The incidence of remission and indicators of inadequate response to advanced therapy in patients with ulcerative colitis: results from medical charts in the United Kingdom

Figures & data

Table 1. Patient characteristics at baseline.

	Overall	Prior use of biologics		p value	Use of CS at start of index therapy		p value
		Bio-naïve	Bio-experienced		Yes	No
Number of patients, n (%)	238 (100)	178 (74.8)	60 (25.2)		84 (35.3)	154 (64.7)
Age at index (years)
Mean (SD)	43.9 (17.7)	44.5 (18.5)	42.1 (15.3)	.333	43.3 (17.3)	44.2 (18.0)	.734
Median (IQR)	42 (29–58)	41 (29–61)	43 (30–49)	.559	42 (30–58)	43 (28–59)	.772
Sex, n (%)
Male	127 (53.4)	91 (51.1)	36 (60.0)	.233	36 (42.9)	91 (59.1)	.016
Female	111 (46.6)	87 (48.9)	24 (40.0)		48 (57.1)	63 (40.9)
Partial Mayo score	N = 136	N = 95	N = 41		N = 39	N = 97
Mean (SD)	5.4 (1.9)	5.5 (2.0)	5.2 (1.6)	.258	5.5 (2.2)	5.4 (1.7)	.899
Median (IQR)	6 (4–7)	6 (4–7)	5 (5–6)	.243	6 (4–7)	5 (4–7)	.668
CRP level^a (mg/L)	N = 154	N = 116	N = 38		N = 54	N = 100
Mean (SD)	20.9 (38.5)	18.9 (36.0)	26.7 (45.5)	.341	24.8 (42.9)	18.7 (36)	.341
Median (IQR)	6 (3–18)	6 (3–18)	6 (3–29)	.859	7 (4–27)	6 (3–17)	.414
FC level^a (μg/g)	N = 63	N = 34	N = 29		N = 10	N = 53
Mean (SD)	533.3 (491.9)	639.2 (621.3)	409.0 (226.2)	.051	378.3 (258.8)	562.5 (521)	.101
Median (IQR)	510 (110–600)	504 (70–854)	510 (180–600)	.663	505 (70–600)	541 (130–600)	.434
Conventional therapies at baseline^b
Any CS^c	154 (64.7)	124 (69.7)	30 (50)	.003	84 (100)	70 (45.5)	<.001
5-aminosalicylic acid	173 (72.7)	141 (79.2)	32 (53.3)	<.001	66 (78.6)	107 (69.5)	.133
Azathioprine	135 (56.7)	97 (54.5)	38 (63.3)	.232	41 (48.8)	94 (61.0)	.069
Other non-advanced therapies^d	53 (22.3)	38 (21.4)	15 (25)	.557	23 (27.4)	30 (19.5)	.162
Duration of UC (years)	N = 229	N = 173	N = 56		N = 83	N = 146
Mean (SD)	8.6 (9.0)	8.2 (8.8)	9.5 (9.4)	.361	7.8 (8.9)	9.0 (9.0)	.353
Median (IQR)	6 (2–11)	6 (2–11)	6 (2–13)	.192	6 (2–10)	6 (2–13)	.203
Follow-up after index (years)
Mean (SD)	29.02 (12.4)	27.3 (11.9)	34.2 (12.5)	<.001	27.5 (12.5)	29.8 (12.3)	.164
Median (IQR)	28.8 (20.3–38.2)	27.2 (19.6–36.1)	35.1 (26.2–45.4)	<.001	28 (19.4–35.9)	29 (20.8–39.0)	.259

Patient baseline characteristics of the overall sample of patients initiating an advanced therapy for the management of UC as well as predefined subgroups.

Abbreviations. Bio, biologic; CRP, C-reactive protein; CS, corticosteroid; FC, fecal calprotectin; IQR, interquartile range; SD, standard deviation; UC, ulcerative colitis.

