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Axial spondyloarthritis (axSpA) is a complex disease characterized by a diverse range of clinical presentations. The primary manifestation is inflammatory lower back pain, often accompanied by other clinical manifestations such as peripheral arthritis, enthesitis, uveitis, psoriasis, and inflammatory bowel disease. However, the presentation of axSpA can vary widely among patients. Despite extensive research, the precise pathogenesis of axSpA remains largely unknown. The lack of complete understanding poses challenges in subgrouping the disease, developing specific treatment approaches, and predicting treatment response. In this review, we will explore the limitations in diagnosing and treating axSpA. In addition, we will examine the current knowledge and potential opportunities provided by various omics and technological advancements in enhancing the diagnosis and personalized treatment of axSpA. Plain language summary: Precision medicine in axial spondyloarthritis: current opportunities and future perspectives The precise pathogenesis of axSpA remains unknown and is likely to be complex. Further efforts are needed to understand the disease mechanism to improve patient classification. Precision diagnosis integrates genetic data, environmental factors, and clinical characteristics to define subcategories. With the rapid advancement of technology, conducting more studies on the mechanism of SpA using multi-omics technology may yield new insights into the disease. It is also important to strike a balance between early treatment and avoiding overtreatment. Future studies should aim to combine multi-omic data, allowing the development of a more precise and individualized treatment strategy for SpA patients. [ABSTRACT FROM AUTHOR]

Objective Bone inflammation (osteitis) in early RA (ERA) manifests as bone marrow oedema (BME) and precedes the development of bone erosion. In this prospective, single-centre study, we developed an automated post-processing pipeline for quantifying the severity of wrist BME on T2-weighted fat-suppressed MRI. Methods A total of 80 ERA patients [mean age 54 years (s. d. 12), 62 females] were enrolled at baseline and 49 (40 females) after 1 year of treatment. For automated bone segmentation, a framework based on a convolutional neural network (nnU-Net) was trained and validated (5-fold cross-validation) for 15 wrist bone areas at baseline in 60 ERA patients. For BME quantification, BME was identified by Gaussian mixture model clustering and thresholding. BME proportion (%) and relative BME intensity within each bone area were compared with visual semi-quantitative assessment of the RA MRI score (RAMRIS). Results For automated wrist bone area segmentation, overall bone Sørensen–Dice similarity coefficient was 0.91 (s. d. 0.02) compared with ground truth manual segmentation. High correlation (Pearson correlation coefficient r  = 0.928, P  < 0.001) between visual RAMRIS BME and automated BME proportion assessment was found. The automated BME proportion decreased after treatment, correlating highly (r  = 0.852, P  < 0.001) with reduction in the RAMRIS BME score. Conclusion The automated model developed had an excellent segmentation performance and reliable quantification of both the proportion and relative intensity of wrist BME in ERA patients, providing a more objective and efficient alternative to RAMRIS BME scoring. [ABSTRACT FROM AUTHOR]

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease with progressive joint destruction. High-resolution peripheral quantitative CT (HR-pQCT) is a novel technique for detailed bone microstructure analysis allowing volumetric assessment of bone erosions. While most patients demonstrating little baseline joint damage on radiography in the early stage of RA, whether achieving simple disease activity index (SDAI) remission can lead to better structural outcome is to be confirmed. Methods Patients with ERA were recruited and treated to the target of simple disease activity index (SDAI) remission using a standardized algorithm. One hundred patients who received the one-year tight-control treatment were grouped by achieving SDAI sustained LDA [SDAI ≤ 1 1 ] at 6, 9 and 12 months (sLDA group) or not (non-sLDA group). HR-pQCT of the second to fourth metacarpophalangeal joints were performed at baseline, month 6 and one-year. Erosion volume and marginal bone mineral density (BMD) were measured. On an individual patient basis, erosion progression was