Chi Hung To

Prevalence of atherosclerotic risk factors and the metabolic syndrome in patients with chronic inflammatory arthritis

To evaluate the prevalence of the metabolic syndrome in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA).

Immunogenicity and safety of a quadrivalent human papillomavirus vaccine in patients with systemic lupus erythematosus: a case–control study

Objectives To evaluate the immunogenicity and safety of GARDASIL, a quadrivalent human papillomavirus (HPV) vaccine, in patients with systemic lupus erythematosus (SLE). Methods Women with SLE aged 18–35 years who had stable disease were recruited to receive GARDASIL vaccination and an equal number of age-matched healthy women were also vaccinated. Seroconversion rates of antibodies to HPV serotypes 6, 11, 16 and 18 at months 7 and 12 and adverse events (AEs) were compared between patients and controls. The rate of disease flares in SLE participants was compared with matched SLE controls. Results 50 patients with SLE and 50 healthy controls were studied. The mean age and disease duration of the patients was 25.8±3.9 years and 6.6±4.5 years, respectively. At month 12 the seroconversion rates of anti-HPV serotypes 6, 11, 16 and 18 in patients and controls were 82%, 89%, 95%, 76% and 98%, 98%, 98%, 80%, respectively. In patients with SLE there were no significant changes in the titres of anti-dsDNA, complements, anti-C1q and SLE Disease Activity Index scores from baseline to months 2, 7 and 12. There was one mild/moderate SLE flare at months 0–2, two mild/moderate flares at months 3–6 and six mild/moderate and two severe flares at months 7–12. Disease flares in patients with SLE occurred at a similar frequency to that of 50 matched SLE controls (0.22/patient/year vs 0.20/patient/year, p=0.81). Injection site reaction was the commonest AE (5%), and the incidence of AEs was comparable between patients with SLE and controls. Conclusions The quadrivalent HPV vaccine is well tolerated and reasonably effective in patients with stable SLE and does not induce an increase in lupus activity or flares.

Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up

Objective To compare the efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) for the initial therapy of lupus nephritis (LN). Study design This is an open randomised controlled parallel group study. Methods Adult patients with biopsy-confirmed active LN (class III/IV/V) were randomised to receive prednisolone (0.6 mg/kg/day for 6 weeks and tapered) in combination with either TAC (0.06–0.1 mg/kg/day) or MMF (2–3 g/day) for 6 months. Good responders were shifted to azathioprine for maintenance. The primary outcome was the rate of complete renal response (CR) at 6 months and the secondary outcomes included partial renal response, renal flares and decline of renal function over time. Results 150 patients (92% women; aged 35.5±12.8 years; 81% class III/IV) were randomised (76 MMF, 74 TAC). At month 6, the rate of CR was 59% in the MMF and 62% in the TAC group (treatment difference: 3.0% (−12%, 18%); p=0.71). Major infective episodes occurred in 9.2% patients treated with MMF and in 5.4% patients treated with TAC (p=0.53). Maintenance therapy with azathioprine was given to 79% patients. After 60.8±26 months, proteinuric and nephritic renal flares developed in 24% and 18% of patients in the MMF group and 35% (p=0.12) and 27% (p=0.21) in the TAC group, respectively. The cumulative incidence of a composite outcome of decline of creatinine clearance by ≥30%, development of chronic kidney disease stage 4/5 or death was 21% in the MMF and 22% in the TAC group of patients (p=0.35). Conclusions TAC is non-inferior to MMF, when combined with prednisolone, for induction therapy of active LN. With azathioprine maintenance for 5 years, a non-significant trend of higher incidence of renal flares and renal function decline is observed with the TAC regimen. Trial registration number Hospital Authority Research Ethics Committee Clinical Trial Registry (HARECCTR0500018; Hong Kong) and US ClinicalTrials.gov (NCT00371319).

Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis

The objective of this study was to evaluate the patterns of clinical manifestations and their mortality in a large cohort of Chinese patients with systemic lupus erythematosus. The cumulative clinical manifestations of a large group of Chinese systemic lupus erythematosus patients who fulfilled at least four American College of Rheumatology criteria for systemic lupus erythematosus were studied. Patients were divided into distinct groups by using the K-mean cluster analysis. Clinical features, prevalence of proliferative lupus nephritis (World Health Organization class III, IV), autoantibody profile, and treatment data were compared and the standardized mortality ratios were calculated for each cluster of patients. There were 1082 patients included in the study (mean age at systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus erythematosus duration 10.3 years). Three distinct groups of patients were identified. Cluster 1 (n = 347) was characterized predominantly by mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having the lowest prevalence of serositis, hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and proliferative lupus nephritis. Patients in cluster 2 (n = 409) had mainly renal and hematological manifestations but having the lowest prevalence of mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were significantly more frequent in cluster 2 than the other clusters. Cluster 3 patients (n = 326) had the most heterogeneous features. Besides having a high prevalence of mucocutaneous manifestations, serositis and hematologic manifestations, renal involvement, and proliferative lupus nephritis was also most prevalent among the three clusters. Patients in cluster 2 had a much higher standardized mortality ratio [standardized mortality ratio 7.23 (6.7—7.7), p < 0.001] than those in cluster 3 [standardized mortality ratio 1.27 (1.1—1.5), p = 0.005] and cluster 1 [standardized mortality ratio 0.95 (0.5—1.7), p = 0.86]. In conclusion, patients with systemic lupus erythematosus could be clustered into prognostically distinct patterns of clinical manifestations. Lupus (2009) 18, 1267—1275.

Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial

Objectives To study the efficacy of raloxifene in preventing bone mineral density (BMD) loss in women receiving long-term glucocorticoids (GC). The study took the form of a parallel-group randomised double-blinded placebo-controlled trial. Methods Postmenopausal women without hypercoagulability risk factors who were prevalent GC users were randomised to receive either raloxifene (60 mg/day) or placebo (1 tablet/day) on top of calcium (1000 mg/day) and calcitriol (0.25 μg/day). BMD of the hip and spine (primary outcome), bone turnover markers and new vertebral fractures (secondary outcomes) at month 12 were assessed. Results Between December 2006 and December 2008, 114 patients were recruited (age 55.3±7.7 years). The duration and dose of prednisolone received was 62.2±64 months and 6.7±5.9 mg/day, respectively. Baseline vertebral fracture was present in six (5%) patients. In all, 57 patients were allocated to each of the treatment arms. Demographic data, osteoporotic risk factors and BMD at various sites were similar between the two groups of patients. At month 12, a significant gain in the lumbar spine (+1.3±0.4%; p=0.004) and total hip BMD (+1.0±0.4%; p=0.01) was observed in patients treated with raloxifene but a significant decrease in BMD of the lumbar spine (−0.9±0.4%; p=0.045) and hip (−0.8±0.3%; p=0.01) occurred in the placebo group. The femoral neck BMD did not change significantly in favour of raloxifene. Three new fractures developed exclusively in the patients treated with placebo. Bone formation (serum osteocalcin and procollagen type I N-terminal) and resorption (urine deoxypyridinoline and type I collagen) markers decreased significantly in the raloxifene group but not in patients treated with placebo. Leg cramps were numerically more frequent in the raloxifene group (7% vs 0%) but thromboembolism was not reported in any patients. Conclusions In postmenopausal women receiving long-term GCs, raloxifene is well tolerated and significantly increases spinal and hip BMD after 12 months of treatment.

Risk and predictors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis: a comparative study.

We conducted the current study to compare the incidence and risk factors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis. We identified patients in whom lupus nephritis and non-lupus primary glomerulonephritis were diagnosed between 1993 and 2003 using our lupus cohort database and pathology registry. We analyzed the cumulative incidence of new arterial thromboembolic events since diagnosis by Kaplan-Meier plot, and studied risk factors by multivariate analysis. We studied 162 patients with lupus and 181 patients with non-lupus primary glomerulonephritis. After a mean observation of 8.1 years, 47 (14%) patients died, 23 (7%) were lost to follow-up, and 38 (11%) developed 42 arterial events (incidence, 15.1/1000 patient-years). Although patients with lupus nephritis were younger and had a significantly lower frequency of smoking, hypertension, obesity, and renal dysfunction, their cumulative risk of arterial event at 5 years was not significantly lower than that of patients with primary non-lupus glomerulonephritis (6.3% vs. 6.6%, p = 0.96). In a Cox regression model, lupus was found to be an independent risk factor for arterial thrombosis (hazard ratio 3.57 [1.07-11.9]; p = 0.04), in addition to increasing age (hazard ratio 1.04 per year; p = 0.02), low-density lipoprotein ≥2.6 mmol/L (hazard ratio 4.46; p = 0.002), and glomerular filtration rate <30 mL/min (hazard ratio 2.67; p = 0.04). We concluded that in immune-mediated glomerulonephritis, having systemic lupus increased the risk of arterial thromboembolism after adjustment for age, renal insufficiency, and other traditional risk factors. Abbreviations: ACE = angiotensin-converting enzyme, ARB = angiotensin II-receptor blockers, AZA = azathioprine, CT = computed tomography, CYC = cyclophosphamide, GFR = glomerular filtration rate, HCQ = hydroxychloroquine, HIRS = Hospital Information Retrieval System, MMF = mycophenolate mofetil, MRI = magnetic resonance imaging, SLE = systemic lupus erythematosus, TIA = transient ischemic attack.

Prevalence of the antiphospholipid syndrome and its effect on survival in 679 Chinese patients with systemic lupus erythematosus: a cohort study.

