Efficacy and safety of belimumab in immune thrombocytopenia secondary to systemic lupus erythematosus

Efficacy and safety of belimumab in immune thrombocytopenia secondary to systemic lupus erythematosus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Efficacy and safety of belimumab in immune thrombocytopenia secondary to systemic lupus erythematosus Yan Liu, Guoxing Zeng, Qingyuan Yang, Junlai Xu, Yaoxiu Liu, Jinyue Huang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7238587/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective We aimed to investigate the safety and effectiveness of belimumab for patients with refractory immune thrombocytopenia (ITP) secondary to systemic lupus erythematosus (SLE) Method This is a multi-centre, retrospective cohort study. Data from patients with SLE–ITP received belimumab in addition to basic drug therapy between January 2017 and January 2025 were retrospectively analysed. Results Fourteen patients were included in the study. The overall response rate of thrombocytopenia was 72.7% at week 2 and week 4, 71.4% at week 12, and 78.6% at week 24. At week 24. Nine patients with OR successfully withdrew glucocorticoids (GCs) to < 15 mg prednisone. The SLE Disease Activity Index (SLEDAI), Physician Global assessment (PGA) scores, and the mean dosage of GCs were significantly decreased (p < .05). The serum C3, lgG, and lgM level did not significantly change, whereas the serum IgA level significantly decreased at week 24 and the serum C4 increased significantly at week 24. There were two patients with adverse effects during weeks 4–12. Conclusion Belimumab appears to be effective, safe, and well-tolerated in refractory ITP patients with SLE; larger studies are needed to confirm the generalizability of these findings. Health sciences/Diseases Biological sciences/Immunology Health sciences/Medical research Health sciences/Rheumatology Belimumab systemic lupus erythematosus immune thrombocytopenia Figures Figure 1 Figure 2 Figure 3 Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-system damage, including hematological abnormalities [ 1 ] . Immune thrombocytopenia (ITP) is a common hematological manifestation of SLE [ 2 ] . The generally accepted definition of systemic lupus erythematosus–associated immune thrombocytopenia (SLE-ITP) is an immunologically mediated thrombocytopenia brought on by SLE, after the ruling out other possible reasons, such as thrombotic microangiopathic syndromes or drug-induced illnesses, in individuals whose platelet counts are less than 100×10 9 /L [ 3 , 4 ] . Compared with primary ITP, the pathogenesis of ITP secondary to SLE is more complicated [ 5 ] . Patients with SLE and thrombocytopenia were found to be associated with an increased risk of mortality and end organ damage [ 6 ] . Intravenous immunoglobulin (IVIG) and glucocorticoids (GCs) are usually the first-line therapy for SLE-ITP. Similar to main ITP, roughly 60–80% of SLE-ITP Patients respond to glucocorticoids initially [ 7 ] . Oral or high-dose intravenous glucocorticoids can provide benefit in most patients with SLE-ITP in the early stages of treatment [ 8 ] , but this treatment is unlikely to be applied in the long term, and there is no agreement on the optimal hormone dosage to maintain. Additionally, with the gradual reduction of hormones, the risk of recurrence of thrombocytopenia in SLE-ITP patients also gradually increases and may develop refractory SLE–ITP [ 9 ] . Although IVIG can quickly raise platelet counts in SLE-ITP patients, its short half-life, high cost, and risk for severe adverse effects make it inappropriate for long-term maintenance treatment of SLE-ITP [ 10 ] . Therefore, the addition of second-line drugs is required for treatment, such as traditional immunosuppressants [ 11 ] .Second-line therapies include rituximab, splenectomy and immunosuppressants such as ciclosporin (CsA), azathioprine (AZA), mycophenolate mofetil (MMF) and cyclophosphamide (CTX) that primarily aim to control the destruction of antibody-coated platelets [ 12 , 13 ] .The involvement of B cells in the pathogenesis of lupus with immune thrombocytopenia is well recognized [ 14 ] .For patients with SLE-ITP, targeted B-cell treatments are now one of the primary therapy options. Over the years, numerous clinical studies of RTX have been conducted on primary ITP and SLE-ITP, with consistent results Rituximab(RTX) is a chimeric monoclonal antibody that has been demonstrated to attach to the B lymphocyte surface's CD20 antigen, preventing autoreactive B cell growth and lowering the generation of pathogenic antibodies [ 15 ] . However, the study showed that the initial response rate of RTX in primary ITP decreased gradually with the extension of treatment [ 16 ] . Other studies found that the B-cell depletion itself, by altering the splenic milieu, promoted the differentiation of short-lived auto-immune plasma cells into long-lived ones. These persistent plasma cells could be the cause of RTX treatment's ineffectiveness and protracted reaction time [ 17 ] . Belimumab(BLM) is a human immunoglobulin G1λ monoclonal antibody that inhibits B-cell survival and differentiation by neutralising soluble B lymphocyte stimulator, has been shown to reduce autoantibody levels in people with SLE and help control disease activity [ 18 ] . However, belimumab has less studied in improving blood system damage. Yuan et al. found that BLM resulted in a better overall response (OR) than RTX at two weeks in CTD-ITP [ 19 ] .BLM may be a safe and effective alternative to RTX for CTD–ITP. A retrospective cohort study showed that belimumab has significantly improved in thrombocytopenia [ 20 ] . Belimumab shows promising clinical outcomes in the treatment on patients with SLE-ITP. However, there is limited study on the effectiveness of belimumab for SLE-ITP. Therefore, in this study, we attempted to address this gap using real-world data by anlysis the efficacy and safety of belimumab in treating SLE–ITP. The findings of the study may help direct clinical practice, impact therapy choices, and enhance outcomes for patients with refractory SLE-ITP. Method Real-world data were collected retrospectively from multi-center(ZhuJiang Hospital, Southern Medical University, and Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital). All inpatients were recruited from January 2017 and January 2025. The inclusion criteria were as follows: (1) diagnosed with SLE according to the