defined as at least one erosion showing (1) an increase in erosion volume exceeding the smallest detectable change [SDC] (0.08 mm 3) AND (2) a decrease in marginal BMD exceeding SDC (7.8 mmHA/cm 3). Erosion healing was defined as at least one erosion showing (1) a reduction in erosion volume greater than SDC AND an increase in BMD exceeding SDC OR complete disappearance of the lesion AND (2) the absence of any erosion progression. Results Fourteen patients (12.8%) achieved sustained SDAI remission from 6-12 months (SDI group). After 12 months, a significant reduction in erosion volume and marginal osteosclerosis was observed in both groups. The SDI group showed a lower incidence of erosion progression (increase in volume > 0.08mm 3 and decrease in marginal osteosclerosis > 7.8mg HA/cm 3 : 0% vs 16%, p=0.135) and exhibited a higher rate of erosion healing (56% vs 29%, p=0.083) compared with the non-SDI group. In the GEE model, patients in the SDI group showed a higher likelihood of erosion healing (OR: 2.976, 95% CI: 1.0 - 8.9, p=0.050). The changes in erosion depth and width were similar between two groups. Conclusion Achieving sustained SDAI remission could improve erosion healing and limit erosion progression in patients with ERA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background This study aimed to ascertain the effect of secukinumab on erosion and enthesiophyte progression in psoriatic arthritis (PsA) by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods This was a one-year double-blind, randomized, placebo-controlled trial (NCT0362386740). Patients with erosion in the metacarpophalangeal joints (MCPJ) 2-4 were randomised in a 1:1 ratio to either the secukinumab or placebo group. HR-pQCT of the MCPJ 2-4 were performed at baseline, week-24 and 1-year. Progression of enthesiophyte were defined as changes in enthesiophyte volume exceeding smallest detectable change (SDC) (0.12mm3) or the identification of any new enthesiophyte. Partial repair of erosion was defined as a reduction in erosion volume greater than SDC (0.1mm3). Results Forty patients (age: 51.9± 13.4 years, 20 [50%] male) were recruited. Thirty-four patients who completed study treatment were included in the per-protocol analysis. The erosion volume at baseline, week-24 and week-48 revealed significant reduction in the secukinumab group while no differences in the placebo group (Figure-3A). There was a trend suggesting that fewer patients developed new-erosions in the secukinumab group (one-erosion in one-patient) compared to the placebo group (six-erosions in five-patients) (p=0.078) (Figure-3B). A significantly higher proportion of erosions with partial healing was observed in the secukinumab group compared with the placebo group [51%vs30%, p=0.029] (Figure-3C). Regarding enthesiophyte, a total of 25-enthesiophytes were identified in both the secukinumab and placebo groups at baseline. The enthesiophyte volume at baseline, week-24 and week-48 revealed significant differences in the secukinumab group while no differences in the placebo group (Figure-3D). While one (one-enthesiophyte in one-patient) and four-enthesiophytes (four-enthesiophytes in three-patients) were newly identified in the secukinumab group and placebo group respectively (Figure-3E), the proportion of enthesiophyte progression was numerically higher in the placebo group than the secukinumab group [40%vs16%, p=0.114] at week 48 (Figure-3F). GEE results showed that the odds ratio (OR) for enthesiophyte progression in the secukinumab group was 0.264 (95% CI: 0.080-0.878, p=0.030), while the OR for partial erosion healing in the secukinumab group was 2.816 (95% CI: 1.109 to 7.153, p=0.029), adjusting for tender-joint-counts. Conclusions Secukinumab demonstrates a potential benefit in facilitating partial erosion repair and preventing enthesiophyte progression in PsA. [ABSTRACT FROM AUTHOR]

