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.

Role of Interleukin 6 Inhibitors in the Management of Rheumatoid Arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is a multisystem disease that affects the joints and various organs, resulting in compromised quality of life and increased mortality. A wide spectrum of treatment options is available for RA. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are the first-line of treatment for RA, whereas tumor necrosis factor α inhibitors are commonly used as a second-line biological disease-modifying antirheumatic drug following inadequate response to csDMARDs. However, remission remains difficult to achieve. No single agent is effective for all patients. It is important to consider patients' comorbidities, perspectives, and preferences when selecting treatment.Interleukin 6 (IL-6) plays a prominent role in the pathophysiology of RA and is an important therapeutic target for RA. Tocilizumab and sarilumab are approved IL-6 inhibitors, which have demonstrated good efficacy and tolerability as combination therapy or monotherapy in RA patients with inadequate response to csDMARDs or tumor necrosis factor α inhibitors. Apart from alleviating joint symptoms, inducing remission, and reducing structural damage, tocilizumab and sarilumab exhibit additional advantages in alleviating extra-articular symptoms, such as fatigue and morning stiffness, and have positive effect on anemia and glucose metabolism. Additionally, evidence showed that certain patient subgroups, such as those with comorbidities including anemia and diabetes mellitus, those with early RA, those with high baseline IL-6 levels, those at high risk of tuberculosis infection, or those intolerant to methotrexate monotherapy, may benefit from IL-6 inhibition. Given these advantages, tocilizumab and sarilumab can be considered earlier as a rational choice for treating RA in suitable patients. Future clinical investigations will help refine the use of these agents.

Myositis-specific autoantibodies and their clinical associations in idiopathic inflammatory myopathies.

BACKGROUND: Myositis-specific autoantibodies (MSAs) have been found to be present predominantly in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the prevalence of MSAs and their associated complications in a cohort of patients with IIMs. METHODS: This was a multicentered prospective study. Consecutive adult Chinese patients with IIMs in the regional hospitals in Hong Kong were followed up from July 2016 to January 2018. Clinical characteristics, treatment history, and disease complications were documented. A commercially available immunoblot assay was used to detect the MSAs. RESULTS: Out of the 201 patients studied, at least one MSA was found in 63.2% of patients. The most common among the identified MSAs were the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) and the anti-transcriptional intermediary factor 1-gamma antibody (anti-TIF1-γ Ab) (both 13.9%), followed by anti-Jo-1 antibody (12.4%). Anti-MDA5 was present exclusively in dermatomyositis (DM) and was strongly associated with digital ulcers, amyopathy, and rapidly progressive interstitial lung disease (RP-ILD). Anti-TIF1γ was strongly associated with refractory rash and malignancy. Independent risk factors of RP-ILD included anti-MDA5 (OR 14.5), clinically amyopathic DM (OR 13.9), and history of pulmonary tuberculosis (OR 12.2). Cox regression analysis showed that anti-TIF1γ (HR 3.55), DM (HR 3.82), and family history of cancer (HR 3.40) were independent predictors of malignancy. CONCLUSIONS: MSA testing enables dividing of patients with IIMs into phenotypically homogeneous subgroups and prediction of potentially life-threatening complications.

DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study.

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

Impact of Motivational Interviewing on Self-Management in Patients With Type 2 Diabetes: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: The nonpharmacological approach to diabetic control in patients with diabetes focuses on a healthy diet, physical activity, and self-management. Therefore, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns and include brief advice and counseling services. Within this context, motivational interviewing (MI) has proven to be effective in changing health behaviors for specific cases. However, stronger evidence is needed on the effectiveness of MI in treating chronic pathologies such as diabetes. OBJECTIVE: This study will obtain preliminary data on the impact of a nurse-led MI intervention in improving glycemic control, as well as clinical, psychosocial, and self-care outcomes for individuals with type 2 diabetes mellitus when compared with usual care, with the aim of improving diabetic control in patients with diabetes. METHODS: An open, two-arm, parallel, randomized controlled, pilot exploratory trial will be performed. Two government outpatient clinics in the New Territories West Cluster in Hong Kong will be involved. In total, 20 to 25 participants will be invited in each arm. Intervention participants will receive face-to-face MI interventions in addition to their usual care from the clinic. Control participants will only receive usual care. Outcomes are assessed at baseline, 6 months, and 12 months. The primary outcome measure is glycated hemoglobin levels. Secondary outcomes include blood pressure, BMI, hip and waist circumference, fasting blood, and psychosocial and self-care measures. RESULTS: This study is currently underway with funding support from the Hong Kong College of Family Physician Research Seed Fund 2017. CONCLUSIONS: MI skills constitute the main strategies primary care nurses use on their patients. Having economical, simple, effective, and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of MI. It will be performed with strict control over the data collection, ensuring the maintenance of therapeutic integrity. TRIAL REGISTRATION: Centre for Clinical Research and Biostatistics CUHK_CCRB00614; https://tinyurl.com/v9awzk6. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15709.

Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong Kong Society of Rheumatology.

The expanding range of treatment options for rheumatoid arthritis (RA), from conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to biological DMARDs (bDMARDs), biosimilar bDMARDs, and targeted synthetic DMARDs, has improved patient outcomes but increased the complexity of treatment decisions. These updated consensus recommendations from the Hong Kong Society of Rheumatology provide guidance on the management of RA, with a focus on how to integrate newly available DMARDs into clinical practice. The recommendations were developed based on evidence from the literature along with local expert opinion. Early diagnosis of RA and prompt initiation of effective therapy remain crucial and we suggest a treat-to-target approach to guide optimal sequencing of DMARDs in RA patients to achieve tight disease control. Newly available DMARDs are incorporated in the treatment algorithm, resulting in a greater range of second-line treatment options. In the event of treatment failure or intolerance, switching to another DMARD with a similar or different mode of action may be considered. Given the variety of available treatments and the heterogeneity of patients with RA, treatment decisions should be tailored to the individual patient taking into consideration prognostic factors, medical comorbidities, drug safety, cost of treatment, and patient preference.

Effect of Achieving Minimal Disease Activity on the Progression of Subclinical Atherosclerosis and Arterial Stiffness: A Prospective Cohort Study in Psoriatic Arthritis.

OBJECTIVE: To investigate the effects of achieving minimal disease activity (MDA) on the progression of subclinical atherosclerosis and arterial stiffness in patients with psoriatic arthritis (PsA). METHODS: A total of 101 consecutive patients with PsA were recruited for this prospective cohort study. All patients received protocolized treatment targeting MDA for a period of 2 years. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. The primary outcome measure was the effect of achieving MDA at 12 months (MDA group) on the progression of subclinical atherosclerosis over a period of 24 months. Secondary objectives were to compare the changes in arterial stiffness markers over 24 months between the MDA and non-MDA groups, as well as the changes in subclinical atherosclerosis and arterial stiffness markers in patients who achieved MDA at each visit from month 12 through month 24 (sustained MDA [sMDA]). RESULTS: Ninety PsA patients (mean ± SD age 50 ± 11 years, 58% male [n = 52]) who completed 24 months of follow-up were included in this analysis. Fifty-seven patients (63%) had achieved MDA at 12 months. Subclinical atherosclerosis and arterial stiffness outcomes were similar between the MDA and non-MDA groups. Forty-one patients (46%) achieved sMDA. As shown by multivariate analysis, achieving sMDA had a protective effect on plaque progression (odds ratio 0.273 [95% confidence interval 0.088-0.846], P = 0.024), and less of an increase in total plaque area, mean intima-media thickness, and augmentation index values after adjustment for covariates. CONCLUSION: Our results support the recommendation that once MDA is achieved, it should ideally be maintained for a prolonged period in order to prevent progression of carotid atherosclerosis and arterial stiffness in patients with PsA.

Bone Mass, Microstructure, and Strength Can Discriminate Vertebral Fracture in Patients on Long-Term Steroid Treatment.

