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BackgroundLupus is a heterogenous diseases which results in significant premature mortality. Most studies have evaluated risk factors for lupus mortality using regression models which considers the phenotype in isolation. Identifying clusters of patients on the other hand may help overcome the limitations of such analyses.ObjectivesThe objectives of this study were to describe the causes of mortality and to analyze survival across clusters based on clinical phenotype and autoantibodies in patients of the Indian SLE Inception cohort for Research (INSPIRE)MethodsOut of all patients, enrolled in the INSPIRE database till March 3st 2022, those who had <10% missing variables in the clustering variables were included in the study. The cause of mortality and duration between the recruitment into the cohort and mortality was calculated. Agglomerative unsupervised hierarchical cluster analysis was performed using 25 variables that define SLE phenotype in clinical practice. The number of clusters were fixed using the elbow and silhouette methods. Survival rates were examined using Cox proportional hazards models: unadjusted, adjusted for age at disease onset, socio-economic status, steroid pulse, CYC, MMF usage and cluster of the patients.ResultsIndian patients with lupus have significant early mortality and the majority of deaths occurs outside the hospital setting.Out of 2211 patients in the cohort, 2072 were included into the analysis. The median (IQR) age of the patients was 26 (20-33) years and 91.7% were females. There were 288 (13.1%) patients with juvenile onset lupus. The median (range) duration of follow up of the patients was 37 (6-42) months. There were 170 deaths, with only 77 deaths occurring in a health care setting. Death within 6 months of enrollment occured in in 80 (47.1%) patients. Majority (n=87) succumbed to disease activity, 23 to infections, 24 to coexisting disease activity and infection and 21 to other causes. Pneumonia was the leading cause of death (n=24). Pneumococcal infection led to death in 11 patients and SARS-COV2 infection in 7 patients. The hierarchical clustering resulted in 4 clusters and the characteristics of these clusters are represented in a heatmap (Figure-1A,B). The mean (95% confidence interval [95% CI] survival was 39.17 (38.45-39.90), 39.52 (38.71-40.34), 37.73 (36.77-38.70) and 35.80 (34.10-37.49) months (p<0.001) in clusters 1, 2, 3 and 4, respectively with an HR (95% CI) of 2.34 (1.56, 3.49) for cluster 4 with cluster 1 as reference(Figure 1C). The adjusted model showed an HR (95%CI) for cluster 4 of 2.22 (1.48, 3.22) with an HR(95%CI) of 1.78 (1.29, 2.45) for low socioeconomic status as opposed to a high socioeconomic status (Table 1).ConclusionIndian patients with lupus have significant early mortality and the majority of deaths occurs outside the hospital setting. Disease activity as determined by the traditional activity measures may not be sufficient to understand the true magnitude of organ involvement resulting in mortality. Clinically relevant clusters can help clinicians identify those at high risk for mortality with greater accuracy.Table 1.Univariate and multivariate Cox regression models predicting mortalityUnivariateMultivariateVariablesHazard ratio (95% Confidence interval)P valueHazard ratio (95% Confidence interval)P valueCluster1Reference-Reference-20.87 (0.57, 1.34)0.5320.89 (0.57, 1.38)0.59831.22 (0.81, 1.84)0.3371.15 (0.76, 1.73)0.51342.34 (1.56, 3.49)<0.0012.22(1.48, 3.22)<0.001Socioeconomic statusLower1.78 (1.29, 2.45)<0.001Pulse steroidYes1.6 (0.99, 2.58)0.051MMFYes0.71 (0.48, 1.05)0.083CYCYes1.42 (0.99, 2.02)0.052Proliferative LNYes0.99 (0.62, 1.56)0.952Date of birth age0.99 (0.98, 1.01)0.657CYC- cyclophosphamide, MMF- Mycophenolate mofetilFigure 1.A. Agglomerative clustering dendrogram depicting the formation of four clusters. B.Heatmap depicting distribution of variables used in clustering C. Kaplan-Meier curve showing the survival function across the 4 clusters[Figure omitted. See PDF]REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone eclared.