Background During the COVID-19 pandemic, 2 types of COVID-19 vaccines were made available in Hong Kong - the mRNA-based vaccine and the inactivated virus vaccine. All residents were required to complete 3 vaccinations. There is concern that immunogenicity acquired from COVID-19 vaccinations could be unsustainable in patients with inflammatory rheumatic disease (IRD) due to the underlying condition and immunosuppressive medication used. Therefore, this study aims to investigate the immunogenicity of COVID-19 vaccines and its sustainability in IRD patients. Methods This single-centre cohort was assembled prospectively from 8/2021 - 2/2022 in Hong Kong. Peripheral blood samples were collected from the patients before, 28 (± 3) days and 12 months after the third dose of COVID-19 vaccination. The neutralising antibody titre against the SARS-CoV-2 virus was quantified by ELISA. Results A total of 83 patients (age: 51.4± 11.7 years; 72.3% female; 17 rheumatoid arthritis, 17 psoriatic arthritis, 12 axial spondylarthritis, 37 systematic lupus erythematosus) attended all 3 visits. The vaccine distribution is summarized in Fig. 1A. Majority (96.4%) of patients had positive neutralising antibodies before the 3rd vaccine dose despite a low mean titre of 38.2± 29.7%. The antibody titre improved significantly after the 3rd dose (85.9± 23.8%) and was maintained at the 12-month visit (87.5± 22.6%). The mean antibody levels pre- and post-3rd dose were higher in patients who took mRNA-based vaccine (Fig. 1B). The presence of COVID-19 infection during the follow-up period led to significantly higher antibody titre at the 12-month visit (Table 1). There were no significant associations between immunogenicity and age, type of IRD, biologic/targeted Disease Modifying Anti-Rheumatic Drugs usage as well as additional booster doses. Conclusion 3 doses of COVID-19 vaccine produced sustained humoral response in IRD patients. The immunogenicity appeared to be dependent on the type of vaccines received in the short term and breakthrough infection in longer term. [ABSTRACT FROM AUTHOR]

Background: To identify contributors to non-traumatic incident fractures on rheumatic disease patients who are on long term glucocorticoids (LTGC) Methods: Two hundred and twenty patients on LTGC (110 with vertebral fracture and 110 without vertebral fracture) who participated in a cross-sectional study in 2014-2015 were invited to have repeated assessments on 1) aBMD using dual-energy X-ray absorptiometry (DXA), 2) volumetric BMD (vBMD), microstructure and bone strength assessment of the wrist and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and 3) spine radiographs in the 5th year. Clinical covariates were recorded on questionnaires, and Fracture Risk Assessment Tool (FRAX) score was calculated accordingly. Non-traumatic incident fracture over the 5-year were documented. Receiver operating characteristic curve (ROC) analysis was performed to compare the strength of fracture prediction tools. Results: Out of the 140 patients who completed the 5th year assessments, 47 (33.6%) developed incident fractures. History of previous fracture, aBMD at hip and lumbar spine, T-score, trabecular vBMD, trabecular bone volume fraction and estimated bone strength at the tibia at baseline remained significantly different after adjusting for age between the group with and without incident fractures. The area under curve (AUC) of a prediction model comprised of age, history of previous fracture and average trabecular vBMD at tibia was comparable with that of the FRAX score (0.710 vs 0.679-0.702), and slightly outperformed than the AUC of DXA aBMD at hip and lumbar spine (0.628-0.668) under ROC analysis. Conclusion: Age, history of previous fracture and average trabecular vBMD at tibia could be the main contributors in building a prediction model for non-traumatic incident fracture in rheumatic disease patients on LTGC. [ABSTRACT FROM AUTHOR]

Background: In patients with axial spondyloarthritis (AxSpA), we have reported that higher inflammatory burden as reflected by a longer disease duration, delay in diagnosis and higher erythrocyte sedimentation rate (ESR) levels were predictors associated with incident hypertension after adjusting for traditional cardiovascular (CV) risk factors (1). Whether this is due to accelerated arterial stiffness progression is worth exploring. Methods: One hundred patients with axSpA who fulfilled the ASAS classification criteria and with active disease (ASDAS ≥ 2.1) were recruited from the out-patient clinic of 6 regional hospitals. All participants will receive a 2-year protocolized treatment aiming to achieve ASDAS low disease activity (LDA) in order to address the effects of treating-to-target (T2T) and vascular outcomes (The Hong Kong AxSpA T2T vascular study). Medical history, medication used, disease activity, serum levels of inflammatory markers, cholesterol and fasting glucose were measured/recorded every 6 months. Brachial-ankle pulse wave velocity (baPWV) and carotid ultrasound were assessed at baseline and yearly. In this interim-analysis, we will focus on baPWV. Results: Ninety-two