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.

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.

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.

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.

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.

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.

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.

[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.

Mezagitamab in systemic lupus erythematosus: clinical and mechanistic findings of CD38 inhibition in an autoimmune disease.

OBJECTIVE: To evaluate safety and mechanism of action of mezagitamab (TAK-079), an anti-CD38 monoclonal antibody, in patients with moderate to severe systemic lupus erythematosus (SLE). METHODS: A phase 1b double-blind, placebo-controlled, multicentre study was conducted in patients with SLE receiving standard background therapy. Eligible patients were adults who met the 2012 SLICC or ACR criteria for diagnosis, had a baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 and were positive for anti-double-stranded DNA antibodies and/or anti-extractable nuclear antigens antibodies. Patients received 45 mg, 90 mg or 135 mg of mezagitamab or placebo every 3 weeks over 12 weeks. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and pharmacodynamics. Exploratory assessments included disease activity scales, deep immune profiling and interferon pathway analysis. RESULTS: 22 patients received at least one dose of either mezagitamab or placebo. In patients exposed to mezagitamab (n=17), drug was well tolerated. Adverse event (AEs) were balanced across treatment groups, with no treatment emergent AEs exceeding grade 2. Responder analyses for Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and SLEDAI-2K did not reveal any observable differences across treatment groups. However, there was a trend for more profound skin responses among patients with higher CLASI scores (>10) at baseline. Pharmacodynamic analysis showed median CD38 receptor occupancy up to 88.4% on CD38+ natural killer cells with concurrent depletion of these cells up to 90% in the 135 mg group. Mean reductions in IgG and autoantibodies were less than 20% in all dose groups. Cytometry by time of flight and type 1 interferon gene analysis revealed unique fingerprints that are indicative of a broad immune landscape shift following CD38 targeting. CONCLUSIONS: Mezagitamab had a favourable safety profile in patients with moderate to severe SLE and elicited a pharmacodynamic effect consistent with CD38+ cell depletion. These findings reveal novel insights into the drug's mechanism of action and support the continued investigation of mezagitamab in autoimmune diseases.

Comparison of late-onset and non-late-onset systemic lupus erythematosus individuals in a real-world electronic health record cohort.

Objective: Late-onset systemic lupus erythematosus (LO-SLE) is defined as SLE diagnosed at age 50 years or later. Current studies on LO-SLE are small and have conflicting results.Methods: Using a large, electronic health record (EHR)-based cohort of SLE individuals, we compared demographics, disease characteristics, SLE-specific antibodies, and medication prescribing practices in LO (n = 123) vs. NLO-SLE (n = 402) individuals.Results: The median age (interquartile range) at SLE diagnosis was 60 (56-67) years for LO-SLE and 28 (20-38) years for NLO-SLE. Both groups were predominantly female (85% vs. 91%, p = 0.10). LO-SLE individuals were more likely to be White than NLO-SLE individuals (74% vs. 60%, p = 0.005) and less likely to have positive dsDNA (39% vs. 58%, p = 0.001) and RNP (17% vs. 32%, p = 0.02) with no differences in Smith, SSA, and SSB. Autoantibody positivity declined with increasing age at SLE diagnosis. LO-SLE individuals were less likely to develop SLE nephritis (9% vs. 29%, p < 0.001) and less likely to be prescribed multiple classes of SLE medications including antimalarials (90% vs. 95%, p = 0.04), azathioprine (17% vs. 31%, p = 0.002), mycophenolate mofetil (12% vs. 38%, p < 0.001), and belimumab (2% vs. 8%, p = 0.02).Conclusion: LO-SLE individuals may be less likely to fit an expected course for SLE with less frequent positive autoantibodies at diagnosis and lower rates of nephritis, even after adjusting for race. Understanding how age impacts SLE disease presentation could help reduce diagnostic delays in SLE.

The economic burden of systemic lupus erythematosus in Taiwan.

