long term safety of infliximab in cvid related inflammatory bowel disease dr nisha verma department...
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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