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

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 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 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

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)

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

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

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

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

Weight on Infliximab

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

Small bowel changes on Capsule Endoscopy – 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