P0533 - Real World Comparison of Long-Term Clinical and Endoscopic Outcomes Between First-Line Biologic Therapies in Ulcerative Colitis

Sunday, October 24, 2021

3:30 PM – 7:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Rahul S. Dalal, MD

Brigham & Women's Hospital
Boston, MA, United States

Rahul S. Dalal, MD¹, Emma L. McClure, BA¹, Jenna Marcus, BS¹, Jessica R. Allegretti, MD, MPH, FACG²
¹Brigham & Women's Hospital, Boston, MA; ²Brigham & Women’s Hospital, Harvard Medical School, Boston, MA

Introduction: Comparisons of long-term outcomes between first-line biologics in ulcerative colitis (UC) are lacking. We sought to compare rates of steroid-free clinical remission (SFCR) and endoscopic remission (ER) at 24 and 48 months (mos) after initiation of infliximab (IFX), adalimumab (ADA), or vedolizumab (VDZ) among biologic-naïve patients with UC.

Methods: Retrospective cohort study of adult, biologic-naïve UC patients initiating IFX, ADA, or VDZ 6/1/14-2/1/19 at a large academic center. Electronic health records were reviewed for clinical data. The primary outcome was SFCR at 24 mos (i.e. simple clinical colitis activity index [SCCAI] ≤2 or provider global assessment when SCCAI was unavailable and no use of oral/IV steroids within 30 days). Secondary outcomes were combined SFCR/ER (Mayo endoscopic subscore ≤1) at 24 mos, SFCR at 48 mos, and combined SFCR/ER at 48 mos. Patients with insufficient follow-up and those who discontinued therapy at < 24 mos for reasons unrelated to treatment efficacy (e.g. adverse effects) were excluded. Due to variable timing of clinical/endoscopic evaluations, we included clinical evaluations at 24-30 mos and 48-54 mos and the closest endoscopic evaluations within 12 mos of these visits. Four multivariable logistic regression (MVLR) models were constructed to determine associations between choice of biologic and outcomes. Confounders were chosen a priori and p< 0.0125 was considered significant.

Results: We included 288 patients (n=105 IFX, 112 ADA, 71 VDZ) with clinical assessment available at 24 mos and 135 patients (n=55 IFX, 64 ADA, 16 VDZ) at 48 mos. When comparing baseline characteristics by biologic, there were significant differences in age, need for dose escalation, Mayo endoscopic subscore, albumin, bowel frequency, and simple clinical colitis activity index (Table 1). Unadjusted outcomes are notable for a significant difference in SFCR at 24 mos (63.8% IFX, 39.3% ADA, 59.2% VDZ, p< 0.01) (Fig 1A). After MVLR (Fig 1B), ADA but not VDZ was associated with significantly lower odds of SFCR at 24 mos (OR 0.3, 95% CI 0.2-0.5), SFCR/ER at 24 mos (OR 0.4, 95% CI 0.2-0.7), and SFCR/ER at 48 mos (OR 0.3, 95% CI 0.1-0.7) compared to IFX. Higher serum albumin (g/dL) was independently associated with SFCR/ER at 24 mos (OR 2.3, 95% CI 1.3-3.9).

Discussion: ADA but not VDZ is associated with lower odds of SFCR and SFCR/ER at 24 mos and SFCR/ER at 48 mos compared to IFX. These data support the use of IFX and VDZ as preferred first-line agents for moderate-to-severe UC.

Figure: Figure 1. A. Clinical outcomes compared by biologic therapy. B. Multivariable logistic regression models.
Raw outcome data: clinical remission 24 months (67/105 infliximab, 44/112 adalimumab, 42/71 vedolizumab), clinical and endoscopic remission 24 months (45/91, 36/110, 29/62), clinical remission 48 months (28/55, 20/64, 8/16), clinical and endoscopic remission 48 months (18/48, 10/54, 7/16). Denominators vary due to patients with limited follow-up time or no endoscopic data.
*Significant at threshold p<0.0125.
†Due to a reduced number of outcomes, only the first 4 covariates were included to limit model overfitting.
Abbreviations: OR = odds ratio, CI = confidence interval

