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Managing Infection R isk in Primary Systemic Vasculitis Patients

Managing Infection R isk in Primary Systemic Vasculitis Patients. Dr Matthew Morgan University of Birmingham. The Problem. ANCA vasculitis causes lung and kidney damage Treatment requires long term immunosuppression. Patient outcomes - EUVAS trials.

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Managing Infection R isk in Primary Systemic Vasculitis Patients

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  1. Managing Infection Risk in Primary Systemic Vasculitis Patients Dr Matthew Morgan University of Birmingham

  2. The Problem • ANCA vasculitis causes lung and kidney damage • Treatment requires long term immunosuppression

  3. Patient outcomes - EUVAS trials 535 patients from 4 EUVAS trials recruited 1995-2002

  4. What are the risk factors for infection? • Direct drug side effects • Neutropenia • Steroids • Cyclophosphamide • Azathioprine/ Methotrexate/ Mycophenolate • Other factors? • Lymphopenia? • B-cell depletion? • Hypogammaglobunaemia?

  5. Birmingham Vasculitis Clinic Experience • 89 PSV patients median follow up 5 years (2-22 years) • 90% had at least 1 episode infection • 57% had severe infection requiring hospital admission and IV antibiotics • Overall infection rate 1.5/patient/year • Severe infections 0.86/patient/year

  6. Immunodeficiency is a risk for infection • IgG <5g/L increased risk of • All infections (p=0.03) • Severe infections (p=0.01)

  7. Does vaccination improve infection risk? • 92 patients in remission • Median age 51 (23-91) • On low dose/no immunosuppression • Received • Prevnar 7 • Menitorix (Hib) • Men A, C, W135, Y • Antibody titres measured at weeks 0, 4, 8 &16 • Serum IgG and lymphocyte subsets measured at baseline

  8. Vasculitis patients have low numbers of lymphocytes Represents median

  9. Immunodeficiency • 22% of patients had IgG <6.0 g/dL • Correlates with • CD19 B-cell count (co-efficient 0.3; p=0.002) • CD4 T-Cell count (co-efficient 0.3; p=0.005) • Low IgG correlates with low anti-Pneumococcal and Diphtheria antibodies • Older age correlates with reduced CD19 and CD4 cells

  10. Response to Prevnar 7

  11. Reponses to other vaccines

  12. Predictors of poor vaccine response • Low immune competence score predicts poor vaccine response (p=0.039) • Low IgG predicts poor vaccine response (p=0.017) • CD4 and CD19 counts do not predict response p=0.039

  13. Summary • Infection is a significant problem in systemic vasculitis • Low IgG is associated with increased infection • Most patients respond to vaccination • Low IgG predicts a poor vaccination response

  14. Acknowledgements • Profs. Lorraine Harper & Mark Drayson • Drs. Alex Richter, Julia Flint, Mark Cobbold • Wellcome Trust Clinical Research Facility Staff • Clinical Immunology – University of Birmingham

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