Managing Infection Risk 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
535 patients from 4 EUVAS trials recruited 1995-2002
What are the risk factors for infection?
Direct drug side effects– Neutropenia– Steroids– Cyclophosphamide– Azathioprine/
Methotrexate/ Mycophenolate
Other factors? Lymphopenia? B-cell depletion? Hypogammaglobunaemia?
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
Immunodeficiency is a risk for infection
IgG <5g/L increased risk of
All infections (p=0.03) Severe infections (p=0.01)
05
1015202530 Error bars indicate
mean95% CI
IgG
leve
l
Control group
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
Represents median
Vasculitis patients have low numbers of lymphocytes
Lymphocyte subset numbers in ANCA positive vasculitis patients
Ly
mp
hs
CD
3
CD
4
CD
8
CD
19
CD
16
/56
0
1000
2000
3000
Lym
ph
ocy
te n
um
ber
s ce
lls/
mm
3
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
Response to Prevnar 7
Serotype
Percentage of patients with titre >0.35
P value Week 0 vs week16
Baseline Week 16
Pn4 23 46 <0.001
Pn6b 48 71 <0.001
Pn9v 55 83 <0.001
Pn14 55 74 <0.001
Pn18c 70 91 <0.001
Pn19f 59 76 <0.001
Pn23f 50 80 <0.001
Reponses to other vaccines
Patients with protective antibody titres
Vaccine Baseline Week 16Baseline vs week 16
HIb 24 26% 55 63%p<0.001
Men A 30 33% 62 71% p=0.001
Men C 8 9% 43 49% p=0.003
Men W135 2 2% 18 21% ns
Men Y 11 12% 44 51% p<0.001
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
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
Acknowledgements
Profs. Lorraine Harper & Mark Drayson Drs. Alex Richter, Julia Flint, Mark Cobbold Wellcome Trust Clinical Research Facility Staff Clinical Immunology – University of
Birmingham