Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases
Although rituximab is widely used off-label for complex pediatric diseases, safety reports are limited. We aimed to report evidence of its use in clinical practice, to describe the incidence of adverse drug reactions (ADR) to rituximab biosimilar Novex® and innovator, and to identify risk factors fo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.785770/full |
| _version_ | 1818715533281853440 |
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| author | Natalia Riva Natalia Riva Manuel Molina Berta L. Cornaló María V. Salvador Andrea Savransky Silvia Tenembaum María M. Katsicas Marta Monteverde Paulo Cáceres Guido Paulo Cáceres Guido Marcela Rousseau Raquel Staciuk Agustín González Correas Pedro Zubizarreta Oscar Imventarza Eduardo Lagomarsino Eduardo Spitzer Marcelo Tinelli Paula Schaiquevich Paula Schaiquevich |
| author_facet | Natalia Riva Natalia Riva Manuel Molina Berta L. Cornaló María V. Salvador Andrea Savransky Silvia Tenembaum María M. Katsicas Marta Monteverde Paulo Cáceres Guido Paulo Cáceres Guido Marcela Rousseau Raquel Staciuk Agustín González Correas Pedro Zubizarreta Oscar Imventarza Eduardo Lagomarsino Eduardo Spitzer Marcelo Tinelli Paula Schaiquevich Paula Schaiquevich |
| author_sort | Natalia Riva |
| collection | DOAJ |
| description | Although rituximab is widely used off-label for complex pediatric diseases, safety reports are limited. We aimed to report evidence of its use in clinical practice, to describe the incidence of adverse drug reactions (ADR) to rituximab biosimilar Novex® and innovator, and to identify risk factors for the development of ADR in a real-life follow-up cohort of pediatric patients with complex diseases. We conducted a prospective, longitudinal, observational, single-centre study in patients that received rituximab for any complex disease, and as part of an intensive pharmacovigilance program. Demographic, pharmacological, clinical, and drug-related data were collected for all patients. ADR-free survival, including infusion-related reactions (IRR) and delayed ADR (dADR), was estimated using Kaplan-Meier curves. Risk factors were evaluated by multivariable Cox regression models. In total, 77 patients (<19 y.o.) received 187 infusions of rituximab Novex® (n = 155) or innovator rituximab (n = 32) for neurologic (Neu), immune-hematologic-rheumatic (IHR), oncologic (O) diseases, and hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation (SOT). We recorded 29 IRR and 58 dADR that occurred in 27 (35.1%) and 29 (37.7%) patients, respectively. The respiratory tract was the most affected during IRR (29.6%) and hypogammaglobulinemia (37.9 %) was the most frequent dADR. First versus subsequent infusions (HR 5.4, CI95% 2.4–12.1, p<0.05), sex (boys vs. girls, HR 0.3, CI95% 0.1–0.8, and p<0.05), and diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 2.3, CI95% 1.02–5.4, and p < 0.05) were significantly associated with the development of IRR. For dADR, risk factors were diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 0.4, CI95% 0.2–0.9, and p < 0.05) and cumulative body surface area-normalized dosage (HR 1.0003, CI95% 1.0001–1.0006, and p < 0.05). The present is the largest real-world safety assessment of rituximab in Latin-American children with complex diseases supporting its use based on the overall acceptable safety. Identification of risk factors may contribute to optimization of off-label rituximab treatment in pediatrics. |
| first_indexed | 2024-12-17T19:04:52Z |
| format | Article |
| id | doaj.art-805357f7b1074ce3885912fd103b3cee |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T19:04:52Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-805357f7b1074ce3885912fd103b3cee2022-12-21T21:36:01ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011210.3389/fphar.2021.785770785770Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex DiseasesNatalia Riva0Natalia Riva1Manuel Molina2Berta L. Cornaló3María V. Salvador4Andrea Savransky5Silvia Tenembaum6María M. Katsicas7Marta Monteverde8Paulo Cáceres Guido9Paulo Cáceres Guido10Marcela Rousseau11Raquel Staciuk12Agustín González Correas13Pedro Zubizarreta14Oscar Imventarza15Eduardo Lagomarsino16Eduardo Spitzer17Marcelo Tinelli18Paula Schaiquevich19Paula Schaiquevich20Unit of Innovative Treatments, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, ArgentinaUnit of Innovative Treatments, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaUnit of Innovative Treatments, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaPharmacy, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaNeurology Service, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaNeurology Service, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaImmunology