Article Text

Download PDFPDF

Definitions of response and remission for the Robarts Histopathology Index
  1. Rish K Pai1,
  2. Reena Khanna2,3,
  3. Geert R D’Haens2,4,
  4. William J Sandborn2,5,
  5. Jenny Jeyarajah2,
  6. Brian G Feagan2,
  7. Niels Vande Casteele2,6,
  8. Vipul Jairath2,3,7
  1. 1 Department of Pathology and Laboratory Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA
  2. 2 Robarts Clinical Trials, London, Ontario, Canada
  3. 3 Department of Medicine, University of Western Ontario, London, Ontario, Canada
  4. 4 Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
  5. 5 Division of Gastroenterology, University of California, San Diego, California, USA
  6. 6 Department of Medicine, University of California, San Diego, California, USA
  7. 7 Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
  1. Correspondence to Dr. Rish K Pai, Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona 85259, USA; pai.rish{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

The Robarts Histopathology Index (RHI) is a recently validated instrument that measures histological disease activity in ulcerative colitis.1 Given the increasing importance and use of histology in UC as a treatment outcome, additional evaluation and clarification of the definitions for histological remission and response using the RHI is needed.

During the development of the RHI, we demonstrated that most patients in clinical or endoscopic remission had an RHI≤6. However, an RHI≤6 should not be used to define histological remission as was recently suggested by Magro et al.2 Rather, the minimal criteria for histological remission should be the absence of neutrophils from the mucosa (both lamina propria and epithelium), as neutrophils have long been used to define histologically active disease.3 Furthermore, the presence of mucosal neutrophils in biopsies from patients in clinical remission predicts clinical relapse.4 Using the RHI, an absence of mucosal neutrophils is defined as RHI≤3 with the additional requirement of subscores of 0 for lamina propria neutrophils and 0 for neutrophils in epithelium. Given that basal plasmacytosis has also been suggested as an important histological predictor of adverse outcomes,5 an alternate histological endpoint that requires both the absence of mucosal neutrophils and basal plasmacytosis defined as an RHI≤1 could be attractive. However, this composite definition might be too high a bar to achieve in clinical drug development during induction therapy and may be a goal for evaluation of maintenance efficacy.

One must also be cautious of translating histological data among indices. Recently, Colombel et al 6 attempted to derive the Nancy index from the Geboes score; however, such conversions should be approached with caution. For example, in their table describing the conversion, incorrect definitions for ulcers and erosion were used to convert the Geboes score into the Nancy index. Only true ulcers (Geboes 5.4) and erosions (Geboes 5.3) are regarded as evidence of Nancy grade 4.7 Finally, it is not possible to accurately derive Nancy grades 2 and 3 from either RHI or Geboes as the Nancy index descriptors of mild, moderate and severe acute inflammation do not map directly on the Geboes score.

We have recently shown that the Geboes score, RHI, Nancy index and modified Riley score are all responsive instruments to change using data from the TOUCHSTONE phase 2 trial of ozanimod, an oral sphingosine-1-phosphate agonist.8 However, the change in RHI that is meaningful is not currently clear. To address this need, we used data from a phase 2 clinical trial of MLN02 (vedolizumab) in ulcerative colitis,9 to calculate the minimum important difference in RHI using an anchor-based approach with common measures of clinical and endoscopic improvement (table 1).10 The change in RHI that correlates with these different measures ranged between 4 and 7. A decrease of ≥7 in the RHI, which represents the most conservative of the anchor-based mean change score analyses, is attractive as such a decrease requires fairly dramatic changes in the components that comprise the RHI such as changes in multiple individual items or resolution of frank ulcers and erosions. Statistically significant differences are seen between placebo and MLN02 treatment groups using these definitions of histological remission and response (table 2).

Table 1

Change in Robarts Histopathology Index (RHI) and change in binary variables with anchor-based minimum important difference (MID)

Table 2

Histological response and remission using Robarts Histopathology Index (RHI)

As histological measurement of disease activity gains acceptance as an important measure of treatment efficacy and mucosal healing, validated measures of histological activity with known operating properties are needed. The RHI can be used to evaluate histological remission using various definitions and, based on the data presented in this letter, can also be used to measure histological response. Refinement of these cutpoints using additional datasets is needed.



  • Contributors All authors contributed to writing and editing the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests RKP has received consulting fees from Seres Therapeutics, Eli Lilly, Protagonist and Genentech outside the submitted work. RK reports fees from Janssen, AbbVie, Shire, Pfizer and Takeda Canada and from Robarts Clinical Trials outside the submitted work. GRD reports consulting fees from Robarts Clinical Trials; personal fees from Ablynx, Amakem, Amgen, AM Pharma, Boehringer-Ingelheim, Bristol Myers Squibb, Cosmo, Celgene, Celtrion, Covidien, Engene, Galapagos, Medimetrics, Mundipharma, Mitsubishi, Novonordisk, Pfizer, Receptos, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Topivert, Versant and Vifor; grants and personal fees from Abbvie, Ferring, Glaxo Smith Kline, Jansen Biologics, Hospira, Merck Sharp Dome, Prometheus Labs, Robarts Clinical Trials, Takeda and Tillotts; and grants from Falk Pharma and Photopill, outside the submitted work. WJS reports consulting fees from University of Western Ontario (previous owner of Robarts Clinical Trials), Abbvie, Akros Pharma, Allergan, Ambrx, Amgen, Ardelyx, Arena Pharmaceuticals, Atlantic Pharmaceuticals, Avaxia, Biogen, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Conatus, Cosmo Technologies, Escalier Biosciences, Ferring, Ferring Research Institute, Forward Pharma, Galapagos, Genentech, Gilead Sciences, Immune Pharmaceuticals, Index Pharmaceuticals, Janssen, Kyowa Hakko Kirin Pharma, Lilly, Medimmune, Mesoblast, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Otsuka, Palatin, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Qu Biologics, Regeneron, Ritter Pharmaceuticals, Robarts Clinical Trials, Salix, Seattle Genetics, Seres Therapeutics, Shire, Sigmoid Biotechnologies, Takeda, Theradiag, Theravance, Tigenix, Tillotts Pharma, UCB Pharma, Vascular Biogenics and Vivelix; research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly and Celgene/Receptos; payments for lectures/speaker’s bureau from Abbvie, Janssen and Takeda; and stock/stock options in Escalier Biosciences, Oppilan Pharma, Precision IBD, Progenity and Ritter Pharmaceuticals. JJ is an employee of Robarts Clinical Trials. BGF reports grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor, Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma and Sigmoid Pharma; and speaker’s bureau fees from UCB, AbbVie and J&J/Janssen outside the submitted work. NVC reports consulting fees from Janssen, Pfizer, Takeda and UCB. VJ has received consulting fees from AbbVie, Sandoz, Takeda, Janssen, Robarts Clinical Trials, Eli Lilly, GlaxoSmithKline, Arena, Topivert; speaker’s fees from Takeda, Janssen, Shire, and Ferring.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.