Immunreconstitution and Infectious Complications After Rituximab Treatment in Children and Adolescents:  What Do We Know and What Can We Learn from Adults?

Worch, Jennifer; Makarova, Olga; Burkhardt, Birgit

doi:10.3390/cancers7010305

Cited by 45 publications

(54 citation statements)

References 95 publications

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“…Hypogammaglobulinemia has been reported with chronic use of rituximab but mostly in patients with hematological malignancies. The incidence of hypogammaglobulinemia can range from 20 to 50% in patients treated for lymphoma [ 20 ] but is much lower in RA and ANCA-associated vasculitis (4% and 4.2%, respectively) [ 17 , 21 ]. A similar low incidence of 3% has been reported in MS patients by Salzer et al [ 11 ], but the drop in the aggregate serum IgG levels was slight.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study

Yamout

El-Ayoubi

Nicolas

et al. 2018

Journal of Immunology Research

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Objective To evaluate the efficacy and safety of rituximab in multiple sclerosis in a clinical practice setting. Methods Clinical data for all adult patients with multiple sclerosis (MS) treated with off-label rituximab at a single MS center in Lebanon between March 2008 and April 2017 were retrospectively collected from medical charts. The main efficacy outcomes assessed were annualized relapse rate (ARR) and proportion of patients free from relapses, disability progression, or magnetic resonance imaging (MRI) activity. Results A total of 89 rituximab-treated patients were included: 59 relapsing-remitting MS (RRMS) and 30 progressive MS (PMS). Patients were treated with 1000 or 2000 mg rituximab IV every 6–12 months for a mean duration of 22.2 ± 24.8 months. The subjects were 65.2% females with a mean age of 40.5 ± 12.3 years and a mean disease duration of 7.9 ± 6.2 years. During treatment, the ARR decreased from 1.07 at baseline to 0.11 in RRMS (p < 0.0001) and from 0.25 to 0.16 in PMS patients (p = 0.593). The mean Expanded Disability Status Scale (EDSS) remained unchanged in both RRMS and PMS patients. Between baseline and the last follow-up, the percent of patients free from any new MRI lesions increased from 18.6% to 92.6% in the RRMS group and from 43.3% to 82% in the PMS group. No evidence of disease activity (NEDA) was achieved in 74% of patients at 1 year of treatment. A total of 64 adverse events (AEs) (71.9%) were recorded with the most common being infusion-related reactions in 25.8% of patients, all mild in nature. Two of our rituximab-treated patients experienced serious AEs requiring surgical interventions: pyoderma gangrenosum vaginalis with perianal abscess and fistula and an increase in the size of a meningioma. No case of progressive multifocal leukoencephalopathy (PML) was detected. Conclusion In our real-world cohort, rituximab was well-tolerated and effective in reducing relapse rate and disability progression in relapsing-remitting and progressive MS patients.

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Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study

Yamout

El-Ayoubi

Nicolas

et al. 2018

Journal of Immunology Research

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“…Hypogammaglobulinemia has been reported with chronic use of rituximab but mostly in patients with hematological malignancies. The incidence of hypogammaglobulinemia can range from 20 to 50% in patients treated for lymphoma [20] but is much lower in RA and ANCA-associated vasculitis (4% and 4.2%, respectively) [17,21]. A similar low incidence of 3% has been reported in MS patients by Salzer et al [11], but the drop in the aggregate serum IgG levels was slight.…”

Section: Discussionmentioning

confidence: 57%

Safety and efficacy of rituximab in multiple sclerosis: A retrospective observational study

