Researchers from Europe have shown that patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may have a decreased malignancy risk with rituximab treatment as opposed to treatment with cyclophosphamide. The study, led by Emma E van Daalen from the Department of Pathology at Leiden University Medical Centre in the Netherlands, examined the long-term malignancy risk malignancy in 323 patients who were treated for AAV between 2000 and 2014 at one clinic in the UK.

Using a retrospective study design and data from patients’ medical records, van Daalen and colleges found that 33 patients subsequently developed 45 malignancies. The age- and sex-adjusted malignancy risk for patients with ANCA-associated vasculitis was 1.89-fold higher than the general population (95% confidence interval [CI] 1.38 to 2.53, P <.001. 

Those patients who developed malignancies and were treated with cyclophosphamide had a 3.10-fold higher risk compared with the general population, whereas patients treated with rituximab had no increased risk (standardized incidence ratio [SIR], 0.67; 95% CI 0.08 to 2.43).

Other key findings included:

  • The malignancy risk in patients treated only with cyclophosphamide was 4.61-fold higher (95% CI 1.16 to 39.98) than in patients treated only with rituximab and was 3.05-fold higher (95% CI 1.40 to 7.35) than in patients treated with both cyclophosphamide and rituximab
  • A positive dose–response relationship was found between cyclophosphamide therapy and overall malignancy risk, and between cyclophosphamide therapy and risk of non-melanoma skin cancer. The inverse was found for patients treated with rituximab — the higher the cumulative rituximab dose, the lower the overall malignancy risk, and the lower the risk of non-melanoma skin cancer.

Summary and Clinical Applicability

“Interestingly, our findings — although the number of patients was relatively low — may point towards the possibility that rituximab has a protective role in the development of malignancies,” the researchers postulated. “This hypothesis is underlined by data showing a trend of an inverse dose–response relationship, and by the difference in malignancy development of the combined treatment group.” 

Ms van Daalen and colleagues pointed out that previous research has led to the hypothesis that rituximab enhances the body’s innate antitumor immune response in studies comparing treatment for non-Hodgkin’s lymphoma.  

“Lowering cyclophosphamide and azathioprine exposure will most likely decrease the malignancy risk. For patients with [AAV] who receive azathioprine, especially those who received cyclophosphamide as induction therapy, regular skin cancer screening should be started to control and prevent the development of non-melanoma skin cancers,” the study authors advised. “Moreover,” they added, “patients should be advised as to how to protect themselves against ultraviolet radiation.”

Limitations

  • The study group came from one medical center in the UK, and results may not be generalizable to other populations
  • It was a retrospective study (excluding patients with unclear or missing data) with a relatively short follow-up duration (mean 5.6 years)
  • The study is limited by its small number of patients, especially in subgroup analyses  

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Reference

van daalen EE, Rizzo R, Kronbichler A, et al. Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis. Ann Rheum Dis. 2016 Nov 29. doi:10.1136/annrheumdis-2016-209925 [Epub ahead of print]

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