Concomitant use of interleukin-2 and tacrolimus suppresses follicular helper T cell proportion and exerts therapeutic effect against lupus nephritis in systemic lupus erythematosus-like chronic graft versus host disease.

Introduction: Defective interleukin-2 (IL-2) production contributes to immune system imbalance in patients with systemic erythematosus lupus (SLE). Recent clinical studies suggested that low-dose IL-2 treatment is beneficial for SLE and the therapeutic effect is associated with regulatory T cell (Treg) expansion. Pharmacological calcineurin inhibition induces a reduction in the number of Tregs because they require stimulation of T cell receptor signaling and IL-2 for optimal proliferation. However, the activation of T cell receptor signaling is partially dispensable for the expansion of Tregs, but not for that of conventional T cells if IL-2 is present. Aim: We examined whether addition of IL-2 restores the Treg proportion even with concurrent use of a calcineurin inhibitor and if the follicular helper T cell (Tfh) proportion is reduced in an SLE-like murine chronic graft versus host disease model. Methods: Using a parent-into-F1 model, we investigated the effect of IL-2 plus tacrolimus on Treg and Tfh proportions and the therapeutic effect. Results: Treatment with a combination of IL-2 and tacrolimus significantly delayed the initiation of proteinuria and decreased the urinary protein concentration, whereas tacrolimus or IL-2 monotherapy did not significantly attenuate proteinuria. Phosphorylation of signal transducer and activator of transcription 3, a positive regulator of Tfh differentiation, was reduced by combination treatment, whereas phosphorylation of signal transducer and activator of transcription 5, a negative regulator, was not reduced. Conclusion: Addition of calcineurin inhibitors as adjunct agents may be beneficial for IL-2-based treatment of lupus nephritis.

[Jianpi Zishen granule inhibits podocyte autophagy in systemic lupus erythematosus: a network pharmacology and clinical study].

OBJECTIVE: To explore the therapeutic mechanism of Jianpi Zishen (JPZS) granules for systemic lupus erythematosus(SLE) in light of podocyte autophagy regulation. METHODS: TCMSP, GeneCards, OMIM, and TTD databases were used to obtain the targets of JPZS granules, SLE, and podocyte autophagy. The protein-protein interaction network was constructed using Cytoscape, and the key active ingredients and targets were screened for molecular docking. In the clinical study, 46 patients with SLE were randomized into two groups to receive baseline treatment with prednisone acetate and mycophenolate mofetil (control group) and additional treatment with JPZS granules (observation group) for 12 weeks, with 10 healthy volunteers as the healthy control group. Urinary levels of nephrin and synaptopodin of the patients were detected with ELISA. Western blotting was performed to determine peripheral blood levels of p-JAK1/JAK1, p-STAT1/STAT1, LC3II/LC3I, and p62 proteins of the participants. RESULTS: Four key active ingredients and 5 core target genes (STAT1, PIK3CG, MAPK1, PRKCA, and CJA1) were obtained, and enrichment analysis identified the potentially involved signaling pathways including AGE-RAGE, JAK/STAT, EGFR, and PI3K/Akt. Molecular docking analysis showed that STAT1 was the most promising target protein with the highest binding activity, suggesting its role as an important mediator for signal transduction after JPZS granule treatment. In the 43 SLE patients available for analysis, treatment with JPZS granule significantly reduced serum levels of p-JAK1/JAK1, p-STAT1/STAT1, and LC3II/LC3I (P < 0.05 or 0.01), increased the protein level of P62 (P < 0.05), and reduced urinary levels of nephrin and synaptopodin (P < 0.05). CONCLUSION: The therapeutic effect of JPZS granules on SLE is mediated probably by coordinated actions of quercetin, kaempferol, ß-sitosterol, and isorhamnetin on their target gene STAT1 to inhibit the JAK/STAT pathway, thus suppressing autophagy and alleviating podocyte injuries in SLE.

Analysis of belimumab prescription and outcomes in a 10-year monocentric cohort: is there an advantage with early use?

