TNFSF13B rs9514828 C>T Polymorphism is Associated with Incidence of Atherosclerosis and Therapeutic Outcomes in Patients with Systemic Lupus Erythematosus.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous clinical manifestations. Organ involvement can aggravate patients with SLE and cause comorbidities such as atherosclerosis. Recently, the TNFSF13B gene has been found to be linked with SLE events. This study aimed to analyze the association between single nucleotide polymorphisms of the TNFSF13B rs9514828 with incidence of atherosclerosis and therapeutic outcomes in patients with SLE. Patients and Methods: This case-control study included 84 SLE patients, of whom 21 patients with SLE with atherosclerosis and 63 patients with SLE without atherosclerosis. Using enzyme-linked immunosorbent assay method, interleukin-6 and interferon gamma levels were quantified. The TNFSF13B gene polymorphism was evaluated using polymerase chain reaction followed by sequencing. The lupus low disease activity state (LLDAS) criteria were used to measure the therapeutic outcomes. Statistical analysis was conducted using binary logistic regression. Results: The genetic variations of TNFSF13B rs9514828 were CC = 35, CT = 41, and TT = 8. There was an association between TNFSF13B rs9514828 C>T polymorphism in patients with SLE with and without atherosclerosis (p = 0.03; odds ratio (OR) 4.72, 95% confidence interval [CI] 1.22-18.37). Furthermore, the TNFSF13B rs9514828 C>T polymorphism had association with the therapeutic outcomes of patients with SLE who manifested with LLDAS (p = 0.00; OR 7.58, 95% CI 2.61-21.99). Conclusion: The association of TNFSF13B rs9514828 C>T polymorphism and incidence of atherosclerosis as well as the therapeutic outcomes in patients with SLE indicate the potential utility of the gene variation as screening tool to employ personalized medicine to undertake preventive measures in order to prevent atherosclerosis and to predict a poor prognosis in SLE patient.

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study.

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

Significant Inverse Correlation of Serum Levels of Osteoprotegerin (OPG) and Transferrin Saturation in Thalassemia Dependent Transfusion (TDT) Patients.

BACKGROUND: Osteoporosis is a major problem in transfusion-dependent thalassemia patients (TDT) patients. Osteoprotegerin (OPG) is one of several bone markers that are closely associated with osteoporosis in TDT patients. OPG is a glycoprotein that functions as a feedback receptor for the Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), which is an alpha tumor necrosis factor receptor. One of the causes of decreased bone mass density is iron toxicity, which can be identified by showing elevated transferrin saturation. Bone mass dual X-ray absorptiometry (DEXA) is a gold standard for the diagnosis of osteoporosis, these procedures are not commonly available in Indonesia. This study was conducted to analyze the correlation between serum levels of OPG and transferrin saturation in TDT patients. METHODS: A correlational study with a cross-sectional approach analyzed data from TDT patients at Hemato-Oncology Medic Outpatient Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia. Primary data were obtained through blood sampling and anthropometry measurement while secondary data were obtained from the patient's medical records. OPG and transferrin saturation levels were assessed using the ELISA method. Research data were analyzed using the rank Spearman correlation test. RESULTS: Data were collected from 51 research subjects (30 women dan 21 men). The median OPG level was 380 (170-1230) pg/mL and the median transferrin saturation level was 89.4 (66.7 - 96.2)%. Analysis of correlation showed a significant correlation between and transferrin saturation level with a coefficient value of r -0.539 and p-value <0.001. CONCLUSION: There was a significant inverse correlation between OPG with transferrin saturation in TDT patients.

