Development of the Lémann Index to Assess Digestive Tract Damage in Patients With Crohn's Disease

doi:10.1053/j.gastro.2014.09.015

Gastroenterology

Volume 148, Issue 1, January 2015, Pages 52-63.e3

https://doi.org/10.1053/j.gastro.2014.09.015 Get rights and content

Background & Aims

There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn’s disease (CD).

Methods

We performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1–3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods.

Results

Data from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall.

Conclusions

In a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment.

Section snippets

Methods

The study was run by the International Program to Develop New Indexes in Crohn’s Disease (IPNIC) group, which is an international working group including 28 gastroenterologists from 15 countries, 1 surgeon, 2 radiologists, and 1 biostatistician.

Patients and Investigators

From August 2008 to December 2010, 381 patients were enrolled in 20 centers and 24 sets (4 centers were allowed to recruit a new set of 10 patients after having recruited a first set). As shown on the patient flow chart (Supplementary Figure 1), 83 patients were excluded due to at least one major protocol deviation: lack of at least one mandatory investigation according to CD location at enrollment (n = 73) or time interval between the first and the last investigational methods >120 days (n =

Discussion

The Lémann Index is the first tool that measures the cumulative bowel damage by using resections and the extent and severity of lesions in the digestive tract of CD patients. In contrast to other indexes that are based only on clinical or endoscopic data and assess the severity of inflammatory activity at a specific time and fluctuate with time, the Lémann Index is more likely to increase with the longer disease duration by assessing irreversible bowel damage along with accumulation of

Acknowledgments

The authors would like to honor the memory of their friend, Prof Marc Lémann, who initiated this study.

The IPNIC Group: Walter Reinisch, Herbert Tilg (Austria), Michael Kamm (Australia), Geert D’Haens, Edouard Louis, Paul Rutgeerts, Gert Van Assche (Belgium), Brian G. Feagan (Canada), Pia Munkholm (Denmark), Jean-Frédéric Colombel, Jacques Cosnes, Maïté Lewin, Jean-Yves Mary, Benjamin Pariente, Laurent Peyrin-Biroulet (France), Jürgen Schölmerich, Stefan Schreiber (Germany), Silvio Danese,

