Ying-Ying Leung

Cardiovascular risk profile of patients with psoriatic arthritis compared to controls—the role of inflammation

OBJECTIVE To examine the distribution of traditional and novel risk factors of cardiovascular disease (CVD) in patients with PsA compared with healthy controls. METHODS We compared risk factors for CVD between 102 consecutive PsA patients and 82 controls, adjusting for BMI. We also assessed the role of inflammation on the CVD risk factor by using a BMI and high-sensitivity CRP (hsCRP)-adjusted model. RESULTS The BMI of PsA patients were significantly higher than healthy controls. After adjusting for the BMI, PsA patients still have a higher prevalence of diabetes mellitus (DM) [odds ratio (OR) 9.27, 95% CI 2.09, 41.09) and hypertension (OR 3.37, 95% CI 1.68, 6.72), but a lower prevalence of low high density lipoprotein (HDL) cholesterol (OR 0.16, 95% CI 0.07, 0.41). PsA patients have significantly increased systolic and diastolic blood pressures, insulin resistance and inflammatory markers (hsCRP and white cell count) compared to controls. PsA patients have higher HDL cholesterol and apolipoprotein (Apo) A1 levels; and lower total cholesterol (TC) and low density lipoprotein cholesterol levels; and a lower TC/HDL ratio. However, the Apo B level (P < 0.05), and the Apo B/Apo A1 ratio (P = 0.07) were higher in PsA patients. Further adjustment for hsCRP level rendered the differences in the prevalence of hypertension and DM; the TC, and sugar levels; and white cell count non-significant between the two groups; while the differences in other parameters remained significant. CONCLUSION These data support the hypothesis that PsA may be associated with obesity, hypertension, dyslipidaemia and insulin resistance because of the shared inflammatory pathway.

Colchicine—Update on mechanisms of action and therapeutic uses

OBJECTIVES To review the literature and provide an update on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. METHODS We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. RESULTS The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and familial Mediterranean fever, to osteoarthritis, pericarditis, and atherosclerosis. CONCLUSION Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions.

Is combination rituximab with cyclophosphamide better than rituximab alone in the treatment of lupus nephritis

OBJECTIVE To assess if combination rituximab and cyclophosphamide is more effective than rituximab monotherapy as an induction therapy for proliferative lupus nephritis. METHODS A randomized open-label pilot study in which 9 patients received rituximab alone and 10 patients received two doses rituximab + intravenous cyclophosphamide. The clinical, laboratory and renal histological changes were assessed after 48 weeks of treatment. RESULTS At week 48, four patients had a complete response, 11 patients achieved partial response, 2 patients remained the same or stable and 2 worsened. There were no statistical differences in the proportion of patients with complete or partial response between the two groups. None of the variables was an independent predictor of response at week 48. Nine patients had significant improvement in activity indices in renal biopsies, but there were no significant differences between the two groups. Overall, 18 out of 19 patients were found to have effective B-cell depletion. The median duration of complete B-cell depletion in all patients was 22 weeks. There were no statistically significant differences in the proportion of patients with complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2. CONCLUSIONS Rituximab monotherapy appears to be effective as induction therapy in lupus nephritis. The addition of cyclophosphamide offers no additional improvement in clinical, laboratory and renal histological assessment or the duration of B-cell depletion at 48 weeks. Large-scale studies with longer duration are needed to confirm these findings.

Socioeconomic burden of psoriatic arthritis in Hong Kong: direct and indirect costs and the influence of disease pattern.

Objective. To estimate the direct costs and indirect costs of patients with psoriatic arthritis (PsA) in Hong Kong. Methods. A retrospective cost-of-illness study was performed on 125 patients with PsA. Participants completed questionnaires on demographics, employment status, and out of pocket expenses. Health resources consumption was recorded by chart review and patient self-report questionnaire. Patients were grouped according to disease pattern, i.e., peripheral and axial disease. Multiple regression was used to determine the predictors of the costs. Results. The average annual direct costs were

Tumour necrosis factor alpha blockade is associated with sustained regression of carotid intima-media thickness for patients with active psoriatic arthritis: a 2-year pilot study

4,141 (2006 US dollars) per patient. Costs of inpatient care accounted for 27% of direct costs, followed by costs of visits to healthcare providers (25%). The estimated average indirect costs were

Infliximab is associated with improvement in arterial stiffness in patients with early rheumatoid arthritis -- a randomized trial.

3,127 per patient-year. Forty-eight (42%) patients had no indirect costs. Sixty percent of patients with peripheral disease were still employed, compared to 39% of patients with axial disease. Patients with axial disease had almost twice the indirect costs compared to those with peripheral disease (p = 0.005). Increased pain and poor function were independently associated with increased direct costs. Worse physical health status, determined by indirect costs borne by the patient, and poor function and old age predicted high costs. Conclusion. PsA imposes substantial economic burden. Pain and function are significantly associated with costs. Improvements in treatments to reduce pain and restore function are likely to reduce the costs incurred by these patients.

