Long-term Outcome of Patients With Acute Severe Ulcerative Colitis Responding to Intravenous Steroids

Robert Salameh; Julien Kirchgesner; Matthieu Allez; Franck Carbonnel; Antoine Meyer; Jean-Marc Gornet; Laurent Beaugerie; Aurelien Amiot

Disclosures

Aliment Pharmacol Ther. 2020;51(11):1096-1104. 

In This Article

Results

Study Population

A total of 447 hospital in-patients with acute flares of UC treated with IVS were screened for inclusion between December 2017 and January 2019 (Figure 1). Among those patients, 70 did not fulfil the modified Truelove and Witts criteria, 30 were treated with biological agent before the response to IVS could be assessed, and 205 did not respond to IVS. A total of 142 patients were therefore included, including 42 patients with previous exposure to immunomodulators (n = 40) and/or biological agents, including anti-TNF (n = 19) and vedolizumab (n = 1). Patient demographic data, baseline disease characteristics and medication history are listed in Table 1. Patients with previous exposure to immunomodulators and/or biological agents were less frequently male (33.3% vs 56.0, P = 0.02), had a longer disease duration (9.6 ± 17.9 years vs 2.5 ± 5.4, P < 0.001), were younger (29.6 ± 14.2 vs 35.6 ± 15.2, P = 0.03), had a lower CRP level (63.4 ± 68.9 vs 81.9 ± 75.4, P = 0.05) and had a lower serum albumin level (29.0 ± 6.3 vs 29.9 ± 6.8, P = 0.05) at the time of admission.

Figure 1.

Flow chart of patients

Evolution of Disease Activity During Hospitalisation

The median duration of hospitalisation was 8.0 (6.0–10.0) days. IVS consisted of intravenous methylprednisolone at a dose of 53.1 ± 8.9 mg per day with 5-ASA and/or steroid enemas in 96 (67.6%) cases. A dramatic improvement in disease activity was observed between the initiation of IVS and days 3 and 5 (Table S1). At the time of discharge, all patients received maintenance therapy: 5-ASA in 59 (41.5%) cases, immunomodulators in 60 (42%), anti-TNF in 18 (13%) and vedolizumab in 5 (3.5%). Patients with previous exposure to immunomodulators and/or biological agents were less frequently treated with 5-ASA (11.9% vs 54.0%, P < 0.001) and more frequently treated with anti-TNF (35.7% vs 3.0%, P < 0.001) or vedolizumab (11.9% vs 0%, P = 0.002), whereas no difference was found for maintenance therapy with immunomodulators (40.5% vs 43.0%, P = 0.85).

Long-term Outcomes After Acute Severe UC Responding to IVS

The flow chart of patients according to maintenance therapy during the first 24 months after discharge is presented in Figure 1. Three patients were not evaluated at month 24 and were censored: one patient died due to pancreatic carcinoma, one patient died of ischaemic chronic heart failure at 80 years old, and one patient discontinued infliximab maintenance therapy during pregnancy. The rates of clinical remission, steroid-free clinical remission, relapse and colectomy at months 3, 6, 12, 18 and 24 are presented in Table 2. After a median follow-up of 4.8 (2.6–7.3) years, 90 (63.4%) had relapsed on their initial maintenance therapy, including 41 (69.5%), 37 (61.7%) and 9 (39.1%) in patients treated with 5-ASA, immunomodulator and biological agents as maintenance therapy respectively. Overall, 13 (9.2%) patients had undergone colectomy for refractory UC. Among relapsers, the magnitude of relapse was similar in the three maintenance therapy group (Table S2).

The probabilities of relapse-free survival were 58%, 48%, 46%, 42% and 40% at 1, 2, 3, 4 and 5 years respectively (Figure 2). In multivariate analysis, the risk of relapse was significantly decreased in patients treated with anti-TNF (HR = 0.37, 95% CI [0.16–0.87], P = 0.02), in patients with a partial Mayo Clinic score <2 at day 5 (HR = 0.41, 95% CI [0.21–0.80], P = 0.009) and in patients with fewer than six liquid stools per day at day 3 (HR = 0.56, 95% CI [0.34–0.91], P = 0.02; Table 3). The Kaplan-Meier curves of relapse-free survival according to maintenance therapy are presented in Figure 3.

Figure 2.

Kaplan-Meier curves of 142 patients with acute severe ulcerative colitis responding to intravenous steroids to assess the probability of clinical relapse

Figure 3.

Kaplan-Meier curves of 142 patients with acute severe ulcerative colitis responding to intravenous steroids to assess the probability of clinical relapse according to the chosen maintenance therapy

The probabilities of colectomy-free survival were 96%, 95%, 93% and 92%, 91% and 88% at 1, 2, 3, 4, 5 and 8 years respectively (Figure 4). The multivariate analysis demonstrated that patients with Lichtiger index >12 at hospital admission (HR = 10.12, 95% CI [1.30–78.55], P = 0.03) were more likely to undergo colectomy (Table S3).

Figure 4.

Kaplan-Meier curves of 142 patients with acute severe ulcerative colitis responding to intravenous steroids to assess the probability of colectomy

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