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. 2024 Nov 4;30(11):1992-2003.
doi: 10.1093/ibd/izad274.

Early Intestinal Ultrasound Predicts Clinical and Endoscopic Treatment Response and Demonstrates Drug-Specific Kinetics in Moderate-to-Severe Ulcerative Colitis

Floris A de Voogd  1 , Steven J Bots  1 , Elsa A van Wassenaer  2 , Maria de Jong  1 , Maarten J Pruijt  1 , Geert R D'Haens  1 , Krisztina B Gecse  1
Affiliations

Early Intestinal Ultrasound Predicts Clinical and Endoscopic Treatment Response and Demonstrates Drug-Specific Kinetics in Moderate-to-Severe Ulcerative Colitis

Floris A de Voogd et al. Inflamm Bowel Dis. .

Abstract

Background: Intestinal ultrasound (IUS) is an emerging modality in monitoring disease activity in ulcerative colitis (UC). Here, we aimed to identify early IUS predictors of treatment response as evaluated by endoscopy and assessed the kinetics of IUS changes.

Methods: This prospective, longitudinal study included UC patients with endoscopic disease activity (endoscopic Mayo score [EMS] ≥2) starting anti-inflammatory treatment. Clinical scores, biochemical parameters and IUS were assessed at baseline (W0), at week 2 (W2), at W6(W6), and at the time of second endoscopy (W8-W26). Per colonic segment, endoscopic remission (EMS = 0), improvement (EMS ≤1), response (decrease in EMS ≥1), and clinical remission (Lichtiger score ≤3) were assessed and correlated with common IUS parameters. Additionally, drug-specific responsiveness of bowel wall thickness (BWT) was assessed.

Results: A total of 51 patients were included and followed, and 33 patients underwent second endoscopy. BWT was lower from W6 onward for patients reaching endoscopic improvement (3.0 ± 1.2 mm vs 4.1 ± 1.3 mm; P = .026), remission (2.5 ± 1.2 mm vs 4.1 ± 1.1 mm; P = .002), and clinical remission (3.01 ± 1.34 mm vs 3.85 ± 1.20 mm; P = .035). Decrease in BWT was more pronounced in endoscopic responders (-40 ± 25% vs -4 ± 28%; P = .001) at W8 to W26. At W6, BWT ≤3.0 mm (odds ratio [OR], 25.13; 95% confidence interval, 2.01-3.14; P = .012) and color Doppler signal (OR, 0.35; 95% confidence interval, 0.14-0.88; P = .026) predicted endoscopic remission and improvement, respectively. Submucosal layer thickness at W6 predicted endoscopic remission (OR, 0.09; P = .018) and improvement (OR, 0.14; P = .02). Furthermore, BWT decreased significantly at W2 for infliximab and tofacitinib and at W6 for vedolizumab.

Conclusions: BWT and color Doppler signal predicted endoscopic targets already after 6 weeks of treatment and response was drug specific. IUS allows close monitoring of treatment in UC and is a surrogate marker of endoscopy.

Keywords: intestinal ultrasound; treatment response; ulcerative colitis.

Plain language summary

Intestinal ultrasound (IUS) is an emerging modality to monitor treatment response in ulcerative colitis. In this study, we investigated the responsiveness of IUS parameters such as bowel wall thickness (BWT) and color Doppler signal after start of treatment and evaluated these parameters early on in treatment follow-up (week 2 and W6). We found that BWT and color Doppler signal at W2 and W6 could predict endoscopic remission and improvement later on in treatment follow-up (between W8 and W26). Furthermore, we provide accurate cutoff values for BWT to predict and determine endoscopic endpoints. The timing of monitoring treatment response is drug specific, and IUS is a surrogate marker of endoscopy.

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Conflict of interest statement

F.A.d.V. received speaker fees or honoraria from AbbVie, Galapagos, and Janssen. S.J.B. has served as speaker for AbbVie, Merck Sharp & Dome, Takeda, Janssen Cilag, Pfizer, and Tillotts. E.A.v.W. has received speaker fees or honoraria from Tillotts and Takeda. M.d.J. received speaker honoraria from Tillotts and Takeda. M.J.P. received speaker honoraria from Tillotts. G.R.D. has served as an advisor for AbbVie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmo, Covidien, Ferring, Dr. Falk Pharma, Engene, Galapagos, Gilead, GlaxoSmithKline, Hospira, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millennium/Takeda, Mitsubishi Pharma, Merck Sharp & Dome, MundiPharma, Novo Nordisk, Pfizer, Prometheus Laboratories/Nestlé, Protagonist, Receptos, Robarts Clinical Trials, Salix, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor; and received speaker fees from AbbVie, Ferring, Johnson and Johnson, Merck Sharp & Dome, MundiPharma, Norgine, Pfizer, Shire, Millennium/Takeda, Tillotts, and Vifor. K.B.G. has received grants from Pfizer Inc, Celltrion, and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, and Takeda; and speaker honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts.

Figures

Figure 1.
Figure 1.
Bowel wall thickness per time point for patients with and without endoscopic improvement, endoscopic response, and endoscopic remission. Data are reported in Supplementary Table 1. CI, confidence interval.
Figure 2.
Figure 2.
Decrease in bowel wall thickness in the sigmoid, descending, transverse, and ascending colon for the total population. CI, confidence interval.
Figure 3.
Figure 3.
Segmental healing during follow-up for patients with a left-sided colitis (≤ descending colon, n = 24) and patients with an extensive colitis (≥ transverse colon, n = 27) at baseline intestinal ultrasound. Data were analyzed with chi-square test for more than 2 groups.
Figure 4.
Figure 4.
Decrease in median percentage bowel wall thickness with regard to baseline regardless of endoscopic response for patients treated with infliximab (n = 18, week 2 [W2]: −26% [interquartile range [IQR], −43% to −6%], P = .001; W6: −23% [IQR, −50% to 4%], P = .019; W8-W26: −23% [IQR, −58 to 0%], P = .009), vedolizumab (n = 14, W2: −14% [IQR, −43 to 5%], P = .11; W6: −22% [IQR, −52% to −16% ], P = .04; W8-W26: −37% [IQR, −57% to −17% ], P = .008), and tofacitinib (n = 14, W2: −33% [IQR, −46% to −5% ], P = .007; W6: −28% [IQR, −38% to −0.5% ], P = .028; W8-W26: −33% [IQR, −50% to −2% ], P = .013).
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