Systematic Review of Safety and Efficacy of Rituximab in Treating Immune-Mediated Disorders

Kaegi, Celine; Wuest, Benjamin; Schreiner, Jens; Steiner, Urs; Vultaggio, Alessandra; Matucci, Andrea; Crowley, Catherine; Boyman, Onur

doi:10.3389/fimmu.2019.01990

Cited by 170 publications

(122 citation statements)

References 109 publications

(167 reference statements)

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“…Possibly exposed was defined as a contact with a confirmed COVID-19 patient for more than 15 minutes, at less than 2 meters, and without adequate safety measures. Because of pre-existing comorbidities, seven patients were under immunosuppressive treatments, which comprised corticosteroids at stable doses, whereas patients taking B cell-depleting agents, such as rituximab, 22 were excluded. For longitudinal analyses of serum and mucosal SARS-CoV-2-specific antibody responses two subjects with mild COVID-19…”

Section: Human Subjects and Patient Characteristicsmentioning

confidence: 99%

Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

Cervia

Nilsson

Zurbuchen

et al. 2020

Preprint

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Background. Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 .Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear.Methods. Using immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR.Findings. On average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9-10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears.Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age.Interpretation. These data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.

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Section: Human Subjects and Patient Characteristicsmentioning

confidence: 99%

Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

Cervia

Nilsson

Zurbuchen

et al. 2020

Preprint

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“…Syeda et al, similarly, found the same treatment combination (rituximab, steroids, plasma exchange) effective in a single case [20]. Kaegi et al analyzed the safety and efficacy of rituximab in multiple immune-mediated disorders [21]. The study included three patients with anti-GBM disease [21].…”

Section: Anti-gbm Diseasementioning

confidence: 99%

“…Kaegi et al analyzed the safety and efficacy of rituximab in multiple immune-mediated disorders [21]. The study included three patients with anti-GBM disease [21]. After a follow-up of 33-49 months, anti-GBM antibodies became undetectable in all three patients, and only one of the patients remained dialysisdependent [21].…”

Section: Anti-gbm Diseasementioning

confidence: 99%

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Use of Rituximab in Management of Rapidly Progressive Glomerulonephritis

Cancarevic

Malik

2020

Cureus

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Rapidly progressive glomerulonephritis (RPGN) is a form of glomerulonephritis characterized by loss of renal function within weeks. Although a variety of underlying causes can trigger RPGN, the ultimate pathologic mechanism is the podocyte and epithelial activation leading to the crescent formation. Rituximab has been increasingly and successfully used for autoimmune conditions in recent years. Treatment of RPGN is based on the underlying condition, but specific clinical guidelines are lacking. In this article, we have tried to establish the role of rituximab in the management of patients with RPGN. All the studies we have used were found in the PubMed database, limited to studies involving adults. Animal studies and studies involving the pediatric population were excluded. The currently available literature does not support switching to rituximab as the first-line agent. It has failed to prove consistently superior to other medications. However, combined with other commonly prescribed treatment regimens, namely corticosteroids, with or without cytotoxic drugs, rituximab has shown efficacy in many studies. Therefore, we have concluded that the most prudent use of rituximab in patients with RPGN would be in those with disease refractory to standard management with corticosteroids and cytotoxic drugs or in those who have intolerable side effects. We believe that clinicians should keep reporting any cases of RPGN treated with rituximab so that a more clear pattern emerges and more exact treatment guidelines can be made.

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“…It has been used as a therapeutic biologic agent in B cell lymphoma and leukemia [12]. A systematic review has discussed about safety and efficacy of RTX in immune-mediated disorders [13]. A meta-analysis has shown high short-term benefit/risk ratio of RTX in AIHA [14].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis

Chao¹,

Chang

Yen³

et al. 2020

Exp Hematol Oncol

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Background: The efficacy and safety of rituximab (RTX) on hemolytic anemia (HA) is unknown. Therefore we retrospectively analyze the efficacy and safety of RTX in autoimmune hemolytic anemia (AIHA) and microangiopathic hemolytic anemia (MAHA) from the previous literature. Methods:Data in clinical trials and observational studies were collected from PubMed, Cochrane, Embase, and Google Scholar until Oct 15, 2018. The efficacy and safety of RTX in patients with AIHA or MAHA were assessed and overall response rates (ORRs), complete response rates (CRRs), adverse events (AEs) and relapse rates (RRs) were extracted if available. A meta-analysis was performed with a random-effects model, estimating mean proportions in all studies, and relative rates in comparative studies.Results: After quality assessment, a total of 37 investigations encompassing 1057 patients eligible for meta-analysis were included. Pooled mean proportion of ORR was 0.84 (95% confidence interval [CI] 0.80-0.88), and that of CRR was 0.61 (95% CI 0.49-0.73). Mean AE rate was 0.14 (95% CI 0.10-0.17), and mean RR was 0.21 (95% CI 0.15-0.26). Relative ORR was 1.18 (95% CI 1.02-1.36), and relative CRR was 1.17 (95% CI 0.98-1.39) fold more than the respective non-RTX counter parts. Relative AE rate was 0.77 (95% CI 0.36-1.63), and relative RR was 0.93 (95% CI 0.56-1.55) fold less than the respective non-RTX counter parts.Conclusion: RTX is more effective than the treatments without RTX for AIHA and MAHA and is well-tolerated. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Systematic Review of Safety and Efficacy of Rituximab in Treating Immune-Mediated Disorders

Cited by 170 publications

References 109 publications

Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

Use of Rituximab in Management of Rapidly Progressive Glomerulonephritis

Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis

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