Clinical and angiographic outcomes of Mycophenolate versus Methotrexate in South Asian patients of Takayasu arteritis: Results from an open-label, randomised controlled trial.

OBJECTIVE: To compare the clinical and angiographic responses of Mycophenolate Mofetil (MMF) versus Methotrexate (MTX) in Takayasu arteritis (TAK). METHODS: This was a open label, outcome assessor blinded trial. Adult patients of TAK with active disease were randomized 1:1 to MMF 1g twice daily or MTX 20 mg once weekly, by computer generated program. All patients were started on 0.5 mg/kg of steroids with a predetermined tapering protocol. Primary outcome was treatment response as defined by Indian Takayasu arteritis score at 9 months. Secondary end points included time to first failure and angiographic progression. RESULTS: A total of 52 patients (26 in each arm) were recruited. The rate of responders was 71.43% (15/21) in the MMF arm and 63.64% (14/22) in the MTX arm (p=0.58). The median time to 1st failure was 9 months (Range: 3-9) and 4.5 months (range: 3-9) in the MMF and MTX arm respectively (p=0.052). In both groups, 15 % of patients (n=3) had progressive disease in angiography. CONCLUSION: The results showed numerically better outcomes towards MMF, with a longer time to first failure than Methotrexate(9 months versus 4.5 months, p=0.052). No significant difference was seen in the angiographic outcomes.

Serum amyloid A as a marker of disease activity and treatment response in Takayasu arteritis.

Assessment of disease activity in Takayasu arteritis (TA) is challenging. We aimed to study utility of serum amyloid A (SAA) to assess disease activity and its association with SAA gene polymorphisms, if any, in our TA patients. Serum of 99 consecutive adult TA patients and 40 healthy controls were assayed for SAA. Depending on the ITAS2010 and ITAS-CRP score, patients were designated as having active disease if ITAS2010 ≥ 2 or ITAS-CRP ≥ 3 and stable disease if ITAS2010 = 0 or ITAS-CRP is ≤1. Clinical ITAS of 0 with raised inflammatory markers scoring a ITAS-CRP of 2 was considered as indeterminate for disease activity assessment. Repeat SAA levels for active group was measured after 6 months from baseline. SAA levels between active and stable disease as well as serial levels were compared. DNA of 40 patients and controls were genotyped for SAA polymorphisms (rs12218, rs2468844) and the allele frequencies were compared. At baseline, SAA levels were higher in patients as compared to controls (137.4 vs 100.8 ng/ml, p = 0.001) and higher in patients with active disease (166.4 ng/ml) than those with stable disease (98.2 ng/ml), p = 0.001. SAA decreased during follow-up in treatment responders (189.9 ng/ml at baseline vs 119.0 ng/ml at follow-up, p = 0.008); in contrast, there was no significant change among non-responders during follow-up. Allelic frequencies of SAA gene polymorphisms did not differ between cases and controls. SAA may be a reliable biomarker to assess disease activity and treatment response in TA.

Hydroxychloroquine-Induced Phospholipidosis - A Forgotten Complication of a Common Drug.

Hydroxychloroquine (HCQ) has immunomodulatory and immunosuppressive properties and is used in many rheumatological conditions like systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome. It is usually a widely used and well-tolerated DMARD (Disease Modifying Anti Rheumatic Drugs). Its most feared toxicities include retinopathy and, rarely, cardiomyopathy. Among its other reported side effects is drug-induced phospholipidosis. Here, we report two cases of HCQ-induced phospholipidosis based on renal biopsy electron microscopy. HCQ-induced phospholipidosis, although uncommon, must be considered as one of the differentials in a patient with persistent proteinuria.

Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort.

BACKGROUND: Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the long-term outcome and treatment response in our large, retrospective cohort of adult South-Asian patients exclusively with IIM. METHODOLOGY: Electronic records of IIM patients satisfying inclusion and exclusion criteria were studied longitudinally at presentation, at 3, 6, 12, 18 and 24 months and thereafter yearly till their last follow up (F/u) visit. Depending on clinical, imaging, and muscle enzyme profile during the F/u period, patients were categorised as complete (CR) and partial responders (PRs). Parameters favouring CR were assessed using multivariate logistic regression analysis. Outcome parameters and flares on immunosuppressants (IS) were then assessed in patients with/without ILD. RESULTS: Two hundred thirty-two patients with median F/u duration of 44.5 months (25-80.25) were included. ILD was seen in 40.1%. Patients with non-Jo1 anti-synthetase antibodies (n=26) were numerically more than those with Jo-1 antibody (n=24). CR status was attained by 50.9% patients. Absence of pericardial effusion (p=0.042, OR 4.223, 95% CI: 1.05-16.9) and presence of Gottron's rash (p=0.044, OR 1.78, 95% CI 1.017-3.121) at baseline predicted CR by multivariate regression. Majority received mycophenolate during the entire F/u period. Discontinuation of steroids was feasible in 51.7% after a median duration of 24 months (18-42). After excluding patients with ILD, flares were numerically lesser in patients only on mycophenolate compared with those only on methotrexate (p=0.06). Further flares were curtailed when switched from other agents to mycophenolate. CONCLUSION: Mycophenolate is an effective treatment option in IIM patients with and without co-existing ILD. Presence of Gottron's rash and absence of pericardial effusion were found to be predictors of favourable clinical outcome in this largest single-centre study.

Unique clinical and autoantibody profile of a large Asian Indian cohort of scleroderma-do South Asians have a more aggressive disease?

