Development of clinical and laboratory biomarkers in an international cohort of 428 children with lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. METHODS: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. RESULTS: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. CONCLUSIONS: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission.

Health and demographic indicators of selected districts of India: An impact of Swasthya Rakshan Programme (SRP).

Swasthya Rakshan Programme (SRP) provides health care services through Ayurveda, an initiative of the Government of India that aims to survey and create alertness of essential health appliances to ameliorate society from its grassroots level. The present study aimed to survey the prevailing health standards of residents in certain districts of India and to record the prevalence of diseases among them according to their living conditions, food habits, lifestyle, education, occupation and other socio-economic status. Data was collected through a community-based cross-sectional survey conducted from April 2018 to March 2019 in 22 Districts of 19 states in India. A stratified multi-stage sampling design was adopted for the survey. Documentation of demographic profile, food habits, lifestyle, hygiene status, and existing health conditions was assessed. A pre-designed semi-structured questionnaire was used for the collection of the data. Before initiating the programme, written consent was obtained. In this study, from 162 selected villages/colonies/areas, a total of 562,913 population and 81,651 households were surveyed. Sixty-nine thousand three hundred nineteen patients were cared for various ailments through health camps. The study found that the most prevalent disease in the concerned population was 'Sandhivata' (Osteo-arthritis), that is, 43.0%, followed by 'Dourbalya' (Debility), that is, 11.7%. The study includes insightful analyses of comprehensive demographic and health indicators classified by various socio-economic categories. The collected data regarding the prevalence of diseases with their sociodemographic correlations may provide a better understanding of the locality and thus may help in all future health endeavours.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-ß2-glycoprotein I(ß2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and ß2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.

Gastrointestinal Manifestations in Systemic Lupus Erythematosus: Data from an Indian Multi-institutional Inception (INSPIRE) Cohort.

OBJECTIVES: To study the prevalence, correlates, and outcomes of GI manifestations in a prospectively enrolled nationwide cohort of SLE in India (INSPIRE). METHODS: It is an observational cohort study with analysis of the baseline database of the INSPIRE cohort with early outcomes assessed till April 10, 2023. Cases with GI manifestations as per the BILAG index were selected, pertinent clinical and laboratory data were retrieved for analysis. Patients with GI manifestations were compared with the rest of the cohort and factors associated with death were determined. RESULTS: Of the 2503 patients with SLE enrolled in the INSPIRE cohort, 243(9.7%) had GI manifestations observed early in the disease course(1,0-3 months). Ascites(162,6.5%), followed by enteritis(41,1.6%), pancreatitis(35,1.4%) and hepatitis(24,0.9%) were the most prevalent manifestations.All patients received immunosuppressive therapy, and four patients required surgery. Twenty-nine patients died(11.9%), with uncontrolled disease activity(17,58.6%) and infection(6,20.7%) accounting for the majority of deaths. Low socioeconomic class[lower(Hazard Ratio (95% Confidence intervals- CI) 2.8(1.1-7.9); upper lower 7.5(2-27.7); reference as upper class] and SLEDAI 2K[1.06(1.02-1.11)] were associated with death in the GI group.GI manifestations were significantly associated with age[Odds Ratio & 95% CI 0.97(0.96-0.99)], pleural effusion[4.9(3.6-6.7)], thrombocytopenia[1.7(1.2-2.4)], myositis[1.7(1.1-2.7)], albumin[0.7(0.5-0.8)], alkaline phosphatase(ALP)[1.01(1.0-1.002)], low C3[1.9(1.3-2.5)], total bilirubin[1.2(1.03-1.3)], alopecia[0.62(0.5-0.96], elevated anti-dsDNA[0.5(0.4-0.8)], and anti-U1RNP antibody[0.8(0.5-0.7)] in model one; and age[0.97(0.96-0.99)], creatinine[1.2(1.03-1.4)], total bilirubin[1.2(1.03-1.3)], ALP[1.01(1.0-1.002)], albumin[0.6(0.5-0.7)], andanti-U1RNP antibody[0.6(0.5-0.8)] in model two in multivariate analysis compared with patients without GI features. The mortality was higher in the GI group(11.9% and 6.6%, p= 0.01) as compared with controls. CONCLUSION: GI manifestations were observed in 9.7% of the cohort and were always associated with systemic disease activity and had higher mortality.

