Impact of the modulator elexacaftor/tezacaftor/ivacaftor (ETI) on the complexity of prescriptions and the clinical stage of children and adolescents with cystic fibrosis
DOI:
https://doi.org/10.33448/rsd-v15i1.50550Keywords:
Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Polypharmacy.Abstract
Cystic fibrosis is an autosomal recessive, multisystem genetic disease associated with high pharmacotherapeutic complexity. This study aims to evaluate the impact of the introduction of ETI on the pharmacotherapy of children and adolescents with CF treated at a referral hospital in Rio de Janeiro, considering its influence on medication deprescribing, prescription complexity, and the number of hospitalizations. This was an observational, retrospective, before-and-after study conducted at a public referral hospital for cystic fibrosis in Rio de Janeiro, Brazil. Thirteen pediatric patients (≥6 years) with confirmed cystic fibrosis who had been using ETI for at least six months were included. The Medication Regimen Complexity Index (MRCI) was applied to two prescriptions per patient: the last prescription prior to ETI initiation and another issued after six months of treatment. Total MRCI scores and Sections A, B, and C were analyzed using paired comparisons with the Wilcoxon test. The mean age was 11 years, with a predominance of females (69.2%). Median MRCI scores were 34.0 points both before and after ETI initiation. An increase in MRCI was observed in 69.2% of patients, while 30.8% showed a reduction. The main variation occurred in Section C, related to additional instructions for use, with statistical significance. Patients with comorbidities presented higher baseline MRCI and less variation after ETI. In the short term, ETI was not associated with reduced pharmacotherapy complexity, highlighting the need for longer follow-up and larger samples.
References
Barros, E. R., Saraiva, G. L., de Oliveira, T. P., & Lazaretti-Castro, M. (2012). Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta. Journal of Pediatric Endocrinology & Metabolism, 25(5–6), 485–491. https://doi.org/10.1515/jpem-2012-0016
Bishop, N., Arundel, P., Clark, E., Dimitri, P., Farr, J., Jones, G., & Ward, L. M. (2016). Fracture prediction and the definition of osteoporosis in children and adolescents: The ISCD 2013 pediatric official positions. Journal of Clinical Densitometry, 17(2), 275–280. https://doi.org/10.1016/j.jocd.2014.01.004
Cestari, C. G., et al. (2022). Osteogênese imperfeita: Revisão de literatura e relato de casos. Revista Unilago, 2(1).
Forlino, A., & Marini, J. C. (2016). Osteogenesis imperfecta. The Lancet, 387(10028), 1657–1671. https://doi.org/10.1016/S0140-6736(15)00728-X
George, S., et al. (2015). Short-term safety of zoledronic acid in young patients with bone disorders: An extensive institutional experience. The Journal of Clinical Endocrinology & Metabolism, 100(11), 4163–4170. https://doi.org/10.1210/jc.2015-2680
ANVISA. (2021). Registro Trikafta® (elexacaftor/tezacaftor/ivacaftor + ivacaftor). Agência Nacional de Vigilância Sanitária.
Amaral, M. D., & de Boeck, K. (2020). Cystic fibrosis: recent advances in understanding and care. F1000Research, 9, F1000 Faculty Rev-1325. https://doi.org/10.12688/f1000research.25203.1
Athanazio, R. A., Silva Filho, L. V., Vergara, A. A., Ribeiro, A. F., Riedi, C. A., Procianoy, E. D. F. A., ... & Dalcin, P. D. T. R. (2017). Brazilian guidelines for the diagnosis and treatment of cystic fibrosis. Jornal Brasileiro de Pneumologia, 43(3), 219–245.
Bell, S. C., Mall, M. A., Gutierrez, H., Macek, M., Madge, S., Davies, J. C., ... & Ratjen, F. (2020). The future of cystic fibrosis care: a global perspective. The Lancet Respiratory Medicine, 8(1), 65–124.
Borowitz, D., Baker, R. D., & Stallings, V. (2002). Consensus report on nutrition for pediatric patients with cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition, 35(3), 246-259.
Brasil. Ministério da Saúde. (2012). Resolução nº 466, de 12 de dezembro de 2012. Diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Conselho Nacional de Saúde.
Brasil. Ministério da Saúde. (2016). Programa Nacional de Triagem Neonatal: manual técnico. Secretaria de Atenção à Saúde.
Brasil. Ministério da Saúde. (2024). Protocolo Clínico e Diretrizes Terapêuticas da Fibrose Cística. Relatório de Recomendação.
Burgel, P. R., Munck, A., Durieu, I., Chiron, R., Mely, L., Prevotat, A., ... & French Cystic Fibrosis Reference Network study group. (2022). Real-life safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in France: a nation-wide study. European Respiratory Journal, 59(3), 2101572.
Colombo, C., Battezzati, P. M., Crosignani, A., Morquillas, A. S., Donegani, E., & Agostoni, C. (2019). Liver disease in cystic fibrosis. Journal of Hepatology, 71(2), 336–350.
CONITEC. (2023). Relatório de Recomendação: Elexacaftor/Tezacaftor/Ivacaftor para Fibrose Cística. Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde.
De Boeck, K., & Amaral, M. D. (2016). Progress in therapies for cystic fibrosis. The Lancet Respiratory Medicine, 4(8), 662-674.
Farrell, P. M., White, T. B., Ren, C. L., Hempstead, S. E., Accurso, F., Derichs, N., ... & Marshall, B. C. (2017). Diagnosis of cystic fibrosis: Consensus guidelines from the Cystic Fibrosis Foundation. The Journal of Pediatrics, 181, S4–S15.