classification criteria respectively; (2) diagnosed with secondary ITP with a platelet count of < 100×10 9 /L; (3)no exposure to B cell-targeted therapy before treatment;(4)The indication for treatment in these patients is SLEDA score greater than 4;(5)All patients received intravenous injections of belimumab at a dosage of 10 mg/kg, initially administered every 2 weeks for the first 3 doses, and then once every 4 weeks. The exclusion criteria were as follows: (1) thrombocytopenia because of an infection, drug use or myeloid proliferative disorders such as aplastic anaemia and myelodysplastic syndrome; (2) Patients with incomplete follow-up information. Other data included the recording of platelet count, C3, C4, IgA, IgM, and IgG levels before and after treatment with Belimumab. SLEDAI, PGA scores, and the mean dosage of GCs were calculated before and after treatment. Adverse drug reactions during treatment were also recorded. The study was performed in accordance with the Declaration of Helsinki and received approval from the institutional ethics committee of Zhujiang Hospital of Southern Medical University(Approval number:2021-KY-062-01). Due to the retrospective nature of the study, the institutional ethics committee of Zhujiang Hospital of Southern Medical University waived the need to obtain informed consent. Response criteria Complete response (CR) was defined as platelet count ≥ 100×10 9 /L with no active bleeding [ 21 ] . Partial response (PR) was defined as a rise in platelet count of 50–100×10 9 /L and twice the baseline count, with no active bleeding. No response was defined as a platelet count that cannot achieve PR or CR. Overall response (OR) was defined as a platelet count that met PR or CR. Statistical analysis Group descriptive statistics were calculated for demographic and baseline characteristics. Continuous variables are reported as (IQR, interquartile range) or mean ± standard deviation (SD) as appropriate, while categorical variables are expressed as count (percentage).Paired sample t-tests were used to compare the data before and after treatment. If the data did not meet the normal distribution, the median (IQR) was used to represent the data, and Wilcoxon’s matched-pairs signed rank test was used to compare the data before and after treatment.The statistical analysis was performed using SPSS 27.0 software.The statistical graphs were plotted using GraphPad Prism 8 software. Results Patient characteristics A total of 14 patients (age 39.29 ± 20.46 years old) with patients were studied. All patients were diagnosed with SLE-ITP and received belimumab treatment chronically. Glucocorticoids and hydroxychloroquine are the basic treatment. The dose of belimumab administered was 10 mg/kg each time at week 0, 2 and 4, and then every 4 weeks, and the follow-up period was 6 months.The current results were analyzed at 2 weeks, 4 weeks ,12 weeks and 24 weeks after patients received treatment. Before receiving belimumab treatment, three initially diagnosed patients had not used other immunosuppressants, eleven patients had used other immunosuppressants. After receiving belimumab treatment, all patients were combined with glucocorticoids and hydroxychloroquine, 9 patients were combined with mycophenolate mofetil, 1 patient was combined with methotrexate, 4 patients were combined with cyclosporine, and 1 patients was combined with cyclophosphamide. Baseline demographics and disease characteristics of all patients are presented in Table 1 . Table 1 Baseline characteristics of and adverse events in patients N = 14 Age 39.29 ± 20.46 Female(%) 9(64.3%) SLE duration 3.06 ± 2.87 ITP duration 2.77 ± 2.76 aPL(%) 3(21.4%) Combined with LN 7(50%) Previous medication before belimumab Glucocorticoid(baseline, converting the dose of different kinds of GC into that of prednisone, mg/day) 42.43 ± 24.11 Mycophenolate mofetil 6(42.9%) Methotrexate 1(7.1%) Hydroxychloroquine 10(71.4%) Cyclosporine 3(21.4%) Tacrolimus 1(7.1%) Medication with belimumab Glucocorticoid(average dose of hormones during follow-up) 17.72 ± 13.38 Mycophenolate mofetil 9(64.3%) Methotrexate 2(14.3%) Hydroxychloroquine 14(100%) Cyclosporine 4(28.6%) Cyclophosphamide 1(7.1%) Adverse events Infection 2(14.3%) Efficacy of belimumab on SLE-ITP Changes in platelet count over time after belimumab treatment are shown in Fig. 1 A. The average of platenet counts before belimumab was 59.57 ± 28.85, the average of platenet counts was 148.50 ± 91.53 at 2 weeks(P = 0.03), 125 ± 62.05 at 4 weeks(P = 0.03), 155.62 ± 83.37 at 12 weeks(P = 0.006), and 178.64 ± 101.23 at 24 weeks(P = 0.004).The platelet counts significantly improved after belimumab.At week 2, 4, 8 and 12, the OR rate was 72.7%, 72.7%,71.4% and 78.6%.(Fig. 1 B) Changes in the immunological component levels in serum The serum C3 level slightly increased after treatment, but not significantly (Fig. 2 A). The serum C4 level at week 2, week 4, week 12 did not change significantly compared with that at week 0, but changed significantly at week 24(0.09 ± 0.07 vs 0.19 ± 0.15, P = 0.01) (Fig. 2 B). The serum IgA level was lower than that at week 0, with a significant decrease observed at week 4 (2.12 ± 0.60 vs 1.56 ± 0.67, p = 0.02)(Fig. 3 C). The serum IgM and IgG levels did not change significantly at any time point compared with those at week 0 (Fig. 2 D, 2 E). Changes in the SLEDAI, PGA score, and the mean dosage of GCs The SLEDAI at week 2(4.00 ± 1.89 vs 12.14 ± 6.27, P = 0.007), week 4(6.70 ± 2.67 vs 12.14 ± 6.27, P = 0.01), week 12(6.21 ± 4.49 vs 12.14 ± 6.27, P = 0.05), and week 24(4.54 ± 3.93 vs 12.14 ± 6.27, P = 0.002) changed significantly compared with that at week 0(Fig. 3 A). The PGA at week 2 (1.75 ± 0.54 vs 2.96 ± 0.69, P = 0.01), at week 4(1.60 ± 0.97 vs 2.96 ± 0.69, P = 0.006), at week 12(1.39 ± 0.53 vs 2.96 ± 0.69, P = 0.004), and at week 24(1.30 ± 0.63 vs 2.96 ± 0.69, P<0.001) were lower than that at week 0, the difference was significant(Fig. 3 B). Converting the dose of different kinds of GC into that of prednisone, the mean dosage of GC at week 12(13.46 ± 6.60 vs 42.43 ± 24.11, P = 0.005), at week 24(14.79 ± 10.37 vs 42.43 ± 24.11, P = 0.017) was lower than that at week 0, and the change was significant. Nine patients successfully withdrew GCs to < 15 mg prednisone with OR by week 24. (Fig. 3 C) Adverse effects Adverse reactions were observed in two patients, all of whom presented with a pulmonary infection that occurred during week 4–12 (Table 