LONG TERM SAFETY OF INFLIXIMAB IN CVID RELATED INFLAMMATORY BOWEL DISEASEDr Nisha VermaDepartment of ImmunologyRoyal Free Hospital, London

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

Age at diagnosis of CVID (years/old)

Other CVID related complications

No. of years of diarrhoea (pre infliximab)

Other treatment given (pre Infliximab)

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

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

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 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

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 Bronchiectasis Granulomatous lung disease,Bronchiectasis

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

Weight (pre infliximab)

Stoolfrequency (pre infliximab)

Histology (pre infliximab)

CMV on biopsy

No. of years on infliximab

Weight (most recent)

Stool frequency (current)

Histology (on infliximab)

Weight (pre infliximab)

Stoolfrequency (pre infliximab)

Histology (pre infliximab)

CMV on biopsy

No. of years on infliximab

Weight (most recent)

Stool frequency (current)

Histology (on infliximab)

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

Weight (pre infliximab)

Stoolfrequency (pre infliximab)

Histology (pre infliximab)

CMV on biopsy

No. of years on infliximab

Weight (most recent)

Stool frequency (current)

Histology (on infliximab)

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

Patient 2 62 year old female

43Kg

2-6x

SMALL BOWEL:Partial villous atrophy; crypt hyperplasia, increased IELs, No plasma cells

+

>10 years

63Kg

1-3x

IMPROVED

Weight (pre infliximab)

Stoolfrequency (pre infliximab)

Histology (pre infliximab)

CMV on biopsy

No. of years on infliximab

Weight (most recent)

Stool frequency (current)

Histology (on infliximab)

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

Patient 2 62 year old female

43Kg

2-6x

SMALL BOWEL:Partial villous atrophy; crypt hyperplasia, increased IELs, No plasma cells

+

>10 years

63Kg

1-3x

IMPROVED

Patient 3 68 year old female

75kg

20x

LARGE BOWEL: A ctive colitis

+

>10 years

78kg

5-7x

IMPROVED

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

Weight (pre infliximab)

Stoolfrequency (pre infliximab)

Histology (pre infliximab)

CMV on biopsy

No. of years on infliximab

Weight (most recent)

Stool frequency (current)

Histology (on infliximab)

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

Patient 2 62 year old female

43Kg

2-6x

SMALL BOWEL:Partial villous atrophy; crypt hyperplasia, increased IELs, No plasma cells

+

>10 years

63Kg

1-3x

IMPROVED

Patient 3 68 year old female

75kg

20x

LARGE BOWEL: A ctive colitis

+

>10 years

78kg

5-7x

IMPROVED

Weight on Infliximab

0 1 2 3 4 5 6 7 8 9 10 11 12 1340

45

50

55

60

65

70

75

80

85

Patient 1

Patient 2

Patient 3

Patient 4

Number of years on Inflixmab

We

igh

t (k

g)

Norovirus infec-tion

1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738394041424344454647480

1

2

3

4

5

6

Infliximab

weeks

Ave

rag

e d

aily

sto

ol/

wee

kantibiotics

Stool chart – patient 4

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

Patient 4 - pre Infliximab

Histology – patient 4 (pre Infliximab)

Positive staining for CMV

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

Thank you for listening

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