Global tuberculosis disease and infection in systemic lupus erythematosus patients: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is one of the most common infections among systemic lupus erythematosus (SLE) patients. We aimed to evaluate the global prevalence of TB infection and disease, its type, and medication risk factors in SLE patients. METHODS: We searched PubMed, Science Direct, EBSCO, and Web of Science databases from inception to April 30, 2023, and included studies assessing TB among SLE patients. We estimated the prevalence of TB disease (including type of TB disease), TB infection, and SLE medication as TB risk factors. Meta-analysis was performed using Stata 14.2 and Review Manager 5.3. RESULTS: Twenty-seven studies met the eligibility criteria. The global prevalence of TB disease was 4% (95% confidence interval (CI): 3-4%, n = 25) and TB infection was 18% (95% CI: 10-26%, n = 3). The pooled prevalence of pulmonary TB, extrapulmonary TB, and disseminated TB were 2% (95% CI: 2-3%, n = 20), 1% (95% CI: 1-2%, n = 17), and 1% (95% CI: 0-1%, n = 6), respectively. The 1-year cumulative glucocorticoid (GC) dose in SLE patients contracting TB was higher than in those without TB, having a mean difference of 2.56 (95% CI: 0.22-4.91, p < .00001, n = 3). The odd ratio of TB was 2.11 (95% CI: 1.01-4.41, p = .05, n = 3) in SLE patients receiving methylprednisolone (MP) pulse therapy as compared to those without MP pulse therapy. Other immunosuppressive agents were not significantly associated with TB. CONCLUSION: TB prevalence in SLE was relatively high and associated with GC. Awareness of TB and lowering GC dose are warranted to alleviate the TB burden in SLE.

Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State In Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus.

OBJECTIVE: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). METHODS: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. RESULTS: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. CONCLUSION: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).

Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study.

OBJECTIVES: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE). 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.

SMART-SLE: serology monitoring and repeat testing in systemic lupus erythematosus-an analysis of anti-double-stranded DNA monitoring.

OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

Genetic Polymorphisms Associated with Cyclophosphamide Outcome and Risk of Toxicity in Patients with Lupus Nephritis.

A 6-month cyclophosphamide induction therapy followed by maintenance therapy every three months is the first-line treatment for Class III, IV, and V lupus nephritis. Among the 139 single nucleotide polymorphisms (SNPs) associated with cyclophosphamide, four SNPs, namely rs4244285, rs4802101, rs7254579 and rs3957356, are related to the response and risk of toxicity in patients with lupus nephritis. Although pharmacogenetic studies in patients with lupus nephritis (LN) have not been conducted previously in Indonesia, data on rs4244285 are available for several ethnic groups, including Papuans, Bataks, Balinese, Dayaks, Javanese, Bugis, Chinese, Timorese and Malays, even though direct evidence in LN patients is less detectable. However, this can be followed up prior to cyclophosphamide therapy based on the identification of genetic markers. Therefore, clinical studies in patients with lupus nephritis are deemed necessary to evaluate the potential of these markers.

Generalized Reddish Skin Nodules.

Diagnosis of nodular red lesions is challenging. The differential diagnosis includes dermal nevus, angioma, pyogenic granuloma, amelanotic melanoma, eccrine poroma, Kaposi's sarcoma, skin malignancy or metastasis. Erythema nodosum is one of the common consideration of the red skin nodules, however fully work up should be done to find the right diagnosis.A 60 years old female admitted to our hospital due to pain dark reddish skin nodules since one month. She had continuously high grade fever of 39 Celsius accompanied by arthralgia and fatigue since two months prior to admission and she lost 6 kg of weight in 2 months. On admission, physical examination revealed slight fever, pale conjunctiva, mild hepatosplenomegaly, tender dark red nodules 0.3 to 2 cm, firm edge, at her cheek, abdominal area and both lower extremities. No lymph nodes enlargement was noticed. Her laboratory test showed haemoglobin 9,1 g/dl, WBC 3,040/mL, PLT 149,000/mL, SGOT 48 U/L, SGPT 43 U/L, urea 12.5 mg/dL, creatinine 0.67 mg/dL. She was found to be non-reactive for HBsAg, HCV, and HIV antigens. Urine routine and microscopic examination was unremarkable.Her histopathology of left foot nodule biopsy revealed cutaneous lymphoma. The immunohistochemical (IHC) stain of CD45, CD20, and CD10 were positive, Ki67 were also positive  with >70% tumor cells, while CD3,CD56, CD30, and Granzyme were negative. Her final diagnosed was Cutaneous Diffuse large B cell lymphoma.Primary cutaneous lymphomas of B-cells occur less frequently than primary cutaneous T-cells lymphomas. Primary extra-nodal diffuse large B-Cell lymphoma (DLBCL) can be seen in up to 40% of cases. However skin involvement is less common and in a large cohort of DLBCL cases, skin involvement at presentation was seen only in 3.3% of cases.It characterized by few lesions, in general showing nodules or infiltrations of relatively fast growth and have no itching. The diagnosis is made by the immunohistochemical findings, clinicopathological correlation, and molecular pathology.  The lymphomas have different clinical behaviours despite being identical in morphological appearance. The primary lymphomas presents with local recurrence in up to 68% of the cases and with rare extra-cutaneous dissemination, with an average rate of 5-year survival varying from 89 to 96%. Cutaneous lymphoma should be always become one of considered diagnosed of skin red nodules even it is rare.