^a CRP and FC levels were reported for values in the 4 weeks before the index date.

^b UC-related conventional therapies were reported for the 12-month baseline period.

^c Any CS included systemic, rectal, and locally acting CS.

^d Other non-advanced therapies included mercaptopurine, methotrexate, ciclosporin, and tacrolimus.

Figure 1. Time to first clinical remission among patients with UC treated with advanced therapy. Abbreviation. UC, ulcerative colitis.

Figure 2. Inadequate response to index therapy by indicator measured at 3, 6, 12, and 24 months. Abbreviations. CS, corticosteroid; ED, emergency department; UC, ulcerative colitis.

Figure 3. Time to any indicator of inadequate response among patients with and without remission within the first 12 months, treated with advanced therapy.

Table 2. Multivariate Cox regression model for the first achievement of clinical remission during index therapy.

Covariate	HR (95% CI)	p value
Age at index (years)	0.997 (0.99–1.01)	.585
Female (n = 84)	0.856 (0.58–1.27)	.436
Index therapy
Anti-TNFα (n = 96)	Reference
Tofacitinib (n = 4)	0.911 (0.21–4.02)	.902
Vedolizumab (n = 77)	1.156 (0.74–1.80)	.522
Prior advanced therapy (n = 46)	0.569 (0.33–0.97)	.038
Active use of CS at index date (n = 56)	1.105 (0.73–1.68)	.642
Other active non-advanced therapies at index date^a (n = 129)	1.115 (0.72–1.73)	.629

Multivariate Cox regression model estimating factors associated with the likelihood of observing first achievement of clinical remission among patients with UC treated with advanced therapies (n = 177).

Abbreviations. CI, confidence interval; CS, corticosteroid; HR, hazard ratio; TNFα, tumor necrosis factor alpha; UC, ulcerative colitis.

^a Other non-advanced therapies included 5-aminosalicylic acid, azathioprine, mercaptopurine, methotrexate, tacrolimus, and ciclosporin.

Table 3. Multivariate Cox regression model for first inadequate response to advanced therapies.

Covariate	HR (95% CI)	p value
Age at index (years)	0.997 (0.99–1.01)	.482
Female (n = 111)	1.375 (0.99–1.91)	.059
Index therapy
Anti-TNFα (n = 128)	Reference
Tofacitinib (n = 5)	0.479 (0.11–2.03)	.318
Vedolizumab (n = 105)	0.468 (0.31–0.71)	<.001
Prior advanced therapy (n = 60)	0.747 (0.46–1.22)	.245
Active use of CS at index date (n = 84)	1.304 (0.93–1.82)	.119
Other active non-advanced therapies at index date^a (n = 172)	1.141 (0.77–1.69)	.506

Multivariate Cox regression model estimating factors associated with the probability of observing indicators of inadequate response among patients with UC treated with advanced therapies (n = 238).

Abbreviations. CI, confidence interval; CS, corticosteroid; HR, hazard ratio; TNFα, tumor necrosis factor alpha; UC, ulcerative colitis.

^a Other non-advanced therapies included 5-aminosalicylic acid, azathioprine, mercaptopurine, methotrexate, tacrolimus, and ciclosporin.

Table 4. Primary reason for discontinuation of index therapy.

Primary reason, n (%)	N = 88
UC signs and/or symptoms worsened or were not controlled satisfactorily	34 (38.6)
Switch to another advanced UC-related therapy	21 (23.9)
Patient experienced a drug-related acute reaction/AE from the advanced therapy	10 (11.4)
Patient developed neutralizing antibodies	6 (6.8)
Patient required a surgical intervention to manage UC	4 (4.6)
Patient decision to terminate the advanced therapy	4 (4.6)

Primary reasons for discontinuing index therapy that were reported only once (n = 11; 12.5%) are not displayed in the table.

Abbreviations. AE, adverse event; UC, ulcerative colitis.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.