Context: Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) was able to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric bone mineral density (vBMD), microarchitecture, and strength that may increase our understanding of fracture susceptibility. Objective: To ascertain whether vBMD, microarchitecture, and estimated bone strength derived from HR-pQCT can discriminate vertebral fractures in patients with glucocorticoid-induced osteoporosis (GIOP) independent of aBMD. Design: A cross-sectional case-control study. Setting: Seven regional hospitals in Hong Kong. Patients: A total of 110 patients on long-term glucocorticoids with vertebral fracture, determined radiographically, and 110 patients on long-term glucocorticoids without fracture. Main Outcome Measures: We assessed vBMD, microarchitecture, and bone strength; aBMD; and fracture risk assessment tool (FRAX). Results: Patients with vertebral fracture had lower total vBMD and a thinner cortex at the distal tibia after adjustment for age, sex, and aBMD or FRAX. In the antiresorptive treatment-naive subgroup, patients with vertebral fracture also had lower total vBMD at both the distal radius and the tibia after adjustment for covariates. Lower total vBMD and a thinner cortex were also noticed in the nonosteoporotic or FRAX score of <10% subgroups with vertebral fracture and were also associated with increasing prevalence of vertebral fracture. Conclusion: Patients with GIOP and vertebral fracture have a significant reduction in total vBMD and cortical thinning independent of aBMD and FRAX. These changes may help identify high-risk patients in the subgroups currently considered to have low fracture risk as assessed by DXA or FRAX.

Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis.

To report our experience in using rituximab (RTX) for treating refractory rapidly progressive interstitial lung disease (RP-ILD) complicating anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive amyopathic dermatomyositis (ADM). Medical records of four ADM patients with refractory RP-ILD treated with RTX therapy were reviewed retrospectively. All four patients were tested positive for anti-MDA5 Ab and failed to respond to high-dose systemic steroid and other intensive immunosuppressive therapies. Respiratory symptoms, lung function tests, and high-resolution computed tomography (HRCT) of the chest were compared before and after the first course of RTX. After RTX treatment, all four patients had improvement in the respiratory symptoms in terms of New York Heart Association classification. Two patients successfully had their supplementary oxygen therapy weaned off. The lung function tests were significantly better in all patients. The HRCT showed improvement in three patients while the other one remained static. The recalcitrant vasculitic rashes associated with the anti-MDA5 Ab were also better in all patients. The average daily prednisolone dose dropped from 20 to 6.25 mg post-treatment. None of the patients died throughout the follow-up period which ranged from 6 months to 2 years. However, two patients developed chest infection and one wound infection within 6 months after the RTX infusion. Our results suggest that RTX may be a useful therapy for anti-MDA5 Ab-positive ADM associated with RP-ILD. However, infection is the major risk.

Effect of Treat-to-target Strategies Aiming at Remission of Arterial Stiffness in Early Rheumatoid Arthritis: A Randomized Controlled Study.

OBJECTIVE: To determine the efficacy of 2 tight control treatment strategies aiming at Simplified Disease Activity Score (SDAI) remission (SDAI ≤ 3.3) compared to 28-joint count Disease Activity Score (DAS28) remission (DAS28 < 2.6) in the prevention of arterial stiffness in patients with early rheumatoid arthritis (RA). METHODS: This was an open-label study in which 120 patients with early RA were randomized to receive 1 year of tight control treatment. Group 1 (n = 60) aimed to achieve SDAI ≤ 3.3 and Group 2 (n = 60), DAS28 < 2.6. Pulse wave velocity (PWV) and augmentation index (AIx) were measured at baseline and 12 months. A posthoc analysis was also performed to ascertain whether achieving sustained remission could prevent progression in arterial stiffness. RESULTS: The proportions of patients receiving methotrexate monotherapy were significantly lower in Group 1 throughout the study period. At 12 months, the proportions of patients achieving DAS28 and SDAI remission, and the change in PWV and AIx, were comparable between the 2 groups. In view of the lack of differences between the 2 groups, a posthoc analysis was performed at Month 12, including all 110 patients with PWV, to elucidate the independent predictors associated with the change in PWV. Multivariate analysis revealed that achieving sustained DAS28 remission at months 6, 9, and 12 and a shorter disease duration were independent explanatory variables associated with less progression of PWV. CONCLUSION: With limited access to biologic disease-modifying antirheumatic drugs, treatment efforts toward DAS28 and SDAI remission had similar effects in preventing the progression of arterial stiffness at 1 year. However, achieving sustained DAS28 remission was associated with a significantly greater improvement in PWV. [Clinical Trial registration: Clinicaltrial.gov NCT01768923.].

