Risk factors associated with COVID-19 in systemic lupus erythematosus: Results from a longitudinal prospective cohort.

INTRODUCTION: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. METHODS: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. RESULTS: Through the study period (April-December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. CONCLUSION: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

Incidence of infection other than tuberculosis in patients with autoimmune rheumatic diseases treated with bDMARDs: a real-time clinical experience from India.

Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16-84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P < 0.01). Infection risk was higher in patients with systemic lupus erythematosus (P = 0.04), other connective tissue disease (P < 0.01) and in patients with comorbidities (P = 0.13). The risk of infection was associated with the use of anti-TNF therapy and more than three csDMARDs, co morbidities and Adds such as systemic lupus erythematosus and connective tissue disease.

The role of biologics in treatment of ANCA-associated vasculitis.

The vast majority of patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) who receive conventional treatment with glucocorticoids and cyclophosphamide experience frequent relapses and treatment-related side-effects. Increasing knowledge of the pathogenesis of AAV has permitted the development of targeted therapies against tumour necrosis factor (TNF)-α and T and B lymphocytes. Therapy with TNF-α blocking drugs has so far proved disappointing, and this approach is not recommended. B cell depletion using rituximab is effective for remission induction, especially in refractory patients. The long-term side-effects and the best method of using rituximab to maintain remission are still to be determined.

A prospective longitudinal study evaluating the influence of immunosuppressives and other factors on COVID-19 in autoimmune rheumatic diseases.

BACKGROUND: We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). METHODS: This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. RESULTS: COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5-20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p < 0.001) compared to the general population of the corresponding geographic region. CONCLUSIONS: Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

Biologics and risk of tuberculosis in autoimmune rheumatic diseases: A real-world clinical experience from India.

AIM: Tuberculosis (TB) is one of the major adverse events of concern associated with the use of biologics for managing autoimmune inflammatory rheumatic diseases (AIRDs). The study presents the data on incidence of TB in relation to biologic used, screening test and TB prophylaxis in a real-world setting. METHODS: The cross-sectional, observational, retrospective study was conducted across 12 centres in Karnataka, India. The study included patients receiving biologics therapy for AIRDs, established based on the respective diagnostic criteria. The development of TB after receiving biologic therapy and other clinical variables and the predictability of the test performed for latent TB were evaluated. RESULTS: One hundred and ninety-five AIRDs patients with an average age of 41 years were initiated on biologic therapy. Twenty-one patients were latent TB positive and were given antitubercular prophylaxis, prior to biologics treatment. During follow-up, seven patients belonging to the negative test group (n = 174) developed TB. The negative predictive values noted for Mantoux test (n = 120) and quantiFERON TB gold test (n = 178) were 96.52% and 96.25%, respectively. Patients on anti-tumor necrosis factor were more likely to develop TB. Presence of comorbidities and steroid use increased the likelihood of developing TB by 1.5 and 4.6 times, respectively. CONCLUSION: Close monitoring of patients receiving biologics is essential for early identification of adverse events, especially in test negative patients. Prophylaxis can effectively reduce the risk of developing TB in patients positive for screening.

Late-onset neutropenia in patients with rheumatoid arthritis after treatment with rituximab.

OBJECTIVE: Late-onset neutropenia (LON) is an adverse effect of rituximab (RTX) in hematological malignancies, a finding that was recently reported in rheumatoid arthritis (RA). The aim of our study was to estimate its incidence in RA. METHODS: We retrospectively reviewed complete blood (cell) count of patients with RA who received RTX between October 2007 and July 2011 to identify neutropenia (≤ 1.5 × 10(9)) up to 12 months following RTX. RESULTS: One hundred eight patients received RTX, median age 64 years (range 25-86). A total of 237 cycles were given. Five patients developed LON after a median of 151 days (71-184). Two developed pneumonia. CONCLUSION: LON occurs infrequently after RTX, but can present with infection.