Comparison of interferon-gamma production between TB1 and TB2 tubes of QuantiFERON-TB Gold Plus: a meta-analysis.

OBJECTIVES: CD8 T-cells play an important role in interferon-gamma (IFN-γ) production as a host defense against tuberculosis (TB) infection. Therefore, QuantiFERON-TB Gold Plus (QFT-Plus) was developed by adding a TB2 tube beside the TB1 tube. This study aimed to compare and analyze the difference in IFN-γ production between the two tubes in general and specific populations. CONTENT: PubMed, Web of Science, and EBSCO were searched for studies reporting IFN-γ production levels in the TB1 and TB2 tubes. Statistical analysis was performed using RevMan 5.3. SUMMARY: A total of 17 studies met the inclusion criteria. The IFN-γ production in the TB2 tube was statistically higher than that in the TB1 tube (mean difference (MD)=0.02, 95 % confidence interval (95 % CI): 0.01-0.03). Further subgroup analysis in specific populations revealed that the MD of IFN-γ production between the TB2 and TB1 tubes was significantly higher in active TB subjects than in latent TB infection (LTBI) subjects (MD=1.13, 95 % CI: 0.49-1.77, and MD=0.30, 95 % CI: 0.00-0.60, respectively). A similar finding was found in immune-mediated inflammatory disease subjects, but not statistically significant. Interestingly, IFN-γ production capacity was lower in active TB subjects than in LTBI subjects in each of the TB1 and TB2 tubes. OUTLOOK: This study is the first to systematically compare IFN-γ production between the TB1 and TB2 tubes. The IFN-γ production was higher in the TB2 tube than in the TB1 tube, representing the host's CD8 T-cell response magnitude to TB infection.

Secukinumab in Ankylosing Spondylitis Patients: A Cost-per-Responder Analysis from the Indonesian Health System Perspective.

OBJECTIVE: There are no publications that have demonstrated economic value for ankylosing spondylitis (AS) treatments in Indonesia. Cost per responder (CPR) is a lean method of economic evaluation. We estimated CPR from Indonesia's health system perspective following AS treatment with secukinumab relative to adalimumab, golimumab, and infliximab. METHODS: In the absence of head-to-head trials, a comparative evidence analysis was conducted in the form of matching-adjusted indirect comparison (MAIC) to estimate the response rate of various competing treatment options against secukinumab. This was followed by a CPR analysis that compared the cost per patient for a defined response level. RESULTS: Based on MAIC, patients on secukinumab had higher Assessment in Spondyloarthritis International Society (ASAS) 20 response (improvement of ≥ 20% and ≥ 1 unit in at least three domains on a scale of 10 and no worsening of ≥ 20% and ≥ 1 unit in remaining domain on a scale of 10) and ASAS 40 response (improvement of ≥ 40% and ≥ 2 units in at least three domains on a scale of 10 and no worsening at all in remaining domain) versus those on adalimumab, golimumab, and infliximab at week 24. The cost per ASAS 20 at week 24 for secukinumab was 75% lower than adalimumab, 65% lower than golimumab, and 80% lower than infliximab. The cost per ASAS 40 at week 24 for secukinumab was 77% lower than adalimumab, 67% lower than golimumab, and 83% lower than infliximab. Secukinumab dominated adalimumab, golimumab, and infliximab at week 24 and adalimumab at week 52, by being more efficacious at lower cost. Threshold analysis revealed that substantial reduction in efficacy or increase in cost of secukinumab would make secukinumab not cost effective, indicating the robustness of the results. CONCLUSION: This study demonstrated that if AS patients in Indonesia were treated with secukinumab instead of comparator therapies, more patients could be treated, and more patients would reach response to treatment for the same budget.

Association of Modified Systemic Lupus Erythematosus Responder Index Attainment With Long-Term Clinical Outcomes: A Five-Year Prospective Study.

OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up. 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 < 0.05 for damage accrual ORs at all time points). CONCLUSION: In SLE patients with active disease receiving standard of care, mSRI attainment predicts favorable outcomes over long-term follow-up, supporting the clinical meaningfulness of SRI attainment as an SLE trial end point.