Analysis of anti-melanoma differentiation-associated gene 5 antibody in Hong Kong Chinese patients with idiopathic inflammatory myopathies: diagnostic utility and clinical correlations.

AIM: To compare the prevalence of the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) in Hong Kong Chinese patients with dermatomyositis (DM) and polymyositis (PM); in addition, to examine the association of anti-MDA5 Ab and the clinical characteristics of these patients. METHODS: Twenty consecutive existing patients with DM being followed up at the Rheumatology Clinic of Kwong Wah Hospital, Hong Kong were recruited. Twenty patients with PM were recruited from the same clinic as the controls. A commercial line blot immunoassay was used to detect the anti-MDA5 Ab in all the participants. The frequencies of anti-MDA-5 Ab in the two groups were compared. The clinical characteristics of the patients with and without the antibody were analyzed. RESULTS: Anti-MDA5 Ab was found in 30% of patients with DM but not in patients with PM. All patients with the antibody exhibited the clinically amyopathic DM (CADM) phenotype. These patients were predominantly male, younger and with shorter disease duration. Anti-MDA5 Ab was significantly associated with rapidly progressive interstitial lung disease (RP-ILD) and digital ulcers. No statistically significant association was found between other disease or treatment variables and the antibody. CONCLUSION: Anti-MDA5 Ab is found exclusively in DM patients of the CADM subtype and is associated with RP-ILD and digital ulcers, suggesting that examination of this antibody is clinically useful in Hong Kong Chinese patients with idiopathic inflammatory myopathies. However, further studies are required to assess its prognostic significance, and to explore the difference of its presentations in various populations.

Local steroid injection versus wrist splinting for carpal tunnel syndrome: A randomized clinical trial.

AIM: We conducted a prospective randomized parallel clinical trial comparing the efficacy of local steroid injection and nocturnal wrist splinting in patients with carpal tunnel syndrome (CTS). METHODS: The well-validated and disease-specific Boston Carpal Tunnel Questionnaire (BCTQ) was employed and its score at 4 weeks after treatment was used as the primary outcome measure. Important secondary outcomes included patient satisfaction, the change of an objective finger dexterity test and the side effects. RESULTS: Twenty-five patients in the local steroid group and 25 patients in the wrist splinting group completed the study procedures. At 4 weeks after treatment, there was significant improvement of the BTCQ scores in both the steroid group and splinting group. There was improvement of the finger dexterity test only in the steroid group but not in the splinting group. However, there was no statistically significant difference in the changes of BTCQ scores between the two groups after treatment. Patient satisfaction score was higher in the steroid group. Patients in the steroid group took fewer painkillers after treatment. Four patients developed side effects after splinting and three after local steroid injection, which was not statistically significant. CONCLUSION: Although local steroid injection and nocturnal wrist splinting were equally effective in the treatment of patients with CTS, only the former improved objective hand function. Local steroid injection also resulted in better patient satisfaction and less painkiller use without causing more side effects.

Increased prevalence of coronary plaque in patients with psoriatic arthritis without prior diagnosis of coronary artery disease.