OBJECTIVE: The objective is to evaluate perscriptions of belimumab (BEL), how these have changed over the years and their impact on clinical outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This is a retrospective analysis of prospectively collected data. We retrieved demographic and clinical data and concomitant therapies at BEL starting (baseline). Disease activity was assessed at baseline and after 6 and 12 months and organ damage at baseline and at the last visit. RESULTS: From 422 patients followed in the Pisa SLE cohort, 102 patients received BEL and were included and 22 (21.6%) were immunosuppressant (IS)-naïve. Lupus Low Disease Activity State (LLDAS) with a glucocorticoid (GC) dosage ≤5 mg/day (LLDAS5) and remission were achieved by 47% and 38% of patients at 6 months, and by 75% and 66% at 12 months. Comparing IS-naïve patients with those who received BEL after at least one conventional IS, we did not find significant differences in baseline characteristics and in the achievement of LLDAS5 and remission. Despite at baseline we did not observe significant differences in mean GC daily dosage, IS-naïve patients were taking a significantly lower GC daily dose at 6 and 12 months. Interestingly, IS-naïve patients were more common in the most recent years. CONCLUSIONS: Our data confirm that BEL is effective in controlling disease activity, and in recent years BEL has been considered as an earlier treatment option before other IS. Early introduction of BEL can be at least as effective as a step-up approach and can help to reduce the GC dosage.

Novel and potential future therapeutic options in systemic autoimmune diseases.

Autoimmune inflammation is caused by the loss of tolerance to specific self-antigens and can result in organ-specific or systemic disorders. Systemic autoimmune diseases affect a significant portion of the population with an increasing rate of incidence, which means that is essential to have effective therapies to control these chronic disorders. Unfortunately, several patients with systemic autoimmune diseases do not respond at all or just partially respond to available conventional synthetic disease-modifying antirheumatic drugs and targeted therapies. However, during the past few years, some new medications have been approved and can be used in real-life clinical settings. Meanwhile, several new candidates appeared and can offer promising novel treatment options in the future. Here, we summarize the newly available medications and the most encouraging drug candidates in the treatment of systemic lupus erythematosus, rheumatoid arthritis, Sjögren's disease, systemic sclerosis, systemic vasculitis, and autoimmune myositis.

Risk factors for initial and recurrent severe infections in first hospitalized patients with systemic lupus erythematosus: A retrospective study of a Chinese cohort.

OBJECTIVE: To evaluate the incidence and associated factors of initial and recurrent severe infections in hospitalized patients with systemic lupus erythematosus (SLE). METHODS: SLE patients that first hospitalized between 2010 and 2021 were studied retrospectively and divided into SLE with and without baseline severe infection groups. The primary outcome was the occurrence of severe infection during follow-up. Cox regression models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for initial and recurrent severe infections. RESULTS: Among 1051 first hospitalized SLE patients, 164 (15.6%) had severe infection on admission. During a median follow-up of 4.1 years, 113 (10.8%) patients reached severe infection outcomes, including 27 with reinfection and 86 with initial severe infection (16.5% vs. 9.7%, p = .010). Patients with baseline severe infection had a higher cumulative incidence of reinfection (p = .007). After adjusting for confounding factors, renal involvement, elevated serum creatinine, hypoalbuminemia, cyclophosphamide, and mycophenolate mofetil treatment were associated with an increased risk of severe infection, especially initial severe infection. Low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use significantly increased the risk of recurrent severe infection, with adjusted HR (95% CI) of 3.15 (1.22, 8.14), 3.60 (1.56, 8.28), and 2.14 (1.01, 5.76), respectively. Moreover, baseline severe infection and low immunoglobulin had a multiplicative interaction on reinfection, with adjusted RHR (95% CI) of 3.91 (1.27, 12.09). CONCLUSION: In this cohort of SLE, patients with severe infection had a higher risk of reinfection, and low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use were independent risk factors for recurrent severe infection.

Effect of hydroxychloroquine blood concentration on the efficacy and ocular toxicity of systemic lupus erythematosus.

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6 months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990-0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ.

Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) frequently experience chronic pain due to the limited effectiveness and safety profiles of current analgesics. Understanding the molecular and synaptic mechanisms underlying abnormal neuronal activation along the pain signaling pathway is essential for developing new analgesics to address SLE-induced chronic pain. Recent studies, including those conducted by our team and others using the SLE animal model (MRL/lpr lupus-prone mice), have unveiled heightened excitability in nociceptive primary sensory neurons within the dorsal root ganglia and increased glutamatergic synaptic activity in spinal dorsal horn neurons, contributing to the development of chronic pain in mice with SLE. Nociceptive primary sensory neurons in lupus animals exhibit elevated resting membrane potentials, and reduced thresholds and rheobases of action potentials. These changes coincide with the elevated production of TNFα and IL-1ß, as well as increased ERK activity in the dorsal root ganglion, coupled with decreased AMPK activity in the same region. Dysregulated AMPK activity is linked to heightened excitability in nociceptive sensory neurons in lupus animals. Additionally, the increased glutamatergic synaptic activity in the spinal dorsal horn in lupus mice with chronic pain is characterized by enhanced presynaptic glutamate release and postsynaptic AMPA receptor activation, alongside the reduced activity of glial glutamate transporters. These alterations are caused by the elevated activities of IL-1ß, IL-18, CSF-1, and thrombin, and reduced AMPK activities in the dorsal horn. Furthermore, the pharmacological activation of spinal GPR109A receptors in microglia in lupus mice suppresses chronic pain by inhibiting p38 MAPK activity and the production of both IL-1ß and IL-18, as well as reducing glutamatergic synaptic activity in the spinal dorsal horn. These findings collectively unveil crucial signaling molecular and synaptic targets for modulating abnormal neuronal activation in both the periphery and spinal dorsal horn, offering insights into the development of analgesics for managing SLE-induced chronic pain.

[Low disease activity and remission status of systemic lupus erythematosus in a real-world study].

OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Non-thyroidal disease syndrome in patients with systemic lupus erythematosus: relation to disease inflammatory activity.

OBJECTIVE: To identify risk factors for the development of non-thyroidal illness syndrome (NTIS) in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective analysis of 517 SLE patients and 1034 age-and sex-matched healthy population was conducted to compare the prevalence of NTIS in these two groups, and to analyze the laboratory and clinical characteristics of SLE patients with NTIS. Finally Logistic regression analysis was used to determine the risk factors for NTIS in SLE patients. RESULTS: The prevalence of NTIS in the SLE patients was significantly higher than that in controls (39.7% vs. 1.0%, P < 0.001). In SLE patients, compared with euthyroidism patients, NTIS patients exhibited higher levels of neutrophils, hepatic enzymes, kidney damage markers, inflammatory markers and SLE disease activity index (SLEDAI). They also had a higher incidence of organ insufficiency and positive antibodies such as anti-ds-DNA antibodies and anti-SSA antibodies. However, NTIS patients had lower levels of hemoglobin, lymphocytes, platelets, serum albumin, and complement. Additionally, NTIS patients had a shorter duration of lupus and lower utilization of disease-modifying antirheumatic drugs (DMARDs) (P < 0.05). Logistic regression analysis showed that elevated SLEDAI (OR = 1.060, 95%CI 1.022-1.099, P = 0.002), elevated systemic immune-inflammation index (SII) (OR = 1.003, 95%CI 1.001-1.007, P = 0.026), elevated erythrocyte sedimentation rate (ESR) (OR = 1.019, 95%CI 1.010-1.028, P < 0.001), and hepatic insufficiency (OR = 1.916, 95% CI 1.173-3.131, P = 0.009) were independent risk factors for the development of NTIS in SLE. DMARDs treatment (OR = 0.495, 95% CI 0.306-0.799, P < 0.001) was an independent protective factor for NTIS. CONCLUSIONS: Inflammatory activity in SLE patients is associated with the development of NTIS. Key Points • Inflammatory activity indexes such as SLEDAI, SII, and ESR are independent risk factors for NTIS in SLE patients.

Rhupus syndrome in the pediatric population: A comprehensive systematic literature review.

INTRODUCTION: The term "Rhupus" was employed to descriptively illustrate the overlap observed in some pediatric patients displaying features of both juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE). Although "Rhupus" is traditionally used in adults, we applied it broadly to emphasize this clinical overlap. METHODS: We sought to identify studies that registered signs, symptoms, imaging characteristics, and treatments given to patients with JIA and SLE. We searched four databases using a Boolean search string, resulting in 231 articles after duplicate removal. Title and abstract screening yielded 57 articles for full-text assessment. Full reviewed 13 extracted data regarding sex, age of onset, serologic and imaging findings, and management strategies. The NIH quality assessment tool was applied to ensure the internal validity of the articles. RESULTS: From the 13 articles evaluated that meet inclusion criteria, none had standardized diagnostic algorithms. The total number of patients in those articles is 26, without discussing treatment guidelines. DISCUSSION: Clinical presentation, diagnostic parameters, and treatment of pediatric Rhupus were synthesized in this review. Fundamental keys help distinguish the joint presentation when Juvenile Idiopathic Arthritis or Lupus is present, compared with the signs and symptoms when developing the overlapping syndrome. We highlight the importance of physicians knowing about this rare condition and call all specialists to report new cases of the disease so a consensus can be reached to establish standardized guidelines for diagnosing and treating Rhupus syndrome.

Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count.

OBJECTIVE: To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values. METHODS: This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment. RESULTS: Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values. CONCLUSIONS: In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation.

Characterization of the patterns of care, access, and direct cost of systemic lupus erythematosus in Brazil: findings from the Macunaíma study.

BACKGROUND: A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil. METHODS: This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources.Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE. RESULTS: Overall, 300 patients with SLE were included (92.3% female,mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001). CONCLUSION: These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country.

Effect of remission, clinical remission with active serology, and glucocorticoid dosage on the pregnancy outcome of pregnant patients with systemic lupus erythematosus.

BACKGROUND: Remission is a key treatment target in systemic lupus erythematosus (SLE) management. Given the direct correlation between lupus flares and elevated risks of adverse pregnancy outcomes (APOs), securing remission before conception becomes crucial. However, the association between clinical remission with active serology, and the risk of APOs is not thoroughly understood. Additionally, determining the optimal glucocorticoid dosage during pregnancy to mitigate APO risks remains under-researched. This study investigated the risk of APOs in relation to remission/serological activity status in patients in clinical remission/glucocorticoid dosage. METHODS: Pregnant patients with SLE, who were followed up at two Japanese tertiary referral centers, and had their remission status assessed at conception, were included in this study. We categorized the patients into two groups based on whether they achieved Zen/Doria remission at conception and analyzed the APO ratio. We also examined the influence of serological activity in pregnant patients with clinical remission and analyzed the optimal glucocorticoid dosage to minimize the APO ratio. RESULTS: Of the 96 pregnancies included, 59 achieved remission at conception. Pregnant patients who achieved remission showed a significant decrease in the APO ratio compared with those who did not. (overall APO: odds ratio (OR) 0.27, 95% confidence interval (CI) 0.11-0.65, p < 0.01, maternal APO: OR 0.34, 95%CI 0.13-0.85, p = 0.021, neonatal APO: OR 0.39, 95%CI 0.17-0.90, p = 0.028). Conversely, no statistical difference was observed in the APO ratio based on serological activity in pregnant patients with clinical remission. (overall APO: OR 0.62, 95%CI 0.21-1.79, p = 0.37, maternal APO: OR 1.25, 95%CI 0.32-4.85, p = 0.75, neonatal APO: OR 0.83, 95%CI 0.29-2.39, p = 0.73). A glucocorticoid dose of prednisolone equivalent ≥ 7.5 mg/day at conception correlated with increased APO. (overall APO: OR 3.01, 95%CI 1.23-7.39, p = 0.016, neonatal APO: OR 2.98, 95% CI:1.23-7.22, p = 0.016). CONCLUSIONS: Even with active serology, achieving clinical remission can be a clinical target for reducing APOs in patients who wish to conceive. In addition, if clinically feasible, reducing the glucocorticoid dosage to < 7.5 mg/day before conception could be another predictive factor.

The economic burden of systemic lupus erythematosus in United Arab Emirates.

AIMS: Our study aims to provide an enhanced comprehension of systemic lupus erythematosus (SLE) burden in United Arab Emirates (UAE), over a five-year period from payer and societal perspective. MATERIALS AND METHODS: A Markov model was established to simulate the economic consequences of SLE among UAE population. It included four health states: i) the three phenotypes of SLE, representing mild, moderate, and severe states, and ii) death. Clinical parameters were retrieved from previous literature and validated using the Delphi panel-the most common clinical practice within the Emirati healthcare system. We calculated the disease management, transient events, and indirect costs by macro costing. One-way sensitivity analysis was conducted. RESULTS: The estimated number of SLE patients in our study was 13,359. The number of SLE patients with mild, moderate, and severe phenotypes was 3,914, 8,109, and 1,336, respectively. Disease management costs, including treatment of each phenotype and disease follow-up, were AED 2 billion ($0.89 billion), whereas the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were AED 1 billion ($0.44 billion). The productivity loss costs among adult-employed patients with SLE in the UAE were estimated at AED 7 billion ($3.1 billion). The total SLE cost over five years from payer and societal perspectives is estimated at AED 3 ($1.3 billion) and 10 billion ($4.4 billion), respectively. Additionally, the costs per patient per year from the payer and societal perspectives were AED 45,960 ($20,610) and AED 148,468 ($66,578), respectively. CONCLUSION: Our findings demonstrate that the burden of SLE in the UAE is enormous, mainly because of the costly complications and productivity loss. More awareness should be created to limit the progression of SLE and reduce the occurrence of flares, necessitating further economic evaluations of novel treatments that could help reduce the economic consequences of SLE in the UAE.

