Efficacy and safety of rituximab in comparison with common induction therapies in pediatric active lupus nephritis

Basu, Biswanath; Roy, Birendranath; Babu, Binu George

doi:10.1007/s00467-017-3583-x

Cited by 41 publications

(40 citation statements)

References 33 publications

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“…Three patients died during the follow-up period (due to invasive histoplasmosis, complications of surgery, and disease progression). In the controlled trials,13,33,35,36 the relative risks of the following adverse events were not significantly different between RTX and other immunosuppressive agents (CYC/MMF): infection, 0.81 (95% CI: 0.46–1.43, P >0.05) and infusion reaction, 2.18 (95% CI: 0.43–10.98, P >0.05).…”

Section: Resultsmentioning

confidence: 90%

<p>Clinical efficacy and safety of rituximab in lupus nephritis</p>

Zhong¹,

Li²,

Zhong

et al. 2019

DDDT

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BackgroundLong-term treatment programs with low toxicity represent a therapeutic challenge in lupus nephritis (LN). Although a therapeutic benefit of rituximab (RTX) has been reported in LN patients who have failed conventional treatment, the results are controversial. We aimed to assess the clinical efficacy and safety of RTX as a new immunosuppressive medicine in the treatment of LN with a meta-analysis.MethodsBased on predetermined criteria, PubMed, Embase, and Cochrane Library were used to identify the eligible studies. Cochrane Review Manager version 5.3 was applied to pool the data extracted from individual investigations and provide summary effect estimates.ResultsTwenty-four studies with 940 patients were analyzed. In case series trials with specific LN assessment, the complete remission (CR) rate at 12 months was 35.9% (95% CI: 24.2%–49.5%), and total remission (TR: CR plus partial remission) was 73.4% (95% CI: 66.0%–79.7%). In controlled trials, RTX was associated with a higher probability of TR (OR =2.02, 95% CI: 1.23–3.32, P<0.01). The CR in the RTX group was higher than that in the control group, although there was no significant difference between the two groups (OR =1.98, 95% CI: 0.90–4.39, P>0.05). Additionally, RTX treatment significantly decreased proteinuria (mean difference: −2.79, 95% CI: −3.95 to −1.62, P<0.01) as well as the renal activity index in patients with LN (mean difference: −3.46, 95% CI: −4.43 to −2.50, P<0.01). In controlled trials, the relative risks of the adverse events of infection and infusion reaction were not notably different between the two groups.ConclusionRTX is a promising therapy for the treatment of LN due to significant clinical efficacy and a favorable safety profile. In future studies, larger study populations and longer-term time points may identify additional important patient-centered outcomes.

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Section: Resultsmentioning

confidence: 90%

<p>Clinical efficacy and safety of rituximab in lupus nephritis</p>

Zhong¹,

Li²,

Zhong

et al. 2019

DDDT

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“…With recent advances in understanding of the underlying pathology, utilizing targeted biological agents in SLE patients properly has resulted in a significant improvement in prognosis. Nonetheless, the search for new therapeutic strategies is relentless because of the occurrence of refractory disease [2]. Mesenchymal stem cells (MSCs) are identified as promising and alternative cells because of their self-renewal, pluripotent differentiation ability and low immunogenicity [3].…”

Section: Introductionmentioning

confidence: 99%

Targeting HMGB1 by ethyl pyruvate ameliorates systemic lupus erythematosus and reverses the senescent phenotype of bone marrow-mesenchymal stem cells

Dong

et al. 2019

Aging

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs and systems. Mesenchymal stem cells (MSCs) from SLE patients have demonstrated defects such as impaired growth, senescence phenotype and immunomodulatory functions. Some studies have suggested the close connection between inflammation microenvironment and cellular senescence. In the current study, we detected cytokines levels in bone marrow supernatant by the quantitative proteomics analysis, and found the expression of HMGB1 was remarkably increased in bone marrow from SLE patients. Senescence associated-β-galactosidase (SA-β-gal) staining, F-actin staining and flow cytometry were used to detect the senescence of cells. After stimulation of HMGB1 in normal MSCs, the ratio of SA-β-gal positive in BM-MSCs was increased, the organization of cytoskeleton was disordered, and TLR4-NF-κB signaling was activated. Finally, Ethyl pyruvate (EP) (40 mg/kg and 100 mg/kg, three times a week), a high security HMGB1 inhibitor, was injected intraperitoneally to treat MRL/lpr mice for 8 weeks. We demonstrated that EP alleviated the clinical aspects of lupus nephritis and prolonged survival of MRL/lpr mice. In the meantime, EP reversed the senescent phenotype of BM-MSCs from MRL/lpr mice. HMGB1 could be a promising target in SLE patients, and might be one of the reasons of recurrence after MSCs transplantation.