patients completed the month 12 follow-up. The patients were stratified into two groups based on the duration from symptom onset to diagnosis: less than 2 years (early axSpA group) and 2 years or more (non-early axSpA group). Table 1 summarized the demographic and clinical characteristics of both groups. The baseline baPWV values were comparable between the two groups (1412.4 ± 230.45 and 1325.19 ± 174.75, p > 0.05). However, at Month 12, there was a significant difference in baPWV between the groups (1470.77 ± 233.70 and 1302.09 ± 198.52, p= 0.001) (Figure 2). The early axSpA group showed a decrease of 23.09 cm/s, while the non-early axSpA group exhibited an increase of 59.85 cm/s (p=0.033). A multivariate linear regression analysis was conducted to predict the change in baPWV based on age, gender, early axSpA, use of csDMARDs, and glucocorticoids at baseline. Early axSpA remained the only significant predictor and was associated with a positive effect in reducing baPWV (β = -82.939; p= 0.033). Conclusion: Early diagnosis may be able to prevent progression of arterial stiffness in patients with axial SpA by lowering the cumulative inflammatory burden before effective suppression of inflammation could be given to the patients. [ABSTRACT FROM AUTHOR]

Background: Sacroiliac joints (SIJ) radiography has lower sensitivity and specificity compared to magnetic resonance imaging (MRI) and low-dose CT (ldCT) of the SIJ for detecting axial spondyloarthritis. Whether this is also true for axial psoriatic arthritis (axPsA) remains uncertain. This study aimed to evaluate the performance of ldCT, MRI, and conventional radiography of SIJ and spine in distinguishing axial involvement in PsA patients. Methods: Fifty-one consecutive PsA patients (70.6% male, age 41 ± 13 years) meeting the CASPAR classification criteria, regardless of back pain, were included. All patients underwent SIJ and whole-spine radiography, SIJ MRI as well as SIJ ldCT, while 25 (49%) of 51 patients also underwent whole-spine MRI and ldCT. One rheumatologist with expertise in imaging and one trained reader evaluated images. The final diagnosis of axPsA was ascertained by two experienced rheumatologists. The sensitivity, specificity, and diagnostic accuracy of the three modalities for discriminating axPsA were compared. Results: AxPsA was diagnosed in 33.3% (17) of 51 patients. In discerning axial involvement in PsA patients, MRI exhibited superior sensitivity (92.9%) compared with ldCT (83.3%) and radiography (67.9%), while ldCT demonstrated higher specificity (97.1%) than MRI (86.4%) and radiography (72.7%). LdCT achieved the highest diagnostic accuracy (92%) among the three modalities, surpassing radiography (71%) and being comparable to MRI (89%). In the subgroup of patients with whole spine imaging, the combination of MRI and ldCT SIJ had the best diagnostic accuracy, reaching 93%. Including SIJ ldCT in addition to SIJ MRI further improved specificity (86.7% vs. 73.3%) with unchanged sensitivity (100%), while incorporating SIJ MRI alongside SIJ ldCT further improved sensitivity from 83% to 100%, with a modest decrease in specificity (86.7% vs. 93.3%). However, incorporating spine MRI/ldCT alongside SIJ MRI/ldCT did not further improve sensitivity or specificity in discriminating axial involvement in PsA patients. Conclusion: LdCT demonstrated superior diagnostic performance in distinguishing axial involvement in PsA patients compared to MRI or radiography, although MRI was more sensitive for detecting active sacroiliitis. The highest diagnostic performance was achieved with both MRI and ldCT of the SIJ. Additional spine imaging did not further increase diagnostic performance. [ABSTRACT FROM AUTHOR]

Background: Janus kinases inhibitor (JAKi) is a potent drug in treating patients with rheumatoid arthritis (RA). However, the effect of JAKi on finite structural changes remained uncertain. This study aims to investigate the effect of JAKi on erosion repair evaluated by high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active 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 15mg 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± 3.26mm3vs 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 to 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. [ABSTRACT FROM AUTHOR]

