Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response

Abstract

ObjectivesWe aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission.DesignOutcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015–2020, n=110; All India Institute of Medical Sciences, New Delhi 2018–2020, n=62).ResultsIn the 2015–2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992–1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992–1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%–11%.ConclusionsEmergency colectomy rates for ASC have halved in 25 years to 8%–15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.

Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring

“…A recently published multicenter study on acute severe UC demonstrated similar observations with CRP in the Indians being lowest as compared to British and Australians. 19 Albumin plays a cardinal role in drug transport and metabolism by binding several drugs with a high affinity, thereby slowing their elimination rates. 20 Low albumin concentration is a marker of underlying pathologic processes, such as malnutrition and inflammation, and has been linked to poor outcomes in many health disorders.…”

Review article: Updated management of acute severe ulcerative colitis: From steroids to novel medical strategies

“…A new prognosis index has recently been developed in a cohort study of 117 patients and validated in 172 patients. This four‐point model includes a CRP level ≥100 mg/L, albumin ≤25 g/L and UCEIS ≥4 or ≥7 on admission 31 . A score ≥3 predicted steroid failure in 84% of the patients (OR 11.9, 95%CI [confidence interval] 10.8–13.0).…”

“…Regarding short-term use of ciclosporin, an RCT of 73 patients comparing ciclosporin dosesT A B L E 4Score: Stool frequency/day +0.14 � CRP Ho et al66 Mean stool number on first 3 days, albumin <30 g/L on admission, colonic dilatation >5.5 cm on Xray 85% of steroids failure when score ≥4Gibson et al67 3 stools per day and CRP/albumin ratio on day 3 Relative risk of steroids failure of 3.9 (95% CI 2.1-7.2)Adams et al31 Albumin <25 g/L, CRP ≥100 mg/L, UCEIS ≥4 or ≥ 7 on admission 84% of steroids failure when score ≥3 CALMÉJANE ET AL.…”

Letter: ‘No first among equals’—Authors' reply

“…Early scores that predict response to these advanced therapies are needed, particularly since there has been a significant increase in the proportion of patients who do not respond to steroids. 8 We propose to create a new score that avoids these limitations.To that end, we propose to develop an endoscopic index of severity for ASUC, to validate this endoscopic index in a prospective, multi-centre fashion and to incorporate clinical, biomarker and ultrasound parameters with the endoscopic index pre-and post-therapy to create the definitive score to predict outcomes in ASUC.…”

“…Early scores that predict response to these advanced therapies are needed, particularly since there has been a significant increase in the proportion of patients who do not respond to steroids. 8 We propose to create a new score that avoids these limitations.…”