Clinical metabolomics by NMR revealed serum metabolic signatures for differentiating sarcoidosis from tuberculosis.

BACKGROUND: Pulmonary sarcoidosis (SAR) and tuberculosis (TB) are two granulomatous lung-diseases and often pose a diagnostic challenge to a treating physicians. OBJECTIVE: The present study aims to explore the diagnostic potential of NMR based serum metabolomics approach to differentiate SAR from TB. MATERIALS AND METHOD: The blood samples were obtained from three study groups: SAR (N = 35), TB (N = 28) and healthy normal subjects (NC, N = 56) and their serum metabolic profiles were measured using 1D 1H CPMG (Carr-Purcell-Meiboom-Gill) NMR spectra recorded at 800 MHz NMR spectrometer. The quantitative metabolic profiles were compared employing a combination of univariate and multivariate statistical analysis methods and evaluated for their diagnostic potential using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and several lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.). CONCLUSION: The metabolic disturbances not only found to be well in concordance with various previous reports, these further demonstrated very high sensitivity and specificity to distinguish SAR from TB patients suggesting serum metabolomics analysis can serve as surrogate method in the diagnosis and clinical management of SAR.

International cohort of 382 children with lupus nephritis - presentation, treatment and outcome at 24 months.

BACKGROUND: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. METHODS: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. RESULTS: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y-9y, 5m) (14y, 2m-18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. CONCLUSION: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clusters based on demography, disease phenotype, and autoantibody status predicts mortality in lupus: data from Indian lupus cohort (INSPIRE).

OBJECTIVES: SLE is associated with significant mortality, and data from South Asia is limited. Thus, we analysed the causes and predictors of mortality and hierarchical cluster-based survival in the Indian SLE Inception cohort for Research (INSPIRE). METHODS: Data for patients with SLE was extracted from the INSPIRE database. Univariate analyses of associations between mortality and a number of disease variables were conducted. Agglomerative unsupervised hierarchical cluster analysis was undertaken using 25 variables defining the SLE phenotype. Survival rates across clusters were assessed using non-adjusted and adjusted Cox proportional-hazards models. RESULTS: Among 2072 patients (with a median follow-up of 18 months), there were 170 deaths (49.2 deaths per 1000 patient-years) of which cause could be determined in 155 patients. 47.1% occurred in the first 6 months. Most of the mortality (n = 87) were due to SLE disease activity followed by coexisting disease activity and infection (n = 24), infections (n = 23), and 21 to other causes. Among the deaths in which infection played a role, 24 had pneumonia. Clustering identified four clusters, and the mean survival estimates were 39.26, 39.78, 37.69 and 35.86 months in clusters 1, 2, 3 and 4, respectively (P < 0.001). The adjusted hazard ratios (HRs) (95% CI) were significant for cluster 4 [2.19 (1.44, 3.31)], low socio-economic-status [1.69 (1.22, 2.35)], number of BILAG-A [1.5 (1.29, 1.73)] and BILAG-B [1.15 (1.01, 1.3)], and need for haemodialysis [4.63 (1.87,11.48)]. CONCLUSION: SLE in India has high early mortality, and the majority of deaths occur outside the health-care setting. Clustering using the clinically relevant variables at baseline may help identify individuals at high risk of mortality in SLE, even after adjusting for high disease activity.

Delay in diagnosis of rheumatoid arthritis: reasons and trends over a decade.