BACKGROUND: Our cost-of-illness (COI) model adopted both payer and societal perspectives over a time horizon of 5 years to measure the economic burden of systemic lupus erythematosus (SLE) in Taiwan. METHODOLOGY: A prevalence-based model was established to estimate the economic consequences of SLE after diagnosis in Taiwan. The model included four health states: (i) the three phenotypes representing mild, moderate, and severe SLE, and (ii) death. The inputs were obtained from a literature review of all the clinical trials and validated using a Delphi panel. The Delphi panel's insights included commonly used treatment strategies for patients with SLE within the Taiwanese healthcare system. The costs mentioned in this model are disease management, monitoring, transient event, and indirect costs. One-way sensitivity analyses were conducted to assess the model uncertainty. RESULTS: The number of patients with SLE in our COI model was 20,189. At diagnosis, the number of SLE patients with mild, moderate, and severe phenotypes was 5,916, 12,255, and 2019, respectively. The total SLE cost in Taiwan over 5 years from both payer and societal perspectives was estimated at TWD 3.9 and 47 billion, respectively. The costs per patient per year from the payer and societal perspective were TWD 38,775 ($2,758) and TWD 466,119 ($33,152), respectively. CONCLUSION: The findings demonstrated that the burden of SLE in Taiwan over a time horizon of 5 years is substantially high, mainly due to the consequences of economic loss as it affects women and men during their working age, in addition to the costs of SLE management and its consequences, such as flares, infection, and organ damage. Therefore, more attention should be paid to limiting the progression of SLE and the occurrence of flares, and further economic evaluations are necessary to assess novel treatment strategies that could control the disease.

A single-agent fusion of human IL-2 and anti-IL-2 antibody that selectively expands regulatory T cells.

The occurrence of many autoimmune diseases takes root on the disrupted balance among Treg cells, Teff cells, etc. Low-dose interleukin-2 (IL-2) cytokine demonstrates promising clinical efficacy in the expansion of Treg cells and the treatment of autoimmune diseases. However, its clinical application is hindered by the small therapeutic index and short half-life. Previous studies have shown that non-covalent complex of human IL-2 and anti-IL-2 antibody biases cytokine activity towards Treg cells and extends IL-2's half-life. The clinical translation of such complex is non-trivial. In this study, we discover an anti-human IL-2 antibody and engineer a covalently-linked single-agent fusion of human IL-2 and its antibody that selectively expands Treg cells and exhibits superior disease control activity in animal models of ulcerative colitis and systemic lupus erythematosus, with proper safety profile and good developability. These studies pave the road for its clinical development in diverse autoimmune diseases.

Pancytopenia with aplastic anemia in systemic lupus erythematosus: case series and literature review.

Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.

TYK2: an emerging therapeutic target in rheumatic disease.

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis. In vitro and animal studies substantiate these findings, highlighting a role for TYK2 in diseases currently managed by antagonists of cytokines that signal through TYK2. Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Phase II trials of deucravacitinib have also reported positive results in the treatment of psoriatic arthritis and systemic lupus erythematosus, with a preliminary safety profile that seems to differ from that of the JAK1, JAK2 and JAK3 inhibitors. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors.

The economic burden of systemic lupus erythematosus in Mexico.

AIMS: Our cost of illness study aimed to provide an estimate of the burden related to systemic lupus erythematosus (SLE) in the Mexican context. METHODS: Our model was used to simulate the resource utilization and economic consequences over a period of 5 years for patients with SLE in Mexico. The model simulated four health states-three phenotypes of SLE, including mild, moderate, and severe states, and death. Clinical parameters were retrieved from the literature. Resource utilization in our model represents the most common practice in the Mexican healthcare system. These include disease management, transient events (e.g. infections, flares, and complications due to SLE-related organ damage), and indirect costs. Direct non-medical costs were not considered. One-way sensitivity analysis was performed. RESULTS: The number of targeted Mexican SLE patients was 57,754. The numbers of SLE patients diagnosed with mild, moderate, and severe phenotypes were 8,230, 44,291, and 5,233, respectively. Disease management costs, including the treatment of each phenotype and disease follow-up, were MXN 4 billion ($ 415 million); the costs of transient events (infections, flares, and consequences of SLE-related organ damage) were MXN 5 billion ($ 478 million). Productivity loss costs among adult employed Mexican patients with SLE were estimated at MXN 17 billion ($ 1.6 billion). The total SLE cost in Mexico over 5 years from the payer and societal perspectives is estimated at MXN 9 billion ($ 893 million) and 26 billion ($ 2.5 billion), respectively. Over 5 years, the costs per patient per year from the payer and societal perspectives were MXN 32,131($ 3,095) and MXN 91,661($ 8,830), respectively. CONCLUSION: The findings pointed out the substantial economic burden associated with SLE, including the costs of disease progression and SLE transient events, such as flare-ups, infections, and organ damage, in addition to productivity loss due to work capacity impairment.

Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

OBJECTIVES: For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96 weeks of belimumab. METHODS: This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200 mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96 weeks. RESULTS: Forty-seven patients were enrolled, with a median daily prednisolone of 5 mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96 weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96 weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96 weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96 weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96 weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). CONCLUSIONS: Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96 weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.