Economic burden of systemic lupus erythematosus in Malaysia.

INTRODUCTION: Our cost-of-illness (COI) model adopted the perspective of both payer and society over a time horizon of 5 years to measure the economic burden of systemic lupus erythematosus (SLE) in Malaysia. METHODOLOGY: Our COI model utilized a prevalence-based model to estimate the costs and economic consequences of SLE in Malaysia. The clinical parameters were obtained from published literature and validated using the Delphi panel. Direct and indirect medical costs were measured, including disease management, transient events, and indirect costs. One-way sensitivity analysis was also performed. RESULTS: The number of target Malaysian patients with SLE in the COI model was 18,121. At diagnosis, the numbers of SLE patients with mild, moderate, and severe phenotypes were 2,582, 13,897, and 1,642, respectively. The total SLE cost in Malaysia over 5 years from both payer and society perspectives was estimated at MYR 678 million and 2 billion, respectively. The results showed a considerable cost burden due to productivity losses resulting from SLE-related morbidity and mortality. Over a 5-year time horizon, the costs per patient per year from the payer and society perspectives were MYR 7,484 ($4766) and 24,281($15,465), respectively. CONCLUSION: Our study demonstrated the substantial economic burden of SLE in Malaysia over a time horizon of 5 years. It affects adults of working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Our COI model indicated that disease management costs among patients with higher disease severity were higher than those among patients with a mild phenotype. Hence, more attetion should be paid to limiting the progression of SLE and the occurrence of flares, with the need for further economic evaluation of novel treatments that could lead to better outcomes.

Microsimulation model of the cost-effectiveness of anifrolumab compared to belimumab in the United Arab Emirates.

INTRODUCTION: SLE imposes a significant morbidity and mortality as well as a substantial burden on the healthcare system. The model aimed to measure the cost-effectiveness of anifrolumab implementation against belimumab as an add-on-therapy to the standard of care (SoC) over a lifetime horizon for Emirati patients. METHODOLOGY: A microsimulation model was used to assess the cost-effectiveness of anifrolumab against belimumab (IV/SC) as an add-on therapy to SoC in a hypothetical cohort of adult Emirati patients with systemic lupus erythematosus (SLE) over a lifetime horizon. The clinical data was captured from published clinical trials as; TULIP-1, TULIP-2, BLISS-52, BLISS-76 and BLISS-SC. Health utility scores were constructed according to a linear regression model from the pooled data of the two TULIP Phase III trials of anifrolumab. Our model captures direct SLE-related medical costs from the Dubai Health Authority. Sensitivity analyses were conducted to assess model uncertainty. RESULTS: Using BICLA as a response criterion in the Johns Hopkins cohort, anifrolumab was found to be more effective than belimumab (IV/SC; the incremental discounted QALY of anifrolumab against belimumab was 0.42). The incremental cost-effectiveness ratio (ICER) of anifrolumab against belimumab IV and belimumab SC were AED 466,371 ($209,135) and AED 252,612 ($113,279), respectively, these ICERs are below the cost-effectiveness threshold in the United Arab Emirates (UAE) (three times gross domestic product capita; AED 592,278). In the Toronto lupus cohort, the ICER of anifrolumab against belimumab IV and belimumab SC were AED 491,403 ($220,360) and AED 276,642 ($124,055), respectively (anifrolumab was a cost-effective option vs. belimumab IV and belimumab SC). CONCLUSION: The addition of anifrolumab to SoC is a cost-effective option versus belimumab for the treatment of adult patients with active, autoantibody-positive SLE, despite being allocated to SoC. Cost-effectiveness was demonstrated by a reduction in complications and organ damage, which reflected costs and outcomes.

Identifying pregnancy episodes and estimating the last menstrual period using an administrative database in Korea: an application to patients with systemic lupus erythematosus.

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.