Adverse events linked with the use of chimeric and humanized anti‐CD20 antibodies in children with idiopathic nephrotic syndrome

Bonanni, Alice; Calatroni, Marta; D’Alessandro, Matteo; Signa, Sara; Bertelli, Enrica; Cioni, Michela; Marco, Eddi Di; Biassoni, Roberto; Caridi, Gianluca; Ingrasciotta, Giulia; Bertelli, Roberta; Donato, Andrea; Bruschi, Maurizio; Canepa, Alberto; Piaggio, Giorgio; Ravani, Pietro; Ghiggeri, Gian Marco

doi:10.1111/bcp.13548

Cited by 44 publications

(43 citation statements)

References 48 publications

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“…Rituximab is generally well-tolerated in most published studies of its use in childhood NS. The most common adverse events are mild infusion-related reactions, with a reported frequency between 5 and 53%, which typically resolve with antihistamines and antipyretics as well as slowing the infusion rate (35, 113, 114). Although very few children develop severe anaphylactic reactions or hypotension (30), rituximab can be associated with more serious side effects, and its long-term safety in children with NS is not fully known.…”

Section: Side Effects Of Rituximabmentioning

confidence: 99%

“…Although very few children develop severe anaphylactic reactions or hypotension (30), rituximab can be associated with more serious side effects, and its long-term safety in children with NS is not fully known. Serious complications include arthritis (113), lung injury (113, 115, 116), serum sickness (117), prolonged and severe neutropenia that may develop up to 6 months after infusion (118, 119), inflammatory bowel disease (120, 121) and acute demyelinating neuropathy (122). Expectedly, rituximab also increases the risk of infections, including serious infections such as sepsis (75), Pneumocystis jiroveci pneumonia (123, 124), viral myocarditis (125), fatal hepatitis B infection (126) and severe and/or prolonged hypogammaglobulinemia (127–129).…”

Section: Side Effects Of Rituximabmentioning

confidence: 99%

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Rituximab Use in the Management of Childhood Nephrotic Syndrome

2019

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Childhood nephrotic syndrome is a challenging and often persistent renal disorder, and its incidence varies between different ethnicities and regions. Corticosteroids have been the main treatment for decades and are effective in most children with idiopathic NS, although 10–15% of these children become steroid resistant. Furthermore, some initially steroid sensitive children follow a steroid dependent or frequently relapsing course and are therefore at increased risk for developing steroid toxicity. In such children, alternative immunosuppressive medications are used to induce and/or maintain remission of NS. One such drug, rituximab, is a monoclonal antibody directed against the B lymphocyte CD20 marker which induces depletion of B cells, and has shown promising results in the management of NS in children. In this review, we summarize recent studies on the efficacy and safety of rituximab in the different types of childhood nephrotic syndrome, the known and potential mechanisms of action of rituximab, its possible complications and side effects, and the available and potential biomarkers of rituximab activity.

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Section: Side Effects Of Rituximabmentioning

confidence: 99%

Section: Side Effects Of Rituximabmentioning

confidence: 99%

Rituximab Use in the Management of Childhood Nephrotic Syndrome

2019

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“…Reduced IgG levels were also observed after 2 years of a standardized protocol of four single rituximab infusions at 6-months interval in children with difficult-to-treat INS (11). In contrast, a retrospective short-term analysis of anti-CD20-related adverse events in a large cohort of multidrug-dependent INS children treated with rituximab or ofatumumab (a fully human anti-CD20 monoclonal antibody) showed normal total IgG levels and stability of anti-tetanus and anti-hepatitis B virus (HBV) IgG titers, albeit at 12-months (12).…”