Background: Despite the widespread advocacy of the treat-to-target(T2T) strategy for managing psoriatic arthritis (PsA), a significant number of patients fail to achieve minimal disease activity (MDA) even with advanced therapies. While a universal definition of difficult-to-treat(D2T) PsA is absent, investigating the heterogeneity of D2T PsA within a real-life T2T-cohort can offer valuable insights into comprehending this concept. Methods: This analysis included the first 111 PsA patients enrolled in the APLAR SpA registry who underwent 1-year T2T management. They were recruited from 6 Asia-Pacific regions. D2T was defined as the failure to achieve MDA despite receiving ≥ 1 conventional synthetic disease-modifying anti-rheumatic drugs(csDMARDs) and ≥ 1 biologic/targeted synthetic DMARDs(b/tsDMARDs) over 6-months. Results: A total of 111 patients (mean age: 48± 13 years, 59 [53%] male, mean disease duration: 5.3± 7.3 years) were included. At baseline, the patients exhibited moderate disease activity, with only 35% achieving MDA. After 1-year, a significant improvement in Disease Activity in Psoriatic Arthritis (DAPSA) was observed (16.3± 14.0 at baseline vs 10.1± 9.7 at 1-year, p<0.001), with 56% of patients achieving MDA. At one-year, 17(15%) patients fulfilled the definition of D2T-PsA. Compared to the non-D2T group, patients in the D2T group had lower education level, longer disease duration, worse disease activity across domains, and higher functional disability at baseline (Table 1). During the 1-year treatment, the T2T adherence rate was significantly lower in the D2T group (71% vs 90%, p=0.028). Reasons for not escalating treatment in the D2T group included patients' preference (60%), physician's decision (20%), and no alternative treatment available (20%). Using multivariate logistic regression, a lower education level (OR:4.64, 95%CI:1.16-16.9, p=0.029) and higher Ankylosing Spondylitis Disease Activity Score (ASDAS) (OR: 1.81, 95%CI:1.07-3.04, p=0.026) were significantly associated with D2T after adjusting for baseline disease duration, number of dactylitic digits, MDA status and protocol adherence. Conclusions: Despite the implementation of the T2T-strategy and increased utilization of b/tsDMARDs, more than 40% of patients were unable to achieve MDA. Factors such as higher axial disease activity and lower education level were associated with D2T PsA. Further studies are required to determine whether a more aggressive treatment approach focusing on the axial domain should be implemented for these individuals. [ABSTRACT FROM AUTHOR]

Background Despite the wide availability of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) for treating psoriatic arthritis (PsA), there remain controversies regarding the positioning of b/tsDMARDs in the management algorithm for patients with active peripheral disease. While the European League Against Rheumatism (EULAR) recommends conventional synthetic DMARDs (csDMARDs) as the first-line treatment (1), the American College of Rheumatology (ACR) guideline takes a more aggressive approach, and suggests upfront use of b/tsDMARDs (2). The study aimed to evaluate whether earlier use of b/tsDMARDs might increase the likelihood of achieving minimal disease activity (MDA) in patients with PsA under the treat-to-target framework. Method Consecutive patients with PsA who fulfilled the CASPSA criteria with active peripheral disease were recruited in this prospective cohort study. The analysis included patients who were (1) given b/tsDMARDs during the study period and (2) completed 1-year follow-up. A standardized treat-to-target strategy was adopted. Patients were categorized into csDMARDs-naïve group, single-csDMARD-inadequate response (IR) group and multiple-csDMARDs-IR group. The rate of achieving MDA at the end of one year was compared. Result A total of 100 PsA patients were recruited and 27 patients (mean age: 51± 13, 15 [68%] male, disease duration: 5.6± 6.9 years) were included in the analysis. At baseline, all patients exhibited moderate to high disease activity. Prior to initiating b/tsDMARDs, 4 patients were csDMARDs-naïve, 10 patients had failed 1 csDMARD and 13 patients had failed 2 or more csDMARDs. There was no significant difference between clinical features and disease activity among the 3 groups at baseline (Table 1). Within the study period, 3 (11%) and 24 (89%) patients were given anti-TNF and anti-IL-17 agents respectively. After 1-year, there was substantial improvement in disease activity in the whole cohort (Disease Activity in Psoriatic Arthritis [DAPSA]: 22.7 at baseline vs 9.0 at 1-year, p=0.039), and 17(63%) patients achieved MDA. A differential MDA achievement rate was observed across different groups. All csDMARDs-naïve patients achieved MDA, compared to 70% in the single-csDMARD-IR and 46.2% in the multiple-csDMARDs-IR groups (p=0.046) (Figure 1). There was also a trend of better DAPSA response at one-year in the csDMARDs-naïve group (4.9± 1.6 vs 10.2± 11.8 [single-csDMARD-IR] and 9.4± 8.1 [multiple-csDMARDs-IR]). Conclusion A lower MDA achievement rate was observed in b/tsDMARDs users with prior csDMARD exposure. Earlier initiation of b/tsDMARDs might improve treatment outcome in PsA. [ABSTRACT FROM AUTHOR]