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Background: We assessed the risk factors and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRD) who contracted infection while on background treatment with tofacitinib. Method(s): This is a non-interventional, cross-sectional, questionnaire based telephonic study which included consecutive AIRD patients on tofacitinib co-treatment. Data related to the AIRD subset, disease modifying anti rheumatic drugs (DMARDs) including glucocorticoids and comorbidities, was collected from 7 rheumatology centers across Karnataka during the second wave of COVID-19 pandemic. The information about COVID-19 occurrence and COVID-19 vaccination was recorded. Result(s): During the study period (June-July 2021), 335 AIRD patients (80.6% female) on treatment with tofacitinib were included. The mean duration of tofacitinib use was 3.4 +/- 3.1 months. Thirty-six (10.75%) patients developed COVID-19. Diabetes mellitus P = 0.04 (OR 2.60 [1.13-5.99]) was identified as a risk factors for COVID-19 in our cohort. Almost half of our cohort was COVID-19 vaccinated with at least one dose, with resultant decline in incidence of COVID-19 (OR 0.15 [0.06-0.39]) among the vaccinated. Recovery among COVID-19 infection group was 91.2%. Conclusion(s): The AIRD patients on co-treatment with tofacitinib had a higher incidence of COVID-19 than the general population during the same time period. Diabetes mellitus was identified as an independent risk factor in our cohort. COVID-19 vaccinated patients contracted COVID-19 at a significantly lesser rate than the non-vaccinated patients.
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Background: The differential influence and outcome of various risk factors on occurrence of COVID-19 among patients with autoimmune rheumatic diseases (AIRD) during different COVID-19 peaks is underreported. Aim(s): To assess the impact and outcome of conventional risk factors, immunosuppressants and comorbidities on the risk of COVID-19 among AIRD patients during the first two COVID-19 peaks. Design(s): Prospective, non-interventional longitudinal cohort study. Method(s): This is a subset of the KRA COVID19 cohort undertaken during the initial wave of COVID-19 (W1) (Apr-Dec 2021);and the 2nd-wave (W2) (Jan-Aug 2021). Data collected included description of AIRD subsets, treatment characteristics, comorbidities and COVID-19 occurrence. Risk factors associated with mortality were analyzed. The incidence rate was compared with that of the general population in the same geographic region. Result(s): AIRD patients (n = 2969) had a higher incidence of COVID-19 in the W2 (7.1%) than in the W1 (1.7%) as compared to the general population (Government bulletin). Age (P < 0.01) and duration of AIRD (P < 0.001) influenced COVID-19 occurrence in W2 while major disease subsets and immunosuppressants including glucocorticoids did not. The W2 had lower HCQ usage (aRR-0.81) and comorbidities like hypertension (aRR-0.54) and pre-existing lung disease (aRR-0.38;0.19-0.75) compared to W1. Older age (aRR-1.11) and coexistent diabetes mellitus (aRR 6.74) were independent risk factors associated with mortality in W2. Conclusion(s): We report 1.7 times higher occurrence and no influence of major disease subsets or immunosuppressants including glucocorticoids on COVID 19. Age and diabetes were independent risk factors for mortality.
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Objectives: This study was conducted to describe the use of tofacitinib in severe and critical Coronavirus disease -2019 (COVID-19), and to explore the association of drug initiation time with survival. Method(s): This was a retrospective chart review of inpatients with severe or critical COVID-19 at a tertiary care hospital, who received generic tofacitinib for at least 48 hours. The baseline demographics, comorbidities, treatment, adverse effects and outcomes (i.e. mortality at day 28) were analysed. The severity of COVID-19 was categorised as per WHO classification. Patients were further grouped based on median duration of symptomatic illness prior to tofacitinib administration, as early or late initiation groups. Result(s): Forty-one patients [(85.4% males), mean age 52.9 +/- 12.5 years], were studied. 65.9% (n = 27) of patients had severe COVID-19, while 34.1% (n = 14) were critically ill. Death occurred in 36.6% patients (n = 15). The median time to prescription of tofacitinib was 13 (9.50, 16.0) days of symptom onset. Tofacitinib was initiated early (8-13 days) in 56.1% of patients (n = 23), while the remaining received it beyond day 14 of symptom onset (late initiation group). The proportion of survivors was significantly higher in the early initiation group (21/23, 91.3%) compared to the late group (5/18, 27.8%) (P < 0.0001). Among severe COVID-19 patients, 100% and 62.5% of the patients were survivors among early and late initiation groups respectively (P < 0.01). In the critical COVID-19 patients, 50% were alive on day 28 in the early group while all died in the hospital in the late initiation group (P = 0.06). Multivariate logistic regression adjusted for age, presence of diabetes mellitus (DM) and illness duration prior to hospitalisation demonstrated higher odds of survival (AOR-19.3, 95% C.I. 2.57, 145.2) in the early initiation group, compared to the late initiation group. Conclusion(s): Early initiation of tofacitinib in severe and critical COVID-19 has potential to improve survival odds. (Table Presented).
