Early diagnosis of lupus: A possibilty. A multicentric study from SLE Special Interest Group (SIG) of Indian Rheumatology Association (IRA).

INTRODUCTION: Systemic Lupus Erythematosus (SLE) warrants an early diagnosis and prompt management. Delay in diagnosis can result in repeated flares, permanent damage, and even death. There is a large variability in the time taken to diagnose SLE across the world. We undertook this study to determine the time taken for diagnosis of SLE in India and to identify the factors associated. METHODS: Patients with SLE diagnosed within the previous 1 year as per Systemic Lupus Erythematosus International Collaborating Clinics criteria (SLICC) 2012 criteria were included in a cross-sectional multicentre questionnaire-based survey. Demographic profile, self-reported socioeconomic status as per Kuppuswamy classification of socioeconomic status (version 2022) (SES), and several healthcare related parameters including referral pattern were recorded. Median time taken for diagnosis was used to demarcate early or late diagnosis and associated factors were explored. RESULTS: We included 488 patients with SLE from 10 rheumatology centres. The median time to diagnosis was 6 months Interquartile Range (IQR 3,14.7) and within 3 months in about one third [150(30.7%)]. Very early diagnosis (<1 month) was established in 78(16.0%) patients. The mean SLE Disease Activity Index (SLEDAI) at diagnosis was 10.28+7.24. In univariate analysis, an older age, lower SES, non-southern state of residence and larger family size were significantly associated with late diagnosis. In the multivariate analysis, higher SES (AOR 0.95, 95% CI: 0.92-0.98), multiple organ system involvement at initial presentation (AOR1.75 95%CI: 1.08-2.84) and place of residence in south Indian states (AOR1.92 95%CI: 1.24-2.97) had lesser odds of being associated with late diagnosis. Distance from the closest medical centre/professional did not influence the time to diagnosis. Majority of patients had first consulted a medical graduate (42.5%) or postgraduate doctor (48.2%), and referral to rheumatologist was largely done by postgraduate (65%) doctors. More than half of our patients (61%) self-finance their treatment. CONCLUSION: Median time to diagnosis of SLE was 6 months, 1/3rd being diagnosed within 3 months and 78(16.0%) with 1 month of symptom onset. Delay in diagnosis was noted in those belonging to lower socioeconomic strata and those with single organ disease. Distance to the health care facility did not influence time to diagnosis.

Clinical profiling, treatment characteristics and outcome in Behcet's Disease (BD)-A retrospective cohort study from Karnataka Rheumatology Association (KRA).

BACKGROUND: Behcet's disease (BD) has a heterogeneous and unpredictable phenotype that differs in various geographical areas. OBJECTIVE: To describe the clinical phenotype & outcome of Behcet's disease(BD) from Karnataka, India and compare them with large cohorts from endemic regions. METHODS: Databases of practising rheumatologists from Karnataka were reviewed to retrieve clinical characteristics, course of illness, prescribing information and outcome at last follow-up of patients clinically diagnosed as BD. The classification criteria, namely revised International criteria for Behcet's disease (rICBD) and International study group (ISG) criteria were applied. Outcome was defined as complete or partial remission, persistent disease or relapse. RESULTS: We included 72 patients, equal gender distribution and mean age 37.4 ± 12.8 years from 8 rheumatology centres. Commonest presentations were recurrent oral aphthosis 58(80.6%), genital ulcers 36(50%) and ocular manifestations 40(55.6%). Three-quarters [51/72(70.8%)] fulfilled rICBD criteria whereas only half [36/72(50%)] fulfilled ISG criteria. Apart from glucocorticoids [53/72(73.6%)], frequently prescribed therapies were colchicine 39(54.2%) and azathioprine 35(48.6%). Eleven-patients received biologics(anti-TNF-α) and JAK inhibitors to treat severe organ involvement. HLA-B*51 and pathergy tests were positive in 27/45(60%) and 12/34(35.3%) patients respectively. Outcomes were documented in 94.4%(68/72) patients at median follow-up of 24 (12;36) months. Majority [46/68(67.6%)] had complete remission, 17/68(25%) had partial remission, 4/68(5.9%) had persistent while 1/68(1.5%) had relapsing course. CONCLUSION: Majority of BD patients had orogenital aphthosis and ocular manifestations and an excellent response to treatment. Key Points • In our region, Behçet's Disease primarily manifests with recurrent oral aphthae and ocular involvement, with comparatively lower incidence of severe genital ulcers and neurological involvement than in endemic regions. • Apart from glucocorticoids, colchicine and azathioprine are the most commonly used agents. Biologics and JAK inhibitors are prescribed infrequently, primarily in cases of severe organ involvement. • A significant proportion of patients achieved either complete or partial remission during follow-up, with no observed mortality suggesting a milder disease course and better outcome compared to endemic regions. • Gender, HLA-B*51 status, and pathergy response did not exert any significant influence on the clinical profile or outcome in BD patients in Karnataka.