Background: Unlike axial spondyloarthritis (axSpA), no classification criteria are currently available for axial psoriatic arthritis (axPsA). This study aimed to evaluate the performance of the proposed cut-offs from the Assessment of Spondyloarthritis International Society (ASAS) data-driven definitions for active and structural magnetic resonance imaging (MRI) lesions typical of axSpA in distinguishing axial involvement in patients with psoriatic arthritis (PsA). Methods: Seventy-two consecutive PsA patients (67% male, aged 45± 14 years) meeting the CASPAR classification criteria, regardless of the presence of back pain, were included. All patients underwent radiography of the pelvis and spine, as well as sacroiliac joint (SIJ) MRI, while 52 (72%) of 72 patients also underwent whole-spine MRI. The final diagnosis of axPsA was ascertained by two experienced rheumatologists. One rheumatologist with expertise in imaging and one trained reader evaluated the radiography and MRI images. Results: AxPsA was diagnosed in 27/72 (38%) patients. The proposed cut-offs for active sacroiliitis demonstrated high specificity (95.6%) but relatively low sensitivity (51.9%) in distinguishing patients with and without axPsA. When structural lesions of the SIJ were included in addition to active lesions, the sensitivity significantly improved (96.3% vs. 51.9%) with a modest decrease in specificity (86.7% vs. 95.6%). Incorporating MRI spine lesions (using the proposed cut-offs for positive spine MRI from the SPACE cohort) alongside SIJ lesions did not further change sensitivity or specificity compared with assessing SIJ alone. Conclusion: The ASAS-proposed cut-offs for identifying active and structural lesions of SIJ demonstrated satisfactory performance in discriminating axial involvement in PsA patients. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of rheumatoid arthritis (RA) is crucial for timely intervention and improved outcomes. Although research on the preclinical phase of RA is a prominent topic, there remains an unmet need to effectively stratify patients at risk of developing RA based on basic clinical assessment and laboratory investigations. This prospective longitudinal study aimed to identify risk factors for RA development in individuals experiencing arthralgia. Method: Two hundred consecutive adults with arthralgia were enrolled from new referrals to our rheumatology clinic. Patients with synovitis or a known arthritis diagnosis were excluded. Follow-up assessments were conducted every 6 months, or sooner if symptoms worsened, for a maximum of 2 years. The study endpoint was the development of RA, according to the 2010 ACR/EULAR classification criteria. Baseline demographic characteristics, clinical parameters, serology, and acute phase reactant levels were compared between patients who developed RA and those who did not. In addition, the classification score based on the 2010 ACR/EULAR classification criteria was utilised as a composite weighted score summarising the clinical presentation in the cohort, although the patients were deemed not fulfilling the mandatory criteria of having synovitis at baseline. Results: By May 2024, 104 patients had been followed up for at least one year, with a median duration of 78 weeks (IQR: 58-97). The baseline symptom duration was 51 weeks (IQR: 29 – 97). Among these patients, 23 (22.1%) developed RA after a median follow-up duration of 41 weeks (IQR: 25 – 52). Patients who developed RA had a significantly higher proportion of joint symptoms <1 year, difficulty making a fist, positive rheumatoid factor (RF), anti-CCP antibodies, and elevated ESR and CRP levels at baseline. Multivariate logistic regression identified difficulty making a fist (OR: 4.87, 95% CI: 1.40 – 17.04, p = 0.013) and positive anti-CCP antibodies (OR: 13.04, 95% CI: 3.74 – 45.44, p < 0.001) as independent predictors for RA development. Meanwhile, patients who developed RA had significantly higher baseline scores extrapolating from the 2010 ACR/EULAR classification criteria compared to the non-RA group. Conclusion: Difficulty making a fist and positive anti-CCP antibodies are independent predictors of RA development. Additionally, patients who developed RA exhibited significantly higher baseline scores on the 2010 ACR/EULAR classification criteria. Early recognition of these variables and taking reference from the score of classification criteria may aid in RA risk stratification. Further research is needed to validate these findings and explore additional predictive markers. