Dr Paul Henderson

Background

Following my successful PhD thesis submitted, based on my research, performed between 2009-2012, I have been actively involved in multiple areas of research in paediatric gastroenterology. I have active interests mainly in the area of paediatric inflammatory bowel disease but also in clinical nutrition, coeliac disease, endoscopy and liver disease. Following my appointment as an NRS Clinician I have been able to expand my portfolio of research to include regional and national epidemiological studies, EU-funded observational studies work and most recently randomised-controlled trials. In addition to this research I currently work full time as an NHS Consultant. This involves busy inpatient and outpatient service, as well as a general paediatric oncall commitment. My current role of co-lead for Paediatric Inflammatory Disease (PIBD)services and lead for paediatric liver disease in South-East Scotland gives me access to a large and well-defined cohort of patients. Additionally my close links with the other two main academic paediatric gastroenterology units in Scotland allow for more coordinated and meaningful research to be performed. Through my research I hope to provide clearer evidence of therapeutic efficacy, evaluate cost-effectiveness and improve individualised patient care.

Research Overview

 

Prospective Epidemiology

• Scotland-wide Incidence

Background:

Our group published the only incidence study of Paediatric Inflammatory Bowel Disease (PIBD) in Scotland within the past 15 years. We now hold the database of all children diagnosed with PIBD in Scotland spanning back many years.

Specific aims:

1. Consolidation of prospective PIBD incidence databases in the major Scottish academic centres (Edinburgh, Glasgow and Aberdeen) through already established relationships
2. Ascertainment of missing incident cases of PIBD to allow accurate study of incidence trends from 1969 - Present (i.e. 50 years)
3. Correlation/association of incidence trends in with other environmental factors to generate hypotheses for future studies

 

• South-East Scotland epidemiology

Background:

We currently hold a prospectively collected database of all children with PIBD looked after in South-East Scotland (SES) since 1997. This database of nearly 500 children has been continuously developed and contains information on phenotype, medical therapies, surgery and transition to adult services.

Specific aims:

1. Collection of prospective phenotypic information and data on diagnostic pathways, therapeutic effectiveness, outcome measures (e.g. surgery) and post-transition care
2. Analysis of phenotypic trends (especially with regard to early-onset disease) to allow stratification of disease and tailored therapy
3. Prospective evaluation of “real-life” therapeutic efficacy in clinical practice to inform further clinical trials

 

• UK-wide epidemiology

Background:

The last UK-wide epidemiological study in PIBD was performed nearly 20 years ago.

Specific aims:

1. A prospective, UK-wide, epidemiological study principally looking at the incidence and prevalence of PIBD
2. Utilise established electronic data capture (e.g. IBD audit) to allow the investigation of incidence/prevalence trends in real-time

 

• European-wide epidemiology

Background:

We have close links with IBD centres both in Scotland, the UK and further afield. Our group have consistently collaborated with groups in Europe to help lead research in the field of long term outcomes in paediatric IBD, such as mortality, malignancy risk, adverse effects of long term medications and surgery outcomes.

Specific aims:

1. Participating in a EU-funded inception cohort of newly diagnosed IBD patients with long term (20 year) follow up
2. Multiple smaller projects looking at the outcomes of, for example, acute severe colitis

 

Therapeutic efficacy

Background:

Much of our current knowledge of medical therapies in PIBD is extrapolated from adult studies, especially given the apprehension regarding the use of placebo in paediatric trials. Despite these reservations there is a need to evaluate the optimum treatment strategies in children.

Specific aims:

1. Involvement in a multi-centre trial into the dosing regimen for rescue therapy with biologicals in PIBD patients with acute severe colitis
2. Involvement in international randomised-controlled trials stratifying patients into high and low risk groups at diagnosis
3. Participate in multi-centre trials in novel therapeutics such as probiotics and new oral medications for the treatment of paediatric inflammatory bowel disease

 

Autophagy

I continue to work closely with Dr Stevens on translational science, especially in the field of autophagy. We have already published work on the potential effects of certain IBD medications on the process of autophagy and have ongoing lab work and clinical studies to assess this in paediatric IBD patients.

Sources of Funding

• Principal Investigator - Risk-stratified randomized controlled trial in paediatric Crohn’s Disease: Methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or at high risk for aggressive disease course, respectively – a treatment strategy – European Commission: H2020 (2016-2019) – total award €5,966,000
• Principal Investigator - The PREdiCCt Study: The PRognostic effect of Environmental factors in Crohn’s and Colitis – Chief Scientists Office, Cure Crohn’s and Colitis, 3Cs, Edinburgh and Lothian Health Fund (2016-2018) - total award £624,927
• Principal Investigator - Paediatric Inflammatory Bowel Diseases Network for Safety, Efficacy, Treatment and Quality improvement of care: The PIBD-NET inception cohort and safety registry – European Commission: H2020 (2016-2019) – total award €5,966,000
• Joint Chief Investigator - CICRA PhD Fellowship: The effect of IBD drugs on autophagy – Crohn’s in Childhood Research Association (2014-2017) - total award £73,832.
• Co-investigator - A Phase 1 randomised, double-blind, placebo-controlled study to assess the safety and tolerability of Bacteroides thetaiotaomicron in young people aged 16 to 18 years with stable Crohn's disease – 4D Pharma (2015-2017) – industry sponsored

Selected Publications

Sahnan K, Tozer P, Adegbola S, et al, ...and the ENiGMA collaborative. Developing a core outcome set for Fistulising Perianal Crohn’s Disease. Gut 2018; doi:10.1136/gutjnl-2017-315503 [Epub ahead of press][Henderson P as part of the ENiGMA collaborative] (PMID: 29437911)