AbstractIn this work we evaluate the prevalence of the antiphospholipid syndrome (APS) and its impact on survival in Chinese patients with systemic lupus erythematosus (SLE). We studied a prospective cohort of southern Chinese patients who fulfilled ≥4 American College of Rheumatology criteria for SLE. The cumulative rate of survival over time was calculated by the Kaplan-Meier method. APS was defined by the 2006 updated consensus criteria. We evaluated the prevalence and manifestations of APS, and compared the survival of patients with and without APS. We followed 679 patients with SLE (92% women; age of onset, 32.5 ± 14 yr) for 9.7 ± 7.3 years. Sixty-eight (10%) patients died and 33 (4.9%) patients were lost to follow-up. Forty-four (6.5%) patients met the criteria for APS, manifested by the following: ischemic stroke (55%), deep venous thrombosis (32%), obstetric morbidity (14%), cardiovascular events (9%), and peripheral vascular disease (9%). Nine (9/44 [20%]) APS patients died, which was more frequent than the non-APS patients (59/635 [9%]; p = 0.02). The cumulative mortality of patients with APS was 4.6% at 5 years, 7.8% at 10 years, and 22.2% at 15 years, which was not significantly higher than that of non-APS patients (5.4% at 5 years, 9.2% at 10 years, and 11.3% at 15 years; p = 0.14). However, if we considered only patients with APS caused by arterial thrombosis, the presence of APS was significantly associated with mortality (hazard ratio, 2.29; 95% confidence interval, 1.13–4.64; p = 0.02). We conclude that the presence of APS increases the mortality risk of Chinese patients with SLE, which is mainly contributed by arterial thrombotic events.Clinical significance: 1) APS is infrequent in southern Chinese patients with SLE compared to white patients. 2) Arterial thrombosis is a more common manifestation of APS than venous thrombosis in Chinese SLE patients. 3) APS related to arterial thrombosis is associated with increased mortality in Chinese patients with SLE.

Referral strategy for early recognition of axial spondyloarthritis: consensus recommendations from the Hong Kong Society of Rheumatology

Low back pain is one of commonest problems prompting a visit to the family physician. Up to 5% of patients with chronic low back pain in the primary care setting are diagnosed as having spondyloarthritis, which includes the prototype disease ankylosing spondylitis. Making a diagnosis of ankylosing spondylitis is often delayed for years, leading to significant pain, impairment of quality of life, disability and productivity loss. A recent breakthrough in the treatment of spondyloarthritis is the anti‐tumor necrosis factor‐alpha biologics, which lead to rapid relief of pain and inflammation, and improvement in all clinical parameters of the disease. Patients with early spondyloarthritis often respond better than those with late established disease. With proper recognition of inflammatory back pain, and the use of magnetic resonance imaging, spondyloarthritis can now be diagnosed much earlier before features are evident on plain radiographs. Referral to the rheumatologist based on onset of back pain (> 3 months) before the age of 45 years, and an inflammatory nature of the pain, or the presence of human leukocyte antigen‐B27, or sacroiliitis by imaging, have been confirmed in multi‐center international studies to be a pragmatic approach to enable early diagnosis of spondyloarthritis. This referral strategy has recently been adopted by the Hong Kong Society of Rheumatology for primary care physicians and non‐rheumatology specialists.

SAT0147 Serum levels of the anti-tnf biologics correlate with clinical efficacy in patients with inflammatory arthritis

