Introduction
Intestinal ultrasound (IUS), in particular bowel wall thickness (BWT), is accurate in determining endoscopic disease activity in ulcerative colitis (UC). Reduction of BWT six weeks into advanced anti-inflammatory treatment predicted endoscopic response and clinical remission. Filgotinib is a preferential JAK1-inhibitor effective in UC. Currently, there is no data on IUS-kinetics or early prediction of treatment response with filgotinib.
Aims & Methods
In this study, we aimed to identify early IUS predictors of treatment response to filgotinib in patients with moderate to severe UC. This prospective observational study included UC patients with active endoscopic disease (i.e. endoscopic MAYO score (EMS) ≥2) starting with filgotinib. Clinical scores (UCEIS, Lichtiger), biochemical parameters and IUS parameters of the sigmoid were assessed at baseline, after 4 weeks (W4) and at the time of the second endoscopy (between W8 and W23). Endoscopic remission (i.e. EMS=0), endoscopic response (i.e. decrease in EMS ≥1 compared to baseline) and clinical remission (SCCAI ≤2 or Lichtiger score ≤3) were assessed. IUS response (i.e. defined as a reduction in BWT of >25% or >2.0 mm, or >1.0 mm and one colour Doppler signal) was assessed at week 4. All normally distributed data were reported in mean ± standard deviation [SD] and non-normally distributed in median and interquartile range [IQR]. Mann–Whitney U tests were used to compare continuous non-parametric variables, chi square tests for dichotomous variables.
Results
A total of 20 patients were included. 13 patients underwent second endoscopy, 2 refused a follow-up endoscopy and 5 patients were still in follow-up. At baseline, 9 patients (9/20, 45%) had received ≥2 biologicals, 16 patients (16/20, 80%) had previous anti-TNF exposure, and no patients were exposed to other JAK-inhibitors. 8 patients (8/20, 40%) had severe endoscopic disease at baseline (i.e. EMS=3). 5 patients (5/13, 38%) were endoscopic responders at W8-23, and no patient reached endoscopic remission. BWT was significantly lower in the sigmoid colon from W4 onwards for patients reaching endoscopic response (Table 1). Decrease in BWT compared to baseline was statistically greater in endoscopic responders from W4 onwards (Table 1). IUS response was seen at W4 in 6 patients, of which 5 were endoscopic responders (83%, p=0.002). Decrease in BWT from W4 onwards was statistically greater in patients reaching clinical remission at W8-23 (-45% (-55% to -36.6%) vs -9% (-25% to +8%), p=0.014).
| Time point | Endoscopic response (n=5) | Endoscopic non-response (n=8) | p-value |
Median BWT (IQR) at baseline
| 4.5 mm (3.2-6.2) | 5.1 mm (3.6-6.5) | p=0.61 |
| Median BWT (IQR) at W4 | 1.9 mm (1.8-3.8) | 4.7 mm (3.3-5.9) | p=0.019 |
| Median BWT (IQR) at W8-23 | 2.2 mm (1.8-3.7) | 5.3 mm (4.3-6.7) | p=0.008 |
| Median decrease in BWT (IQR) W4 | -42% (-53% to -38%) | -3% (-16% to +9%) | p=0.003 |
| Median decrease in BWT (IQR) W8-23 | -45% (-51% to -35%) | -10% (-1% to +24%) | p=0.003 |
Conclusion
On IUS, UC patients treated with filgotinib have significantly lower BWT from week 4 onwards compared to baseline, which could predict endoscopic response.
Disclosure
MP received speakers fees from Janssen and Tillotts
CT received speakers fees from Tillotts
FV received speaker or honoraria fees from AbbVie, Janssen and Tillotts
ML received consultancy/lecturefees from Abbvie, Bristol Myers Squibb , Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda and Tillotts.
RG Received speakers fee from Janssen and Tillotts
GD has served as a consultant and/or received speaker’s fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, Glaxo SmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts, Ventyx Biosciences.
KG 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’s honoraria from Abbvie, Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.