Impact of low disease activity, remission, and complete remission on flares following tapering of corticosteroids and immunosuppressive therapy in patients with systemic lupus erythematous: a multinational cohort study.

BACKGROUND: Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission. METHODS: This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission. FINDINGS: Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare. INTERPRETATION: Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months. FUNDING: AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.

Management of non-renal manifestations of systemic lupus erythematosus: A systematic literature review for the APLAR consensus statements.

The prevalence of systemic lupus erythematosus (SLE) is higher in Asians than Caucasians, with higher frequency of renal and other major organ manifestations that carry a poorer prognosis. The outcome of SLE is still unsatisfactory in many parts of the Asia Pacific region due to limited access to healthcare systems, poor treatment adherence and adverse reactions to therapies. The Asia Pacific League of Associations for Rheumatology (APLAR) SLE special interest group has recently published a set of consensus recommendation statements for the management of SLE in the Asia Pacific region. The current article is a supplement of systematic literature search (SLR) to the prevalence and treatment of non-renal manifestations of SLE in Asian patients.

The association of psychosocial stressors and psychiatric disorders with fatigue in systemic lupus erythematosus patients.

BACKGROUND: In systemic lupus erythematosus (SLE), fatigue is the most common and aggravating symptom which has been reported to be influenced by several factors, such as disease activity, psychosocial stressors, and psychiatric disorders. Therefore, this study aims to determine the association between disease activity, psychosocial stressors, and psychiatric disorders with fatigue in SLE patients. METHOD: In this cross-sectional study, 73 female SLE patients were accepted to participate by filling out the informed consent. Besides, disease activity was divided into Lupus Low Disease Activity State (LLDAS) and non-LLDAS. The Holmes-Rahe Stress Scale and Fatigue Severity Scale (FSS) were employed to assess psychosocial stress and fatigue severity. The Mini-International Neuropsychiatric Interview (MINI) ICD-10 was used to examine psychiatric disorders. The Chi-square test was conducted to determine the association between dependent variables (fatigue) and independent variables (psychosocial stress, psychosocial stress severity, and psychiatric disorders). RESULT: Out of the participants, 49 (67.1%) suffered from fatigue, and the LLDAS group contained fewer individuals than non-LLDAS, 46.6% versus 53.4%. The majority (86.3%) also experienced psychosocial stress, ranging from mild to severe, and 56 (76.7%) patients had psychiatric disorders. No significant association was discovered between SLE disease activity and fatigue. However, fatigue had significant associations with psychiatric disorders in both LLDAS (p = 0.02) and non-LLDAS groups (p = 0.04), as well as with psychosocial stress severity (p = 0.02). Histories of major personal illness (p = 0.01) and changes in eating habits (p = 0.02) were associated with fatigue among the LLDAS participants. CONCLUSION: Psychosocial stressors and psychiatric disorders were significantly associated with fatigue in SLE. Histories of major personal disease and changes in eating habits were also significantly associated with fatigue in the LLDAS participants. Therefore, early recognition of these factors is necessary to manage and prevent fatigue in SLE patients.

Tuberculosis Among Patients With Systemic Lupus Erythematosus in Indonesia: A Cohort Study.

Background: In previous studies, researchers have identified systemic lupus erythematosus (SLE) as a risk factor for tuberculosis (TB), but data from TB-endemic countries are still relatively scarce. We examined TB in a large cohort of SLE patients in Indonesia. Methods: All patients registered in a lupus registry of the top referral hospital for West Java between 2008 and 2020 were included. Data on SLE characteristics and treatment were retrieved from the registry, and data on TB diagnosis, localization, and outcome were extracted from medical records. Cox-proportional hazard model was used to examine risk factors for development of TB. Results: Among 1278 SLE patients observed over a total of 4804 patient-years, 131 patients experienced 138 episodes of TB, a median of 2 years (interquartile range, 0.6-5.4) after diagnosis of SLE. A total of 113 patients (81.9%) had pulmonary involvement and 61 (44.2%) had extrapulmonary involvement, with disseminated disease in 26 of 138 episodes (18.8%), and 13 of 131 patients (9.9%) died from TB. The estimated TB incidence was 2873 cases per 100 000 person years. In multivariate cox regression analysis, development of TB was associated with household TB contact (hazard ratio [HR], 7.20; 95% confidence interval [CI], 4.05-12.80), pulse methylprednisolone therapy (HR, 1.64; 95% CI, 1.01-2.67), and age ≤25 years old at SLE diagnosis (HR, 1.54; 95% CI, 1.00-2.35). Conclusions: There is a high burden of TB in SLE patients in this TB-endemic setting, underlining the need for evaluation or implementation of TB preventive strategies.

