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Extended report
Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis
  1. Emma E van Daalen1,
  2. Raffaella Rizzo2,3,
  3. Andreas Kronbichler3,4,
  4. Ron Wolterbeek5,
  5. Jan A Bruijn1,
  6. David R Jayne3,
  7. Ingeborg M Bajema1,
  8. Chinar Rahmattulla1,3
  1. 1Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands
  2. 2Nephrology, Dialysis and Hypertension Unit, St Orsola-Malpighi University Hospital, Bologna, Italy
  3. 3Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK
  4. 4Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, Innsbruck, Austria
  5. 5Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands
  1. Correspondence to Emma Elisabeth van Daalen, Department of Pathology, L1-Q (P0-107), Leiden University Medical Centre, P.O. Box 9600, Leiden 2300 RC, The Netherlands; E.E.van_Daalen{at}


Objectives Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with cyclophosphamide have an increased malignancy risk compared with the general population. We investigated whether treatment with rituximab instead of cyclophosphamide has decreased the malignancy risk in patients with AAV.

Methods The study included patients with AAV treated at a tertiary vasculitis referral centre between 2000 and 2014. The malignancy incidence in these patients was compared with the incidence in the general population by calculating standardised incidence ratios (SIRs), adjusted for sex, age and calendar year. Malignancy incidence was compared between rituximab-treated and cyclophosphamide-treated patients.

Results Of the 323 included patients, 33 developed a total of 45 malignancies during a mean follow-up of 5.6 years. This represented a 1.89-fold increased (95% CI 1.38 to 2.53) malignancy risk, and a non-significantly increased risk if non-melanoma skin cancer was excluded (SIR, 1.09; 95% CI 0.67 to 1.69). The risk of non-melanoma skin cancer was 4.58-fold increased (95% CI 2.96 to 6.76). Cyclophosphamide-treated patients had an increased malignancy risk compared with the general population (SIR, 3.10; 95% CI 2.06 to 4.48). In contrast, rituximab-treated patients had a malignancy risk similar to the general population (SIR, 0.67; 95% CI 0.08 to 2.43). The malignancy risk in cyclophosphamide-treated patients was 4.61-fold higher (95% CI 1.16 to 39.98) than in rituximab-treated patients.

Conclusions The malignancy risk in patients with AAV was lower in rituximab-treated patients than in cyclophosphamide-treated patients. Notably, rituximab treatment was not associated with an increased malignancy risk compared with the general population. Rituximab could therefore be a safe alternative to cyclophosphamide in the treatment of AAV.

  • Systemic vasculitis
  • Cyclophosphamide
  • DMARDs (biologic)
  • Outcomes research

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  • Handling editor Tore K Kvien

  • Contributors EEvD, DRJ, IMB and CR conceived and designed the study. RR, AK and CR acquired the data. EEvD, RW and CR performed statistical analyses. EEvD wrote the first draft of the manuscript. All authors critically revised the manuscript and approved the final version. EEvD is the guarantor of the study.

  • Competing interests None declared.

  • Ethics approval Following the Governance Arrangements for research ethics committees, this study did not require review by a research ethics committee, since it used non-identifiable information that was previously collected for normal care.

  • Provenance and peer review Not commissioned; externally peer reviewed.