Flume, P. A., O’Sullivan, B. P., Robinson, K. A., Goss, C. H., Mogayzel, P. J., Willey-Courand, D. B., ... & Cystic Fibrosis Foundation Pulmonary Therapies Committee. (2007). Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. American Journal of Respiratory and Critical Care Medicine, 176(10), 957-969.
Gibson, L. E., & Cooke, R. E. (1959). A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics, 23(3), 545–549.
Graeber, S. Y., Vitzthum, C., Pallenberg, S. T., Naehrlich, L., Stahl, M., Rohrbach, A., ... & Mall, M. A. (2021). Effects of elexacaftor/tezacaftor/ivacaftor therapy on CFTR function in children with cystic fibrosis aged 6–11 years with a Phe508del allele. American Journal of Respiratory and Critical Care Medicine, 204(5), 545–556.
Griese, M., Costa, S., Linnemann, R. W., Mall, M. A., McKone, E. F., McNally, P., ... & VX18-445-106 Investigator Group. (2021). Safety and efficacy of elexacaftor/tezacaftor/ivacaftor for 24 weeks in children aged 6–11 years with cystic fibrosis and at least one F508del allele: a double-blind, randomised, phase 3 trial. The Lancet Respiratory Medicine, 9(12), 1321-1332.
Heijerman, H. G., McKone, E. F., Downey, D. G., Van Braeckel, E., Rowe, S. M., Müller, K., ... & VX17-445-102 Study Group. (2019). Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. The Lancet, 394(10212), 1940–1948.
Jacquot, J., Delion, M., Gangloff, S., Braux, J., & Velard, F. (2016). Bone disease in cystic fibrosis: mechanisms and clinical management. Osteoporosis International, 27(4), 1401–1412.
McKinzie, C. J., Shekerdemian, L. S., Boyer, D., & Nelson, Gullet. (2022). Cost-effectiveness of CFTR modulators in pediatric populations: a systematic review. Clinical Therapeutics, 44(2), 207–222.
Melchiors, A. C., Correr, C. J., & Fernández-Llimos, F. (2007). Tradução e validação para o português do Medication Regimen Complexity Index. Arquivos Brasileiros de Cardiologia, 89(4), 210–218.
Middleton, P. G., Mall, M. A., Dřevínek, P., Lands, L. C., McKone, E. F., Polineni, D., ... & VX17-445-102 Study Group. (2019). Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. New England Journal of Medicine, 381(19), 1809–1819.
Moran, A., Brunzell, C., Cohen, R. C., Katz, M., Marshall, B. C., Onady, G., ... & CFRD Guidelines Committee. (2010). Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care, 33(12), 2697–2708.
Pereira, A. S. et al. (2018). Metodologia da pesquisa científica. (Free ebook). Santa Maria. Editora da UFSM.
Ratjen, F., Bell, S. C., Rowe, S. M., Goss, C. H., Quittner, A. L., & Bush, A. (2015). Cystic fibrosis. Nature Reviews Disease Primers, 1(1), 1-22.
Ratjen, F., & Stephenson, A. L. (2021). CFTR modulator therapy: the road ahead. Chest, 159(1), 19–27.
REBRAFC. (2023). Registro Brasileiro de Fibrose Cística: Relatório anual 2023. Grupo Brasileiro de Estudos de Fibrose Cística.
Riordan, J. R., Rommens, J. M., Kerem, B. S., Alon, N., Rozmahel, R., Grzelczak, Z., ... & Tsui, L. C. (1989). Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science, 245(4922), 1066-1073.
Rowe, S. M., Miller, S., & Sorscher, E. J. (2005). Cystic fibrosis. New England Journal of Medicine, 352(19), 1992-2001.
Sawicki, G. S., Sellers, D. E., & Robinson, W. M. (2009). High treatment burden in adults with cystic fibrosis: challenges to disease self-management. Journal of Cystic Fibrosis, 8(2), 91-96.
Shitsuka, R. et al. (2014). Matemática fundamental para tecnologia. (2ed). Editora Érica.
Siler, T. M., Bruce, N. J., & Plosker, G. L. (2020). Cost-effectiveness of CFTR modulators. Journal of Medical Economics, 23(6), 613-624.
Sosnay, P. R., Siklosi, K. R., Van Goor, F., Kaniecki, K., Yu, H., Sharma, N., ... & Cutting, G. R. (2013). Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nature Genetics, 45(10), 1160–1167.
Taylor-Cousar, J. L., & Mall, M. A. (2021). Real-world impact of highly effective CFTR modulators in cystic fibrosis. Current Opinion in Pulmonary Medicine, 27(6), 543–551.
Toassi, R. F. C. & Petry, P. C. (2021). Metodologia científica aplicada à área da saúde. (2ed). Editora da UFRGS.
Vendrusculo, F. M., Moreira, E. A., Souza, G. C., & Rosa, J. S. (2021). Cystic fibrosis in Brazil: achievements in survival and challenges in care. Jornal de Pediatria, 97(5), 503–511.
Vieira, S. (2021). Introdução à bioestatística. Editora GEN/Guanabara Koogan.
Whiting, P., Al, M., Burgers, L., Westwood, M., Ryder, S., Hoogendoorn, M., ... & Kleijnen, J. (2014). Ivacaftor for cystic fibrosis in people with the G551D mutation: a systematic review and economic evaluation. Health Technology Assessment, 18(18).
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