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.

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.

Influence of disease duration and socioeconomic factors on the prevalence of infection and hospitalization in rheumatoid arthritis: KRAC study.

AIM: The use of healthcare resources by rheumatoid arthritis (RA) patients can be related to the presence of disease, comorbid conditions, use of steroids, and the combined use of immunosuppressants. This study evaluated the risk factors associated with infection and hospitalization in RA. METHODS: This multicenter, cross-sectional study enrolled 3247 RA subjects fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria to examine the prevalence of hospitalization and episodes of documentable non-tubercular infections as a part of the "Karnataka rheumatoid arthritis comorbidity" study (KRAC). The study included 2081 subjects and 1166 were excluded due to incomplete data. Demographic, clinical and treatment variables were collected, and the events related to infections and hospitalization were extracted from the medical records. Comparative analysis and multivariate logistic regression were performed. RESULTS: Around 22% of the subjects had hospitalizations and 2.9% had infections. Infections were pertaining to dental (1.3%), urinary tract (1.6%) and candidiasis (0.2%). Skin- and soft tissue-related infections were found in 1.8% and 0.3% of patients, respectively. Increased need of hospitalization in RA patients was associated with advanced age (≥60 years), lower education, family income, and longer duration of RA. Presence of comorbidity, usage of three or more disease-modifying anti-rheumatic drugs (DMARDs) and family income influenced the likelihood of infection. Dental infections were less likely in working subjects and more likely in patients with increased disease duration, higher family income, comorbidities and those between the age group 40-59 years. Urinary tract infection was associated with DMARD usage. CONCLUSION: Patient-specific risk factors should be considered to improve treatment strategies and to reduce the risk of infection and hospitalization in RA patients.

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.

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.

Factors influencing remission in rheumatoid arthritis patients: results from Karnataka rheumatoid arthritis comorbidity (KRAC) study.

AIM: To study the prevalence of remission in rheumatoid arthritis (RA) patients and the influence of different factors like literacy, socioeconomic status, presence of comorbidity and treatment strategy in achieving remission. METHODS: The study involved 1990 RA patients who were recruited for the Karnataka Rheumatoid arthritis comorbidity (KRAC) study. Based on the factors evaluated, the study participants were classified as follows: age, < 30 years, 30-39 years, 40-49 years, 50-59 years and ≥ 60 years; educational status, illiterate/no formal education, high school or less, graduate, post-graduate and doctorate; family income (₹ per annum), < 50 000, 50-100 000, 100-500 000, and > 500 000; duration of illness prior (DOIP): ≤ 6 months, 6-24 months, 24-120 months and > 120 months. Joint counts were performed by a rheumatologist or trained joint assessor. To assess the treatment outcome, the disease activity score was calculated using the Disease activity Score of 28 joints - erythrocyte sedimentation rate (DAS 28-3 ESR). RESULTS: As per the DAS 28-3 ESR score, around 20% (n = 397) of the study subjects achieved remission. The corresponding mean ± SD of DAS 28-3 ESR noted for remission and non-remission groups were 2.13 ± 0.42 and 4.32 ± 1.28. The majority of the patients were treated with double disease-modifying anti-rheumatic drugs (DMARDs) (60.7%). The likelihood of remission was found to be more in patients who reported DOIP ≤ 6 months. Furthermore, the chances of remission reduced with increase in patient's age and the highest remission rate was noted for 30-39 years age group (59%), followed by 40-49 years (35.4%) and 50-59 years (19.7%). CONCLUSION: The prevalence of remission noted was around 20%. Early treatment, escalating dose of DMARDs, and patient counseling are important contributing factors for attaining remission.

Reduced incidence of extra-articular manifestations of RA through effective disease control: Karnataka Rheumatoid Arthritis Comorbidity (KRAC) study.

AIM: To estimate the prevalence of extra-articular manifestations (EAM) in rheumatoid arthritis (RA) patients and the impact of demographic, clinical and treatment factors. METHOD: The study was carried out as a part of 'Karnataka Rheumatoid arthritis comorbidity (KRAC) study' conducted at 14 centers across Karnataka, India between September 2014 and July 2015. The data were collected by trained clinical research associates using a structured pro forma, under the supervision of the consulting rheumatologists. Based on the factors evaluated, the study participants were classified as follows: age, < 30 years, 30-39 years, 40-49 years, 50-59 years and ≥ 60 years; and duration of illness prior to visiting rheumatologist (DOIP), ≤ 6 months, > 6 months-2 years, 2-10 years and > 10 years. The Disease Activity Score of 28 joints-3 (erythrocyte sedimentation rate) score was calculated for each patient by three variable methods. RESULTS: The total number of patients considered for the study after exclusion was 1716. The subjects had a mean (SD) age of 48.1 (12.71) years, the male-to-female ratio was 1 : 5, and median (range) of duration of RA was 48 (0.5-484) months. The prevalence of EAM noted was around 13%. EAM were more likely during the first 2 years of the disease (odds ratio [OR]: 1.465; P = 0.047) and increased with longer DOIP. The incidence was less in patients with low disease activity (OR: 0.657) and worse with the presence of deformities (OR: 2.1). CONCLUSION: The study corroborates the current concept of effective disease control to reduce the incidence/likelihood of EAM in RA patients.