DCES-PA: Deformation-controllable elastic shape model for 3D bone proliferation analysis using hand HR-pQCT images.

Bone proliferation is an important pathological feature of inflammatory rheumatic diseases. Although recent advance in high-resolution peripheral quantitative computed tomography (HR-pQCT) enables physicians to study microarchitectures, physicians' annotation of proliferation suffers from slice inconsistency and subjective variations. Also, there are only few effective automatic or semi-automatic tools for proliferation detection. In this study, by integrating pathological knowledge of proliferation formation with the advancement of statistical shape analysis theory, we present an unsupervised method, named Deformation-Controllable Elastic Shape model, for 3D bone Proliferation Analysis (DCES-PA). Unlike previous shape analysis methods that directly regularize the smoothness of the displacement field, DCES-PA regularizes the first and second-order derivative of the displacement field and decomposes these vector fields according to different deformations. For the first-order elastic metric, DCES-PA orthogonally decomposes the first-order derivative of the displacement field by shearing, scaling and bending deformation, and then penalize deformations triggering proliferation formation. For the second-order elastic metric, DCES-PA encodes both intrinsic and extrinsic surface curvatures into the second-order derivative of the displacement field to control the generation of high-curvature regions. By integrating the elastic shape metric with the varifold distances, DCES-PA achieves correspondence-free shape analysis. Extensive experiments on both simulated and real clinical datasets demonstrate that DCES-PA not only shows an improved accuracy than other state-of-the-art shape-based methods applied to proliferation analysis but also produces highly sensitive proliferation annotations to assist physicians in proliferation analysis.

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.

Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study.

BACKGROUND: To explore the trajectory of, and factors contributing to, achievement of individual criteria of minimal disease activity (MDA) in patients with active psoriatic arthritis (PsA) treated with guselkumab. METHODS: The Phase 3, randomized, placebo-controlled DISCOVER-2 study enrolled adults (N = 739) with active PsA despite standard therapies who were biologic/Janus kinase inhibitor-naive. Patients were randomized 1:1:1 to guselkumab 100 mg every 4 weeks; guselkumab 100 mg at week 0, week 4, then every 8 weeks; or placebo. In this post hoc analysis, patients randomized to guselkumab were included and pooled (N = 493). Longitudinal trajectories of achieving each MDA criterion through week 100 were derived using non-responder imputation. Time to achieve each criterion was estimated with Kaplan-Meier analysis. Multivariate regression for time to achieve each criterion (Cox regression) and achievement at week 100 (logistic regression) was used to identify contributing factors. RESULTS: Continuous improvement across all MDA domains was shown over time. ~70% of patients achieved near remission in swollen joint count (SJC), Psoriasis Area and Severity Index (PASI), and enthesitis through week 100. Median times to achieve individual criteria differed significantly (p < 0.0001), with SJC ≤ 1 (20 weeks), PASI ≤ 1 (16 weeks), and ≤ 1 tender entheses (16 weeks) being faster than patient-reported criteria (pain ≤ 15 mm, patient global assessment of arthritis and psoriasis ≤ 20 mm, Health Assessment Questionnaire-Disability Index ≤ 0.5) and tender joint count ≤ 1. Higher baseline domain scores, older age, worse fatigue, and increased body mass index were significant predictors of longer time to achieve minimal levels of disease activity assessed via patient-reported criteria. CONCLUSIONS: Substantial proportions of guselkumab-treated patients achieved individual MDA criteria, each showing continuous improvement through week 100, although with distinct trajectories. Median times to achieve physician-assessed MDA criteria were significantly faster compared with patient-driven criteria. Identification of modifiable factors affecting the time to achieve patient-reported criteria has the potential to optimize the achievement and sustainability of MDA in the clinic via a multidisciplinary approach to managing PsA, involving both medical and lifestyle interventions. TRIAL REGISTRATION NUMBER: NCT03158285. TRIAL REGISTRATION DATE: May 16, 2017.

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+.

Erosion Identification in Metacarpophalangeal Joints in Rheumatoid Arthritis using High-Resolution Peripheral Quantitative Computed Tomography.

Bone erosions are a pathological feature of several forms of inflammatory arthritis including rheumatoid arthritis (RA). The increased presence and size of erosions are associated with poor outcomes, joint function, and disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides unparalleled in vivo visualization of bone erosions. However, at this resolution, discontinuities in the cortical shell (cortical breaks) that are associated with normal physiological processes and pathology are also visible. The Study grouP for xtrEme Computed Tomography in Rheumatoid Arthritis previously used a consensus process to develop a definition of pathological erosion in HR-pQCT: a cortical break detected in at least two consecutive slices, in at least two perpendicular planes, non-linear in shape, with underlying trabecular bone loss. However, despite the availability of a consensus definition, erosion identification is a demanding task with challenges in inter-rater variability. The purpose of this work is to introduce a training tool to provide users with guidance on identifying pathological cortical breaks on HR-pQCT images for erosion analysis. The protocol presented here uses a custom-built module (Bone Analysis Module (BAM) - Training), implemented as an extension to an open-source image processing software (3D Slicer). Using this module, users can practice identifying erosions and compare their results to erosions annotated by expert rheumatologists.