Effectiveness of generic tofacitinib in idiopathic inflammatory myositis (IIM)-a retrospective analysis from Indian Myositis Registry (MyoIN).

OBJECTIVES: Determine domain-based-outcomes and steroid-sparing efficacy of generic tofacitinib in IIM. METHODS: This is a multicenter retrospective study wherein clinical phenotype, autoantibody profile, prior immunosuppressives, and outcomes at 3, 6, and 12 months were retrieved for IIM patients prescribed tofacitinib. Overall clinical response was assessed as complete or partial remission as per physician judgment. Changes in cutaneous and calcinosis domain were recorded as per physician global assessment (PGA), lung domain as per medical research council (MRC) dyspnea scale, and muscle strength by Manual Muscle Testing-8 (MMT-8). RESULTS: Forty-two patients of IIM with mean age 38.7 ± 16 years; (76.2% (N = 32) women), median duration of illness 48 (19;88) months were included. Commonest indication for initiating tofacitinib was either for refractory or as steroid sparing for cutaneous domain (N = 25/42, 59.5%) followed by calcinosis (N = 16/42, 38%). Overall complete and/or partial remission was achieved in 23/37 (64.8%), 30/35 (85.7%), and 29/30 (96.6%) patients at 3, 6, and 12 months, respectively. At 12-month follow-up, there was a reduction in prednisolone dose, with absolute decrease from a daily dose of 17.5 mg (IQR 5;50) to 2.5 mg (IQR 0;5) (p < 0.001). Individual domain assessments revealed improvement in cutaneous domain [16/25 (64%)] and calcinosis [6/15 (40%)]. Adverse effects included herpes zoster (N = 2/42, 4.8%) and dyslipidemia (N = 4/42, 9.5%). CONCLUSIONS: Treatment with generic tofacitinib significantly reduces the daily dose of corticosteroids and is effective in cutaneous domain including calcinosis in IIM. KEY POINTS: • This multicenter retrospective study is the first real-world data from India, elucidating steroid sparing efficacy of generic tofacitinib in patients with inflammatory myositis. • Domain-based outcome assessment suggests good clinical improvement especially in cutaneous domain, even those with refractory disease. • Modest benefits were evident in calcinosis, but its effect on the muscle and pulmonary domain appears limited.

Critical peripheral ischemia: Higher prevalence in Indian systemic lupus erythematosus inception cohort for research (INSPIRE).

