A hierarchical cluster analysis for clinical profiling of tofacitinib treatment response in patients with rheumatoid arthritis.

Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA.

A summary of the Malaysian Clinical Practice Guidelines on the management of postmenopausal osteoporosis, 2022.

Objectives: The aim of these Clinical Practice Guidelines is to provide evidence-based recommendations to assist healthcare providers in the screening, diagnosis and management of patients with postmenopausal osteoporosis (OP). Methods: A list of key clinical questions on the assessment, diagnosis and treatment of OP was formulated. A literature search using the PubMed, Medline, Cochrane Databases of Systematic Reviews, and OVID electronic databases identified all relevant articles on OP based on the key clinical questions, from 2014 onwards, to update from the 2015 edition. The articles were graded using the SIGN50 format. For each statement, studies with the highest level of evidence were used to frame the recommendation. Results: This article summarizes the diagnostic and treatment pathways for postmenopausal OP. Risk stratification of patients with OP encompasses clinical risk factors, bone mineral density measurements and FRAX risk estimates. Non-pharmacological measures including adequate calcium and vitamin D, regular exercise and falls prevention are recommended. Pharmacological measures depend on patients' fracture risk status. Very high-risk individuals are recommended for treatment with an anabolic agent, if available, followed by an anti-resorptive agent. Alternatively, parenteral anti-resorptive agents can be used. High-risk individuals should be treated with anti-resorptive agents. In low-risk individuals, menopausal hormone replacement or selective estrogen receptor modulators can be used, if indicated. Patients should be assessed regularly to monitor treatment response and treatment adjusted, as appropriate. Conclusions: The pathways for the management of postmenopausal OP in Malaysia have been updated. Incorporation of fracture risk stratification can guide appropriate treatment.

Prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis.

INTRODUCTION: Psoriatic arthritis is a chronic, autoimmune inflammatory arthritis that occurs with psoriasis and has profound impact on patients' physical and psychological well-being. This study aims to determine the prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis. METHODS: A single-center, cross-sectional study was conducted over a 12-month period at the Dermatology Clinic, Hospital Pulau Pinang, Malaysia involving all consecutive psoriasis patients. CASPAR (ClASsification of Psoriatic ARthritis) criteria were used to diagnose psoriatic arthritis. RESULTS: A total of 360 patients with psoriasis were recruited, of whom 107 (29.7%) had psoriatic arthritis. Psoriatic arthritis patients had equal gender distribution and the mean age of arthritis onset was 40.7 ± 12.8 years. Psoriasis preceded arthritis in 81.3% of patients (n = 87) with a mean latency interval of 10.5 years. Polyarthropathy was the predominant subtype affecting 46.8% (n = 50) of patients, followed by oligoarthropathy (22.4%, n = 24), axial joint disease (5.6%, n = 6), predominant distal interphalangeal joint disease (2.8%, n = 3), and mixed subtype (22.4%, n = 24). Enthesitis and dactylitis occurred in 12.1% (n = 13) and 20.6% (n = 22) of arthritis patients, respectively, and deformity was present in 37.4% (n = 40). Psoriatic arthritis was significantly associated with being an ever smoker (adjusted odds ratio [aOR] 0.41; 95% confidence interval [CI] 0.18-0.91, p = .029), genital psoriasis (aOR 2.25; 95% CI 1.17-4.33, p = .015), and increased erythrocyte sedimentation rate (ESR) (aOR 1.02; 95% CI 1.01-1.04, p = .005) and C-reactive protein [CRP] (aOR 1.04; 95% CI 1.00-1.08, p = .040). CONCLUSION: Our study showed a high prevalence of psoriatic arthritis among the psoriasis cohort. Genital involvement, and increased ESR and CRP were associated with psoriatic arthritis among patients with psoriasis.

Clinicohistological and immunopathological features of patients with cutaneous lupus erythematosus at tertiary dermatology centre in Malaysia.

BACKGROUND: Cutaneous lupus erythematosus (CLE) is a chronic, autoimmune skin disease with a wide spectrum of clinical presentations in different populations. AIM: To study the clinicohistological and immunological features of CLE in a multiethnic population and to identify the predictive factors of disease severity based on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). METHODS: This was a cross-sectional study of CLE conducted from March 2019 to February 2020. RESULTS: In total, 111 patients were recruited with a female/male ratio of 4.9 : 1. Acute CLE contributed 47.7%, followed by chronic CLE at 46.9% and subacute CLE at 5.4%. A large majority (84%) of patients had systemic lupus erythematosus. Of patients with chronic CLE, about 67.3% developed systemic involvement. Antinuclear antibody (ANA) was detected in 90.0%. Skin biopsy was taken from 42 patients and showed perivascular lymphocytic infiltration (95.2%), epidermal atrophy (47.6%) and hydropic degeneration of the basal layer (47.6%). Immunoglobulin deposition at the dermoepidermal junction was seen in > 40% of patients, predominantly in a granular pattern. Mean CLASI Total was 6.44 ± 7.70, while CLASI Activity (CLASI-A) was 2.75 ± 4.10 and CLASI Damage (CLASI-D) was 3.71 ± 4.76. Involved body surface area (BSA) was found to be an independent predictive factor for CLASI-A (OR = 1.34, P < 0.02). For CLASI-D, positive predictive factors were involved BSA (OR = 4.14, P < 0.001), discoid lupus erythematosus subtype (OR = 13.10, P = 0.001), cutaneous vascular disease (OR = 26.59; P = 0.014), scalp involvement (OR = 8.7, P < 0.01) and hypocomplementaemia (OR = 5.71, P < 0.5). Mean Dermatology Life Quality Index was 5.91 ± 5.34 and correlated significantly with disease severity. CONCLUSIONS: We observed a high percentage of patients with CLE with systemic manifestations and positive ANA result. More aggressive treatment of patients with positive predictive factors for severe disease combined with significant clinical activity may be warranted.