1 ). No other adverse event, such as an infusion-related reaction, was observed in this cohort. Discussion ITP is a common hematological manifestation of SLE, and it could be the initial symptom [ 22 ] . Severe thrombocytopenia is linked to a high death rate and is a poor prognostic factor for SLE [ 23 ] . B-cells play a role in the pathogenesis of SLE-ITP. Platelet antigens are primarily presented to T helper (Th) cells by macrophages and dendritic cells (DCs) in the spleen to help B cells differentiate into plasma cells that secrete autoantibodies [ 24 ] . B-cell involvement in ITP pathogenesis has led to the development of B-cell targeted therapy such as RTX, which depletes B cells expressing CD20 and inhibits the pathological function of these B cells. However, plasma cells do not express CD20 and thus are not depleted by RTX [ 25 ] .BEL is a human IgG1λ mAb directed at BAFF (also known as B lymphocyte stimulator [BLyS]) [ 26 ] .RTX spares plasma cells, thereby allowing continued pathogenic autoantibody production. Receptors for BAFF are present on plasma cells, so plasma cell function may be inhibited by BEL [ 25 ] .Maybe belimumab which targets the BAFF, has become a supplement to B-cell depletion therapy for primary ITP.However, there are few studies on the efficacy of belimumab for SLE-ITP.In this study, we performed a real-world investigation of beilimuab treatment for patients with SLE-ITP. Our results demonstrated that beilimuab might be an effective therapy for patients with ITP secondary to SLE who did not respond well to standard ITP treatment. In this study, after 14 patients who completed the study were treated with belimumab, C4, Platelet counts significantly increased (p < .05), lgA, SLEDAI, and PGA scores were significantly reduced (p < .05). The results were promising, with BLM achieving an OR rate of 72.7% in patients with SLE–ITP at 2 weeks after treatment, and an OR rate is 72.7% at 4weeks, 71.4% at 12 weeks, and 78.6% at 24 weeks. These results show that belimumab achieves a rapid response and continuous remission in a patient with SLE-ITP. These results demonstrate a significant therapeutic effect of belimumab on patients with SLE-ITP. In our study, eleven patients had used other immunosuppressants before receiving belimumab treatment, but their platelet counts remained low, respectively. Eight patients achieve OR, and the indicators of three patients improved, although they failed to achieve OR after belimumab treatment. This study indicates that it is a new option in patients with SLE–ITP. Three patients had achieved CR at week 12–24, started belimumab treatment at the first time of initial diagnosis of SLE-ILD, suggesting that patients could benefit earlier from early treatment with the drug. Although RTX and BEL each target B cells, rituximab is a monoclonal antibody (mAb) that binds to CD20 on the surface of B cell, and belimumab is a mAb that binds and neutralizes the B cell survival factor BAFF. [ 25 ] . In the pathogenesis of SLE-ITP, the plasma cells serve as the main source of antiplatelet antibodies [ 27 ] . However, RTX spares plasma cells, thereby allowing continued pathogenic autoantibody production. Receptors for BAFF are present on plasma cells, so plasma cell function may be inhibited by BEL [ 25 ] .Yuan et al. showed that the BLM group had a considerably higher OR rate than the RTX group,BLM is associated with a faster treatment response than RTX in refractory CTD–ITP [ 19 ] . Our study also show that beilimuab has a rapid response and continuous remission in a patient with SLE-ITP. Belilumab may also be used as a good option for the treatment of SLE-ITP. SLE-ITP patients frequently experience GC dependence, necessitating repeated high-dose GCs to maintain safe platelet levels. A significant proportion of the early and late damage during SLE treatment could be attributed to GC therapy [ 28 ] , and irreversible organ damage has been reported to be a predictor of morbidity and mortality in SLE [ 29 ] . Therefore, using GCs more restrictively should help prevent serious complications in patients with SLE. In our study, approximately half of the patients with GC dependence successfully reduced the GC dose to < 15 mg prednisone per day and maintained continuous remission. This encouraging result suggests that BLM could be beneficial in reducing GC in patients with SLE–ITP. In our study, two people had lung infection during 4–12 week, which may be associated with the persistently low levels of IgG. None of the patients with infections experienced worsening conditions or life-threatening complications after active treatment in our study. However, Infection should be a major concern in patients with CTD–ITP treated with BLM. There are limits to our investigation. First, our findings may not be as broadly applicable as they may be because of the smup period.The first factor that may restrict the generalizability of our findings is the small cohort size and the fact that the data came from only two centers. Consequently, it will be necessary to conduct large-scale, multi-center studies in the future to confirm its efficacy. The retrospective design also means that bias and missing data are unavoidable. Finally, relapse was not the study's primary objective due to the brief follow-up period. In conclusion, this study provides real-world evidence for BLM treatment as a practical option in patients with SLE–ITP toglucocorticoids (GCs) plus immunosuppressant agents (ISAs), particularly in those requiring a rapid platelet response and reduced the GC dose and maintained continuous remission. However, these suggestions need to be confirmed in large randomised clinical trials. Declarations Consent for publication: All authors have read and approved the final submitted manuscript. Competing Interest: The authors have no conflicts of interest to disclose. Funding: The authors received no funding for this work aPL:anti-phospholipid antibody including lupus anticoagulant, anti-cardiolipin antibody and anti-β2-glycoprotein 1 Author Contribution Y.L. and G.Z. wrote the main manuscript text, Q.Y., J.X., J.S., and Y.L. collected clinical data, and J.H.prepared figures 1-3. All authors reviewed the manuscript. Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References VELO-GARCíA, A., CASTRO S G & ISENBERG D A. The diagnosis and management of the haematologic manifestations of lupus [J]. J. Autoimmun. 