INTRODUCTION: There is limited literature on digital ischemia in systemic Lupus erythematosus (SLE). We report the prevalence, associations and outcome of digital infarcts and gangrene from the Indian SLE inception cohort (INSPIRE). METHODS: From the web-based database of INSPIRE, we extracted information for patients with 'Digital Infarct' and 'Digital gangrene' at enrolment into cohort, together considered as critical peripheral ischemia (CPI); all others were controls. We describe the associations of CPI with SLE clinical phenotype, autoantibodies, and disease activity at enrolment. We also report short term outcomes viz. Digital tissue loss and early mortality up to 6 months and recurrence of digital ischemic events in cases till date. RESULTS: Of 2503 SLE patients enrolled into the INSPIRE cohort, we identified 75 (2.9%) patients with CPI, 72 (96%) women and 6 (8%) children. Of them, 55 (73.3%) had digital gangrene and 21 (28%) patients had digital infarcts. Majority of digital gangrene resulted in amputation distal to terminal phalanx (63.6%). Multivariable analysis showed that pulmonary hypertension AOR [6.34 (1.99, 20.2)], coexistent thrombosis AOR [27.8 (15.7, 48.7)], triple antiphospholipid antibody positivity AOR [5.36 (1.67, 16.9)] and the presence of anti-Scl-70-antibody AOR [5.59 (1.86, 16.7)] were more likely while patients with class 3 or 4 lupus nephritis AOR [0.37 (0.15, 0.95)] and anti-nucleosome antibodies AOR [0.47 (0.23, 0.99)] were less likely to be associated with CPI. SLEDAI and short-term mortality were similar between cases and controls. CONCLUSIONS: CPI occurred in a higher proportion (2.9%) of SLE patients in the INSPIRE cohort as compared to earlier reports. Both prothrombotic state and vasculopathy contribute to its occurrence.

Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry.

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 (n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 (n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 (n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 (n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.

SARS-CoV-2 seroprevalence in patients with autoimmune rheumatic diseases versus family controls: a multi-city cross-sectional survey.

There is uncertainty regarding the effect of the SARS-CoV-2 infection on patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressive drugs. We did a multicity cross-sectional seroprevalence study conducted in five different cities in India before COVID-19 immunization. Patients with a diagnosis of AIRD and DMARDs were included. Relatives of the patients, preferably staying in the same household with no known rheumatic diseases served as controls. Serum IgG antibodies to SARS-CoV-2 Receptor Binding Domain (RBD) of the spike protein and nucleoprotein (NP) were assayed in eight hundred and eighty nine sera (subjects with disease = 379 and in subjects without disease = 510). IgG antibodies to either RBD and/or NP were positive in 135 (36%) subjects with AIRD as compared to 196 (38%) controls. The seroprevalence of anti-RBD and anti-NP varied between different cities but was not significantly different between subjects with and without disease in Mumbai, Ahmedabad, Bengaluru and Bhubaneswar. However, the occurrence of IgG antibodies to RBD was significantly (p < 0.05) lower in subjects with disease (28/65;43%) as compared to subjects without disease (42/65;65%) in Kolkata, where the positivity rate was lower in connective tissue disease group than in inflammatory arthritis group. Overall, patients with rheumatic diseases on DMARDs have IgG antibodies to RBD and NP of SARSCoV-2 at a comparable level with that of subjects without disease, but the level of antibodies to RBD is lower in patients with connective tissue disease on immunosuppressive drugs in one centre.

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.

A study to determine the effect of hydroxychloroquine (HCQ) on central corneal thickness (CCT) in patients with rheumatoid arthritis (RA).

PURPOSE: Corneal thinning is common in rheumatoid arthritis (RA), thereby affecting the central corneal thickness (CCT). Effect of hydroxychloroquine (HCQ) in RA has abounding literature on retinal toxicity, but there is lack of data on its corneal effects. METHODS: A cross-sectional study was carried out to compare CCT in RA patients before treatment initiation (Group 1) with CCT in those on HCQ for ≥3 months (Group 2). RESULTS: Fifty patients were enrolled in each group. The mean age was 44.36 years with similar age, gender distribution and visual acuity in both groups. The mean CCT of patients in the cohort was 521.80 µm ± 32.57 µm and 523.94 µm ± 33.40 µm in the right eye (RE) and left eye (LE), respectively. Mean CCT in Group 1 was (RE) 522.80 µm/(LE) 524.26 µm and in Group 2 was (RE) 520.80 µm/(LE) 523.62 µm, and there was no significant difference in CCT between both the groups. Median duration of HCQ usage in Group 2 was 24 months, with the median cumulative dosage being 171 g and a majority having a dosage of 200 mg/day. There was no significant correlation between the duration/cumulative dosage of HCQ intake and CCT. No corneal deposits were identified in any patient. CONCLUSION: CCT of RA patients was similar to those reported in the Indian literature. However, there was no significant change in CCT or corneal deposits identified with an HCQ dosage of 200-400 mg/day. Longer follow-up would provide clarity on the impact of duration and cumulative dosage of HCQ on corneal changes and CCT.

