Introduction
Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis (UC).1 The PICaSSO Histological Remission Index (PHRI) is a new simple index for UC disease assessment based only on the detection of neutrophils.2 We evaluate PHRI’s correlation with endoscopy and its prognostic value compared to other established indices.
Aims & Methods
Consecutive patients with UC underwent colonoscopy at 2 referral centers (Birmingham, UK and Milan, Italy) and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI] and Robarts [RHI]) and endoscopy (Mayo Endoscopic Score [MES]; Ulcerative Colitis Severity Endoscopic Index of Severity [UCEIS], and PICaSSO score) was calculated as Spearman coefficients.
Cutoffs for remission were: MES = 0, UCEIS ≤ 1, PICaSSO ≤ 3, PHRI = 0, NHI ≤ 1, RHI ≤ 3 with no neutrophils in the lamina propria or epithelium.
Negative clinical outcomes were defined as: UC-related hospitalization, colectomy, use of steroids, increase in dose in UC therapy or medication change due to uncontrolled inflammation.
The diagnostic performance of endoscopy was assessed with ROC curves and outcome stratification with Kaplan-Meier curves and Cox proportional hazard model.
Results
192 patients with UC were enrolled, representing all grades of endoscopic severity. The correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI (Table 1). In particular, PHRI’s correlation with MES, UCEIS, and PICaSSO was 0.75, 0.72, and 0.69, respectively.
Table 1. Spearman correlation coefficients
| Endoscopic score | Robarts | Nancy | PHRI |
| MES | 0.779 | 0.730 | 0.745 |
| UCEIS | 0.769 | 0.725 | 0.718 |
| PICaSSO | 0.736 | 0.694 | 0.694 |
Analyzing the diagnostic performance of endoscopy scores to detect histological remission according to the different definitions we found no difference among endoscopy scores. Instead, all endoscopy measures captured with greater precision PHRI and NHI remission, as compared with RHI remission (p<0.005 for PHRI vs RHI, and NHI vs RHI). The areas under the ROC curve for PHRI were 0.91 (95% CI 0.864 – 0.947), 0.91 (95% CI 0.866 – 0.947), and 0.88 (0.828 – 0.926) for MES, UCEIS, and PICaSSO, respectively; for NHI 0.89 (95% CI 0.837 - 0.934), 0.89 (95% CI 0.842 - 0.938) and 0.87 (95% CI 0.814 - 0.921); and for RHI 0.63 (95% CI 0.553 - 0.711), 0.66 (95% CI 0.582 - 0.736), and 0.67 (95% CI 0.591 - 0.744).
We then stratified the risk of suffering any negative disease outcome, a proxy for flare, in the two years following endoscopy, in patients in remission and in activity according to the different histological definitions. The hazard ratios were statistically similar and numerically higher for PHRI (2.87 for PHRI, 2.75 for RHI, and 2.71 for NHI, respectively) proving that a neutrophil-only assessment predicts risk of flare at least as well as established scores.
Conclusion
PHRI correlates with endoscopy and stratifies the risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.
References
1. Magro F, Doherty G, Peyrin-Biroulet L, et al. ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology. J Crohns Colitis 2020;14:1503-1511.
2. Gui X, Bazarova A, Del Amor R, et al. PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system. Gut 2022;71:889-898.
Disclosure
OMN has served as a speaker for Janssen, Ferring, Takeda, Pfizer, Fresenius Kabi
FF ha received consulting fees from Janssen; speaker’s fees from Pfizer and Janssen
SD has served as a speaker, consultant and advisory board member for Schering Plough, Abbott (AbbVie) Laboratories, Merck and Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Vifor and Johnson and Johnson.
AA has received consulting fees from: AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; speaker’s fees from: AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda; research support from: MSD, Takeda, Pfizer, Biogen.
SG has served as consultant, Steering committee member, Advisory Board Member and Drug Monitoring committee member for Janssen, Pfizer, Takeda, Abbvie, BMS, Gilead, Galapagos, Celltrion, Eli Lilly, Ferring.
MI has received research grants and equipment loans from Pentax USA, Olympus, and Fujifilm; is partially funded by NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham.
The remaining authors declare no conflict of interest.
