THE USE OF CYCLOPHOSPHAMIDE IN THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS
Palavras-chave:
Cyclophosphamide, Efficacy, Systemic Lupus ErythematosusResumo
INTRODUCTION: Cyclophosphamide (CYC) is an agent used to treat neoplasms and autoimmune diseases. This study evaluates the efficacy of CYC in the treatment of systemic lupus erythematosus (SLE), analyzing possible adverse effects, including neoplastic events. METHODOLOGY: Systematic searches were conducted in the BVS, PubMed, SciELO, and LILACS databases using specific descriptors on the efficacy of cyclophosphamide in the treatment of SLE. Articles in English and Portuguese published between 2000 and 2023 were included, excluding theses, unpublished dissertations, duplicate articles, and articles published before 2000. RESULTS AND DISCUSSION: The search resulted in 143 studies, of which 14 were selected for analysis. Cyclophosphamide is widely used in the treatment of systemic lupus erythematosus (SLE), especially in severe cases such as lupus nephritis (LN). Studies demonstrate its efficacy in reducing disease activity and inducing remission. However, prolonged use can lead to significant adverse effects, including hematologic toxicity and neoplastic risks. High doses are associated with serious adverse events and an increased risk of cervical neoplasia. Strategies such as low-dose cyclophosphamide administration and combination with other immunosuppressants have shown similar efficacy with fewer side effects. CONCLUSION: CYC is effective in reducing SLE activity and decreasing the need for corticosteroids, with lower dose regimens presenting fewer adverse effects. Combination with rituximab may improve clinical outcomes in refractory cases, but prolonged toxicity requires close monitoring and dose adjustments.
Referências
BATEMAN, H.; et al. Increased cervical dysplasia in intravenous cyclophosphamide-treated patients with SLE: a preliminary study. Lupus, v. 9, n. 7, p. 542-544, 2000.
CHENG, H.; et al. Efficacy and safety of belimumab/low-dose cyclophosphamide therapy in moderate-to-severe systemic lupus erythematosus. Frontiers in Immunology, v. 13, p. 911730, 2022.
FERNANDES, B. J. D. Enantiomeric pharmacokinetics of CYC in patients with breast cancer. Advisor: Prof. Vera Lucia Lanchote. 2008. 91 p. Thesis (Graduate) - Toxicology, University of São Paulo, Ribeirão Preto, 2008.
FANOURIAKIS, A.; et al. 2019 update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Annals of the Rheumatic Diseases, v. 79, n. 6, p. 713-723, 2020.
GONZALEZ-LOPEZ, L.; et al. Therapy with intermittent pulse cyclophosphamide for pulmonary hypertension associated with systemic lupus erythematosus. Lupus, v. 13, n. 2, p. 105-112, 2004.
JÓNSDÓTTIR, T.; et al. Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Annals of the Rheumatic Diseases, v. 67, n. 3, p. 330-334, 2008.
LEHMAN, T. J.; ONEL, K. Intermittent intravenous cyclophosphamide arrests progression of the renal chronicity index in childhood systemic lupus erythematosus. The Journal of Pediatrics, v. 136, n. 2, p. 243-247, 2000.
MACEDO, R. M.; et al. SLE: relationship between different treatments and clinical evolution. Revista Médica, v. 99, n. 6, p. 573-580, 2020.
OGNENOVSKI, V. M.; et al. Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide. The Journal of Rheumatology, v. 31, n. 9, p. 1763-1767, 2004.
PETRI, M.; et al. High-dose cyclophosphamide versus monthly intravenous cyclophosphamide for systemic lupus erythematosus: a prospective randomized trial. Arthritis & Rheumatism, v. 62, n. 5, p. 1487-1493, 2010.
BRAZILIAN SOCIETY OF RHEUMATOLOGY. LES - SBR Booklet. 2011. Available at: https://reumatologia.org.br/2016/01/31/lupus-eritematoso-sistemico-les-cartilha-da-sbr/. Accessed on: April 18, 2023.
TAM, L. S.; et al. Risk factors for squamous intraepithelial lesions in systemic lupus erythematosus: a prospective cohort study. Arthritis Care & Research, v. 63, n. 2, p. 269-276, 2011.
ZHANG, X. W.; et al. Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: a prospective observational study. Clinical Rheumatology, v. 33, p. 939-945, 2014.
