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A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus
Received date: 2022-08-15
Online published: 2022-12-19
Supported by
the National Natural Science Foundation of China(32000639);the National Natural Science Foundation of China(82171772);the National Natural Science Foundation of China(81871281);Peking University People's Hospital Research and Development Funds(RS2020-01)
Objective: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). Methods: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. Results: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. Conclusion: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.
Key words: Systemic lupus erythematosus; Cyclophosphamide; Adverse events
Miao SHAO , Hui-fang GUO , Ling-yan LEI , Qing ZHAO , Yan-jie DING , Jin LIN , Rui WU , Feng YU , Yu-cui LI , Hua-li MIAO , Li-yun ZHANG , Yan DU , Rui-ying JIAO , Li-xia PANG , Li LONG , Zhan-guo LI , Ru LI . A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus[J]. Journal of Peking University(Health Sciences), 2022 , 54(6) : 1112 -1116 . DOI: 10.19723/j.issn.1671-167X.2022.06.009
| 1 | Fanouriakis A , Kostopoulou M , Alunno A , et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus[J]. Ann Rheum Dis, 2019, 78 (6): 736- 745. |
| 2 | Donadio JV , Holley KE , Ferguson RH , et al. Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide[J]. N Engl J Med, 1978, 299 (21): 1151- 1155. |
| 3 | Boumpas DT , Austin HA , Vaughn EM , et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in sever lupus nephritis[J]. Lancet, 1992, 340 (8822): 741- 745. |
| 4 | Austin HA , Klippel JH , Balow JE , et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs[J]. N Engl J Med, 1986, 314 (10): 614- 619. |
| 5 | Houssiau FA , Vasconcelos C , D'Cruz D , et al. Immunosuppressive therapy in lupus nephritis: The Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide[J]. Arthritis Rheum, 2002, 46 (8): 2121- 2131. |
| 6 | Hussenbocus YA , Jin ZY , Pan WY , et al. Low dosage use of cyclophosphamide improves the survival of patients with systemic lupus erythematosus[J]. Clin Rheumatol, 2022, 41 (7): 2043- 2052. |
| 7 | Durcan L , O'Dwyer T , Petri M . Management strategies and future directions for systemic lupus erythematosus in adults[J]. Lancet, 2019, 393 (10188): 2332- 2343. |
| 8 | Zhang XW , Li C , Ma XX , et al. Short-interval lower-dose intravenous cyclophosphamide as induction and maintenance therapy for lupus nephritis: A prospective observational study[J]. Clinical Rheumatol, 2014, 33 (7): 939- 945. |
| 9 | Hanaoka H , Kiyokawa T , Iida H , et al. Comparison of renal response to four different induction therapies in Japanese patients with lupus nephritis class Ⅲ or Ⅳ: A single-centre retrospective study[J]. PLoS One, 2017, 12 (4): e0175152. |
| 10 | Thomas G , Mancini J , Jourde-Chiche N , et al. Mortality associa-ted with systemic lupus erythematosus in France assessed by multiple-cause-of-death analysis[J]. Arthritis Rheumatol, 2014, 66 (9): 2503- 2511. |
| 11 | Wang Z , Wang Y , Zhu R , et al. Long-term survival and death causes of systemic lupus erythematosus in China: A systemic review of observational studies[J]. Medicine(Baltimore), 2015, 94 (17): e794. |
| 12 | Wang H , Zhou Y , Yu L , et al. Major infection in newly diagnosed systemic lupus erythematosus: An inception cohort study[J]. Lupus Sci Med, 2022, 9 (1): e000725. |
| 13 | Ghobadi MZ , Izadi S , Teymoori-RM , et al. Potential role of viral infection and B cells as a linker between innate and adaptive immune response in systemic lupus erythematosus[J]. Immunol Res, 2021, 69 (2): 196- 204. |
| 14 | Mok CC , Tse SM , Chan KL , et al. Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: A propensity score analysis of a longitudinal cohort[J]. Lupus, 2018, 27 (5): 722- 727. |
| 15 | Tian M , Song XH , Dong LP , et al. Systematic evaluation of different doses of cyclophosphamide induction therapy for lupus nephritis[J]. Medicine (Baltimore), 2017, 96 (51): e9408. |
| 16 | Giambalvo S , Garaffoni C , Silvagni E , et al. Factors associated with fertility abnormalities in women with systemic lupus erythematosus: A systematic review and meta-analysis[J]. Autoimmun Rev, 2022, 21 (4): 103038. |
| 17 | Katsifis GE , Tzioufas AG . Ovarian failure in systemic lupus erythematosus patients treated with pulsed intravenous cyclophosphamide[J]. Lupus, 2004, 13 (9): 673- 678. |
| 18 | Ponticelli C , Escoli R , Moroni G . Does cyclophosphamide still play a role in glomerular diseases?[J]. Autoimmun Rev, 2018, 17 (10): 1022- 1027. |
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