74 , 139–160 (2016). ZHENG, Z. et al. Immune thrombocytopenia in patients with systemic lupus erythematosus [J]. Clin. Rheumatol. 44 (1), 97–104 (2025). NEWMAN, K. et al. 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Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years [J]. Rheumatol. (Oxford) . 48 (6), 673–675 (2009). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7238587","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":507712563,"identity":"ede9d1da-7656-43fa-b230-82b6b9384060","order_by":0,"name":"Yan Liu","email":"","orcid":"","institution":"Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Liu","suffix":""},{"id":507712564,"identity":"e63101a7-af87-4e5a-813b-94299e6725d8","order_by":1,"name":"Guoxing Zeng","email":"","orcid":"","institution":"Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Guoxing","middleName":"","lastName":"Zeng","suffix":""},{"id":507712565,"identity":"f558d1b2-f311-4cbc-bf62-933d9091d8b5","order_by":2,"name":"Qingyuan Yang","email":"","orcid":"","institution":"Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qingyuan","middleName":"","lastName":"Yang","suffix":""},{"id":507712566,"identity":"f755918e-a9fa-4d31-810e-04b245f357a0","order_by":3,"name":"Junlai Xu","email":"","orcid":"","institution":"Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junlai","middleName":"","lastName":"Xu","suffix":""},{"id":507712567,"identity":"cddceb82-5fa2-4fe2-a41b-5d7a535cea88","order_by":4,"name":"Yaoxiu Liu","email":"","orcid":"","institution":"Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yaoxiu","middleName":"","lastName":"Liu","suffix":""},{"id":507712568,"identity":"7b731e1f-ff6f-4305-8870-51c3e06cfafe","order_by":5,"name":"Jinyue Huang","email":"","orcid":"","institution":"Nanchang Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jinyue","middleName":"","lastName":"Huang","suffix":""},{"id":507712569,"identity":"297742b8-ac29-40e5-8ab7-cdac9da04f68","order_by":6,"name":"Ju Shao","email":"","orcid":"","institution":"ZhuJiang Hospital, Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ju","middleName":"","lastName":"Shao","suffix":""},{"id":507712570,"identity":"337ea90e-e100-43e0-a7dd-79b4f0140089","order_by":7,"name":"Shuiming Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIie3PsYrCQBCA4QkLazOYdgKirzAipAr4KhuUVAopU1gEIqa4O671MSyvvCOw16zW6VR8gdhZWBypT9xcd8V+9fzMDIDj/EOyV3zfFBP6vffzSWUre9JHrahJo0HwagSfjLYnQ1pwsG2SiOuFDM5r0eEwNDxBrhA+lzqLcwl++aIsv2zSWZt4+SGp448BkNnvLFuqXdUmwsvDOjYSmJaWhNS4aBMpIEzjjeiSzCfelhNEiSF0S1An0HCEhHJGymi0/jIqCw3qTtPp8fJ1vWWroV++PU9+wb+NO47jOA/9ALyWR9qbo6/+AAAAAElFTkSuQmCC","orcid":"","institution":"Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shuiming","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-07-29 03:38:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7238587/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7238587/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90795005,"identity":"a49b671d-4788-45b4-98eb-f9755db56bac","added_by":"auto","created_at":"2025-09-08 08:49:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16259,"visible":true,"origin":"","legend":"\u003cp\u003eA:Platelet counts of all patients at different time points;B:Response rate of patients receiving belimumab across different time points\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7238587/v1/248e4ff5b92b5a09e3ff9295.png"},{"id":90794193,"identity":"0185a95b-6213-4a5a-b7cf-58609964727b","added_by":"auto","created_at":"2025-09-08 08:41:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":22598,"visible":true,"origin":"","legend":"\u003cp\u003eMonitoring of key laboratory parameters during the study. (A) complement C3 level at different time points; (B) complement C4 level at different time points; (C) serum IgG level ; (D) serum IgA level at different time points; (E) serum IgM level at different time points\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7238587/v1/33a4d88bf3ea9f6bcd8a2a9d.png"},{"id":90795008,"identity":"8c34c854-9364-4a2a-bbd5-a2cf6fbbd413","added_by":"auto","created_at":"2025-09-08 08:49:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15580,"visible":true,"origin":"","legend":"\u003cp\u003e(A) SLEDAI of all patients at different time points;(B) PGA of patients at different time points;(C) The dose of glucocorticoids(prednisone, mg) at different time points\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7238587/v1/ad3f66b8971f7469bf9602c3.png"},{"id":93375265,"identity":"1f97c416-05ac-4956-af6a-7f568eaf66e3","added_by":"auto","created_at":"2025-10-13 07:39:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":651690,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7238587/v1/928b0ac9-ac10-4204-b739-b54f0a978e06.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and safety of belimumab in immune thrombocytopenia secondary to systemic lupus erythematosus","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-system damage, including hematological abnormalities\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Immune thrombocytopenia (ITP) is a common hematological manifestation of SLE\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The generally accepted definition of systemic lupus erythematosus\u0026ndash;associated immune thrombocytopenia (SLE-ITP) is an immunologically mediated thrombocytopenia brought on by SLE, after the ruling out other possible reasons, such as thrombotic microangiopathic syndromes or drug-induced illnesses, in individuals whose platelet counts are less than 100\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Compared with primary ITP, the pathogenesis of ITP secondary to SLE is more complicated\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Patients with SLE and thrombocytopenia were found to be associated with an increased risk of mortality and end organ damage\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIntravenous immunoglobulin (IVIG) and glucocorticoids (GCs) are usually the first-line therapy for SLE-ITP. Similar to main ITP, roughly 60\u0026ndash;80% of SLE-ITP Patients respond to glucocorticoids initially\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Oral or high-dose intravenous glucocorticoids can provide benefit in most patients with SLE-ITP in the early stages of treatment\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, but this treatment is unlikely to be applied in the long term, and there is no agreement on the optimal hormone dosage to maintain. Additionally, with the gradual