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“…Furthermore, it is well tolerated and has a protective effect in reducing damage accrual in the long term and confers a survival benefit in SLE patients. A Danish registry-based cohort reported an found that rituximab may improve several symptoms and signs of SLE [19,[50][51][52]. In the present study, rituximab was utilized by almost 21% of SLE population.…”

Section: Discussionmentioning

confidence: 54%

“…Clinical trials have found a promising part for rituximab in the treatment of SLE [4,50,53]. A combination of rituximab with a short-term intensive steroid treatment and low doses of intravenous cyclophosphamide may be of use as an effective therapeutic strategy to reduce the adverse events related to long-term immunosuppression [7,19,50,51,54]. However, controlled trials especially for long-term outcome studies are awaited to further define its clinical application and to improve the care of patients.…”

Section: Discussionmentioning

confidence: 99%

“…Rituximab leads to apoptosis (cell death) of all the CD20-positive B cells [19,50]. Rituximab is becoming an alternative therapy to the possibly serious toxicities of immunosuppressive agents currently in use [19,51,52]. Trials considered and found that the following percentages of these medication were used in SLE population, 33% for ACEI, 17% ARBs 17% for CCB, 15% B blockers, 21% for diuretics, 9% for anti-diabetic, 60% for calcium with vitamin D and 23% for antihyperlipidemic therapies.…”

Section: Discussionmentioning

confidence: 99%

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2018

J Rheum Dis Treat

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Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that has various manifestations among different populations. This study aims to provide an overview of medical pharmacological management that SLE population received immediately at time of diagnosis. Method: This is a retrospective analysis using patients' registry medical information system. All patients diagnosed with SLE were reviewed by accessing their medical records including pharmacy prescription and dispersions at the Royal hospital from 2006 to 2014. The following comorbidities were analyzed: diabetes mellitus (DM), hypertension (HTN), hyperlipidemia, lung disease, cardiovascular disease (CVD), cerebrovascular accident (CVA), chronic kidney disease (CKD), end-stage kidney disease (ESKD), infections, thyroid disease, malignancy, and miscarriages. Results: There were 966 patients diagnosed with SLE during the period from 2006 to 2014. The Mean (SD) of age at presentation was 35.5 (11.5) years. Most patients were female (88.7%) with mean age of 27.6 (1.4) years. Unsurprisingly anti-malarial drug, hydroxychloroquine was used in 95% of SLE patients and steroid therapy was used in 93% in which 60.95% received Methylprednisolone pulse. The immunosuppressive agent of choice was Cyclophosphamide in 25.04%. Mycophenolic acid (MPA) medication in 39.85% and azathioprine in 37.06% of patients. Anti CD20 monoclonal antibodies, rituximab, was used in 20.91%. Calcineurin inhibitors were used in total of 11% of patients (cyclosporin a in 6.72% and tacrolimus in 4.35%). Conclusion: The complexity of SLE presentation have led to diverse pharmacotherapeutic strategies based on the organ systems involved. Management is individualized and depends on presenting symptoms and reducing the likelihood of permanent damage to organs and tissues. Strengthen health system at primary level and education of public and health work force is the main challenge to further improve the management. The overall aim of management was to determine the extent of disease and prevent extensive organ involvement and deal with various traditional and non-traditional CVD risk factors. The involvement of clinical pharmacist is very important to further strengthen the pharmacological management of lupus patients.

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Efficacy and safety of rituximab in comparison with common induction therapies in pediatric active lupus nephritis

Abstract: Efficacy and medium-term safety of RTX induction followed by MMF maintenance therapy in inducing and maintaining remission among children with LN were evident in this study.

Cited by 41 publications

References 33 publications

<p>Clinical efficacy and safety of rituximab in lupus nephritis</p>

<p>Clinical efficacy and safety of rituximab in lupus nephritis</p>

Targeting HMGB1 by ethyl pyruvate ameliorates systemic lupus erythematosus and reverses the senescent phenotype of bone marrow-mesenchymal stem cells

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