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.

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.

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.

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.

Automatic 3D joint erosion detection for the diagnosis and monitoring of rheumatoid arthritis using hand HR-pQCT images.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. It leads to bone erosion in joints and other complications, which severely affect patients' quality of life. To accurately diagnose and monitor the progression of RA, quantitative imaging and analysis tools are desirable. High-resolution peripheral quantitative computed tomography (HR-pQCT) is such a promising tool for monitoring disease progression in RA. However, automatic erosion detection tools using HR-pQCT images are not yet available. Inspired by the consensus among radiologists on the erosions in HR-pQCT images, in this paper we define erosion as the significant concave regions on the cortical layer, and develop a model-based 3D automatic erosion detection method. It mainly consists of two steps: constructing closed cortical surface, and detecting erosion regions on the surface. In the first step, we propose an initialization-robust region competition methods for joint segmentation, and then fill the surface gaps by using joint bone separation and curvature-based surface alignment. In the second step, we analyze the curvature information of each voxel, and then aggregate the candidate voxels into concave surface regions and use the shape information of the regions to detect the erosions. We perform qualitative assessments of the new method using 59 well-annotated joint volumes. Our method has shown satisfactory and consistent performance compared with the annotations provided by medical experts.

A novel visceral adiposity index predicts bone loss in female early rheumatoid arthritis patients detected by HR-pQCT.

The purpose of this prospective study is to compare the Chinese visceral adiposity index (CVAI) between early rheumatoid arthritis (ERA) patients and healthy controls; and to assess the relationship between CVAI and the bone microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) in ERA patients. 104 female ERA and 100 age-, gender- and BMI-matched healthy controls were recruited for the comparison of CVAI. All ERA patients were prospectively followed for 1 year. HR-pQCT scan of the distal radius, tibia and second metacarpal head were performed at baseline and after one-year. ERA patients were divided into two sub-groups according to the median CVAI value (65.73) (low CVAI and high CVAI groups). CVAI in the ERA group was significantly higher than the controls group (p = 0.01). At baseline, the high CVAI group had a higher ESR level (p = 0.004) while the cortical volumetric bone mineral density (vBMD) was lower (at both the distal radius and tibia, all p < 0.05) compared to the low CVAI group. Linear regression analysis revealed that a higher baseline CVAI was an independent predictor of a lower cortical vBMD at month 12 (distal radius: B = - 0.626, p = 0.022, 95%CI - 1.914 to - 0.153; tibia: B = - 0.394, p = 0.003, 95%CI - 1.366 to - 0.290); and a greater reduction in trabecular vBMD (tibia: B = 0.444, p = 0.001, 95%CI 0.018-0.063; distal radius: B = 0.356, p = 0.008, 95%CI 0.403-0.063). In summary, CVAI is an independent predictor of trabecular bone loss in female patients with ERA, which may be augmented by a chronic inflammatory state in patients with visceral dysfunction of fat metabolism.Trial registration: http://Clinicaltrial.gov no: NCT01768923, 16/01/2013.

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study.

OBJECTIVES: This study explored whether the excess cardiovascular (CV) disease (CVD) risk in RA could be ameliorated by suppression of inflammation using a treat-to-target (T2T) approach. We compared the CV event (CVE) incidence among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population and a historical RA cohort (HRA). METHODS: This was an observational study using the city-wide hospital data and the ERA registry. ERA patients received T2T management while HRA patients received routine care. Each ERA/HRA patient was matched to three non-RA controls according to age, gender and CV risk factors. Patients on antiplatelet/anticoagulant agents, with pre-existing CVD, chronic kidney disease or other autoimmune diseases were excluded. All subjects were followed for up to 5 years. The primary end point was the first occurrence of a CVE. RESULTS: The incidence of CVE in the ERA cohort (n = 261) and ERA controls were similar with a hazard ratio of 0.53 (95% CI 0.15, 1.79). In contrast, the incidence of CVE in the HRA cohort (n = 268) was significantly higher than that of the HRA controls with a hazard ratio of 1.9 (95% CI 1.16, 3.13). The incidence of CVE in the ERA cohort was significantly lower than that of the HRA cohort and the difference became insignificant after adjusting for inflammation, the use of methotrexate and traditional CV risk factors. CONCLUSION: ERA patients managed by a T2T strategy did not develop excess CVE compared with CV risk factor-matched controls over 5 years.