Zeineddine¹

2017

Preprint

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Objective. To evaluate the efficacy and safety of rituximab in multiple sclerosis in a clinical practice setting. Methods. Clinical data for all adult patients with multiple sclerosis (MS) treated with off-label rituximab at a single MS center in Lebanon between March 2008 and April 2017 were retrospectively collected from medical charts. The main efficacy outcomes assessed were annualized relapse rate (ARR) and proportion of patients free from relapses, disability progression, or magnetic resonance imaging (MRI) activity. Results. A total of 89 rituximab-treated patients were included: 59 relapsing-remitting MS (RRMS) and 30 progressive MS (PMS). Patients were treated with 1000 or 2000 mg rituximab IV every 6-12 months for a mean duration of 22.2 ± 24.8 months. The subjects were 65.2% females with a mean age of 40.5 ± 12.3 years and a mean disease duration of 7.9 ± 6.2 years. During treatment, the ARR decreased from 1.07 at baseline to 0.11 in RRMS (p < 0 0001) and from 0.25 to 0.16 in PMS patients (p = 0 593). The mean Expanded Disability Status Scale (EDSS) remained unchanged in both RRMS and PMS patients. Between baseline and the last follow-up, the percent of patients free from any new MRI lesions increased from 18.6% to 92.6% in the RRMS group and from 43.3% to 82% in the PMS group. No evidence of disease activity (NEDA) was achieved in 74% of patients at 1 year of treatment. A total of 64 adverse events (AEs) (71.9%) were recorded with the most common being infusionrelated reactions in 25.8% of patients, all mild in nature. Two of our rituximab-treated patients experienced serious AEs requiring surgical interventions: pyoderma gangrenosum vaginalis with perianal abscess and fistula and an increase in the size of a meningioma. No case of progressive multifocal leukoencephalopathy (PML) was detected. Conclusion. In our real-world cohort, rituximab was well-tolerated and effective in reducing relapse rate and disability progression in relapsing-remitting and progressive MS patients.

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“…In this regards, reports showed that RTX treatment is associated with immune reconstitution and B-cells recovery, which usually starts 6 months after therapy with complete recovery to normal levels in 9-12 months. 30 Moreover, it was also demonstrated that patients who receive extended RTX treatment showed no evidence of increasing clinically relevant infection. 30 Our study adds support to the concept of using this drug for extended time.…”

Section: Discussionmentioning

confidence: 99%

“…30 Moreover, it was also demonstrated that patients who receive extended RTX treatment showed no evidence of increasing clinically relevant infection. 30 Our study adds support to the concept of using this drug for extended time. This approach might help in the adoption of novel management strategies with the aim of sufficiently administrating RTX far enough in advances to prevent disease progression or relapse.…”

Section: Discussionmentioning

confidence: 99%

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

Al‐Ani¹,

Raju²,

Hachim³

et al. 2020

JIR

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Objective: To investigate, in detail, the effects of rituximab (RTX), an off-label drug for treating multiple sclerosis (MS) disease on preventing and/or ameliorating experimental autoimmune encephalomyelitis (EAE). Methods: Using bioinformatics analysis of publicly available transcriptomics data, we determined the accumulation of B cells, plasma cells and T cells in different compartments of multiple sclerosis patients (MS) and healthy individual brains. Based on these observations and on the literature search, we dosed RTX in EAE mice either orally, or injected intraperitoneally (IP). The latter route was used either prophylactically (asymptomatic stage; upon the induction of the disease), or therapeutically (acute stage; upon the appearance of the first sign of the disease). Further, we used RTX as a preventive drug either as a single agent or in combination with other routes of administration. Results: Because no complete recovery was observed when RTX was used prophylactically or therapeutically, we devised another protocol of injecting this drug before the onset of the disease and designated this regiment as prevention. We demonstrated that the 20 μg/mouse prevention completely reduced the EAE clinical score, impaired infiltration of T and B cells into the perivascular space of mice brains, along with inhibiting the inflammation and demyelination. However, the 5 and 10 μg/mouse doses although reduced all aspects of inflammation in these mice, their effects were not as potent as the 20 μg/mouse RTX dose. Finally, we combined the 5 μg/mouse prevention treatment with either the prophylactic or therapeutic regimen and observed a robust effect. Conclusion: We observed that combinatorial regimens resulted in further reduction of inflammation, T and B cell extravasation into the brains of EAE mice and improved the remyelination.

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Immunreconstitution and Infectious Complications After Rituximab Treatment in Children and Adolescents: What Do We Know and What Can We Learn from Adults?

Cited by 45 publications

References 95 publications

Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study

Safety and Efficacy of Rituximab in Multiple Sclerosis: A Retrospective Observational Study

Safety and efficacy of rituximab in multiple sclerosis: A retrospective observational study

<p>Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens</p>

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