1. Dr Nisha Verma Department of Immunology Royal Free Hospital, London
Long term safety of Infliximab in CVID related inflammatory bowel disease
Dr Nisha Verma
Department of Immunology
Royal Free Hospital, London

2. Gastrointestinal Disease in CVID
150 confirmed CVID patients at RFH as diagnosed per ESID criteria
20% report gastrointestinal symptoms
5% diarrhoea
4 patients severe enteropathy
No infective cause; histological changes
No response to steroids
Other treatment options - Infliximab
Complications
Significant weight loss
Malabsorption
Untreated high morbidity and mortality

3. Age at diagnosis of CVID (years/old)
Other CVID related complications
No. of years of diarrhoea (pre infliximab)
Other treatment given (pre Infliximab)

4. Patient 1
45 year old male
Age at diagnosis of CVID (years/old) 21
Other CVID related complications
Nil
No. of years of diarrhoea (pre infliximab)
11 years
Other treatment given (pre Infliximab)
Gluten Free Diet,
Budesonide, oral prednisolone

5. Patient 1
45 year old male
Patient 2
62 year old female
Age at diagnosis of CVID (years/old) 21 32
Other CVID related complications
Nil
Bronchiectasis
No. of years of diarrhoea (pre infliximab)
11 years
14 years
Other treatment given (pre Infliximab)
Gluten Free Diet,
Budesonide, oral prednisolone
Budesonide, oral Prednisolone, Pancreatin, Gluten Free diet, Elemental diet

6. Patient 1
45 year old male
Patient 2
62 year old female
Patient 3
68 year old female
Age at diagnosis of CVID (years/old) 21 32 24
Other CVID related complications
Nil
Bronchiectasis
No. of years of diarrhoea (pre infliximab)
11 years
14 years
6 years
Other treatment given (pre Infliximab)
Gluten Free Diet,
Budesonide, oral prednisolone
Budesonide, oral Prednisolone, Pancreatin, Gluten Free diet, Elemental diet
Imodium, codeine, cholestyramine, oral prednisolone, Budesonide, Ganciclovir

7. Patient 1
45 year old male
Patient 2
62 year old female
Patient 3
68 year old female
Patient 4
63 year old female
Age at diagnosis of CVID (years/old) 21 32 24 49
Other CVID related complications
Nil
Bronchiectasis
Granulomatous lung disease,
No. of years of diarrhoea (pre infliximab)
11 years
14 years
6 years
2-3 years
Other treatment given (pre Infliximab)
Gluten Free Diet,
Budesonide, oral prednisolone
Budesonide, oral Prednisolone, Pancreatin, Gluten Free diet, Elemental diet
Imodium, codeine, cholestyramine, oral prednisolone, Budesonide, Ganciclovir
Steroids, Valganciclovir

8. Weight (pre
infliximab)
Stool
frequency
(pre infliximab)
Histology (pre
CMV on biopsy
No. of
years on
infliximab
Weight (most
recent )
Stool
frequency
(current)
Histology (on
infliximab)

9. Weight (pre
infliximab)
Stool
frequency
(pre infliximab)
Histology (pre
CMV on biopsy
No. of
years on
infliximab
Weight (most
recent )
(current)
Histology (on
Patient 1
45 year old male
57kg 8 - 9x
SMALL BOWEL
Shortened villi;
Increased
intraepithelial
lymphocytes (IELs);
absent plasma cells
> 10 years
65Kg 1 - 3x
UNCHANGED

10. Weight (pre
infliximab)
Stool
frequency
(pre infliximab)
Histology (pre
CMV on biopsy
Patient 1
45 year old male
57kg 8 - 9x
SMALL BOWEL
Shortened villi;
Increased
intraepithelial
lymphocytes (IELs);
absent plasma cells
Patient 2
62 year old
female
43Kg - 6x
SMALL BOWEL:
Partial
villous
atrophy; crypt
hyperplasia,
increased IELs, No
plasma cells +
No. of
years on
infliximab
Weight (most
recent )
Stool
frequency
(current)
Histology (on
infliximab)
> 10 years
65Kg 1 - 3x
UNCHANGED
>10 years
63Kg 1 - 3x
IMPROVED

11. Weight (pre
infliximab)
Stool
frequency
(pre infliximab)
Histology (pre
CMV on biopsy
Patient 1
45 year old male
57kg 8 - 9x
SMALL BOWEL
Shortened villi;
Increased
intraepithelial
lymphocytes (IELs);
absent plasma cells
Patient 2
62 year old
female
43Kg - 6x
SMALL BOWEL:
Partial
villous
atrophy; crypt
hyperplasia,
increased IELs, No
plasma cells +
Patient 3
68 year old
female
75kg
20x
LARGE
BOWEL: A
ctive colitis +
No. of
years on
infliximab
Weight (most
recent )
Stool
frequency
(current)
Histology (on
infliximab)
> 10 years
65Kg 1 - 3x
UNCHANGED
>10 years
63Kg 1 - 3x
IMPROVED
>10 years
78kg 5 - 7x
IMPROVED

12. Weight (pre
infliximab)
Stool
frequency
(pre infliximab)
Histology (pre
CMV on biopsy
No. of
years on
infliximab
Weight (most
recent )
(current)
Histology (on
Patient 1
45 year old male
57kg 8 - 9x
SMALL BOWEL
Shortened villi;
Increased
intraepithelial
lymphocytes (IELs);
absent plasma cells
> 10 years
65Kg 3x
UNCHANGED 2
62 year old
female
43Kg 6x
SMALL BOWEL:
Partial
villous
atrophy; crypt
hyperplasia,
increased IELs, No
plasma cells +
>10 years
63Kg
IMPROVED
Patient 3
68 year old
75kg
20x
LARGE
BOWEL: A
ctive colitis
78kg 5 7x
Patient 4
63 year old
female
55kg 5 - 6x
SMALL BOWEL:
Acute ileitis
with
extensive
ulceration
LARGE BOWEL:
Moderate acute
colitis +
1 year
62kg 1 - 2x
Pending

13. Weight on Infliximab

14. Stool chart – patient 4 Infliximab Average daily stool/week weeks
antibiotics
Infliximab
Average daily stool/week
weeks

15. Small bowel changes on Capsule Endoscopy – patient 4 (pre Infliximab)

16. Histology – patient 4 (pre Infliximab)
Positive staining for CMV

17. Summary Symptomatic improvement Increased weight
Improved quality of life
Avoids steroid related complications
3 patients stable and well.
Patient 1 – chronic norovirus diagnosed 2014
No evidence of malignancy, mycobacterial infections, autoimmunity or other significant infections

18. Thank you for listening

19. Acknowledgements
Clinical Team at RFH (alphabetical order): Dr Siobhan Burns Dr Mari Campbell Dr Ronnie Chee Dr Magdalena Dziadio Professor Bodo Grimbacher Dr David Lowe Dr Suranjith Seneviratne Dr David Webster
Clinical Nurse Specialists at RFH: Sarita Workman Andrew Symes Irene Wahlberg BPL – providing reagents