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.

Conclusion

After ASUC responded to IVS, patients presented a slightly higher risk of relapse compared to what was expected from the overall UC population. More importantly, almost two-thirds of patients experienced clinical relapse as a failure of the chosen maintenance therapy, suggesting a need for a more ambitious strategy after ASUC responds to IVS. Early and complete response to IVS and the use of anti-TNF were predictors of better outcome in this setting. Prospective studies are needed to confirm our results.

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Acknowledgement
Declaration of personal interests
Matthieu Allez has received honoraria from Novo Nordisk, MSD, Abbvie, Ferring, Genentech, Janssen, Pfizer, GSK, Hospira, UCB, Novartis, Takeda and Mayolo-Spindler. Laurent Beaugerie received consulting fees from Janssen, Pfizer and Allergan, lecture fees from Abbvie, Janssen, MSD, Ferring Pharmaceuticals, Mayoly-Spendler, Takeda and Tillots, and research support from Abbott, Ferring Pharmaceuticals, Hospira-Pfizer, Janssen, MSD, Takeda and Tillots. Jean-Marc Gornet has received honoraria from Abbvie, Janssen, Takeda, Tillotts Pharma, Sanofi and Amgen. Aurelien Amiot received consulting fees from Abbvie, Hospira, Takeda, Gilead and Biocodex as well as lecture fees and travel accommodations from Abbvie, Janssen, Biocodex, Hospira, Ferring, Takeda and MSD. This author also received advisory board fees from Gilead, Takeda and Abbvie. No conflict of interest is claimed by the remaining authors.

Authorship
Guarantor of the article
Pr Aurelien Amiot.

Table 1. Demographic, disease characteristics, medication histories and disease activity at baseline of the 142 patients with acute severe ulcerative colitis responding to first-line intensive medical therapy at the time of initiation of intravenous steroids
Characteristic	Previous exposure to immunomodulator and/or biological agent (n = 42)	Naïve of immunomodulator and/or biological agent (n = 100)	Overall (n = 142)	P	Missing values (%)
Age, y	36.9 ± 16.5	38.2 ± 15.8	37.8 ± 15.9	0.76	0
Male gender, n (%)	14 (33.3)	56 (56.0)	70 (49.3)	0.02	0
BMI (kg/m²)	21.5 ± 4.1	21.8 ± 4.4	21.7 ± 4.3	0.69	0.70
Smoking habits, n (%)
Past smoker	10 (23.8)	30 (30.3)	40 (28.4)	0.58	0.70
Active smoker	6 (14.3)	13 (13.1)	19 (13.5)	0.99	0.70
Duration of disease, mo	9.6 ± 17.9	2.5 ± 5.4	4.6 ± 11.2	<0.001	0
Age at diagnosis	29.6 ± 14.2	35.6 ± 15.2	33.8 ± 15.1	0.03	0
A1: ≤16 y	3 (7.2%)	1 (1.0%)	4 (2.8%)	0.08	0
A2: 17–40 y	29 (69.0%)	66 (66.0%)	95 (66.9%)	0.85	0
A3: >40 y	10 (23.8%)	33 (33.0%)	43 (30.3%)	0.32	0
Ulcerative colitis
Proctitis	3 (7.1%)	5 (5.0%)	8 (5.6%)	0.69	0
Left-sided colitis	16 (38.1%)	39 (39.0%)	55 (38.7%)	0.99	0
Extensive colitis	23 (54.8%)	56 (56.0%)	79 (55.6%)	0.99	0
Disease activity
Lichtiger index	13.1 ± 2.2	12.8 ± 2.0	12.8 ± 2.1	0.43	0
Mayo Clinic score	10.0 ± 1.0	10.1 ± 0.9	10.1 ± 0.9	0.76	1.40
Partial Mayo Clinic score	7.7 ± 0.5	7.6 ± 0.5	7.6 ± 0.5	0.37	0
Endoscopic Mayo Clinic subscore	2.3 ± 0.8	2.5 ± 0.7	2.4 ± 0.7	0.37	1.40
UCEIS	4.9 ± 1.3	4.8 ± 1.2	4.8 ± 1.2	0.8	1.40
History of treatment
Aminosalicylates maintenance therapy	32 (76.2%)	57 (57.0%)	89 (62.7%)	0.04	0
Steroids	25 (59.5%)	12 (12.0%)	37 (26.1%)	<0.001	0
Immunomodulator	40 (95.2%)	0	40 (28.2%)	<0.001	0
Purine analogues	40 (95.2%)	0	40 (28.2%)	<0.001	0
Methotrexate	4 (%)	0	4 (2.8%)	0.007	0
Anti-TNF therapy, n (%)	19 (45.2%)	0	19 (13.4%)	<0.001	0
One anti-TNF agent	16 (38.1%)	0	16 (11.3%)	<0.001	0
≥2 anti-TNF agents	3 (7.1%)	0	3 (2.1%)	<0.001	0
Vedolizumab	1 (2.4%)	0	1 (0.7%)	0.3	0
Biologic variables
Haemoglobin level (g/dL)	11.2 ± 2.0	11.4 ± 2.0	11.3 ± 2.0	0.65	10.60
Leukocytes count, 10⁹/L	10 141 ± 5145	9701 ± 4475	9826 ± 4660	0.37	13.40
Platelets count, 10⁹/L	391 ± 176	410 ± 132	405 ± 146	0.5	7.70
CRP level, mg/L	63.4 ± 68.9	89.5 ± 77.0	81.9 ± 75.4	0.05	1.40
Serum albumin, g/L	32.0 ± 7.6	29.0 ± 6.3	29.9 ± 6.8	0.05	14.80

