Impact of COVID-19 pandemic on use of rituximab among children with difficult nephrotic syndrome

Sinha, Rajiv; Marlais, Matko; Sarkar, Subhankar; Обухова, В А; Lucchetti, Laura; Vasudevan, Anil; Jaimes, Diana; Weaver, Donald J.; Stańczyk, Małgorzata; López-González, Mercedes; Schaefer, Franz; Tullus, Kjell

doi:10.1038/s41390-021-01744-8

Cited by 8 publications

(7 citation statements)

References 11 publications

(11 reference statements)

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“…One particular concern of rituximab use is the vulnerability to coronavirus disease 2019 (COVID-19) during the pandemic. Fortunately, the risk of acquiring COVID-19, symptomatic disease, and dismal outcomes do not appear to be increased among children receiving rituximab for NS, compared with the general pediatric population 44 , 45 . Nonetheless, vaccination is strongly recommended to protect susceptible patients against COVID-19, and additional vaccine doses may be warranted to achieve adequate immunogenicity 46 …”

Section: Discussionmentioning

confidence: 99%

“…Fortunately, the risk of acquiring COVID-19, symptomatic disease, and dismal outcomes do not appear to be increased among children receiving rituximab for NS, compared with the general pediatric population. 44,45 Nonetheless, vaccination is strongly recommended to protect susceptible patients against COVID-19, and additional vaccine doses may be warranted to achieve adequate immunogenicity. 46 Persistent hypogammaglobinemia is another important long-term sequela from rituximab.…”

Section: Discussionmentioning

confidence: 99%

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Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Chan

Yu²,

Angeletti

et al. 2022

JASN

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Background: Long-term outcomes following multiple rituximab courses among children with frequently-relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. Methods: A retrospective cohort study at 16 pediatric nephrology centers from 10 countries in Asia, Europe, and North America included children with FRSDNS who received ≥2 rituximab courses. Primary outcomes were relapse-free survival and adverse events. Results: 346 children (age 9.8 years, IQR 6.6-13.5; 73% boys) received 1149 rituximab courses. 145, 83, 50, 28, 22, and 18 children received 2, 3, 4, 5, 6 and ≥7 courses, respectively. Median follow-up was 5.9 years (IQR, 4.3-7.7). Relapse-free survival differed by treatment courses (clustered log-rank test p<0.001). Compared to the first course (10.0 months, 95% CI, 9.0-10.7), relapse-free period and relapse risk progressively improved following subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01-0.18; ps<0.001). B-cell depletion duration remained similar with repeated treatments (6.1 months, 95% CI, 6.0-6.3). Adverse events were mostly mild, most commonly hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 vs 3.3 years; p=0.05) and at first rituximab (8.0 y vs 10.0 years; p=0.01) and history of steroid resistance (28% vs 18%; p=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% vs 20%, p=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. Conclusion: Children receiving repeated rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable but significant complications can occur. These findings support repeated rituximab use in FRSDNS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Chan

Yu²,

Angeletti

et al. 2022

JASN

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“…It is currently being investigated in adults whether the transient halt of MMF therapy increases the rate of vaccine responders without an undue risk of kidney allograft rejection [28,29]. However, severe COVID-19 in pediatric patients on immunosuppressive therapy is rare [30][31][32]. This is especially true for the currently predominant omicron variants that are associated with less severe disease than the previous variants [33].…”

Section: Discussionmentioning

confidence: 99%

Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease

et al. 2022

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Background Data on humoral immune response to standard COVID-19 vaccination are scarce in adolescent patients and lacking for children below 12 years of age with chronic kidney disease including kidney transplant recipients. Methods We therefore investigated in this retrospective two-center study (DRKS00024668; registered 23.03.2021) the humoral immune response to a standard two-dose mRNA vaccine regimen in 123 CKD patients aged 5–30 years. A live-virus assay was used to assess the serum neutralizing activity against the SARS-CoV-2 omicron (BA.1) variant. Results Children aged 5–11 years had a comparable rate and degree of immune response to adolescents despite lower vaccine doses (10 µg vs. 30 µg BNT162b2). Treatment with two (odds ratio 9.24) or three or more (odds ratio 17.07) immunosuppressants was an independent risk factor for nonresponse. The immune response differed significantly among three patient cohorts: 48 of 77 (62.3%) kidney transplant recipients, 21 of 26 (80.8%) patients on immunosuppressive therapy, and 19 of 20 (95.0%) patients with chronic kidney disease without immunosuppressive therapy responded. In the kidney transplant recipients, immunosuppressive regimens comprising mycophenolate mofetil, an eGFR of < 60 mL/min/1.73 m2, and female sex were independent risk factors for nonresponse. Two of 18 (11.1%) and 8 of 16 (50.0%) patients with an anti-S1-RBD IgG of 100–1411 and > 1411 BAU/mL, respectively, showed a neutralization activity against the omicron variant. Conclusion A standard mRNA vaccine regimen in immunosuppressed children and adolescents with kidney disease elicits an attenuated humoral immune response with effective live virus neutralization against the omicron variant in approximately 10% of the patients, underlying the need for omicron-adapted vaccination. Graphical abstract

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“…In addition, the data reported are from high- or upper middle-income countries, which may limit the generalizability of the findings. Preliminary data from developed countries have shown that COVID-19 appears to have a benign clinical course in children with underlying KD [ 21 – 23 ]. For instance, Mastrangelo et al [ 24 ] reported findings of the COVID-19 Task Force of the Italian Society of Pediatric Nephrology.…”

Section: Discussionmentioning

confidence: 99%

Outcomes and risk factors for death among hospitalized children and adolescents with kidney diseases and COVID-19: an analysis of a nationwide database

et al. 2022

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Background Patients with kidney diseases (KD) appear to be at particularly high risk for severe COVID-19. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with KD. Methods We performed an analysis of all pediatric patients with KD and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 16, 2020, and May 29, 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. Results Among 21,591 hospitalized patients with COVID-19, 290 cases (1.3%) had KD. Of these, 59 (20.8%) had a fatal outcome compared with 7.5% of the non-KD cohort ( P < 0.001). Pediatric patients with KD had an increased hazard of death compared with the non-KD cohort (Hazard ratio [HR] = 2.85, 95% CI 2.21–3.68, P < 0.0001). After adjustment, the factors associated with the death among KD patients were living in Northeast (HR 2.16, 95% CI 1.13–4.31) or North regions (HR 3.50, 95% CI 1.57–7.80), oxygen saturation < 95% at presentation (HR 2.31, 95% CI 1.30–4.10), and presence of two or more associated comorbidities (HR 2.10, 95% CI 1.08–4.04). Conclusions Children and adolescents with KD had a higher risk of death compared with the non-KD cohort. The higher risk was associated with low oxygen saturation at admission, living in socioeconomically disadvantaged regions, and presence of other pre-existing comorbidities. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information Supplementary Information The online version contains a graphical abstract available at 10.1007/s00467-022-05588-0.

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Impact of COVID-19 pandemic on use of rituximab among children with difficult nephrotic syndrome

Cited by 8 publications

References 11 publications

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease

Outcomes and risk factors for death among hospitalized children and adolescents with kidney diseases and COVID-19: an analysis of a nationwide database

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