reduction of hormones, the risk of recurrence of thrombocytopenia in SLE-ITP patients also gradually increases and may develop refractory SLE\u0026ndash;ITP\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Although IVIG can quickly raise platelet counts in SLE-ITP patients, its short half-life, high cost, and risk for severe adverse effects make it inappropriate for long-term maintenance treatment of SLE-ITP\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTherefore, the addition of second-line drugs is required for treatment, such as traditional immunosuppressants\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.Second-line therapies include rituximab, splenectomy and immunosuppressants such as ciclosporin (CsA), azathioprine (AZA), mycophenolate mofetil (MMF) and cyclophosphamide (CTX) that primarily aim to control the destruction of antibody-coated platelets\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.The involvement of B cells in the pathogenesis of lupus with immune thrombocytopenia is well recognized\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.For patients with SLE-ITP, targeted B-cell treatments are now one of the primary therapy options. Over the years, numerous clinical studies of RTX have been conducted on primary ITP and SLE-ITP, with consistent results Rituximab(RTX) is a chimeric monoclonal antibody that has been demonstrated to attach to the B lymphocyte surface's CD20 antigen, preventing autoreactive B cell growth and lowering the generation of pathogenic antibodies\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. However, the study showed that the initial response rate of RTX in primary ITP decreased gradually with the extension of treatment\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Other studies found that the B-cell depletion itself, by altering the splenic milieu, promoted the differentiation of short-lived auto-immune plasma cells into long-lived ones. These persistent plasma cells could be the cause of RTX treatment's ineffectiveness and protracted reaction time\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBelimumab(BLM) is a human immunoglobulin G1λ monoclonal antibody that inhibits B-cell survival and differentiation by neutralising soluble B lymphocyte stimulator, has been shown to reduce autoantibody levels in people with SLE and help control disease activity\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. However, belimumab has less studied in improving blood system damage. Yuan et al. found that BLM resulted in a better overall response (OR) than RTX at two weeks in CTD-ITP\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.BLM may be a safe and effective alternative to RTX for CTD\u0026ndash;ITP. A retrospective cohort study showed that belimumab has significantly improved in thrombocytopenia\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Belimumab shows promising clinical outcomes in the treatment on patients with SLE-ITP. However, there is limited study on the effectiveness of belimumab for SLE-ITP.\u003c/p\u003e\u003cp\u003eTherefore, in this study, we attempted to address this gap using real-world data by anlysis the efficacy and safety of belimumab in treating SLE\u0026ndash;ITP. The findings of the study may help direct clinical practice, impact therapy choices, and enhance outcomes for patients with refractory SLE-ITP.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eReal-world data were collected retrospectively from multi-center(ZhuJiang Hospital, Southern Medical University, and Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital). All inpatients were recruited from January 2017 and January 2025. The inclusion criteria were as follows: (1) diagnosed with SLE according to the classification criteria respectively; (2) diagnosed with secondary ITP with a platelet count of \u0026lt;\u0026thinsp;100\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L; (3)no exposure to B cell-targeted therapy before treatment;(4)The indication for treatment in these patients is SLEDA score greater than 4;(5)All patients received intravenous injections of belimumab at a dosage of 10 mg/kg, initially administered every 2 weeks for the first 3 doses, and then once every 4 weeks. The exclusion criteria were as follows: (1) thrombocytopenia because of an infection, drug use or myeloid proliferative disorders such as aplastic anaemia and myelodysplastic syndrome; (2) Patients with incomplete follow-up information.\u003c/p\u003e\u003cp\u003eOther data included the recording of platelet count, C3, C4, IgA, IgM, and IgG levels before and after treatment with Belimumab. SLEDAI, PGA scores, and the mean dosage of GCs were calculated before and after treatment. Adverse drug reactions during treatment were also recorded. The study was performed in accordance with the Declaration of Helsinki and received approval from the institutional ethics committee of Zhujiang Hospital of Southern Medical University(Approval number:2021-KY-062-01). Due to the retrospective nature of the study, the institutional ethics committee of Zhujiang Hospital of Southern Medical University waived the need to obtain informed consent.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResponse criteria\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eComplete response (CR) was defined as platelet count\u0026thinsp;\u0026ge;\u0026thinsp;100\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L with no active bleeding\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePartial response (PR) was defined as a rise in platelet count of 50\u0026ndash;100\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L and twice the baseline count, with no active bleeding.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eNo response was defined as a platelet count that cannot achieve PR or CR.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eOverall response (OR) was defined as a platelet count that met PR or CR.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eGroup descriptive statistics were calculated for demographic and baseline characteristics. Continuous variables are reported as (IQR, interquartile range) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) as appropriate, while categorical variables are expressed as count (percentage).Paired sample t-tests were used to compare the data before and after treatment. If the data did not meet the normal distribution, the median (IQR) was used to represent the data, and Wilcoxon\u0026rsquo;s matched-pairs signed rank test was used to compare the data before and after treatment.The statistical analysis was performed using SPSS 27.0 software.The statistical graphs were plotted using GraphPad Prism 8 software.