Abbreviations: CRP, high sensitivity C-reactive protein; GI, Gastrointestinal; TNF, tumor necrosis factor-α. UCEIS, ulcerative colitis endoscopic index of severity.
Variables are presented as n (%), mean ± SD or median (interquartile range).

Table 2. Outcome measures of 142 with acute severe ulcerative colitis responding to intravenous steroids during the first 2 y after discharge
	Month 3 (n = 142)	Month 6 (n = 142)	Month 12 (n = 142)	Month 18 (n = 141)	Month 24 (n = 139)
Steroid-free clinical remission	83 (58.5%)	87 (61.3%)	80 (56.3%)	68 (48.2%)	65 (46.8%)
Clinical remission	106 (74.6%)	90 (63.4%)	80 (56.3%)	69 (48.9%)	65 (46.8%)
Relapse	26 (18.3%)	55 (38.7%)	60 (42.3%)	72 (51.1%)	72 (51.8%)
Colectomy	1 (0.7%)	5 (3.5%)	6 (4.2%)	6 (4.3%)	7 (5.0%)

Clinical remission was defined as a partial Mayo Clinic score <3 with a combined stool frequency and rectal bleeding subscore of ≤1 for patients with ulcerative colitis. The proportions of patients who met the criteria for the latter end points during the present trial of maintenance therapy were analyzed with the reference to the whole population included at week 0. Patients who relapsed or underwent colectomy were not considered in clinical remission at the following time points.

Table 3. The baseline predictors associated with clinical relapse-free survival in 142 patients with acute sever ulcerative colitis responding to intravenous steroids
Risk factors	Univariate analysis		Multivariate analysis
Risk factors	HR (95%CI)	P value	HR (95%CI)	P value
Anti-TNF maintenance therapy	0.45 (0.20–0.99)	0.05	0.37 (0.16–0.87)	0.02
A partial Mayo Clinic score <2 at day 5	0.66 (0.42–1.05)	0.08	0.41 (0.21–0.80)	0.009
Less than six liquid stools per day 3	0.54 (0.31–0.95)	0.03	0.56 (0.34–0.91)	0.02
5-ASA maintenance therapy	1.61 (0.98–2.64)	0.06	—	NS
CRP <30 mg/L at day 3	0.57 (0.33–0.97)	0.04	—	NS
Leukocytes >10 000/mm³ at admission	0.67 (0.43–1.05)	0.08	—	NS
Previous exposure to oral or intravenous steroids	0.52 (0.28–0.96)	0.04	—	NS

Abbreviations: CI, confidence interval; CRP, high sensitivity C-reactive protein; HR, hazard ratio.
Hazard ratio (HR) with 95% confidence interval (CI) was estimated using Cox models.