AIM AND METHODS: A single-centre retrospective study was conducted using electronic medical records (EMR) of inpatients and outpatients with the diagnosis of "scleroderma" or "systemic sclerosis" visiting our clinic over the preceding 5 years. RESULTS: A total of 327 patients' charts met our selection criteria; 301 were females. The median (IQR (inter quartile range)) age at onset of first non-Raynaud's symptom was 34.67 (27-43) years and median (IQR) disease duration prior to presentation to our department was 2.5 (1-5) years. Of these, 310 (94.8%) belonged to diffuse systemic sclerosis variety, 13 (4%) had limited systemic sclerosis, and 4 (1.2%) were of sine scleroderma type. A total of 289/302 (95.7%) patients were positive for ANA; of them, 245/327 (74.9%) were Scl-70 antibody-positive and 4% were CENP antibody-positive. Interstitial lung disease (ILD) was present in 288/327 (88.1%) patients. Among patients with available baseline forced vital capacity (FVC) data, 20% had a normal lung function and 28.4% had severe restriction. Pulmonary hypertension as assessed by echocardiography was present in 8.1% of patients. A significant association of Scl-70 antibody positivity with the presence of interstitial lung disease (ILD) (p = 0.000) and pulmonary hypertension (p = 0.035) was seen. On the other hand, presence of CENP antibody showed a protective trend against muscle weakness and/or muscle enzyme elevation (p = 0.052). Presence of arthritis was protective against development of digital ulceration (p = 0.021) and PAH (0.004). Patients younger than 40 years of age had significantly higher frequency of Scl-70 positivity (p = 0.038), whereas CENP antibody positivity was more likely in those aged > 40 years (p = 0.002). CONCLUSION: Younger age of onset and high prevalence of Scl-70 antibody are unique South Asian features common with large Indian, Thai, and Chinese series. High prevalence of ILD is a feature common to Indian and Chinese series. Strong correlation of Scl-70 antibody with younger age and pulmonary hypertension were unique features of our cohort. KEY POINTS: • Asian Indian scleroderma patients are younger by 2 decades compared to Caucasian series. • Higher prevalence of Scl-70 antibody, its association with young age, interstitial lung disease and pulmonary hypertension are features of our cohort. • High prevalence of interstitial lung disease (88.1%) was noted ; among those with baseline spirometry data (141/327), two thirds(66%) had moderate to severe restriction. • Younger age at onset, higher prevalence of Scl-70 antibody are features common to other Indian, Thai and Chinese series.

C-reactive protein gene polymorphisms (rs1205) in Asian Indian patients with Takayasu arteritis: Associations and phenotype correlations.

BACKGROUND/PURPOSE: Normal C-reactive protein (CRP) in active Takayasu arteritis (TA) is a dilemma. We attempted to validate our pilot study finding of rs1205 in CRP gene being protective against TA. METHODS: Genomic DNA of 104 patients and 185 sex-matched healthy controls were genotyped for rs1205 by Taqman assay. Clinical details, demography, angiographic and activity scores (Indian Takayasu arteritis score 2010) were recorded prospectively at baseline and during follow-up visits for 12 months. Minor allele frequency (MAF) and genotype distribution between patients and controls as well as patient subgroups were compared using χ2 test with Bonferroni correction (pc ) and logistic regression was performed to determine independent associations. RESULTS: The majority of patients (n = 84) and controls (n = 166) were females. MAF of T allele of rs1205 was less frequent in patients (27%) as compared to controls (37.6%), P = 0.013, pc = 0.026 with an odds ratio of 0.632 irrespective of gender. Frequency of CC genotype was higher in cases (53.8%) than controls (37.3%), P = 0.006, pc = 0.018. A dominant model of genotype-phenotype association revealed CC to be associated with more frequent coronary arterial and ascending aorta involvement than the other genotypes clubbed together (P = 0.01 and P = 0.014, respectively). Blunted CRP response seems to be less frequent in patients with CC genotype (P = 0.064). CONCLUSION: T allele of rs1205 in CRP gene was less frequent in TA. CC genotype was associated with involvement of coronary arteries and ascending aorta. CC genotype was less commonly associated with blunted CRP response (CT + TT > CC).

TNFα blockers followed by continuation of sulfasalazine and methotrexate combination: a retrospective study on cost saving options of treatment in Spondyloarthritis.

High cost deters continuous use of tumor necrosis factor α blockers (TNFi) in developing countries. The objective of this study was to evaluate outcome and expenditure incurred in Spondyloarthritis (SpA) patients beyond a year of follow-up after receiving four doses of infliximab (IFX) over and above background therapy of methotrexate (MTX) and sulfasalazine (SSZ) combination. Electronic medical records were screened for patients with SpA satisfying the Assessment of Spondyloarthritis International Society (ASAS) criteria between 2008 and 2014. Patients who completed at least 1 year of follow-up after receiving four doses of IFX (5 mg/kg at 0, 2, 6, and 14 weeks) on a background therapy of MTX (10-25 mg/week) and SSZ (2-3 g/day) combination were enrolled after obtaining an informed consent. Primary outcome assessed was "time to disease flare". Changes in acute phase reactants, patient reported outcomes (BASDAI, BASFI), and cost were also assessed. Forty-five patients were enrolled. Mean (SD) duration of follow up after fourth IFX dose was 28.9 (18.7) months. Disease flare occurred in 33.3% (15/45) after a mean (SD) duration of 14.5 (10.8) months as compared to 4-6 months described in literature on discontinuing TNFi. Reduction in ESR, CRP, BASDAI and BASFI continued to be statistically significant at follow-up as compared to baseline. As compared to continuous IFX therapy, this treatment reduced cost by 57.1% for each patient-month of follow-up. Short course IFX dosing followed by continuation of MTX and SSZ combination can prolong time to disease flare and decrease requirement for additional IFX dose in SpA. This regimen could be a cost saving option for patients with SpA.