INTRODUCTION: Delay in diagnosis and treatment initiation often lead to poorer outcomes in rheumatoid arthritis (RA). Most of the data on delay in diagnosis and management are from western population with no data from India. Additionally, with improved health care services, whether the delay has changed over years is not known. In this longitudinal observational study, we investigated delay to diagnosis and disease-modifying antirheumatic drugs (DMARDs) initiation over past 9 years. METHODS: Patients aged ≥ 18 years having RA fulfilling 2010 ACR/EULAR criteria were enrolled from January to June in years 2012, 2017 and 2021. Diagnoses received before presenting to clinic, socioeconomic status, educational level and other demographic variables were recorded. RESULTS: Each year, 323 patients (mean age 49.5-52.01 years) were enrolled. There was a significant reduction in delay in diagnosis from a median (IQR) of 36 (12-84, range 1-288) months in 2012 to 12 (4-36, range 1-180) months in 2017 and 10 (5-24, range 1-120) months) in 2021 (p < 0.0001). A significant improvement in time to initiating DMARDs from 2012 [48 (24-96) months] to 2017 [12 (6-36) months] (p < 0.0001) and from 2017 to 2021 [12 (5-24) months] (p = 0.03) was seen. Higher education, more patients opting for treatment from rheumatologists, and urbanisation contributed significantly to improvement in delay. There was no impact of age or gender on delay. CONCLUSION: Delay in diagnosis has improved significantly between 2012 and 2021. However, delay still remains long as most patients miss the 3-month therapeutic window. Future work focussing on reasons for delays in the patient pathway could help improve consultation pathways in India.

Early onset of immune-mediated diseases in minority ethnic groups in the UK.

BACKGROUND: The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. METHODS: This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). RESULTS: After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. CONCLUSION: Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.

A Delphi consensus statement for the management of post-COVID interstitial lung disease.

INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach. AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members. EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

Circulatory Cytokine Levels as a Predictor of Disease Severity in COVID-19: A Study from Western India.

Inflammatory response in COVID-19 responsible for acute respiratory distress syndrome (ARDS) and multiorgan failure and play a major role in morbidity and mortality of patients. The present study was undertaken to assess serum level of cytokines and its association with other inflammatory markers and disease severity in COVID-19 and hence their prognostic significance. METHODS: This was a retrospective observational study of 175 admitted COVID-19 patients. The patient's clinical data, laboratory investigations, inflammatory markers and serum level of cytokines [interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumour necrosis factor α (TNFα)] were extracted from their medical records. All patients were divided into three groups viz. group A had asymptomatic patients, group B had mild to moderate ill patients and group C had severe or critical ill patients. Above parameters were analysed and comparative evaluation with severity of disease was done. RESULTS: & In present study 55% patients were asymptomatic, 24% patients were mild to moderate illness and remaining 21% patients had severe or critical illness. Fever, cough, dyspnoea and co-morbidities including hypertension and diabetes were more common in group C. Absolute lymphocyte count (ALC), lymphocyte monocyte ratio (LMR) showed decreasing trend whereas absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and eosinophil-lymphocyte (ELR) showed increasing trend with increase in disease severity. Serum IL-6 was found to be significantly higher in group C (64.98±111.18pg/mL) as compared to group B (15.51±20.66pg/mL) and group A (5.04±56.1pg/mL) (P<0.001). Receiver operating characteristic (ROC) curve for IL-6 to differentiate the patients with severe disease from asymptomatic and mild symptomatic disease showed a cut-off of 6.75pg/ml. CONCLUSION: Elevated IL-6 levels lead to adverse clinical events so IL-6 level might serve as a potential prognostic marker for severity of disease in COVID-19. Inhibition of IL-6 might be helpful to prevent serious adverse events in COVID-19 infection.

Defining renal remission in an international cohort of 248 children and adolescents with lupus nephritis.

OBJECTIVE: We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. METHODS: Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.

Clinical features, severity and outcome of acute pancreatitis in systemic lupus erythematosus.

Acute pancreatitis (AP) is a rare but life threatening manifestation of Systemic Lupus Erythematosus (SLE). The current study aims to study the clinical characteristics, severity, mortality, and outcome of SLE-related AP in Indian population. We retrospectively reviewed medical records of patients with SLE who had AP in the past. Data from 13 rheumatology centers across India were compiled. All patients satisfied SLICC criteria for SLE and ATLANTA criteria for AP. AP was classified in to mild, moderate and severe using revised Atlanta classification. Patients with known risk factors like gall stone and alcohol were excluded.Sixty-six patients (six, children) were studied. Majority of patients were females (82%). The median age of presentation was 24 (11-63) years and most patients (57.5%) presented within first year of diagnosis of lupus. AP occurred mostly in the setting of active lupus (89%). Active nephritis was seen in 39% while a fourth had CNS disease. Patients with severe AP had lower C3. Ascites and sepsis were most common local and systemic complications, respectively. Mortality was 17%. Hypocalcemia, presence of sepsis and shock predicted mortality. In the multivariate analysis, only presence of shock remained as independent predictor of death (OR 63.0, 95% CI: 5.2-760.3). Pancreatitis is an early manifestation of SLE and is associated with active disease. Significant mortality is seen particularly with severe pancreatitis.

Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre randomized, placebo-controlled trial.

INTRODUCTION: Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. Hence, Ivermectin is under investigation as a repurposed agent for treating COVID-19. METHODS: In this pilot, double blind, randomized controlled trial, hospitalized patients with mild-to-moderate COVID-19 were assigned to a single oral administration of an elixir formulation of Ivermectin at either 24 mg or 12 mg dose, or placebo in a 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment. Safety outcomes included total and serious adverse events. The primary outcomes were assessed in patients who had positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes were assessed in all patients who received the intervention (intention-to-treat population). RESULTS: Among the 157 patients randomized, 125 were included in modified intention-to-treat analysis. 40 patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg arm, 35.0%; and placebo arm, 31.1%; p-value = 0.30). The decline of viral load at day 5 was similar in each arm. No serious adverse events occurred. CONCLUSIONS: In patients with mild and moderate COVID-19, a single oral administration of Ivermectin did not significantly increase either the negativity of RT-PCR or decline in viral load at day 5 of enrolment compared with placebo.

Clinical spectrum of active tuberculosis in patients with systemic lupus erythematosus.

INTRODUCTION: There is paucity of data on tuberculosis in Indian patients with systemic lupus erythematosus (SLE). We retrospectively studied clinical features and outcome of tuberculosis in SLE. METHODS: Medical records of patients who developed tuberculosis simultaneous or after the diagnosis of SLE were retrospectively reviewed. All patients fulfilled 1997 ACR and/or SLICC 2012 classification criteria for SLE. A diagnosis of tuberculosis required bacteriological, histopathological or CT/MRI suggestive of tuberculosis and initiation of four drug antituberculous therapy. Baseline parameters were compared with the rest of cohort to identify predictors of tuberculosis. RESULTS: In our cohort of 1335 SLE patients, 48 (3.6%) developed tuberculosis. Incidence of tuberculosis was calculated to be 733 per 100,000 patient years and occurred after a mean disease duration of 3.0 ± 4.1 years. Extrapulmonary tuberculosis (n = 37) was commoner than pulmonary tuberculosis (n =11). Most common radiological pattern in pulmonary tuberculosis was miliary and musculoskeletal TB was most common extrapulmonary TB. A microbiological diagnosis was obtained in 52.1% patients. Male gender was associated with higher risk of tuberculosis [OR 3.30 (1.55-7.05)]. Mortality was 14.5% and all patients who died had either disseminated (n = 5) or central nervous system (CNS) tuberculosis (n = 2). CONCLUSION: Incidence of tuberculosis in SLE is higher than general population and is associated with different phenotype and higher mortality. Male gender was associated with increased risk of tuberculosis in SLE.

Low-dose rituximab protocol in rheumatoid arthritis-outcome and economic impact.

OBJECTIVES: A significant proportion of RA patients, particularly those associated with poor prognostic factors, fail on conventional DMARDs (cDMARDs). Although rituximab (RTX) has been effective in these patients, the cost of therapy makes it unaffordable, particularly in poor and developing countries. Numerous, albeit small, studies using lower doses have shown contradictory results. We aimed to analyse the effectiveness of a low-dose RTX protocol based on clinical outcomes in RA patients. METHODS: Seropositive RA patients with moderate to high disease activity (DAS28-ESR > 3.2) despite combination cDMARDs, treated with RTX, were included in retrospective analysis. All patients were treated according to a predefined protocol, using 500 mg RTX with ongoing cDMARDs at baseline and repeat dosing at 6 weeks or beyond, on lack of moderate to good EULAR response. The B cell count was assessed at baseline, 2 and 24 weeks. RESULTS: At 12 weeks, 93% of 166 patients [mean (s.d.) age, 51.5 (11.96) years, 25 men and 141 women, with a disease duration of 10.4 (6.29) years] achieved moderate to good EULAR response. At 24 weeks, 90.8% of patients achieved moderate to good EULAR response, 19.8% achieved low disease activity and 29.5% achieved remission, with a mean change in DAS28-ESR from baseline of 2.9 (1.3). RTX failure and relapse were seen in 5.4% and 3.6%, respectively. The response was maintained for 12.3 (7.2) months with a mean RTX dose 521.1 (100.8) mg. Adverse events were seen in 9.6%. When compared with the standard dosing regimen with the originator molecule, a cost reduction of 90% was achieved. CONCLUSION: A low-dose RTX regimen achieved reasonably good clinical outcomes at the end of 6 months, with a significantly lower cost.