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.

Comparison of Risk Factors During First and Second Wave of COVID-19 in Patients with Autoimmune Rheumatic Diseases (AIRD): Results from KRACC Subset.

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: 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: Prospective, non-interventional longitudinal cohort study. Methods: This is a subset of the KRA COVID19 cohort undertaken during the initial wave of COVID-19 (W1) (Apr-Dec2021); and the 2nd-wave (W2) (Jan-Aug2021). Data collected included description of AIRD subsets, treatment characteristics, comorbidities, and COVID-19 occurrence. Risk factors associated with mortality were analysed. The incidence rate was compared with that of the general population in the same geographic region. Results: 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 (Adjusted Odds Ratio [AOR]-0.81) and comorbidities like hypertension (AOR -0.54) and pre-existing lung disease (AOR -0.38;0.19-0.75) compared to W1. Older age (1.11) and coexistent diabetes mellitus (AOR 6.74) were independent risk factors associated with mortality in W2. Conclusions: 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.

Occurrence and outcome of COVID-19 in AIRD patients on concomitant treatment with Tofacitinib- results from KRA COVID COHORT (KRACC) subset.

INTRODUCTION: 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. METHODS: 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. RESULTS: During the study period (Jun-July 2021), 335 AIRD patients (80.6% female) on treatment with tofacitinib were included. The mean duration of tofacitinib use was 3.4+/-3.1months. 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 factor 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 amongst COVID-19 infection group was 91.2%. CONCLUSIONS: The subset of AIRD patients who were on treatment with tofacitinib were found to have a higher rate of COVID-19 infection as compared to our KRACC cohort. Pre-existing comorbidity of diabetes mellitus was the significant risk factor in our cohort. This subset of the KRACC cohort shows RA patients had a lesser infection and PsA patients had a higher infection.

Severe thrombocytopenia is associated with high mortality in systemic lupus erythematosus-analysis from Indian SLE Inception cohort for Research (INSPIRE).

Thrombocytopenia in patients with systemic lupus erythematosus (SLE) is associated with higher morbidity and mortality. We report frequency, associations and short-term outcome of moderate-severe thrombocytopenia in a prospective inception cohort from India (INSPIRE). We evaluated consecutive SLE patients classified per SLICC2012 for the occurrence of thrombocytopenia and its associations. The outcomes assessed included bleeding manifestations, kinetics of thrombocytopenia recovery, mortality and recurrence of thrombocytopenia. Among a total of 2210 patients in the cohort, 230 (10.4%) had incident thrombocytopenia, of whom moderate (platelet count [PC] 20-50 × 109/L) and severe thrombocytopenia (PC < 20 × 109/L) were noted in 61 (26.5%) and 22 (9.5%), respectively. Bleeding manifestations were generally limited to the skin. Compared to controls, cases had a higher proportion of autoimmune haemolytic anaemia (p < 0.001), leukopenia (p < 0.001), lymphopenia (p < 0.001), low complement (p < 0.05), lupus anticoagulant (p < 0.001), higher median SLEDAI 2 K (p < 0.001) and lower proportion of anti-RNP antibody (p < 0.05). There was no significant difference in these variables between moderate and severe thrombocytopenia. There was a sharp rise in PC by 1 week that was sustained in the majority through the period of observation. There was three times higher mortality in the severe thrombocytopenia group as compared to moderate thrombocytopenia and controls. The thrombocytopenia relapse and lupus flare rates were similar across categories. We report a low occurrence of major bleeds and higher mortality in those with severe thrombocytopenia as compared to moderate thrombocytopenia and controls. Key Points • Severe thrombocytopenia occurs in 1% of patients with SLE; however, major bleeds are uncommon. • Thrombocytopenia has a strong association with other lineage cytopenias and lupus anticoagulants. • Response to initial glucocorticoids therapy is quick and is well sustained with additional immunosuppressants. • Severe thrombocytopenia increases mortality threefold in SLE.

