BMD was not significantly different between IIM, RA, and SLE patients but the mean hip BMD was the lowest in the IIM group (0.641 ± 0.152 g/cm2versus 0.663 ± 0.102g/cm2 in the RA group versus 0.708 ± 0.132 g/cm2 in the SLE group, p = 0.035). Lower body mass index and more advanced age were independently associated with lower BMD in IIM patients. Conclusion: Reduced BMD was more prevalent in IIM patients than in non-rheumatological controls. Hip BMD was lower in patients with IIMs than RA or SLE. Close monitoring and early treatment are encouraged especially in patients with risk factors.

Telemedicine for follow-up of systemic lupus erythematosus during the 2019 coronavirus pandemic: A pragmatic randomized controlled trial.

INTRODUCTION: Patients with systemic lupus erythematous were vulnerable to severe coronavirus disease 2019 infection and the negative impact of disrupted healthcare delivery. Telemedicine has been a popular alternative to standard in-person care during the pandemic despite the lack of evidence. METHODS: This was a 1-year pragmatic randomized-controlled trial. Patients followed at the lupus nephritis clinic were randomized to either telemedicine or standard follow-up in a 1:1 ratio. Patients in the telemedicine group were followed up via videoconferencing. Standard follow-up group patients continued conventional in-person outpatient care. The primary outcome of the study was the proportion of patients in low disease activity after 1 year. Secondary outcomes included cost-of-illness, safety, and various patient-reported outcomes. RESULTS: From 6/2020 to 12/2021, 144 patients were randomized and 141 patients (telemedicine: 70, standard follow-up: 71) completed the study. At 1 year, 80.0% and 80.2% of the patients in the telemedicine group and standard follow-up group were in lupus low disease activity state or complete remission, respectively (p = 0.967). Systemic lupus erythematous disease activity indices, number of flares and frequency of follow-ups were also similar. There were no differences in the cost-of-illness, quality of life or mental health scores. However, significantly more patients in the telemedicine group (41.4% vs 5.6%; p < 0.001) required switch of mode of follow-up and higher proportion of them had hospitalization during the study period (32.9% vs 15.5%; p = 0.016). Being in the telemedicine group or not in low disease activity at baseline were the independent predictors of hospitalization (odds ratio: 2.6; 95% confidence interval: 1.1-6.1, odds ratio: 2.7, 95% confidence interval: 1.1-6.7, respectively) in the post hoc analysis. CONCLUSIONS: In patients with systemic lupus erythematous, telemedicine predominant follow-up resulted in similar 1-year disease control compared to standard care. However, it needed to be complemented by in-person visits, especially in patients with unstable disease.

Inflammation is associated with incident hypertension in patients with axial spondyloarthritis: A longitudinal cohort study.

OBJECTIVES: To elucidate the risk factors for the development of incident hypertension (IHT) in patients with axial spondyloarthritis (axSpA). METHODS: We conducted a retrospective cohort study in axSpA patients who were recruited from 2001 to 2019 from a university clinic in Hong Kong. Patients with HT and/or anti-hypertensive drug use at baseline were excluded. They were followed until the end of 2020. The outcome was IHT, defined by a diagnosis and a prescription for an antihypertensive drug. Baseline and time-varying Cox regression analyses adjusting for age, sex, and body mass index (BMI), were used to assess the relationship between drug use, inflammatory burden, and IHT. RESULTS: Four hundred and thirteen patients [age: 34(25-43) years, male: 319 (77.2%)] were recruited. After a median follow-up of 12 (6-17) years, 58 patients (14%) developed IHT (IHT+group). Among all the baseline variables, disease duration and delay in diagnosis were the independent predictors for IHT based on the Cox regression model. In the multivariate Cox regression analysis, baseline disease duration, delay in diagnosis and time-varying ESR levels were independent predictors associated with an increased risk of IHT. IHT risk was significantly increased in patients with disease duration >5 years. The use of anti-inflammatory drugs was not associated with the development of IHT. CONCLUSION: Higher inflammatory burden as reflected by a longer disease duration, delay diagnosis and higher ESR levels, were predictors associated with IHT after adjusting for traditional CV risk factors. These data support routine screening for hypertension in axSpA patients, especially those with longer disease duration.

What is already known about this subject?• Patients with axial spondyloarthritis (axSpA) have a higher risk of cardiovascular (CV) disease compared with the general population. Hypertension (HT) is one of the most important modifiable risk factors. Whether increased inflammatory pathways or the use of anti-inflammatory therapies contribute toward the increased prevalence of HT in axSpA remained controversial.What does this study add?• First, higher inflammatory burden as reflected by a longer baseline disease duration, delay in diagnosis and higher ESR levels were predictors of incident HT (IHT) after adjusting for traditional CV risk factors in axSpA. Second, IHTrisk was significantly increased in pati\ents with disease duration >5 years.How might this impact on clinical practice or future developments?• Early diagnosis and adequate control of systematic inflammation may be important to prevent the development of HT. Routine screening for hypertension in axSpA patients should be considered, especially in patients with longer disease duration.

The Hong Kong Society of Rheumatology consensus recommendations for the management of gout.

Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains suboptimal. Like other countries, the treatment goal in Hong Kong usually focuses on relieving symptoms of gout but not treating the serum urate level to target. As a result, patients with gout continue to suffer from the debilitating arthritis, as well as the renal, metabolic, and cardiovascular complications associated with gout. The Hong Kong Society of Rheumatology spearheaded the development of these consensus recommendations through a Delphi exercise that involved rheumatologists, primary care physicians, and other specialists in Hong Kong. Recommendations on acute gout management, gout prophylaxis, treatment of hyperuricemia and its precautions, co-administration of non-gout medications with urate-lowering therapy, and lifestyle advice have been included. This paper serves as a reference guide to all healthcare providers who see patients who are at risk and are known to have this chronic but treatable condition.

High inflammatory burden predicts cardiovascular events in patients with axial spondyloarthritis: a long-term follow-up study.

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.

Serum Calprotectin Level Is Independently Associated With Carotid Plaque Presence in Patients With Psoriatic Arthritis.

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.

Nonsteroidal anti-inflammatory drugs and cardiovascular disease risk in spondyloarthritis-spectrum diseases.

PURPOSE OF REVIEW: Increased cardiovascular (CV) risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is well recognized in the general population. This may limit the use of this effective therapy in patients with spondyloarthritis (SpA), a population already at high CV risk. RECENT FINDINGS: Increased CV diseases and their risk factors in patients with SpA were consistently shown in recent population-level data. NSAIDs remained commonly prescribed in SpA, though their structural benefit remained controversial and the dispensing practice was variable in different regions in the world. A previous observation study suggested NSAIDs in SpA might be cardio-protective, possibly via their modulation of the chronic inflammatory state. A recent meta-analysis of nonrandomized studies also revealed no increased risk of a CV event. Interestingly, there is growing evidence that different NSAIDs might impose differential CV risk on patients with SpA. SUMMARY: Recent evidence suggested NSAIDs were associated with a neutral and possibly lower CV risk in patients with SpA, which provided some reassurance for their use.