Risk of alanine aminotransferase flare in patients with previous hepatitis B virus exposure on biological modifier therapies-A population-based study.

BACKGROUND: It is uncertain whether biological therapies would increase the risk of hepatitis among patients with past hepatitis B virus (HBV) infection. This study aimed to evaluate the risk of alanine aminotransferase (ALT) flare in patients with past HBV infection while using biological therapies. METHODOLOGY: Patients who received biological therapies for ≥3 months from 2000 to 2019 were identified from a population-based database in Hong Kong. Patients with past HBV infection were compared with a control group without prior HBV exposure. The primary endpoint was development of ALT flare within 5 years of starting biological therapies, defined as ALT >80 IU/L. RESULTS: There were 2471 and 2394 patients with and without past HBV infection respectively. There was a non-significant increase in risk of ALT flare among the HBV-exposed group (27.6% vs. 23.7%, p = .055). In multivariable analysis, using prednisolone-equivalent dose of >20 mg daily, male sex and concomitant immunosuppressants were risk factors for ALT flare. The risk of ALT flare was significantly higher with anti-CD20 when compared to other biological agents (36.1% vs. 14.5%, p < .01), but was not significantly different among anti-tumour necrosis factor, anti-cytokine, Janus kinase inhibitors and T cell/B cell inhibitors or anti-integrin (15.2% vs. 14.6% vs. 11.7% vs. 11.1%, p = .82). Among patients with documented hepatitis B surface antigen seroreversion, 96% were on anti-CD20. CONCLUSIONS: Our study further supports the current suggestion of prophylactic anti-viral before starting anti-CD20 in HBV-exposed patients. While other biological therapies appear to have a lower risk for ALT flare, this result needs further confirmation.

Comparative effectiveness of guselkumab in psoriatic arthritis: updates to a systematic literature review and network meta-analysis.

OBJECTIVE: The IL-23 p19-subunit inhibitor guselkumab has been previously compared with other targeted therapies for PsA through network meta-analysis (NMA). The objective of this NMA update was to include new guselkumab COSMOS trial data, and two key comparators: the IL-23 inhibitor risankizumab and the Janus kinase (JAK) inhibitor upadacitinib. MATERIAL AND METHODS: A systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand-search identified newer agents up to July 2021. Bayesian NMAs were performed to compare treatments on ACR response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs). RESULTS: For ACR 20, guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) were comparable (i.e. overlap in credible intervals) to most other agents, including risankizumab, upadacitinib, subcutaneous TNF inhibitors and most IL-17A inhibitors. For PASI 90, guselkumab Q8W and Q4W were better than multiple agents, including subcutaneous TNF and JAK inhibitors. For vdH-S, guselkumab Q8W was similar to risankizumab, while guselkumab Q4W was better; both doses were comparable to most other agents. Most agents had comparable SAEs. CONCLUSIONS: Guselkumab demonstrates better skin efficacy than most other targeted PsA therapies, including upadacitinib. For vdH-S, both guselkumab doses are comparable to most treatments, with both doses ranking higher than most, including upadacitinib and risankizumab. Both guselkumab doses demonstrate comparable ACR responses to most other agents, including upadacitinib and risankizumab, and rank favourably in the network for SAEs.

Efficacy and safety of guselkumab in biologic-naïve patients with active axial psoriatic arthritis: study protocol for STAR, a phase 4, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Axial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read. METHODS: The STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA (N =  405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein [CRP] ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W); guselkumab at week (W) 0, W4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0-10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24; multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire - Disability Index (HAQ-DI), Investigator's Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints. DISCUSSION: This study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04929210 , on 18 June 2021. PROTOCOL VERSION: Version 1.0 dated 14 April 2021.

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.

Spondyloarthritis: How far are we from precision medicine?

Spondyloarthritis (SpA) is a family of heterogenous diseases consisting of different phenotypes. The exact disease mechanism remains unclear but evidence shows the complex pathophysiology with interplay between genome, microbiome, and immunome. Biologic DMARDs have markedly improved patients' disease control and quality of life. However, treatment response varies among patients. There is a growing need to identify biomarkers for the diagnosis, prognosis, prevention, and treatment of SpA. Genomic studies have been the research focus in the past two decades and have identified important genes involved in SpA. In recent years, emerging evidence supports the link between gut and joint inflammation in SpA, in which the role of gut microbiome in SpA is of great interest. Herein, potential genetic and gut microbial biomarkers for predicting treatment response are discussed. Novel strategies targeting dysbiosis in SpA are also summarized. These results represent a significant step toward precision medicine for patients with SpA.