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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (6): 1112-1116. doi: 10.19723/j.issn.1671-167X.2022.06.009

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A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus

Miao SHAO1,Hui-fang GUO2,Ling-yan LEI2,Qing ZHAO3,Yan-jie DING3,Jin LIN4,Rui WU5,Feng YU6,Yu-cui LI7,Hua-li MIAO7,Li-yun ZHANG7,Yan DU8,Rui-ying JIAO9,Li-xia PANG9,Li LONG10,Zhan-guo LI1,*(),Ru LI1,*()   

  1. 1. Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China
    2. Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
    3. Department of Rheumatology and Immunology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan, China
    4. Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
    5. Department of Rheumatology and Immunology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
    6. Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China
    7. Department of Rheumatology and Immunology, Shanxi Bethune Hospital, Taiyuan 030032, China
    8. Department of Rheumatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
    9. Department of Rheumatology and Immunology, Hulunbuir People's Hospital, Hulunbuir 021008, Inner Mongolia, China
    10. Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, Chengdu 610071, China
  • Received:2022-08-15 Online:2022-12-18 Published:2022-12-19
  • Contact: Zhan-guo LI,Ru LI E-mail:Li99@bjmu.edu.cn;doctorliru123@163.com
  • 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)

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Abstract:

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

CLC Number: 

  • R593.2

Figure 1

Comparison of reasons for stopping intravenous cyclophosphamide in SLE patients with SILD IV-CYC and HD-IV-CYC management SILD IV-CYC, short-interval low-dose intravenous cyclophosphamide; HD IV-CYC, high-dose intravenous cyclophosphamide; SLE, systemic lupus erythematosus. * P < 0.05."

Table 1

Characteristics of SLE patients in the study"

Items SILD IV-CYC(n=506) HD IV-CYC(n=256) P value
Female/male, n 463/43 234/22 1.000
Age/years, M(P25，P75) 40 (31, 51) 39 (30, 50) 0.699
Age/years, M(P25，P75) 32 (24, 43) 31.5 (23.0, 42.0) 0.421
CYC course/months, M(P25，P75) 6.0 (3.0, 10.63) 6.0 (4.0, 8.75) 0.471
Accumulated dose of CYC/g, M(P25，P75) 4.8 (2.4, 8.4) 5.6 (3.2, 8.0) 0.139
Lupus nephritis, M(P25，P75) 269 (53.16) 149 (58.20) 0.187
NPSLE, M(P25，P75) 70 (13.83) 30 (11.72) 0.414
Respiratory system, M(P25，P75) 65 (12.85) 23 (8.98) 0.115
Hematologic system, M(P25，P75) 136 (26.88) 58 (22.66) 0.206
Diabetes mellitus, M(P25，P75) 19 (3.75) 10 (3.91) 0.918
Hypertension, M(P25，P75) 92 (18.18) 60 (23.43) 0.086
Coronary heart disease, M(P25，P75) 12 (2.37) 4 (1.56) 0.462
Hyperlipemia, M(P25，P75) 24 (4.74) 17 (6.64) 0.273
Glucocorticoid dose/ (mg/d)，M(P25，P75) 20.0 (10.0, 45.0) 18.75 (10.0, 35.0) 0.089
HCQ, n (%) 450 (88.93) 221 (86.33) 0.295
SLEDAI, M(P25，P75) 6.0 (2.0, 9.0) 6.0 (2.0, 9.0) 0.316

Table 2

Adverse effects of SILD IV-CYC and HD IV-CYC treatment in SLE patients"

Adverse events Patients(n=762) SILD IV-CYC (n=506) HD IV-CYC (n=256) P values
n % n % n %
Infection 123 16.14 66 13.04 57 22.27 0.001*
Gastrointestinal reaction 168 22.05 88 17.39 80 31.25 < 0.001*
Myelosuppression 100 13.12 49 9.68 51 19.92 < 0.001*
Abnormal menstruation 127a 30.02 71b 25.18 56c 39.72 0.001*
Drug-induced hepatic injury 46 6.04 27 5.34 19 7.42 0.253
Hemorrhagic cystitis 4 0.52 3 0.59 1 0.39 1.000
Fatigue 46 6.04 33 6.52 13 5.08 0.429
Alopecia 117 15.35 68 13.44 49 19.14 0.039*
Rash 12 1.57 10 1.98 2 0.78 0.355
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