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) is a heterogeneous inflammatory disease predominantly affecting the spine and the sacroiliac joints. Patient-centered care must remain a central concept with patient satisfaction, quality of life and productivity as the goals for the care of patients with SpA. Comorbidities are common in SpA patients as a result of the interaction between systematic inflammation and the treatment received. The associated factors of depression and anxiety include joint pain, disability, inflammatory processes and lower quality of life, which are common in SpA patients. [Extracted from the article]

Objective Anti-melanoma differentiation-associated protein 5 (MDA5)-positive DM is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors of mortality and RP-ILD. Methods Anti-MDA5-positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. Results Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed RP-ILD [hazard ratio (HR) 9.735 (95% CI 3.905, 24.272)], age >52 years [HR 4.750 (95% CI 1.692, 13.333)], ferritin level >2800 pmol/l [HR 3.042 (95% CI 1.323, 6.997)] and lactate dehydrogenase (LDH) >400 IU/l [HR 2.290 (95% CI 1.009, 5.198)] were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years [HR 2.640 (95% CI 1.277, 5.455)], LDH >300 IU/l [HR 3.189 (95% CI 1.469, 6.918)], fever [HR 1.903 (95% CI 0.956, 3.790)] and neutrophil:lymphocyte ratio >7.0 [HR 1.967 (95% CI 0.942, 4.107)]. We proposed a prediction model based on fever, LDH, age and white cell count (FLAW) to stratify the risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75%, respectively. Conclusions Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The FLAW model maybe useful to predict the development of RP-ILD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate whether the 2017 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) could appropriately classify the diagnosis in adult patients with anti–melanoma differentiation–associated protein 5 (anti–MDA‐5)–positive IIM. In addition, this study sought to determine whether a status of anti–MDA‐5 positivity could be incorporated into the EULAR/ACR IIM classification criteria set and whether the recently modified criteria based on the presence of myositis‐specific autoantibodies (MSAs) could be used to appropriately classify the diagnosis in patients with anti–MDA‐5–positive IIM. Methods: Consecutive adult patients clinically diagnosed as having anti–MDA‐5–positive IIM from 10 hospitals in Hong Kong were retrospectively recruited; patient characteristics were obtained from electronic medical records. We used a commercial line blot immunoassay to detect MSAs. We also determined a proposed set of phenotypic‐serologic classification criteria specific for anti–MDA‐5. Results: In the patient cohort (n = 120; 31.7% with dermatomyositis, 68.3% with clinically amyopathic dermatomyositis [CADM]), the diagnosis could be classified with the EULAR/ACR criteria in 86 patients (71.7%) and with the Bohan and Peter criteria in 49 patients (40.8%). However, when combined with criteria specifically modified for CADM, the diagnosis could be classified by the Bohan and Peter criteria in 76.7% of patients. We observed that the sensitivity of the EULAR/ACR criteria could be improved to 98.3% if anti–MDA‐5 antibody–positive status was considered as one of the criteria. The MSA‐based criteria had 100% sensitivity. When we applied our proposed specific phenotypic‐serologic criteria for the classification of patients with anti–MDA‐5 antibodies, 97.5% of patients were able to be classified as having IIM. Conclusion: In this cohort of patients with anti–MDA‐5–positive IIM, the diagnosis could not be classified by the EULAR/ACR criteria in almost 30% of patients. We suggest incorporating anti–MDA‐5 antibody positivity as a criterion into existing criteria sets or developing specific criteria for patients with anti–MDA‐5–positive IIM. [ABSTRACT FROM AUTHOR]