and Rheumatology Service, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaNephrology Unit, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaPharmacy, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaUnit of Clinical Pharmacokinetics, Pharmacy, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaHealth Technology Assessment Coordination, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaBone Marrow Transplant Service, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaBone Marrow Transplant Service, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina0Hematology and Oncology Service, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina1Liver Transplant Service, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaPharmacy, Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina2Laboratorio Elea-Phoenix S.A., Scientific Department, Los Polvorines, Argentina2Laboratorio Elea-Phoenix S.A., Scientific Department, Los Polvorines, ArgentinaUnit of Innovative Treatments, Hospital de Pediatría JP Garrahan, Buenos Aires, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, ArgentinaAlthough rituximab is widely used off-label for complex pediatric diseases, safety reports are limited. We aimed to report evidence of its use in clinical practice, to describe the incidence of adverse drug reactions (ADR) to rituximab biosimilar Novex® and innovator, and to identify risk factors for the development of ADR in a real-life follow-up cohort of pediatric patients with complex diseases. We conducted a prospective, longitudinal, observational, single-centre study in patients that received rituximab for any complex disease, and as part of an intensive pharmacovigilance program. Demographic, pharmacological, clinical, and drug-related data were collected for all patients. ADR-free survival, including infusion-related reactions (IRR) and delayed ADR (dADR), was estimated using Kaplan-Meier curves. Risk factors were evaluated by multivariable Cox regression models. In total, 77 patients (<19 y.o.) received 187 infusions of rituximab Novex® (n = 155) or innovator rituximab (n = 32) for neurologic (Neu), immune-hematologic-rheumatic (IHR), oncologic (O) diseases, and hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation (SOT). We recorded 29 IRR and 58 dADR that occurred in 27 (35.1%) and 29 (37.7%) patients, respectively. The respiratory tract was the most affected during IRR (29.6%) and hypogammaglobulinemia (37.9 %) was the most frequent dADR. First versus subsequent infusions (HR 5.4, CI95% 2.4–12.1, p<0.05), sex (boys vs. girls, HR 0.3, CI95% 0.1–0.8, and p<0.05), and diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 2.3, CI95% 1.02–5.4, and p < 0.05) were significantly associated with the development of IRR. For dADR, risk factors were diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 0.4, CI95% 0.2–0.9, and p < 0.05) and cumulative body surface area-normalized dosage (HR 1.0003, CI95% 1.0001–1.0006, and p < 0.05). The present is the largest real-world safety assessment of rituximab in Latin-American children with complex diseases supporting its use based on the overall acceptable safety. Identification of risk factors may contribute to optimization of off-label rituximab treatment in pediatrics.https://www.frontiersin.org/articles/10.3389/fphar.2021.785770/fullRituximabBiosimilar PharmaceuticalsMonoclonal AntibodyPediatricAdverse Drug ReactionsHypersensitivity |
| spellingShingle | Natalia Riva Natalia Riva Manuel Molina Berta L. Cornaló María V. Salvador Andrea Savransky Silvia Tenembaum María M. Katsicas Marta Monteverde Paulo Cáceres Guido Paulo Cáceres Guido Marcela Rousseau Raquel Staciuk Agustín González Correas Pedro Zubizarreta Oscar Imventarza Eduardo Lagomarsino Eduardo Spitzer Marcelo Tinelli Paula Schaiquevich Paula Schaiquevich Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases Frontiers in Pharmacology Rituximab Biosimilar Pharmaceuticals Monoclonal Antibody Pediatric Adverse Drug Reactions Hypersensitivity |
| title | Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases |
| title_full | Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases |
| title_fullStr | Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases |
| title_full_unstemmed | Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases |
| title_short | Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases |
| title_sort | intensive safety monitoring of rituximab biosimilar novex r and the innovator in pediatric patients with complex diseases |
| topic | Rituximab Biosimilar Pharmaceuticals Monoclonal Antibody Pediatric Adverse Drug Reactions Hypersensitivity |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.785770/full |
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