Characteristics	Infliximab (n=105)	Adalimumab (n=112)	Vedolizumab (n=71)	P-value*
Female sex, fraction (%)	52/105 (49.5)	60/112 (53.6)	40/71 (56.3)	0.68
Age, median (IQR), y	34 (28, 46)	36 (27, 52)	56 (39, 68)	< 0.01
Disease duration, median (IQR), y	4.3 (1.5, 11.5)	5.6 (1.6, 11.6)	6.4 (1.9, 15.4)	0.27
BMI^†, median (IQR), kg/m², n=96, 104, 71	24.3 (22.0, 27.6)	24.9 (22.0, 28.8)	25.5 (22.6, 28.9)	0.40
Race or ethnicity, fraction (%)				0.27
White	91/105 (87.7)	102/112 (91.1)	65/71 (91.6)
Black	3/105 (2.9)	1/112 (0.9)	1/71 (1.4)
Hispanic	5/105 (4.8)	1/112 (0.9)	2/71 (2.8)
Asian	1/105 (1.0)	6/112 (5.4)	1/71 (1.4)
Native American or Hawaiian	0/105 (0.0)	0/112 (0.0)	0/71 (0.0)
Other or unknown	5/105 (4.8)	2/112 (1.8)	2/71 (2.8)
Dose escalation^‡, fraction (%)	77/105 (73.3)	46/112 (41.1)	33/71 (46.7)	< 0.01
Current immunomodulator, fraction (%)	18/105 (17.1)	24/112 (21.4)	14/71 (19.7)	0.95
Current corticosteroids, fraction (%)				0.04
Prednisone or methylprednisolone	76/105 (72.4)	70/112 (62.5)	35/71 (49.3)
Oral budesonide	10/105 (9.5)	18/112 (16.1)	10/71 (14.1)
Corticosteroid enemas only	1/105 (1.0)	3/112 (2.7)	3/71 (4.2)
Current smoking, fraction (%)	5/105 (4.8)	4/112 (3.6)	1/71 (1.4)	0.61
Current cannabis, fraction (%)	12/105 (11.4)	20/112 (17.9)	5/71 (7.0)	0.10
Current opioids, fraction (%)	11/105 (10.5)	6/112 (5.4)	6/71 (8.5)	0.36
Last Mayo endoscopic subscore, fraction (%)				< 0.01
0, normal or inactive	3/104 (2.9)	4/108 (3.7)	5/70 (7.1)
1, mild	7/104 (6.7)	20/108 (18.5)	16/70 (22.9)
2, moderate	49/104 (47.1)	61/108 (56.5)	29/70 (41.4)
3, severe	45/104 (43.3)	23/108 (21.3)	20/70 (28.6)
Last endoscopic disease extent, fraction (%)				0.25
Normal or inactive	3/104 (2.9)	4/111 (3.6)	5/71 (7.0)
Proctitis	5/104 (4.8)	7/111 (6.3)	4/71 (5.6)
Left sided or pancolitis	96/104 (92.3)	100/111 (90.1)	62/71 (87.3)
Last serum albumin^†, median (IQR), g/dL, n=98, 99, 68	3.9 (3.3, 4.3)	4.2 (3.7, 4.5)	4.2 (3.7, 4.4)	< 0.01
Last C-reactive protein^†, median (IQR), mg/L, n=91, 88, 62	10.2 (1.9, 57)	4.8 (1.6, 18.4)	4.4 (1.4, 14)	0.02
Last fecal calprotectin^† >120 µg/g , fraction (%)	28/31 (90.3)	22/25 (88.0)	20/22 (90.9)	1.00
Last daily bowel frequency^†, median (IQR), n=85, 94, 62	8 (4, 10)	5 (3, 9)	5 (3, 8)	< 0.01
Last SCCAI^†, median (IQR), n=80, 92, 63	6 (4, 9)	4 (2, 7.5)	4 (2, 7)	< 0.01

Table: Table 1. Baseline characteristics compared by biologic therapy.
*Calculated using Kruskal-Wallis test for continuous data and Fisher’s exact test for categorical data.
†The most recent values for continuous variables documented within 3 months prior to biologic initiation were used. Older values were excluded. Reduced sample sizes are noted.
‡Dose escalation refers to dose increase or dosing interval reduction of biologic agent at any point after treatment initiation.
Abbreviations: IQR=interquartile range, CMV=cytomegalovirus, BMI=body mass index, SCCAI=simple clinical colitis activity index

Disclosures:

Rahul Dalal indicated no relevant financial relationships.

Emma McClure indicated no relevant financial relationships.

Jenna Marcus indicated no relevant financial relationships.

Jessica Allegretti: Artugen – Consultant. Finch Therapeutics – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Merck – Grant/Research Support. Pandion – Consultant. Pfizer – Consultant. Servatus – Consultant. Takeda – Consultant.

Rahul S. Dalal, MD¹, Emma L. McClure, BA¹, Jenna Marcus, BS¹, Jessica R. Allegretti, MD, MPH, FACG². P0533 - Real World Comparison of Long-Term Clinical and Endoscopic Outcomes Between First-Line Biologic Therapies in Ulcerative Colitis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.