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003ePatient characteristics\u003c/h2\u003e\u003cp\u003eA total of 14 patients (age 39.29\u0026thinsp;\u0026plusmn;\u0026thinsp;20.46 years old) with patients were studied. All patients were diagnosed with SLE-ITP and received belimumab treatment chronically. Glucocorticoids and hydroxychloroquine are the basic treatment. The dose of belimumab administered was 10 mg/kg each time at week 0, 2 and 4, and then every 4 weeks, and the follow-up period was 6 months.The current results were analyzed at 2 weeks, 4 weeks ,12 weeks and 24 weeks after patients received treatment. Before receiving belimumab treatment, three initially diagnosed patients had not used other immunosuppressants, eleven patients had used other immunosuppressants. After receiving belimumab treatment, all patients were combined with glucocorticoids and hydroxychloroquine, 9 patients were combined with mycophenolate mofetil, 1 patient was combined with methotrexate, 4 patients were combined with cyclosporine, and 1 patients was combined with cyclophosphamide. Baseline demographics and disease characteristics of all patients are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics of and adverse events in patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.29\u0026thinsp;\u0026plusmn;\u0026thinsp;20.46\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(64.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSLE duration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.06\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eITP duration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eaPL(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(21.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined with LN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(50%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious medication before belimumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlucocorticoid(baseline, converting the dose of different kinds of GC into that of prednisone, mg/day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.43\u0026thinsp;\u0026plusmn;\u0026thinsp;24.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMycophenolate mofetil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(42.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMethotrexate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(7.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHydroxychloroquine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10(71.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCyclosporine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(21.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTacrolimus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(7.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedication with belimumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlucocorticoid(average dose of hormones during follow-up)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17.72\u0026thinsp;\u0026plusmn;\u0026thinsp;13.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMycophenolate mofetil\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(64.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMethotrexate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(14.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHydroxychloroquine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14(100%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCyclosporine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(28.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCyclophosphamide\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(7.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse events\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(14.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEfficacy of belimumab on SLE-ITP\u003c/h3\u003e\n\u003cp\u003eChanges in platelet count over time after belimumab treatment are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA. The average of platenet counts before belimumab was 59.57\u0026thinsp;\u0026plusmn;\u0026thinsp;28.85, the average of platenet counts was 148.50\u0026thinsp;\u0026plusmn;\u0026thinsp;91.53 at 2 weeks(P\u0026thinsp;=\u0026thinsp;0.03), 125\u0026thinsp;\u0026plusmn;\u0026thinsp;62.05 at 4 weeks(P\u0026thinsp;=\u0026thinsp;0.03), 155.62\u0026thinsp;\u0026plusmn;\u0026thinsp;83.37 at 12 weeks(P\u0026thinsp;=\u0026thinsp;0.006), and 178.64\u0026thinsp;\u0026plusmn;\u0026thinsp;101.23 at 24 weeks(P\u0026thinsp;=\u0026thinsp;0.004).The platelet counts significantly improved after belimumab.At week 2, 4, 8 and 12, the OR rate was 72.7%, 72.7%,71.4% and 78.6%.(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eChanges in the immunological component levels in serum\u003c/h3\u003e\n\u003cp\u003eThe serum C3 level slightly increased after treatment, but not significantly (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). The serum C4 level at week 2, week 4, week 12 did not change significantly compared with that at week 0, but changed significantly at week 24(0.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 vs 0.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15, P\u0026thinsp;=\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). The serum IgA level was lower than that at week 0, with a significant decrease observed at week 4 (2.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.60 vs 1.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67, p\u0026thinsp;=\u0026thinsp;0.02)(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). The serum IgM and IgG levels did not change significantly at any time point compared with those at week 0 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD,\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eChanges in the SLEDAI, PGA score, and the mean dosage of GCs\u003c/h2\u003e\u003cp\u003eThe SLEDAI at week 2(4.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89 vs 12.14\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27, P\u0026thinsp;=\u0026thinsp;0.007), week 4(6.