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Background: Vaccine against COVID-19 is an effective preventive measure;however, systemic lupus erythematosus (SLE) patients were excluded from the vaccine trials, which leads to questions regarding vaccine safety and efficacy, giving rise to vaccine hesitancy. We aim to study the prevalence of vaccine hesitancy among SLE patients and study the factors affecting it. Method(s): The study is a cross-sectional telephone-based survey done on SLE patients. The questionnaire included a series of 15 questions pertaining to their baseline characteristics, COVID-19 infection and vaccination details, and their perceptions regarding the COVID-19 vaccine. Nonvaccinated individuals were defined as 'willing' and 'hesitant' based on their intent to get vaccinated. Result(s): Among 418 (93% women) participants, about 8% had contracted COVID-19 infection in the past. Nearly half had been vaccinated against COVID-19, and 83% had experienced one or more side effects which were largely mild. Out of the 215 nonvaccinated participants, 84% were 'willing' and 16% were 'hesitant.' Among the reasons for hesitancy, hasty vaccine production, fear of SLE flares, general vaccine refusal and limited transport facilities were significant. On the whole, 65.1% had a positive attitude toward the vaccine. Conclusion(s): Despite a low-hesitancy rate, the number of SLE patients with a negative attitude toward the COVID-19 vaccine is reasonably high, with more than half of the patients yet to be vaccinated. This highlights that the mistrust and negative perceptions of the vaccine still persists. The role of health-care providers in vaccine acceptance in SLE patients is crucial. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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Background: Patients with autoimmune rheumatic diseases (AIRD) may be at an increased risk for COVID-19 infection and poorer outcomes when compared with the general population. We undertook this study to estimate the risk of COVID-19 infection in our AIRD population and determine parameters which contribute to its occurrence. Methods: We prospectively recruited all consecutive AIRD patients on immunosuppressive therapy from 14 specialist rheumatology centers across south Indian state of Karnataka during current COVID-19 pandemic and followed them longitudinally. Results: Among 3807 participants, the majority were women (2.9:1), mean age was 43.8 (+14.3) years, rheumatoid arthritis (52.1%), and systemic lupus erythematosus (14.8%) were the most frequent diagnosis. Twenty-three (0.6%) patients contracted SARS-CoV-2 infection. Age >60 years (P = 0.01), diabetes (P = 0.009), hypertension (P = 0.001), preexisting lung disease (P = 0.0002), current prescription of either angiotensin-converting enzyme inhibitor or angiotensin receptor blockers (P = 0.01), and higher glucocorticoids dosage (P = 0.002) were identified as potential risk factors in our cohort. The past use of cyclophosphamide (P = 0.0001) or mycophenolate mofeti (P = 0.003) or biologics (P = 0.001) also had a significant association with COVID-19 infection. Hydroxychloroquine use did not influence occurrence or outcome. The presence of underlying lung disease (relative risk - 3.08, 95% confidence interval - 1.21, 8.44, P = 0.029) was the only independent risk factor associated with the risk of COVID positivity in the multivariate analysis. Incidence rate of COVID-19 infection was similar to that of the general population (P = 0.22). Conclusions: The incidence of SARS CoV-2 infection in AIRD population is comparable to the general population. Underlying lung disease was the most important risk factor apart from older age, diabetes, hypertension, and a higher glucocorticoid dosage. © 2021 Wolters Kluwer Medknow Publications. All rights reserved.