Table S1. Evolution of disease activity in 142 patients with acute severe ulcerative colitis responding to first-line intensive medical therapy with intravenous steroids during the index hospitalization.
Characteristic	At day 0	At day 3	P value for day 3 vs day 0	Missing values (%)	At day 5	Missing values (%)	P value for day 5 vs day 0
Clinical activity Lichtiger index Partial Mayo Clinic score ≥ 6 episodes of bloody diarrhea per day Positive Oxford criteria	12.8 ± 2.1 7.6 ± 0.5 142 (100%) 133 (93.7%)	7.1 ± 2.5 4.5 ± 1.9 34 (23.9%) 24 (16.9%)	<0.001 <0.001 <0.001 <0.001	12.0% 12.0% 0% 0%	4.0 ± 1.9 1.9 ± 1.5 3 (2.1%) 2 (1.4%)	9.6% 9.6% 0.7% 0.7%	<0.001 <0.001 <0.001 <0.001
Biologic variables Haemoglobin level, g/dL Leukocytes count, 10⁹/L Platelets count, 10⁹/L CRP level, mg/L serum albumin, g/L	11.3 ± 2.0 9,826 ± 4,660 405 ± 146 81.9 ± 75.4 29.9 ± 6.8	10.9 ± 1.8 9,866 ± 4593 409 ± 127 26.4 ± 27.3 28.4 ± 5.4	0.005 0.42 0.95 <0.001 0.34	21.1% 26.1% 26.8% 7.0% 82.4%	11.2 ± 1.8 11,200.9 ± 5776 414 ± 131 10.9 ± 13.8 30.8 ± 5.8	24.6% 22.5% 23.2% 14.8% 76.1%	0.52 0.005 0.52 <0.001 0.09

CRP: C-reactive protein.
P values are for all comparisons among the three groups. P values are based on chi² test and Wilcoxon's matched-pair signed-rank test whenever appropriate.

Table S2. Magnitude of relapse in 142 patients with acute severe ulcerative colitis responding to first-line intensive medical therapy with intravenous steroids during the index hospitalization according to maintenance therapy.
	5-ASA maintenance therapy (n = 41)	Immunomodulator maintenance therapy (n = 39)	Biological agent maintenance therapy (n = 9)	P
Ambulatory care	19 (46.3%)	17 (45.9%)	3 (33.3%)	0.87
Hospitalization care	12 (29.3%)	13 (35.1%)	3 (33.3%)
Hospitalization care for recurrence of ASUC	10 (24.4%)	7 (18.9%)	3 (33.3%)

ASUC: acute severe ulcerative colitis.
P values are for all comparisons among the three groups. P values are based on chi² test.

Table S3. The baseline predictors associated with colectomy in 142 patients with acute sever ulcerative colitis responding to intravenous steroids.
Risk factors	Univariate analysis		Multivariate analysis
Risk factors	HR (95%CI)	P value	HR (95%CI)	P value
Lichtiger index > 12 at hospital admission	10.87 [1.39–83.33]	0.02	10.12 [1.30–78.55]	0.03
History of infliximab therapy	3.47 [0.94–12.99]	0.06	-	NS
Inaugural flare of ulcerative colitis	0.21 [0.03–1.65]	0.09	-	NS

HR: hazard ratio; CI: confidence interval. Hazard ratio (HR) with 95% confidence interval (CI) was estimated using Cox models.

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