malignancies in patients with anca-associated vasculitis · 29th european congress of pathology...
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29th European Congress of Pathology
Malignancies in patients with ANCA-associated vasculitis
Chinar Rahmattulla
06-09-2017
ANCA-associated vasculitis (AAV)
Systemic autoimmune disease
• Granulomatosis with polyangiitis (GPA)
• Microscopic polyangiitis (MPA)
10-Oct-172 Insert > Header & footer
ANCAs
• ANCA = Anti-Neutrophil Cytoplasmic Autoantibody
• Directed against components in the primary granules of the neutrophil
• GPA – usually proteinase 3 (PR3)-ANCA
• MPA – usually myeloperoxidase (MPO)–ANCA
Presentation of ANCA associated vasculitis
Berden,
BMJ 2012
Prognosis
• Life-threatening when untreated
• 1-year mortality: 80%
• Immunosuppressive therapy has dramatically improved prognosis
• 1-year remission rate: 90%
• Therapy regimen
• Induction therapy: cyclophosphamide + prednisone
• Remission therapy: azathioprine / mycophenolate mofetil (MMF)
Malignancy risk in AAV
• Better prognosis attention shifted to long-term complications
Interpretation of previous studies
• Data on malignancy based on patient or physician questionnaires
• Reporting bias
• Follow-up limited to 5 years
• Observation period in most studies dated from the 1960s to the 1990
• Immunosuppressive therapy regimens have changed significantly
Current study
We investigated malignancies occurrence in 138 AAV patients treated with
current immunosuppressive therapy regimens, with a mean follow-up of 10
years.
Material & methods
• 138 patients with histopathologically confirmed AAV
• Primary malignancies were identified via the Dutch National Pathology
Database
• Nationwide accurate malignancy data reporting
• Malignancy occurrence was compared to that in the general population by
determining standardized incidence ratios (SIRs)
• National cancer incidence rate data provided by the Netherlands Cancer Registry
• Matching for sex, age (5-year age groups), and calendar-year period (1-year time
periods)
Included patients
Malignancy occurence
Subgroup analyses
• Increased malignancy risk in GPA and/or with PR3-ANCA as compared to
MPA/MPO-ANCA
• Malignancy risk not increased in patients treated after publication of
CYCAZAREM
• Three times less cyclophosphamide exposure
SIR according to cyclophosphamide treatment
Conclusion
• Malignancy risk is 2.21 times increased as compared to the general
population
• Attributable solely to the occurrence of NMSC
• No increased risk of other malignancies
• bladder cancer, leukemia, or malignant lymphomas
• Most likely reflect the changes in AAV treatment regimens over the years
• Malignancy occurrence directly associated with cyclophosphamide exposure
• Not increased in patients treated < 1 year
Rahmattulla et al. Arthritis & Rheumatology 2015
Acknowledgement
• Prof. dr. J.A. Bruijn (Department of pathology, LUMC)
• Dr. I.M. Bajema (Department of pathology, LUMC)
• S.W. Wakker (Department of pathology, LUMC)
• Dr. A.E. Berden (Department of internal medicine, LUMC)
• Dr. M.E.J. Reinders (Department of internal medicine, LUMC)
• Dr. M. Galli (Department of internal medicine, Medical Center Haaglanden)
• Dr. M. van Buren (Department of internal medicine, HagaZiekenhuis)
• Dr. H. Ablij (Department of internal medicine, Diaconessehuis)
• Dr. B. Gabreëls (Department of internal medicine, Rijnland Ziekenhuis)
• Dr. H. Peltenburg (Department of internal medicine, Groene Hart Ziekenhuis)
• Dr. H. Boom Department of internal medicine, (Reinier de Graaf Gasthuis)
• Dr. M. van Sandwijk (Department of internal medicine, Academic Medical Center)
• Dr. R. Nette (Department of internal medicine, Sint Franciscus Gasthuis)
• Dr. A. Lavrijssen (Department of internal medicine, Admiraal De Ruyter Ziekenhuis)
• Dr. M. G. H. Betjes (Department of internal medicine, Erasmus Medical Center, Rotterdam)