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: Conflict of interests These authors disclose the following: Benjamin Pariente has received speaker fees from AbbVie and MSD. Jean-Yves Mary has received lecture and consultation fees from AbbVie and Janssen and consultation fees from Pharmacosmos. Silvio Danese is a speaker, consultant, and advisory board member for Schering-Plough, Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson. Geert D’Haens has received consulting and/or lecture fees from AbbVie, ActoGeniX, AM Pharma, Boehringer Ingelheim GmbH, Centocor, ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, Engene, Dr Falf Pharma, Ferring, Galapagos, Giuliani SpA, Given Imaging, GlaxoSmithKline, Jansen Biologics, Merck Sharp and Dohme Corp, Millennium Pharmaceuticals Inc. (now Takeda), Neovacs, Novonordisk, Otsuka, PDL Biopharma, Pfizer, Receptos, Salix, Setpoint, Shire Pharmaceuticals, Schering-Plough, Tillotts Pharma, UCB Pharma, Versant and Vifor Pharma; research grants from Abbott Laboratories, Jansen Biologics, Given Imaging, MSD, DrFalk Pharma, Photopill; and speaking honoraria from Abbott Laboratories, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, and Shire. Edward V. Loftus Jr has received consulting fees from AbbVie, UCB, Janssen, Takeda, Immune Pharmaceuticals and research/grant support from AbbVie, UCB, Janssen, Takeda, Amgen, Bristol-Myers Squibb, Braintree, Genentech, Pfizer, Shire, GlaxoSmithKline, and Robarts Clinical Trials. Edouard Louis has received research grant from AstraZeneca, Schering-Plough, and Abbott; served on advisory boards at Abbott, AbbVie, Ferring, UCB, MSD, Millenium, Mitsubishi Pharma, and Takeda; and a consultant for AbbVie. Julian Panés has received consulting fees from AbbVie, Boehringer Ingelheim, BMS, Genentech, MSD, Novo-Nordisk, NSP, Pfizer, Roche, Topivert, and Tygenix. Jürgen Schölmerich has received consultancy fees from AbbVie and Falk Pharma (last 3 years). Stefan Schreiber has received consulting and speaker fees from AbbVie. Maurizio Vecchi has received financial support for research from Giuliani Pharma and Sofar and consulting fees from Nycomed, MSD, AbbVie, Hospira, and Ferring. Gionata Fiorino has received consultancy fees from MSD, AbbVie, Takeda and Janssen Pharmaceuticals. Michael A. Kamm is a consultant for AbbVie, Janssen, and Ferring and has received research support from AbbVie and Ferring. Ingrid Ordas has received grant support from AbbVie and FAES Farma and consultation fees from Prometheus and Shire. Jordi Rimola received grant support from AbbVie and Bristol Meyers Squibb; speaker fees from AbbVie, MSD, Bristol Meyers Squibb, and Genentech (Roche group); and is a consultant for AbbVie and Robarts medical trials. Maria Nachury has received consulting fees from AbbVie and Tigenix. William Sandborn has received consulting fees from ActoGeniX NV, AGI Therapeutics, Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas Pharma, Athersys, Inc., Atlantic Healthcare Limited, Axcan Pharma (now Aptalis), BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research Inc., Elan Pharmaceuticals, EnGene, Inc., Eli Lilly, Enteromedics, Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc., Funxional Therapeutics Limited, Genzyme Corporation, Genentech (now Roche), Gilead Sciences, Given Imaging, Glaxo Smith Kline, Human Genome Sciences, Ironwood Pharmaceuticals (previously Microbia Inc.), Janssen (previously Centocor), KaloBios Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals (previously Alaven Pharmaceuticals), Merck Research Laboratories, MerckSerono, Millennium Pharmaceuticals (subsequently merged with Takeda), Nisshin Kyorin Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc., PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix Pharmaceuticals, Inc., Santarus, Schering Plough Corporation (acquired by Merck), Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S.L.A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG (acquired by Zeria Pharmaceutical Co., Ltd), TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Limited (VBL), Warner Chilcott UK Limited, and Wyeth (now Pfizer). Jean-Frédéric Colombel is a consultant, advisory board member, or speaker for AbbVie Amgen, Bristol Meyers Squibb, Celltrion, Ferring, Genentech, Giuliani SPA, Given Imaging, Janssen and Janssen, Merck & Co., Millenium Pharmaceuticals Inc., Nutrition Science Partners Ltd., Pfizer Inc. Prometheus Laboratories, Receptos, Sanofi, Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma, Vertex, Dr. August Wolff GmbH & Co; has received lecture fees from Bristol Meyers Squibb, and Janssen (previously Centocor) and research support from Bristol Meyers Squibb, Genentech, Glaxo Smith Kline, Janssen (previously Centocor), Millennium Pharmaceuticals (now Takeda), Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals, and UCB Pharma. Jacques Cosnes has received consultancy fees from AbbVie. The remaining authors disclose no conflicts.

: Funding This study was conducted by the IPNIC group (see Acknowledgments). AbbVie provided funding to the IPNIC group, including honoraria for their attendance at IPNIC meetings. No payments were made to the authors for the development of this article. AbbVie participated in developing the content for the IPNIC meetings, but was not involved in the development or review of this article with the authors or the vendor. Medical writing and editing services (including for the slides at the IPNIC meetings) were provided by Margaux-Orange, and financial support for these services was provided by AbbVie.

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Original ResearchFull Report: Clinical—Alimentary TractDevelopment of the Lémann Index to Assess Digestive Tract Damage in Patients With Crohn's Disease

Background & Aims

Methods

Results

Conclusions

Section snippets

Methods

Patients and Investigators

Discussion

Acknowledgments

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease

Gut

Long-term evolution of disease behavior of Crohn's disease

Inflamm Bowel Dis

The natural history of adult Crohn’s disease in population-based cohorts

Am J Gastroenterol

Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health

Gut

Original Research
Full Report: Clinical—Alimentary Tract
Development of the Lémann Index to Assess Digestive Tract Damage in Patients With Crohn's Disease