Long term follow-up of Behçet’s syndrome patients treated with cyclophosphamide

Abstract

Objectives CYC remains an important treatment option for Behçet’s syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients. Methods We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome. Results Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15–26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients. Conclusion Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC.

Improved clinical outcomes of tocilizumab versus cyclophosphamide for IgG4-related disease: insights from a prospective IgG4-related disease registry

“…However, CYC also has some adverse effects, of which reproductive toxicity is an important issue, since it was seen in 30% of patients within 25 years of follow-up. 26 In addition, hemorrhagic cystitis, a less common adverse effect of CYC in the Chinese population, was still seen in one of our patients in the CYC group. In contrast, the adverse reactions of tocilizumab, such as transient mild liver function impairment and thrombocytopenia, were tolerable.…”

Pharmacotherapy for Behçet’s Disease and the Risk of Malignancy

“…Short-term adverse events include gastrointestinal disturbances, hemorrhagic cystitis, alopecia bone marrow suppression, and infections (Brummaier et al, 2013), while the incidence of secondary malignancies and infertility are long-term and rare adverse events (Appel et al, 2009;Mok, 2016). Gurcan et al (2020) recently found that BD patients treated with CYC were associated with a higher incidence of malignancy in a dose-dependent manner through a retrospective cohort study. In the present investigation, we also identified a higher risk of cancer in patients with BD who used CYC.…”

“…Systemic glucocorticoids (GCs) and immunosuppressive or cytotoxic agents including thalidomide, azathioprine (AZA), cyclophosphamide (CYC) and cyclosporine (CsA) are usually combined to treat refractory symptoms or multiple organ involvement ( Lopalco et al, 2020 ). Although the symptoms of BD patients have effectively improved, the adverse reactions associated with long-term drug use given its chronic disease course are also of concern ( Gurcan et al, 2020 ).…”

Advances in the Treatment of Behcet’s Disease

“…This observation may be explained by selection (funneling) bias, as azathioprine is used more in mild cases, whereas biologics are preferred in patients with severe disease manifestations [104,105]. Among cISs, cyclophosphamide should be reserved for remission induction in patients with severe arterial disease due to its high teratogenicity and risk for causing malignancy [106]. Hepatotoxicity, cytopenias, and gastro-intestinal intolerance are among the main limitations of cIS use; however, their relative safety for infections is important for long-term management decisions.…”