Indian SLE Inception cohort for Research (INSPIRE): the design of a multi-institutional cohort.

Systemic lupus erythematosus (SLE) cohorts across the world have allowed better understanding of SLE, including its bimodal mortality, and the impact of social factors and ethnicity on outcomes. The representation of patients from South Asia has been poor in the existing SLE cohorts across the world. Hence, we planned to initiate an inception cohort to understand the diversity of lupus in India. Indian SLE Inception cohort for REsearch (INSPIRE), planned over 5 years is a multi-centric cohort of adult and childhood lupus patients of Indian origin, fulfilling the SLICC-2012 classification criteria, with an aim to provide cross-sectional information on demography, ethnicity, socio-economic status, standard disease variables, quality of life, and prospective information on new events like hospitalization, infections, pregnancies, changes in disease activity, and damage. One of the other deliverables of this project is the establishment of a biorepository. The instruments to be used for each variable and outcome were finalized, and a web-enabled case report form was prepared to encompass SLEDAI, BILAG, SLICC damage scores, and Lupus quality-of-life index.Ten centers located in different geographic areas of India would enroll patients who are seen for the first time after the start of the study. In the first 8 months, 476 patients (63 children, 36 males) have been enrolled with a median disease duration of 10 (IQR 4-17) months and mucocutaneous features being the most prevalent clinical manifestations. INSPIRE is the first prospective Indian SLE cohort to study the diversity of Indian patients.

Macrophage activation syndrome in systemic lupus erythematosus and systemic-onset juvenile idiopathic arthritis: a retrospective study of similarities and dissimilarities.

Macrophage activation syndrome (MAS) is a serious complication of rheumatic diseases. Fever and hyperferritinemia are common in active systemic-onset juvenile idiopathic arthritis (sJIA) and cytopenia in active systemic lupus erythematosus (SLE), thus recognizing MAS in them is a challenge. We compared clinical and laboratory parameters, various classification criteria, and outcomes of MAS in SLE and sJIA. Clinical and laboratory data were extracted from case records of patients with clinician diagnosed cases of SLE-MAS (adult and pediatric) and sJIA-MAS, admitted (2004-2018) at a tertiary care hospital. Ravelli, International consensus, HLH-2004, and criteria proposed by Parodi et al. were applied and compared. Among 33 patients (18 females) with MAS, 19 had SLE (7, childhood-onset SLE) and 14 had sJIA. MAS was more likely to be the presenting manifestation of disease in SLE (p < 0.05). There were no differences in the clinical features among them. Patients with SLE-MAS had lower baseline total leucocyte and platelet counts (p < 0.01), whereas patients with sJIA-MAS had significantly higher median CRP (p = 0.002), fall in TLC (p = 0.012), delta ESR/CRP ratio (p = 0.02), and lower fibrinogen level (p = 0.006). Neutrophil-to-lymphocyte ratio, ferritin/CRP ratio, and the number of patients with ferritin/ESR > 80 were similar. Only 6/33(18%) fulfilled the HLH criteria. Criteria meant for sJIA-MAS or SLE-MAS performed well for both diseases and the majority of patients could be diagnosed using them. Two patients died in each group. MAS in SLE and sJIA is more similar than dissimilar in clinical features and outcome. Criteria meant for MAS in sJIA or SLE-MAS performed equally well in both diseases.