Richmond L, Curtis L, Garrick V, Rogers P, Wilson ML, Tayler R, Henderson P, Hansen R, Wilson DC, Russell RK. Biosimilar infliximab use in paediatric IBD. Arch Dis Child. 2018;103(1):89-91. (PMID: 28988215)

Holtman GA, Lisman-van Leeuwen Y, Day AS, Fagerberg UL, Henderson P, Leach ST, Perminow G, Mack D, van Rheenen PF, van de Vijver E, Wilson DC, Reitsma JB, Berger MY. Added value of laboratory markers to symptoms for inflammatory bowel disease, an individual patient data meta-analysis of 1120 pediatric patients. JAMA Pediatr. 2017;171(10):984-991. (PMID: 28806445)

De Lange KM, Moutsianas L, Lee JC, Lamb CA, Yang L, Kennedy NA, Jostins L, Rice DL, Gutierrez-Achury J, Ji S, Heap G, Nimmo ER, Edwards C, Henderson P, Mowat C, Sanderson J, Satsangi J, Simmons A, Wilson DC, Tremeling M, Hart A, Mathew CG, Newman WG, Parkes M, Lees CW, Uhlig H, Hawkey C, Prescott NJ, Ahmad T, Mansfield JC, Anderson C, Barrett JC. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet. 2017;49(2):256-261 (PMID: 28067908)

Hooper KM, Barlow PG, Stevens C, Henderson P. Inflammatory bowel disease drugs: a focus on autophagy. J Crohns Colitis. 2017;11(1):118127 (PMID: 27381462)

Merrick VM, Henderson P. Transition of patients with paediatric IBD to adult services. Frontline Gastroenterol. 2016;7(4):333-334. (PMID: 28839875)

Cleynen I, Boucher G, Jostins L, et al. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. Lancet. 2016 Jan 9;387(10014):156-67. [Henderson P as part of the IIBDGC group] (PMID: 206490195)

Henderson P, Kennedy NA, Van Limbergen J, et al. Serum C-reactive protein and CRP genotype in pediatric inflammatory bowel disease: influence on phenotype, natural history and response to therapy. Inflamm Bowel Dis. 2015;21(3):596-605 (PMID: 25636121)

Degraeuwe, P, Beld M, Ashorn M, Berni Canani R, Day A, Diamanti A, Fagerberg U, Henderson P, et al. Faecal calprotectin in suspected paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2015;60(3):339-346 (PMID: 25373864)

Barclay AR, Henderson P, Gowen H, et al. The continued rise of paediatric home parenteral nutrition use: implications for service and the improvement of longitudinal data collection. Clin Nut. 2014;S0261-5614(14)00290-8 (PMID: 25476040)

White LE, Merrick VM, Bannerman E, Russell RK, Basude D, Henderson P, et al. The rising incidence of celiac disease in Scotland. Pediatrics. 2013 Oct;132(4):e924-31 (PMID: 24019416)

Henderson P, Anderson NH, Wilson DC. Fecal calprotectin for the diagnosis of pediatric inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109(5):637-45 (PMID: 23670113)

Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119-124 [Henderson P as part of the IIBDGC group] (PMID:23128233)

Henderson P, Stevens C. The role of autophagy in Crohn's disease. Cells. 2012;1(3):492-519 (PMID:24710487)

Stevens C, Henderson P, Nimmo ER, et al. The intermediate filament protein vimentin is a regulator of NOD2 activity. Gut. 2013;62(5):695-707 (PMID: 22684479)

Henderson P, Casey A, Lawrence SJ, et al. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease. Am J Gastroenterol. 2012;107(6):941-949 (PMID:22370604)

Henderson P, Hansen R, Cameron FL, et al. Rising incidence of pediatric inflammatory bowel disease in Scotland. Inflamm Bowel Dis. 2012;18(6):999-1005. (PMID: 21688352)

Henderson P, van Limbergen J, Anderson NH, Nimmo E, Russell RK, Satsangi J, Wilson DC.  Letter: Variation in ICOSLG influences Crohn’s disease susceptibility. Gut. 2011;60:1444. (PMID: 21335567)

Henderson P, van Limbergen J, Schwarze J, Wilson DC. Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease. Inflamm Bowel Dis. 2011;17(1):382-395. (PMID: 20645321)

Henderson P, van Limbergen J, Wilson DC, Satsangi J, Russell RK. Genetics of childhood-onset inflammatory bowel disease. Inflamm Bowel Dis. 2011;17(1):346-361. (PMID: 20839313)

Honours and Awards

• Poster of Distinction – BSPGHAN Glasgow (Jan 2017)
• Best abstract and Digital Oral Prize – ECCO Barcelona (Feb 2015)
• Shire Travel Bursary to attend ECCO Barcelona (Feb 2015)
• Best Case Presentation - SSPGHAN Annual Meeting (Nov 2013)
• Two Posters of Distinction - Dr Falk Symposium 190 (Oct 2013)
• Alex Mowat Prize for Best Abstract - BSPGHAN Annual Meeting (Jan 2011)
• Shire Innovation Award Grant for SpRs - total award £7,500 (Nov 2010)
• Best poster - BSPGHAN Annual Meeting (Jan 2010)

Public Engagement Activities

Work closely with various paediatric IBD charities, including family days for CICRA and CCUK

Other Responsibilities

• Treasurer of the Scottish Society of Paediatric Gastroenterology, Hepatology and Nutrition (2016-Present)
• Member of the IBD working group of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (2016-Present)
• Clinical Lead for Paediatric Hepatology in South-East Scotland
• Co-clinical Lead for Paediatric IBD in South-East Scotland

Collaborators

Dr Craig Stevens – Edinburgh Napier University