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67 vs 12.14\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27, P\u0026thinsp;=\u0026thinsp;0.01), week 12(6.21\u0026thinsp;\u0026plusmn;\u0026thinsp;4.49 vs 12.14\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27, P\u0026thinsp;=\u0026thinsp;0.05), and week 24(4.54\u0026thinsp;\u0026plusmn;\u0026thinsp;3.93 vs 12.14\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27, P\u0026thinsp;=\u0026thinsp;0.002) changed significantly compared with that at week 0(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). The PGA at week 2 (1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54 vs 2.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69, P\u0026thinsp;=\u0026thinsp;0.01), at week 4(1.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97 vs 2.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69, P\u0026thinsp;=\u0026thinsp;0.006), at week 12(1.39\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53 vs 2.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69, P\u0026thinsp;=\u0026thinsp;0.004), and at week 24(1.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63 vs 2.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69, P\u0026lt;0.001) were lower than that at week 0, the difference was significant(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Converting the dose of different kinds of GC into that of prednisone, the mean dosage of GC at week 12(13.46\u0026thinsp;\u0026plusmn;\u0026thinsp;6.60 vs 42.43\u0026thinsp;\u0026plusmn;\u0026thinsp;24.11, P\u0026thinsp;=\u0026thinsp;0.005), at week 24(14.79\u0026thinsp;\u0026plusmn;\u0026thinsp;10.37 vs 42.43\u0026thinsp;\u0026plusmn;\u0026thinsp;24.11, P\u0026thinsp;=\u0026thinsp;0.017) was lower than that at week 0, and the change was significant. Nine patients successfully withdrew GCs to \u0026lt;\u0026thinsp;15 mg prednisone with OR by week 24. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC)\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAdverse effects\u003c/h3\u003e\n\u003cp\u003eAdverse reactions were observed in two patients, all of whom presented with a pulmonary infection that occurred during week 4\u0026ndash;12 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No other adverse event, such as an infusion-related reaction, was observed in this cohort.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eITP is a common hematological manifestation of SLE, and it could be the initial symptom\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Severe thrombocytopenia is linked to a high death rate and is a poor prognostic factor for SLE\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. B-cells play a role in the pathogenesis of SLE-ITP. Platelet antigens are primarily presented to T helper (Th) cells by macrophages and dendritic cells (DCs) in the spleen to help B cells differentiate into plasma cells that secrete autoantibodies\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. B-cell involvement in ITP pathogenesis has led to the development of B-cell targeted therapy such as RTX, which depletes B cells expressing CD20 and inhibits the pathological function of these B cells. However, plasma cells do not express CD20 and thus are not depleted by RTX\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.BEL is a human IgG1λ mAb directed at BAFF (also known as B lymphocyte stimulator [BLyS])\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e.RTX spares plasma cells, thereby allowing continued pathogenic autoantibody production. Receptors for BAFF are present on plasma cells, so plasma cell function may be inhibited by BEL\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.Maybe belimumab which targets the BAFF, has become a supplement to B-cell depletion therapy for primary ITP.However, there are few studies on the efficacy of belimumab for SLE-ITP.In this study, we performed a real-world investigation of beilimuab treatment for patients with SLE-ITP. Our results demonstrated that beilimuab might be an effective therapy for patients with ITP secondary to SLE who did not respond well to standard ITP treatment.\u003c/p\u003e\u003cp\u003eIn this study, after 14 patients who completed the study were treated with belimumab, C4, Platelet counts significantly increased (p\u0026thinsp;\u0026lt;\u0026thinsp;.05), lgA, SLEDAI, and PGA scores were significantly reduced (p\u0026thinsp;\u0026lt;\u0026thinsp;.05). The results were promising, with BLM achieving an OR rate of 72.7% in patients with SLE\u0026ndash;ITP at 2 weeks after treatment, and an OR rate is 72.7% at 4weeks, 71.4% at 12 weeks, and 78.6% at 24 weeks. These results show that belimumab achieves a rapid response and continuous remission in a patient with SLE-ITP. These results demonstrate a significant therapeutic effect of belimumab on patients with SLE-ITP.\u003c/p\u003e\u003cp\u003eIn our study, eleven patients had used other immunosuppressants before receiving belimumab treatment, but their platelet counts remained low, respectively. Eight patients achieve OR, and the indicators of three patients improved, although they failed to achieve OR after belimumab treatment. This study indicates that it is a new option in patients with SLE\u0026ndash;ITP. Three patients had achieved CR at week 12\u0026ndash;24, started belimumab treatment at the first time of initial diagnosis of SLE-ILD, suggesting that patients could benefit earlier from early treatment with the drug.\u003c/p\u003e\u003cp\u003eAlthough RTX and BEL each target B cells, rituximab is a monoclonal antibody (mAb) that binds to CD20 on the surface of B cell, and belimumab is a mAb that binds and neutralizes the B cell survival factor BAFF.\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. In the pathogenesis of SLE-ITP, the plasma cells serve as the main source of antiplatelet antibodies\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. However, RTX spares plasma cells, thereby allowing continued pathogenic autoantibody production. Receptors for BAFF are present on plasma cells, so plasma cell function may be inhibited by BEL\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.Yuan et al. showed that the BLM group had a considerably higher OR rate than the RTX group,BLM is associated with a faster treatment response than RTX in refractory CTD\u0026ndash;ITP\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Our study also show that beilimuab has a rapid response and continuous remission in a patient with SLE-ITP. Belilumab may also be used as a good option for the treatment of SLE-ITP.