title: Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Emma E
authors.initials: EE
authors.lastname: van Daalen
authors.affiliation: Nephrology, Dialysis and Hypertension Unit, St Orsola-Malpighi University Hospital, Bologna, Italy.|Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rizzo
authors.affiliation: Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.|Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kronbichler
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Wolterbeek
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.affiliation: Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Jayne
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.|Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, UK.
authors.forename: Chinar
authors.initials: C
authors.lastname: Rahmattulla
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000453:epidemiology*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D000069283:Rituximab / Q000008:administration & dosage / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000453:epidemiology
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab; D003520:Cyclophosphamide
keywords: Cyclophosphamide; DMARDs (biologic); Outcomes research; Systemic vasculitis