Psoriatic arthritis in Asia

We have reported that psoriatic arthritis (PsA) patients without overt cardiovascular diseases have evidence of premature atherosclerosis as indicated by an increased carotid intima-media thickness (IMT).1 Whether an increase in IMT reflects current (but reversible) inflammation of the vessel wall rather than more permanent structural vessel changes in PsA has never been assessed. We undertook a prospective, observational study to determine whether a 12-week treatment of tumour necrosis factor alpha (TNFα) blockers may reduce IMT in patients with active PsA, and whether the changes in IMT can be sustained in patients who were continued on long-term TNFα blockers. Twenty consecutive PsA patients with active disease were recruited to receive TNFα blockers. After 12 weeks, nine patients continued (group 1) while 11 patients discontinued TNFα blockers due to financial constraints (group 2). Twenty PsA patients who were naive to TNFα blockers were recruited as controls (group 3). Patients …

Testing scaling assumptions, reliability and validity of medical outcomes study short-form 36 health survey in psoriatic arthritis

Objective. To determine the efficacy of methotrexate (MTX) with infliximab (IFX) compared with MTX alone in the prevention of atherosclerosis and arterial stiffness in patients with early rheumatoid arthritis (RA). Methods. A randomized, open-label study in which early RA patients with active disease were treated with MTX alone (n = 20) and MTX plus IFX (n = 20) for 6 months. Patients were assessed every 3 months. Patients from the MTX-alone group who failed to achieve 28-joint Disease Activity Score remission (DAS28 ≤ 2.6) at 6 months were permitted to escape to open-label IFX. Intima-media thickness (IMT), pulse wave velocity (PWV), and augmentation index (AIx) were measured at baseline, 6 months, and 12 months. Results. At 6 months, there was a significantly greater reduction in PWV in the MTX-alone group (0.18 ± 1.59 m/s) compared with the MTX plus IFX group (−0.78 ± 1.13 m/s; p = 0.044), accompanied by significantly greater reduction in patient’s global assessment, number of swollen joints, C-reactive protein, and DAS28 in the MTX plus IFX group compared to the MTX-alone group. The changes in IMT and AIx were similar between the 2 groups. At 12 months, there was a trend favoring early combination treatment with regard to the reduction in PWV (p = 0.06). Conclusion. MTX plus IFX causes a more significant reduction in PWV than MTX alone in patients with early RA after 6-month treatment, and further improvement may be achieved in patients who continued on longterm tumor necrosis factor-α blockers, suggesting that early, effective suppression of inflammation may prevent progression of atherosclerosis by improving vascular function.

Psoriatic arthritis as a distinct disease entity

Geographic or ethnic differences in the occurrence of disease often provide insights into causes of disease and possible opportunities for disease prevention. A wide variation on the incidence and prevalence of PsA was reported in different countries. The prevalence in China was similar to the rest of the world, whereas the incidence and prevalence of PsA was much lower in Japan. Among patients with psoriasis, 6-42% of the Caucasians were reported to have PsA, but figures were lower from Asian countries (1-9%). Divergent distribution of HLA in different ethnic groups and other genetic determinants may account for these differences in prevalence. PsA affects men and women almost equally in Chinese, Japanese and Iranians, which is similar to their Caucasian counterparts. Polyarthritis developing in the fourth decade was the commonest pattern of arthritis among Chinese, Indians, Iranians, Kuwaiti Arabs and Malays. Arthritis mutilans and eye lesions have rarely been reported in Asian countries. Chinese patients with nail disease and DIP joints involvement have a significantly higher risk of developing deformed joints. More data are required on the safety, efficacy and cost effectiveness of TNF blockers for the treatment of PsA in Asia. Premature atherosclerosis has been recognized as an important co-morbidity in Asian patients with PsA. Increased prevalence of traditional cardiovascular risk factors associated with PsA suggested that the two conditions may share the same inflammatory pathway. Carotid intima-media thickness can identify PsA patients with subclinical atherosclerosis who may benefit from early intervention.

Measuring Disease Activity in Psoriatic Arthritis

OBJECTIVES The Medical Outcome Survey short-form 36 (SF-36) is widely used in studies of PsA. We test the fundamental scaling assumptions for the validity of SF-36 eight scales and two summary scores in PsA. METHODS We tested the five scaling criteria according to the International Quality of Life Assessment project and the validity of the physical component summary (PCS) and mental component summary (MCS) scores. The construct validity for SF-36 in PsA was evaluated. RESULTS A total of 168 PsA subjects according to CASPAR criteria (46.4% females) with SF-36 data were analysed. The mean (S.D.) age and duration of illness were 47.7 (11.9) and 8.4 (7.3) years. PsA subjects had poorer quality of life as compared with normal population. The norm-based mean (S.D.) PCS and MCS were 31.6 (14.2) and 45.2 (12.7), respectively. The Pearsons correlations between an item and its hypothesized scale were all >0.4, indicating item internal consistency. All item-own scale correlations exceed item-other scale correlations, except minor scaling failure in general health. The Cronbachs alpha-coefficients of internal reliability (Cronbachs alpha) were all above the standard value of 0.7, indicating a unique concept in each scale. Principal component analysis explained 69.4 and 73.7-99.9% of the total variance and total reliable variance in all SF-36 scales. The two-factor model is supported. CONCLUSIONS PsA had high impact on quality of life. All eight scales and two summary scores of SF-36 satisfied criteria for scaling assumption. SF-36 is a valid measurement for quality of life in PsA. The reporting of PCS and MCS in PsA is supported.