From Paris to Montreal: disease regression is common during long term follow-up of paediatric Crohn’s disease

Abstract

Introduction: Paediatric Crohn’s disease (PCD) often presents with extensive and a frequent pan-enteric phenotype at onset. However, its long term evolution into adulthood, especially since the widespread use of biological agents, is not well characterised. We conducted a single centre cohort study of all PCD patients transitioned to adult care to assess the long term disease evolution in the era of biologic therapy.

Methods: We conducted a retrospective observational, study of all PCD patients who were subsequently transferred to the care of an adult gastroenterology unit and had a minimum follow up of 2 years. We examined the case notes for evolution of disease location and behaviour. Disease location and behaviour was characterised using Paris classification at diagnosis and Montreal classification at last follow-up. In addition, we examined variables associated with complicated disease behaviour and the need for CD related intestinal resection.

Results: In total, 132 patients were included with a median age at diagnosis of 13 (IQR 11–14) and a median follow up of 11 years (range 4–14). At diagnosis, 23 (17.4%), 39 (29.6%) and 70 (53%) patients had ileal, colonic and ileocolonic disease respectively. In addition, 31 (23.5%) patients had L4a or L4b disease at diagnosis (proximal or distal to the ligament of treitz respectively) and 13 patients (9.8%) had both whilst 27 (20.4%) patients had perianal disease. At diagnosis, 27 (20.4%) patients had complicated disease behaviour but 83 (62.9)% of patients had an extensive ‘pan-enteric’ phenotype. Of these patients only 55 (66.3%) retained the pan-enteric phenotype at last follow-up (p = .0002). Disease extension was noted in 25 (18.9%) of patients and regression was noted in 47 (35.6%) of patients, whereas upper GI disease was noted in significantly fewer patients at last follow-up (21, 15.9%) (p = .0001). More patients had complicated disease behaviour (46 patients, 34.9%, p = .0018) at last follow-up. There was a high exposure to both thiopurines 121 (91.7%) and biologics 84 (63.6%). The cumulative probability (95% CI) of surgery was 0.05 (0.02, 0.11) at 1 year, 0.17 (0.11, 0.24) at 3 years and 0.22 (0.15, 0.30) at 5 years. Neither disease location nor behaviour were associated with the need for intestinal resectional surgery.

Conclusions: Over the course of an extended follow-up period, there appeared to be changes in both disease location and behaviour in PCD. Interestingly, a significant proportion of patients had disease involution which may be related to a high rate of exposure to thiopurines and biologics. We were unable to identify any variables associated with complicated disease course or the need for intestinal surgery.

Keywords:

• Crohn's disease
• paediatrics
• phenotype
• biologics
• evolution

Author contributions

MD, AR, MC, BG, GP and AK were involved in data collection and drafting of the manuscript. SS, JC and AK were involved in data analysis, drafting and final revision of the manuscript. SS and MD were involved in study design, data collection, analysis, drafting and revision of the manuscript. PC, PJS, MKHA, CT, ST, ER, CB and MVN were involved in the drafting of the final manuscript.

Disclosure statement

SS has received speaker fee from MSD, Actavis, Abbvie, Dr Falk pharmaceuticals, Shire and received educational grant from MSD, Abbvie, Actavis and is an advisory board member for Abbvie, Dr Falk pharmaceutics, Janssen and Vifor pharmaceuticals. MKHA has received speaker fees from Abbvie, and travel grants from Abbvie, Dr Falk pharmaceuticals, MSD/Janssen and Nutricia. CT has received speaker fees from Abbvie, Sanofi, Nutricia, Nestle and received travel grants from Abbvie and Merck. PC has received speaker fees from Shire, Abbvie, MSD, Warner-Chillcott and Falk pharma. He has received educational grants from Warner Chilcott, MSD and Ferring pharmaceuticals. He has served as an Advisory Board member for Falk pharma. PJS has received speaker fees from Abbvie and Janssen. MD, AK, AR, MC, BG, JC, FC, ST, ER, CB, MVN and GP report no conflicts of interest. All authors concur with the submission. The material submitted for publication is not under consideration for publication elsewhere.