2021 Asia-Pacific League of Associations for Rheumatology clinical practice guideline for treatment of gout.

BACKGROUND: Gout is the most prevalent inflammatory arthritis in the Asia-Pacific region and worldwide. This clinical practice guideline (CPG) aims to provide recommendations based on systematically obtained evidence and values and preferences tailored to the unique needs of patients with gout and hyperuricemia in Asia, Australasia, and the Middle East. The target users of these guidelines are general practitioners and specialists, including rheumatologists, in these regions. METHODS: Relevant clinical questions were formulated by the Steering Committee. Systematic reviews of evidence were done, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation methodology. A multi-sectoral consensus panel formulated the final recommendations. RESULTS: The Asia-Pacific League of Associations for Rheumatology Task Force developed this CPG for treatment of gout with 3 overarching principles and 22 recommendation statements that covered the treatment of asymptomatic hyperuricemia (2 statements), treatment of acute gout (4 statements), prophylaxis against gout flare when initiating urate-lowering therapy (3 statements), urate-lowering therapy (3 statements), treatment of chronic tophaceous gout (2 statements), treatment of complicated gout and non-responders (2 statements), treatment of gout with moderate to severe renal impairment (1 statement), and non-pharmacologic interventions (5 statements). CONCLUSION: Recommendations for clinically relevant scenarios in the management of gout were formulated to guide physicians in administering individualized care.

Real-world clinical experience of biological disease modifying anti-rheumatic drugs in Malaysia rheumatoid arthritis patients.

The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p < 0.001). Overall, 16.9% achieved DAS28 remission at 6 months. A third (35.6%) of patients reported adverse events, three commonest being infections (46.5%), allergy (22.9%) and laboratory abnormalities (12.9%). 3.7% of our patients had tuberculosis. Biologic DMARDs were effective in treating RA in real-world practice in Malaysia, despite a lower remission rate compared to developed countries. Except for higher rates of tuberculosis, the AEs were similar to the published reports.

Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

Takayasu Arteritis in Major Rheumatology Centers in Malaysia.

OBJECTIVE: There is paucity of data for Takayasu arteritis (TAK) among South Asians. We aimed to evaluate the clinical features, angiographic findings, as well as treatment and outcome of TAK among Malaysian multiethnic groups. METHODS: This is a retrospective review of 40 patients with TAK seen in major rheumatology centres in Malaysia between April 2006 and September 2013. RESULTS: Majority were female patients (92.5%), with a female-to-male ratio of 12:1. Median duration of disease from diagnosis was 66 months (interquartile range, 33-177 months). Fifteen (37.5%) were Malays, 9 (22.5%) each were Indians and indigenous from East Malaysia and 7 (17.5%) were Chinese. Indian and indigenous from East Malaysia were overrepresented in this disease. The mean (SD) age of symptom onset and diagnosis were 25.5 (8.1) and 27.4 (8.4), respectively. The 3 most common clinical presentations at diagnosis were diminished or absent pulse, which occurred in 80% of the patients, followed by blood pressure discrepancy (60%) and arterial bruit (52.5%). There was no difference in clinical presentation among ethnic groups. The subclavian artery was the commonest vessel involved (72.5%), followed by the carotid artery (65%) and renal artery (47.5%). Eight patients had coronary artery involvement, and 2 patients had pulmonary artery involvement. Type I arterial involvement was the commonest (80.0%), followed by type IV (35%), present in isolation or mixed type. Glucocorticoid was the main medical treatment (90.0%). Nineteen patients (47.5%) underwent revascularization procedures. Five patients died during the follow-up period. CONCLUSIONS: The Malaysian TAK cohort had similarities with and differences from other published TAK cohort. A nationwide TAK registry is needed to determine the prevalence of the disease among different ethnic groups.

Lemierre syndrome.

Lemierre syndrome is an uncommon disease which commonly arise from acute bacterial oropharyngeal infection. This disease was first described in 1900 by Courmont and Cade Lemierre. It is commonly caused by Fusobacterium necrophorum. Lemierre syndrome has been reported to be serious and potentially fatal in the preantibiotic era. It is characterized by an oropharyngeal infection leading to secondary septic thrombophlebitis of the internal jugular vein with embolization to the lungs and other organs. The incidence has become relatively rare at present and is usually only diagnosed when unsuspected culture results are available. We report a case of Lemierre syndrome which was recently diagnosed in our centre.

The prevalence of rheumatoid factor isotypes and anti-cyclic citrullinated peptides in Malaysian rheumatoid arthritis patients.

AIM: The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti-cyclic citrullinated peptides (anti-CCP) in Malaysian rheumatoid arthritis (RA) patients. METHODS: In this cross-sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme-linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second-generation anti-CCP were performed and the prevalence of each auto-antibody was compared in the three ethnic groups. RESULTS: The anti-CCP was the most prevalent auto-antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti-CCP-RF IgM combination provided the best test sensitivity. Seroprevalence of anti-CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti-CCP did not increase or decrease with advancing age, age at onset and disease duration. CONCLUSION: When used alone, anti-CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti-CCP assay, step-wise serum testing with IgM RF followed by anti-CCP may provide a more economically sensible option to optimize test sensitivity for RA.