Comparison of clinical presentation and outcome of childhood-onset and adulthood-onset of systemic lupus erythematosus among Indonesian patients.

INTRODUCTION: The clinical presentation of childhood-onset systemic lupus erythematosus (SLE) is generally perceived to differ from that of adult-onset SLE. OBJECTIVE: We aimed to compare the demographic and clinical manifestation between childhood-onset vs. adult-onset SLE in a cohort of Indonesian patients at tertiary care centers. METHODS: This retrospective study included patients in the Hasan Sadikin Lupus Registry from 2008 until December 2017. The demographics, clinical presentations, and outcomes were compared between childhood-onset SLE (<18 years old) (Group 1) and adult-onset SLE (≥18 years old) (Group 2). RESULTS: Eight hundred seventy patients were involved into this study. The proportion of childhood-onset SLE was 20% (174 patients). The mean age of group 1 versus group 2 was 13.56 ± 3.04 vs 30.41 ± 8.54 years. The following clinical manifestations at SLE diagnosis were significantly more common in childhood-onset than in adult-onset SLE patients: hematological disorder (p = 0.033) and arthritis (p = 0.006). While discoid rash (p = 0.036) and photosensitivity (p < 0.001) were significantly found higher in adult-onset SLE. Cyclophosphamide therapy was significantly more common to be used in childhood-onset (38.5% vs 21.0%, p = <0.001). However, frequency of mortality on follow-up tended to be higher in childhood-onset group (11.5% vs 7.0%, p = 0.208). CONCLUSION: Arthritis and hematologic involvements at SLE diagnosis were more prominent in childhood-onset compared to adult-onset patients, and mortality in childhood-onset SLE during follow-up relatively higher. This data may suggest the need for more aggressive management approach to childhood-onset patients with SLE.

Genetic Polymorphisms and the Clinical Response to Systemic Lupus Erythematosus Treatment Towards Personalized Medicine.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a broad spectrum of clinical manifestations, an aberrant autoimmune response to self-antigens, which affect organs and tissues. There are several immune-pathogenic pathways, but the exact one is still not well known unless it is related to genetics. SLE and other autoimmune diseases are known to be inseparable from genetic factors, not only pathogenesis but also regarding the response to therapy. Seventy-one human studies published in the last 10 years were collected. Research communications, thesis publication, reviews, expert opinions, and unrelated studies were excluded. Finally, 32 articles were included. A polymorphism that occurs on the genes related to drugs pharmacokinetic, such as CYP, OATP, ABC Transporter, UGT, GST or drug-target pharmacodynamics, such as FCGR, TLR, and BAFF, can change the level of gene expression or its activity, thereby causing a variation on the clinical response of the drugs. A study that summarizes gene polymorphisms influencing the response to SLE therapy is urgently needed for personalized medicine practices. Personalized medicine is an effort to provide individual therapy based on genetic profiles, and it gives better and more effective treatments for SLE and other autoimmune disease patients.

'Not at target': prevalence and consequences of inadequate disease control in systemic lupus erythematosus-a multinational observational cohort study.

BACKGROUND: The unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes. METHODS: Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) > 4, or ever experiencing high disease activity status (HDAS; SLEDAI-2K ≥10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI). RESULTS: A total of 3384 SLE patients were followed over 30,313 visits (median [IQR] follow-up 2.4 [0.4, 4.3] years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 [1.4, 4.9]; 34% of patients had AMS > 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS>4, and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR [95% CI] = 4.98 [2.07, 12.0], p<0.001) and HDAS-ever (adjusted hazard ratio (HR) [95% CI] = 5.45 [2.75, 10.8], p<0.001) patients. CONCLUSION: Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.

Patterns of Medication Use in Systemic Lupus Erythematosus: A Multicenter Cohort Study.

OBJECTIVE: Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort. METHODS: Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) and medication details, captured at every visit from 2013-2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time-to-discontinuation of medications, stratified by SLE disease activity. RESULTS: Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment; GC, AM, or IS only; GC plus AM; GC plus IS; AM plus IS; and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits, and biologics in only 3%. Time-to-discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time-adjusted mean SLEDAI-2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS. CONCLUSION: Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.