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.

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.

Low-dose rituximab is efficacious in refractory idiopathic inflammatory myopathies.

OBJECTIVES: Rituximab (RTX) use early in the course of refractory idiopathic inflammatory myopathy (IIM) is not well studied. This study sought to determine the short-term efficacy of RTX in a registry-based cohort of refractory IIM. METHODS: Registry-based observational data about IIM patients receiving RTX between 2018 and 2021 were included. Total improvement score was calculated from the core set measures as per International Myositis Assessment and Clinical Studies group (IMACS) at baseline, 6 months and 12 months of follow-up. RESULTS: Forty-two patients (F:M, 29:13), with a mean (s.d.) age of 39.5 (11.5) years were studied. Majority of patients received RTX for refractory myositis, after a median (interquartile range) duration of 8 (4,18) months. Twenty-eight received RTX at a dosage of 1 g × two doses, while 14 received 500 mg × two doses with an interval of 15 days. At 6 months and 12 months post-RTX, the improvement was recorded in manual muscle testing (MMT-8) scores, physician global assessment (PGA), patient global assessment (PtGA) and median steroid dosage as compared with the baseline (P < 0.01 for all). A mean (s.d.) improvement of 44.5 (16) and 48.7 (19.2) in total improvement score was recorded at 6 and 12 months, respectively. The change in MMT-8, PGA and PtGA scores from baseline between the two dosage regimens of RTX were comparable at 6 and 12 months. Severe lower respiratory tract infections requiring hospitalization occurred in three patients of the cohort. CONCLUSION: RTX improved IMACS core set measures and had steroid sparing efficacy at 6 and 12 months in patients with IIM in this registry-based study. Rituximab as an induction regimen of two doses of 500 mg can be as efficacious as 1 g at 6 months and 12 months of follow-up.

Long Term Outcomes in Idiopathic Inflammatory Myositis: An Observational Epidemiologic Study over 15 Years.

Background: We report a longitudinal observational cohort of idiopathic inflammatory myositis (IIM) focusing on the long-term clinical outcome and associated parameters. Methods: IIM patients were classified as per Bohan and Peter criteria. In those with ≥ 24 months of follow-up; the treatment response, functional outcomes, and damage at last follow-up were recorded. Complete clinical response and clinical remission as defined by Oddis et al., was used to define outcomes at last follow-up. Results: The cohort consists of 175 patients, mean age 40.9 (+12.6) years, M:F 1:3.3; and the major subsets were dermatomyositis (44.6%), overlap myositis (25.7%), antisynthetase syndrome (6.3%), polymyositis (14.3%), and juvenile DM/OM (8.6%). Ninety-four patients have followed up for 24 months or more, with the median (IQR) of 65(35,100.7) months. Of them, 74.1% and 11.8% had complete and partial clinical responses respectively at the last follow-up. In our cohort 40.2% were off-steroids and 13.8% were in clinical remission at the last follow-up. Complete clinical response was associated with better functional outcomes and lesser damage as determined by HAQ-DI of 0[OR10.9; 95%CI (3.3,160)], MRS [OR 3.2; 95%CI (1.4,7.3)] and lesser MDI [OR 1.7; 95% CI (1.1,2.7)] respectively as compared to partial response (unadjusted analysis). Baseline parameters and IIM subsets did not significantly influence the functional outcome and damage. The mortality rate in our cohort is 24/175 (13.7%), the disease-specific mortality rate being 9.1%. Large majority of deaths were early, associated with active disease. Conclusion: We report good long-term outcomes in all major myositis subsets. Partial clinical response to treatment is associated with worse functional outcomes and damage accrual. Death occurs early in association with active disease.