Objectives To study the correlation between levels of the anti-TNF biologics and clinical efficacy in patients with inflammatory arthritis Methods Adult patients who fulfilled the criteria for rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PSA) and were commenced on standard doses of the anti-TNF biologics were recruited. Serum samples saved at baseline, month 6 and 12 were assayed for the trough levels of the biologics (± anti-drug antibodies) retrospectively. Patients were followed longitudinally and efficacy analyses were conducted at 3-month intervals without the knowledge of the drug levels. Biologics would be discontinued from 6 months onwards according to protocol-based improvement criteria for each disease. Clinical efficacy of the anti-TNF biologics was compared among patients with different levels of the drug by statistical methods. Results 112 patients were studied (58 RA, age 51.2±10.9 years, disease duration 72.9±67 months; 41 SpA, age 39.1±9.9 years, disease duration 74.3±81.6 months; 13 PSA, age 53.5±10.7 years, disease duration 44.3±35.4 years). The number of patients treated with infliximab (IFX), adalimumab (ADM), golimumab (GLM) and etanercept was 3, 31, 36 and 42, respectively. At month 12, neutralizing antibodies against IFX, ADM and GLM were present in 2 (67%), 14 (45%) and 1 (3%) of the patients, respectively. In ADM users, the drug level was significantly lower in those with antibodies than those without (1.81±2.63 vs 8.02±4.14 ug/ml; p<0.001). Antibody titer against ADM correlated negatively with the levels of ADM (Rho -0.72; p<0.001). Patients were stratified arbitrarily into 3 groups for each biologic according to the trough levels of the drugs. Low drug concentrations were defined as levels ≤1.30 ug/ml, 0.05 ug/ml and 0.60 ug/ml in ADM, ETN and GLM users, respectively. In patients with RA/PSA (N=71), patients with the lowest anti-TNF drug level group (N=30) had a non-significant trend of less improvement in DAS28, CDAI scores at month 12 when compared to others (N=41). However, significantly more patients withdrew treatment due to inefficacy at month 12 in this group compared to others (67% vs 7.3%, p<0.001). In patients with SpA (N=41), patients with lowest anti-TNF drug levels stratum (N=9) had significantly less improvement in ASDAS compared with others at month 12 (N=32) (-0.57±0.63 vs -1.93±1.28; p=0.003). The proportion of patients who achieved an ASAS20 response was also significantly lower in this group of patients (33% vs 75%; p=0.04). In all the 112 patients studied, the cumulative withdrawal rate of the anti-TNF biologics at month 12 (by Kaplan-Meiers analysis) was significantly higher in those with low drug levels when compared to others (26.1% vs 54.6%; p<0.001 by log rank test). Conclusions The presence of neutralizing antibodies to the anti-TNF monoclonals is associated with lower trough levels of the drugs. Trough level of the anti-TNF biologics is useful for optimizing the clinical efficacy of the drugs in patients with inflammatory arthritis. Disclosure of Interest None declared

THU0308 Use of Complementary and Alternative Medicine (CAM) in Chinese Patients with Rheumatic Diseases: Prevalence and Associated Demographic, Clinical and Social Factors

Objectives To study the frequency of use of complementary and alternative medicine (CAM) in Chinese patients with rheumatic diseases and the associated demographic, clinical and social factors. Methods A cross-sectional questionnaire study on the use of CAM was carried out in patients who attended the rheumatology clinics of Tuen Mun and Pok Oi Hospital between June and December 2014. Inclusion criteria: adult patients (≥18 years) with chronic autoimmune rheumatic diseases. Exclusion criteria: illiterate or mentally incapable. Basic demographic, psychosocial factors and clinical information were obtained by questionnaire completion and medical record review. The self-perceived control of the underlying disease process was assessed on a visual analog scale (0-100), with higher score being a more sense of disease remission. Missing information was clarified with phone contact of the participants by our research assistants. A multivariate logistic regression model was established to study the factors associated with the use of CAM. Results 1335 patients were studied (75% women, age 48.4±13 years). The underlying rheumatic diseases were: rheumatoid arthritis (RA) (N=642), systemic lupus erythematosus (SLE) (N=347), spondyloarthritis (SpA) (N=142), psoriatic arthritis (PSA) (N=91), systemic sclerosis (SSc) (N=39), inflammatory myopathies (N=14), systemic vasculitides (N=10) and miscellaneous rheumatic disorders (N=50). The mean disease duration was 9.7±8.4 years and the mean years of education in the participants was 10.4±2.9 years. 473 (35%) patients were single/divorced/widowed and 142 (11%) patients were receiving government subsidy for living (poverty). 400 (30%) patients had religious belief: Buddhism (46%), Christianity (43%). The self-perceived score of disease control was 64.8±23. CAM was ever used in 705 (53%) patients and the most common forms of CAM were: traditional Chinese medicine (TCM)(59%), acupuncture (44%), massage (24%), cupping (17%) and omega-3 fatty acid (15%). The proportions of patients with different underlying diseases who had ever used CAM were: SpA (64%), PSA (60%), SSc (59%), RA (54%), SLE (44%), systemic vasculitides (40%). Only 41% of these patients had informed medical staff about the use of CAM and 4% patients had altered the dosage of western medicine without advice from their attending rheumatologists. 505 (72%) patients found CAM somehow effective in alleviating their symptoms. Logistic regression analysis showed that the use of CAM was associated with the presence of religious belief (odds ratio [OR] 1.29 [1.00-1.67]; p=0.047), years of education (OR 1.08 [1.02-1.13]; p=0.005), disease duration (per year) (OR 1.02 [1.006-1.04]; p=0.005) and self-perceived score for disease control (per point) (OR 0.992 [0.99-0.997]; p=0.003). Age, sex, family income and marital status were not associated with the use of CAM. Conclusions The use of CAM is common in Chinese patients with rheumatic diseases, and may affect treatment adherence or aggravate the toxicities of existing therapies. Associated factors for CAM use are inflammatory arthritis, longer disease duration, higher educational background and a lower sense of perceived disease control. Better communication on the use of CAM should be made to our patients, particularly those who are more likely to adopt these measures. Disclosure of Interest None declared