OBJECTIVES: To evaluate coronary atherosclerosis in patients with psoriatic arthritis (PsA) and control subjects using coronary CT angiography (CCTA). METHODS: Ninety consecutive patients with PsA (male: 56(62.2%); 50.3±11.1 years) were recruited. 240 controls (male: 137(57.1%); 49.6±10.7 years) without known cardiovascular (CV) diseases who underwent CCTA due to chest pain and/or multiple CV risk factors were recruited for comparison. RESULTS: Patients with PsA and controls were matched in age, gender and traditional CV risk factors (all p>0.2). The prevalence of overall plaque (54(60%)/84(35%), p<0.001), calcified plaque (CP) (29(32%)/40(17%), p=0.002), mixed plaque (MP) (20(22%)/18(8%), p<0.001), non-calcified plaque (NCP) (39(43%)/53(22%), p<0.001) and combined MP/NCP (46(51%)/62(26%), p<0.001) were all significantly higher in patients with PsA. Three-vessel disease was diagnosed in 12(13%) patients with PsA and 7(3%) controls (p<0.001), while obstructive plaques (>50% stenosis) were observed in 8(9%) patients with PsA and 7(3%) controls (p=0.033). After adjusting for traditional CV risk factors, PsA remained an independent explanatory variable for all types of coronary plaques (OR: 2.730 to 4.064, all p<0.001). PsA was also an independent explanatory variable for three-vessel disease (OR: 10.798, p<0.001) and obstructive plaque (3.939, p=0.024). In patients with PsA, disease duration was the only disease-specific characteristic associated with more vulnerable plaques (MP/NCP) in multivariate analysis (1.063, p=0.031). The other independent explanatory variables were age ≥55 years (5.636, p=0.005) and male gender (8.197, p=0.001). CONCLUSIONS: Patients with PsA have increased prevalence, burden and severity of coronary atherosclerosis as documented by CCTA. Longer disease duration was independently associated with the presence of vulnerable MP/NCP plaques in patients with PsA. TRIAL REGISTRATION NUMBER: NCT02232321.

Hong Kong Chinese adults' knowledge of exercise recommendations and attitudes towards exercise.

BACKGROUND: Physical inactivity is known to be one of the major risk factors for many chronic conditions. AIM: To determine Hong Kong Chinese adults' physical activity (PA) knowledge, its relationship with certain variables including sex, education, age, and its correlation with different types of chronic diseases, such as heart disease, cerebrovascular disease, diabetes mellitus, obesity, and others. The Hong Kong Chinese adults' general attitudes towards PA will also be examined. DESIGN & SETTING: Cross-sectional study in one primary care centre. METHOD: A randomized sample of Chinese adults aged >18 years with anonymous self-administered questionnaires. RESULTS: The mean percentage of correct responses for exercise guidelines was 62.3%, 84.5% for traditional PA, and 48.4% for lifestyle PA, respectively. Traditional PA refers to exercises which use large muscle groups. Lifestyle PAs include activities which can be done throughout the day. The total mean percentage of correct responses was 67% (knowledge score 13.4 +/- 3.34). There were no significant differences between PA knowledge and sex, education levels, age groups, and presence of chronic diseases (P>0.05), but the knowledge level for lifestyle PA was less than that of traditional PA (P<0.001). A weak correlation was found between responders' activeness for a health benefit and the PA knowledge levels (P>0.05). Two hundred and sixy-six (93.3%) responders reported a willingness to maintain or start exercise. CONCLUSION: The results suggest a need for more education about the latest PA recommendations, especially lifestyle PA. The weak correlation between PA knowledge and actual behaviour showed that PA knowledge itself might not affect PA behaviour. The enhancement of the general public's knowledge, motivation, and psychosocial support along with stage-of-change interventions and the provision of counselling skills may result in PA behaviour change, which in turn can lead to the achievement of health benefits.

Cutting edge: Endoplasmic reticulum stress licenses macrophages to produce mature IL-1ß in response to TLR4 stimulation through a caspase-8- and TRIF-dependent pathway.

The accumulation of improperly folded proteins within the endoplasmic reticulum (ER) generates perturbations known as ER stress that engage the unfolded protein response. ER stress is involved in many inflammatory pathologies that are also associated with the production of the proinflammatory cytokine IL-1ß. In this study, we demonstrate that macrophages undergoing ER stress are able to drive the production and processing of pro-IL-1ß in response to LPS stimulation in vitro. Interestingly, the classical NLRP3 inflammasome is dispensable, because maturation of pro-IL-1ß occurs normally in the absence of the adaptor protein ASC. In contrast, processing of pro-IL-1ß is fully dependent on caspase-8. Intriguingly, we found that neither the unfolded protein response transcription factors XBP1 and CHOP nor the TLR4 adaptor molecule MyD88 is necessary for caspase-8 activation. Instead, both caspase activation and IL-1ß production require the alternative TLR4 adaptor TRIF. This pathway may contribute to IL-1-driven tissue pathology in certain disease settings.