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.

Co-existence of Marfan syndrome and systemic sclerosis: A case report and a hypothesis suggesting a common link.

FBN1 gene encodes for the connective tissue protein fibrillin-1 which can also regulate the profibrotic cytokine transforming growth factor (TGF)-ß1. Mutations in the FBN1 gene cause Marfan syndrome (MFS), a genetic condition with defective connective tissues. FBN1 haplotypes and single nucleotide polymorphisms have also been reported to be associated with systemic sclerosis (SSc), a connective tissue disease characterized by fibrosis of multiple organs. Furthermore, the duplication of the Fbn1 gene causes a SSc-like disease in the TsK1 mouse model. To the best of our knowledge, there are no reports of MFS and SSc co-existing in a patient. Here, we describe a 46-year-old woman who presented with cardiac failure. She had a family history of MFS. Physical examination revealed marfanoid habitus and scleroderma features. Echocardiography demonstrated dilated cardiomyopathy with aortic root dilatation, aortic regurgitation and mitral regurgitation. Cardiac magnetic resonance imaging was consistent with dilated cardiomyopathy, mid-wall fibrosis at basal septal wall and dilated aortic root. Extractable nuclear antigen panel detected anti-Scl 70. She fulfilled Ghent criteria for MFS and satisfied American College of Rheumatology/ European League Against Rheumatism classification criteria for SSc. Although we do not have the FBN1 sequence in our patient, the co-existence of MFS and SSc in this patient raises the possibility of co-existence of distinct mutations in the FBN1 gene that could affect TGF-ß signaling differently, resulting in divergent pathologic consequences - loss of structural integrity in MFS versus increased extracellular matrix deposition in SSc, and different clinical manifestations.

Self-reported symptoms of depression, anxiety and stress among patients with Rheumatoid Arthritis in a Malaysian rheumatology centre - prevalence and correlates

Objective: To determine the prevalence, correlates andindependent predictors of self-reported depression, anxietyand stress in Rheumatoid arthritis (RA) patients in Hospital Melaka.Methods: This was a cross-sectional survey usingconvenient sampling of 192 RA patients who attended theRheumatology Clinic outpatient appointment, HospitalMelaka from June 2013 to December 2013. Depression,Anxiety and Stress Scale (DASS21) questionnaire was usedto evaluate symptoms of depression, anxiety and stress. RAdisease activity was assessed using the DAS28-ESRformula. Functional status was assessed via the HealthAssessment Questionnaire Disability Index (HAQ-DI).Results: Out of 189 completed questionnaires, 46%(n=86)patients reported psychological distress symptoms, and25%(n=48) experienced more than one negative emotionalstates. The prevalence of depression, anxiety and stressamong our patients were 23.3%(n=44), 42.3%(n=80) and20.1%(n=38) respectively. There were significant positivecorrelations (p<0.05) between these psychologicalsymptoms with disease activity, number of tender joints,general health, pain and HAQ score. Age was inverselycorrelated with depression, anxiety and stress. Highernumber of swollen joints correlated positively withdepression but not with anxiety and stress. HAQ was theonly independent predictor for depression (Odds Ratio[OR]=2.07; 95%CI: 1.19 to 3.61) and anxiety (OR=1.81;95%CI: 1.1 to 3.0) whilst pain was found to be independentpredictor for stress (OR=1.04; 95%CI: 1.0 to 1.1).Conclusion: The incidence of depression and anxiety in ourMalaysian sample of RA patient was comparable to thatobserved in Caucasian populations. Functional status wasan independent predictor of depression and anxiety,whereas pain was an independent predictor of stress.

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.