Section: Introductionmentioning

confidence: 97%

Prolonged Impairment of Immunological Memory After Anti-CD20 Treatment in Pediatric Idiopathic Nephrotic Syndrome

et al. 2019

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Anti-CD20 therapy is effective in idiopathic nephrotic syndrome (INS). However, transient or sustained hypogammaglobulinemia predisposing to an increased risk of infectious diseases can follow treatment in some patients. We analyzed the long-term effects of anti-CD20 therapy on immunological memory in 27 frequently-relapsing/steroid-dependent INS pediatric patients after more than 4 years from the first and at least 2 years from the last anti-CD20 infusion. Twenty-one INS children, never treated with anti-CD20 and under an intense oral immunosuppression with prednisone, mycophenolate mofetil, and calcineurin inhibitors were also included as control group. Levels of circulating B-cell subpopulations, total serum immunoglobulins and IgG and memory B cells directed against hepatitis B virus (HBV) and tetanus were determined and correlated with clinical characteristics. Nine patients never relapsed after more than 2 years from the last anti-CD20 administration (5 after the first, 3 after the second, and 1 after the fifth infusion). At last follow-up, most patients showed a complete recovery and normalization of total (27/27), transitional (27/27), and mature-naïve B cells (25/27). However, a sustained and significant reduction of total memory (20/27) and switched memory (21/27) B cells was found in most patients. 11/27 patients showed hypogammaglobulinemia at last follow-up and, among these, four presented with a severe hypogammaglobulinemia (IgG < 160 mg/dl). In contrast, no patient in the control group developed a severe hypogammaglobulinemia. Age at the time of first anti-CD20 administration was positively associated with IgG levels at last follow-up ( p = 0.008); accordingly, younger patients had an increased risk of hypogammaglobulinemia ( p = 0.006). Furthermore, severe hypogammaglobulinemia and delayed switched memory B-cell reconstitution were more frequent in non-relapsing patients. Reduced IgG levels against HBV and tetanus were observed at baseline and further declined at last follow-up. Antigen-specific memory B-cells were induced by re-immunization, but specific IgG titers remained low. In conclusion, anti-CD20 therapy can be disease-modifying in some INS patients. However, a prolonged impairment of immunological memory occurs frequently, independently from the number of anti-CD20 infusions, particularly in younger patients. Re-immunization may be necessary in these patients.

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“…The side effects, however, were more prevalent with ofatumumab than RTX in the study by Bonanni et al [121]. They investigated treatment outcomes in steroid-and multidrug-dependent nephrotic syndrome using RTX in 137 and ofatumumab in 37 patients.…”

Section: Ofatumumabmentioning

confidence: 99%

Current understandings in treating children with steroid-resistant nephrotic syndrome

et al. 2020

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Steroid-resistant nephrotic syndrome (SRNS) remains a challenge for paediatric nephrologists. SRNS is viewed as a heterogeneous disease entity including immune-based and monogenic aetiologies. Because SRNS is rare, treatment strategies are individualized and vary among centres of expertise. Calcineurin inhibitors (CNI) have been effectively used to induce remission in patients with immune-based SRNS; however, there is still no consensus on treating children who become either CNI-dependent or CNI-resistant. Rituximab is a steroid-sparing agent for patients with steroid-sensitive nephrotic syndrome, but its efficacy in SRNS is controversial. Recently, several novel monoclonal antibodies are emerging as treatment option, but their efficacy remains to be seen. Non-immune therapies, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, have been proven efficacious in children with SRNS and are recommended as adjuvant agents. This review summarizes and discusses our current understandings in treating children with idiopathic SRNS.

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Adverse events linked with the use of chimeric and humanized anti‐CD20 antibodies in children with idiopathic nephrotic syndrome

Abstract: Overall, the toxicity of anti-CD20 monoclonal antibodies was limited to post-infusion side effects in children with more complex disease. The relatively safe profile of anti-CD20 antibodies supports their use as steroid-sparing agents in children with INS.

Cited by 44 publications

References 48 publications

Rituximab Use in the Management of Childhood Nephrotic Syndrome

Rituximab Use in the Management of Childhood Nephrotic Syndrome

Prolonged Impairment of Immunological Memory After Anti-CD20 Treatment in Pediatric Idiopathic Nephrotic Syndrome

Current understandings in treating children with steroid-resistant nephrotic syndrome

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