Timing of tofacitinib therapy is critical to improving outcomes in severe-critical COVID-19 infection: A retrospective study from a tertiary care hospital.

Describe the use of tofacitinib in severe and critical coronavirus disease-2019 (COVID-19), and explore the association of drug initiation time with survival. A retrospective study of inpatients with severe or critical COVID-19 at a tertiary care hospital, who were prescribed generic tofacitinib for at least 48 hours, was conducted. Baseline demographics, comorbidities, illness severity, treatment, adverse effects and outcomes were analyzed. Patients were grouped based on median duration of symptomatic illness prior to tofacitinib administration, as early or late initiation groups. Forty-one patients ([85.4% males], mean age 52.9 ±â€…12.5 years), were studied. 65.9% (n = 27) 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). Multivariate logistic regression adjusted for age, presence of diabetes mellitus and illness duration prior to hospitalization demonstrated higher odds of survival (adjusted odds ratio 19.3, 95% confidence interval 2.57, 145.2) in the early initiation group, compared to the late initiation group. Early initiation of tofacitinib in severe and critical COVID-19 has potential to improve survival odds.

Neuropsychiatric manifestations are associated with increased mortality in Indian patients with lupus: A single centre retrospective observational study.

OBJECTIVE: To study the prevalence of different NPSLE manifestations in our cohort and to compare clinical and immunological features and outcomes including mortality of patients with NPSLE and SLE controls without NP involvement. METHODS: This was a retrospective study in a tertiary care referral centre. All patients of SLE seen in the last 10 years and fulfilling the SLICC criteria with neuropsychiatric manifestations as per the ACR definitions were included. Patients of SLE without NP involvement were sequentially assigned as controls in a ratio of 1:2. RESULTS: Of the 769 patients diagnosed with SLE from Jan 2011 to December 2020, 128 (16.6%) had NPSLE manifestations as per the ACR definitions. The commonest NPSLE manifestation was seizures (6.5%) followed by cerebrovascular accident (3.9%). NPSLE manifestation occurred at the first presentation of SLE in 99/128 (77.3%) patients and 58 (45.3%) patients had more than one NPSLE manifestation. Lupus anticoagulant and anticardiolipin antibody were tested in 120 patients and were positive in 16 (13.3%) and 12 (10%), respectively. No difference was found in anti-ribosomal p, lupus anticoagulant and anticardiolipin antibodies between the cases and controls. Twenty-one (16.4%) deaths occurred in patients with NPSLE (median follow-up of 40 months) as compared to 13 (5%) in controls (median follow-up of 32 months) (p = <0.001). The cumulative survival of patients with NPSLE was lower as compared to controls (p < 0.001). Relapse of NPSLE was seen in 11(8.6%) patients and was associated with mortality (p = 0.017). CONCLUSIONS: Seizures and cerebrovascular accidents are the commonest NPSLE syndromes in our patients. The presence of NPSLE was associated with high mortality in Indian patients with lupus.

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.

Current approach to diagnosis of inflammatory myopathies: Clinical features and myositis antibody profiles.

Diagnosis of inflammatory myositis has been made easier with the availability of commercial assays for myositis-specific and myositis-associated antibodies. Clinico-serological association studies have permitted a better definition of clinical subsets. Myositis-specific auto-antibodies are highly specific and non-overlapping, whereas myositis-associated antibodies are those seen also in other connective tissue disorders such as systemic lupus erythematosus, primary Sjogren's syndrome, and idiopathic pulmonary auto-immune fibrosis. Their value is pronounced when clinical features are subtle or non-specific or when the muscle is not the primary organ involved. Overall, the muscle-specific and myositis-associated antibodies have changed the landscape in terms of diagnostic utility, prognostication, and the approach to organ-specific evaluation and management of idiopathic inflammatory myopathies (IIMs).