A single-centre experience of febuxostat as a second-line urate-lowering therapy.

INTRODUCTION: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate-lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease. METHODS: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 µmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals. RESULTS: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported. CONCLUSION: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.

A single-centre experience of febuxostat as a second-line urate-lowering therapy

@#Introduction: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease. Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals. Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported. Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.

Atypical case of diffuse idiopathic skeletal hyperostosis mimicking ankylosing spondylitis in a young woman with polycystic ovary syndrome

@#Both diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis present with similar clinical manifestations of restricted spinal mobility and postural abnormalities, and radiographic resemblances including axial spine involvement and enthesopathy. Nonetheless, they are two entirely different diseases. We report an unusual case of DISH in a young woman whose diagnosis was established based on radiologic features. This case report aims to highlight the under-recognised radiologic aspects of the differential diagnosis between DISH and AS in order to avoid an inaccurate diagnosis.

Vitamin D status in a monocentric cohort of systemic lupus erythematosus (SLE) patients and correlations with clinical and immunological profile

@#Introduction: Numerous studies have found that a majority of systemic lupus erythematosus (SLE) patients have suboptimal vitamin D levels. The major contributory factor is most likely attributed to sun protection measures in order to avoid SLE flares. The objectives of this research included the assessment of vitamin D status and its association with clinical manifestations of SLE, cardiovascular risk factors, autoantibodies, SLE disease activity and damage accrual. Method: This retrospective study involved SLE patients who attended the Rheumatology Clinic at the Hospital Kuala Lumpur from January 2014 to December 2016. Vitamin D was categorised as normal, insufficient or deficient, and the clinical variables were compared across vitamin D categories with chi-squared tests and Pearson correlation coefficient. Results: We included 216 patients. The mean 25(OH)D concentration was 51.3(Standard Deviation; SD 14.8) nmol/L. Fifty (23.1%) patients had vitamin D deficiency, 120 (55.6%) had vitamin D insufficiency, while 46 (21.3%) had adequate vitamin D levels. There were statistically significant associations between vitamin D status and ethnic group, lupus nephritis and hypertension. No correlations were observed between vitamin D status with SLEDAI score (Pearson correlation coefficient -0.015, p=0.829) as well as SDI score (Pearson correlation coefficient -0.017, p=0.801). Conclusion: SLE patients should be screened for vitamin D concentrations and their levels optimised.

Evaluation of creatine kinase and liver enzymes in identification of severe dengue.

BACKGROUND: Existing biomarkers such as AST, ALT and hematocrit have been associated with severe dengue but evidence are mixed. Recently, interests in creatine kinase as a dengue biomarker have risen. These biomarkers represent several underlying pathophysiological processes in dengue. Hence, we aimed to assess AST, ALT, CK and hematocrit in identification of severe dengue and to assess the correlational relationship amongst common biomarkers of dengue. METHODS: This was a retrospective cohort study of confirmed dengue patients who were warded in Kuala Lumpur Hospital between December 2014 and January 2015. CK, AST, ALT, hematocrit, platelet count, WBC and serum albumin were taken upon ward admission and repeated at timed intervals. Composite indices based on admission AST and ALT were analyzed. Correlation coefficients and coefficients of determination were computed. RESULTS: Among the 365 cases reviewed, twenty-two (6%) patients had severe dengue. AST and ALT were found to be good at identification of severe dengue. The AST2/ALT composite index was the most accurate (AUC 0.83; 95% CI 0.73 - 0.93). Optimal cutoff was 402 with a sensitivity of 59.1% (95% CI: 36.4 - 79.3%) and specificity of 92.4% (95% CI: 89.1 - 95.0%). Modified cutoff of 653 had a sensitivity of 40.9% (95% CI: 20.7 - 63.7%) and specificity of 97.4% (95% CI: 95.1 - 98.8%). Our analyses also suggested that several underlying biological processes represented by biomarkers tested were unrelated despite occurring in the same disease entity. Also, markers of plasma leakage were discordant and AST was likely hepatic in origin. CONCLUSIONS: The composite index AST2/ALT may be used as a marker for identification of severe dengue based on admission AST and ALT, with two choices of cutoff values, 402 and 653. AST is most likely of liver origin and CK does not provide additional value.

Hydroxychloroquine-related retinal toxicity.

HCQ is widely used for the treatment of rheumatic diseases, particularly lupus and RA. It is generally well tolerated, but retinopathy is a concern. Retinopathy is rare, but is sight threatening, generally irreversible and may progress even after cessation of therapy. Damage may be subclinical. Although a number of risk factors have been proposed (such as duration of therapy and cumulative dose), the many exceptions (e.g. retinopathy on low-dose HCQ, or no retinopathy after a very large cumulative dose of HCQ) highlight our limited understanding of the disease process. Novel technologies such as optical coherence tomography (OCT), fundus autofluorescence (FAF) and multifocal electroretinogram (mfERG) may provide the earliest structural and functional evidence of toxicity in these stages. Along with the well-established technique of central visual field testing (10-2 visual fields), these modalities are increasingly being used as part of screening programmes. The ideal single test with high sensitivity and high specificity for HCQ retinopathy has still not been achieved. Screening for HCQ retinopathy remains an area of considerable debate, including issues of when, who and how to screen. Commonly accepted risk factors include receiving >6.5 mg/kg/day or a cumulative dose of >1000 g of HCQ, being on treatment for >5 years, having renal or liver dysfunction, having pre-existing retinopathy and being elderly. HCQ continues to be a valuable drug in treating rheumatic disease, but clinicians need to be aware of the associated risks and to have arrangements in place that would enable early detection of toxicity.

New biologic therapy for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogenous multi-systemic autoimmune disease that is associated with considerable morbidity and mortality. Rituximab is one of the earliest biologic therapies used in SLE. It performed well in off-label studies but failed to demonstrate efficacy in randomised controlled trials. Abatacept is a biologic developed for inflammatory arthritis but has shown promise in SLE. Belimumab is the first biologically approved therapy in fifty years for treatment of SLE. The development of biological therapies for SLE parallels the increasing understanding of the immunopathogenesis of SLE and looks promising. New drugs in development are those targeting the co-stimulatory modulation, cytokines and the B and T cells. Of interest are epratuzumab, the interferon antagonists and peptide-based therapies.