METHODS: This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual.
RESULTS: Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p
METHODS: Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0.
FINDINGS: Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5-3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9-8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01-1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02-1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0-5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03-1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03-1·23], p=0·0144), and age at enrolment (1·04 [1·01-1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43-2·06], p=0·8675).
INTERPRETATION: Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity.
FUNDING: UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).
METHODS: Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses.
RESULTS: Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia.
CONCLUSION: Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.
METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied.
RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P
METHODS: We included patients from a multicentre longitudinal cohort (recruited between May 1, 2013, and Dec 31, 2019) with active SLE (SLEDAI-2K ≥6) coinciding with an abnormality in at least one of 13 routine laboratory tests, at a visit designated as baseline. At 12 months, we analysed associations between thresholds of improvement in individual laboratory test results, measured as continuous variables, and five clinical outcomes using logistic regression. Primary outcomes were damage accrual and lupus low disease activity state (LLDAS), and secondary outcomes were modified SLE responder index (mSRI), physician global assessment (PGA) improvement of at least 0·3, and flare.
FINDINGS: We included 1525 patients (1415 [93%] women and 110 [7%] men, 1328 [87%] Asian ethnicity) in separate subsets for each laboratory test. The strongest associations with LLDAS and damage protection were seen with improvements in proteinuria (complete response: adjusted odds ratio [OR] 62·48, 95% CI 18·79-208·31 for LLDAS, OR 0·22, 95% CI 0·10-0·49 for damage accrual), albumin (complete response: adjusted OR 6·46, 95% CI 2·20-18·98 for LLDAS, OR 0·42, 95% CI 0·20-1·22 for damage accrual), haemoglobin (complete response: adjusted OR 1·97, 95% CI 1·09-3·53 for LLDAS, OR 0·33, 95% CI 0·15-0·71 for damage accrual), erythrocyte sedimentation rate (complete response: adjusted OR 1·71, 95% CI 1·10-2·67 for LLDAS, OR 0·53, 95% CI 0·30-0·94 for damage accrual), and platelets (complete response: adjusted OR 4·82, 95% CI 1·54-15·07 for LLDAS, OR 0·49, 95% CI 0·20-1·19 for damage accrual). Improvement in serological tests were mainly associated with PGA and mSRI. White cell and lymphocyte count improvements were least predictive.
INTERPRETATION: Improvements in several routine laboratory tests correspond with clinical outcomes in SLE over 12 months. Tests with the strongest associations were discrepant with laboratory tests included in current trial endpoints, and associations were observed across a range of improvement thresholds including incomplete resolution. These findings suggest the need to revise the use of laboratory test results in SLE trial endpoints.
FUNDING: Abbvie.
METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred.
RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day.
CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.