\u003c/p\u003e\u003cp\u003eSLE-ITP patients frequently experience GC dependence, necessitating repeated high-dose GCs to maintain safe platelet levels. A significant proportion of the early and late damage during SLE treatment could be attributed to GC therapy\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, and irreversible organ damage has been reported to be a predictor of morbidity and mortality in SLE\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Therefore, using GCs more restrictively should help prevent serious complications in patients with SLE. In our study, approximately half of the patients with GC dependence successfully reduced the GC dose to \u0026lt;\u0026thinsp;15 mg prednisone per day and maintained continuous remission. This encouraging result suggests that BLM could be beneficial in reducing GC in patients with SLE\u0026ndash;ITP.\u003c/p\u003e\u003cp\u003eIn our study, two people had lung infection during 4\u0026ndash;12 week, which may be associated with the persistently low levels of IgG. None of the patients with infections experienced worsening conditions or life-threatening complications after active treatment in our study. However, Infection should be a major concern in patients with CTD\u0026ndash;ITP treated with BLM.\u003c/p\u003e\u003cp\u003eThere are limits to our investigation. First, our findings may not be as broadly applicable as they may be because of the smup period.The first factor that may restrict the generalizability of our findings is the small cohort size and the fact that the data came from only two centers. Consequently, it will be necessary to conduct large-scale, multi-center studies in the future to confirm its efficacy. The retrospective design also means that bias and missing data are unavoidable. Finally, relapse was not the study's primary objective due to the brief follow-up period.\u003c/p\u003e\u003cp\u003eIn conclusion, this study provides real-world evidence for BLM treatment as a practical option in patients with SLE\u0026ndash;ITP toglucocorticoids (GCs) plus immunosuppressant agents (ISAs), particularly in those requiring a rapid platelet response and reduced the GC dose and maintained continuous remission. However, these suggestions need to be confirmed in large randomised clinical trials.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConsent for publication:\u003c/h2\u003e\u003cp\u003e All authors have read and approved the final submitted manuscript.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting Interest:\u003c/strong\u003e\u003cp\u003eThe authors have no conflicts of interest to disclose.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThe authors received no funding for this work\u003c/p\u003e\u003cp\u003eaPL:anti-phospholipid antibody including lupus anticoagulant, anti-cardiolipin antibody and anti-β2-glycoprotein 1\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eY.L. and G.Z. wrote the main manuscript text, Q.Y., J.X., J.S., and Y.L. collected clinical data, and J.H.prepared figures 1-3. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVELO-GARC\u0026iacute;A, A., CASTRO S G \u0026amp; ISENBERG D A. The diagnosis and management of the haematologic manifestations of lupus [J]. \u003cem\u003eJ. Autoimmun.\u003c/em\u003e \u003cb\u003e74\u003c/b\u003e, 139\u0026ndash;160 (2016).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZHENG, Z. et al. Immune thrombocytopenia in patients with systemic lupus erythematosus [J]. \u003cem\u003eClin. Rheumatol.\u003c/em\u003e \u003cb\u003e44\u003c/b\u003e (1), 97\u0026ndash;104 (2025).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNEWMAN, K. et al. 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(Oxford)\u003c/em\u003e. \u003cb\u003e48\u003c/b\u003e (6), 673\u0026ndash;675 (2009).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Belimumab, systemic lupus erythematosus, immune thrombocytopenia","lastPublishedDoi":"10.21203/rs.3.rs-7238587/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7238587/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eWe aimed to investigate the safety and effectiveness of belimumab for patients with refractory immune thrombocytopenia (ITP) secondary to systemic lupus erythematosus (SLE)\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eThis is a multi-centre, retrospective cohort study. Data from patients with SLE\u0026ndash;ITP received belimumab in addition to basic drug therapy between January 2017 and January 2025 were retrospectively analysed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eFourteen patients were included in the study. The overall response rate of thrombocytopenia was 72.7% at week 2 and week 4, 71.4% at week 12, and 78.6% at week 24. At week 24. Nine patients with OR successfully withdrew glucocorticoids (GCs) to \u0026lt;\u0026thinsp;15 mg prednisone. The SLE Disease Activity Index (SLEDAI), Physician Global assessment (PGA) scores, and the mean dosage of GCs were significantly decreased (p\u0026thinsp;\u0026lt;\u0026thinsp;.05). The serum C3, lgG, and lgM level did not significantly change, whereas the serum IgA level significantly decreased at week 24 and the serum C4 increased significantly at week 24. There were two patients with adverse effects during weeks 4\u0026ndash;12.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eBelimumab appears to be effective, safe, and well-tolerated in refractory ITP patients with SLE; larger studies are needed to confirm the generalizability of these findings.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of belimumab in immune thrombocytopenia secondary to systemic lupus erythematosus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-08 08:41:45","doi":"10.21203/rs.3.rs-7238587/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"44d62bbb-9c77-4622-b1e8-cd8c516578cc","owner":[],"postedDate":"September 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53930716,"name":"Health sciences/Diseases"},{"id":53930717,"name":"Biological sciences/Immunology"},{"id":53930718,"name":"Health sciences/Medical research"},{"id":53930719,"name":"Health sciences/Rheumatology"}],"tags":[],"updatedAt":"2025-10-13T07:39:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-08 08:41:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7238587","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7238587","identity":"rs-7238587","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}