Abstract Background Refractory ulcerative colitis (UC) remains a therapeutic challenge. Hyperbaric oxygen therapy (HBOT) is a treatment that delivers 100% oxygen in a pressurized chamber. HBOT enhances tissue oxygenation and neovascularization and proved clinical efficacy in post-radiation proctitis and enteritis, perianal fistulizing Crohn’s disease, and acute severe UC1-3. We studied tolerability, preliminary efficacy, and mechanistic effects including perfusion kinetics measured with intestinal ultrasound (IUS) of 10 and 20 sessions of HBOT in refractory UC. Methods We designed an investigator-initiated, prospective, open label, uncontrolled, dose-finding pilot trial (PARADOX) in biologic-experienced refractory moderate-to-severe UC patients with 26 weeks follow-up (Mayo score 5, MES ≥2, failed ≥2 classes advanced therapies). Patients (n = 16; 8 per arm) continued optimized stable dose background therapy and received 10 or 20 sessions HBOT (2.4 ATA, 120 minutes per day with two 5-minute air breaks). The primary efficacy outcome was predefined as composite clinical and endoscopic response (3-point and 30% decrease in Mayo score, RB = 0 and 1-point decrease in MES) at week (W)12. Other outcomes included tolerability; clinical, symptomatic, endoscopic, histological and biochemical response, and transmural response assessed by IUS including contrast-enhanced ultrasound (CEUS) to evaluate bowel wall thickness and perfusion kinetics. Recordings of endoscopy and IUS were centrally read and adjudicated. Results Both cohorts were comparable with median age: 48 vs 64 years; disease duration: 12 vs 9 years; ≥4 prior advanced therapies: 3/8 in both; Mayo score: 10.5 vs 9. At W12, the composite primary outcome was met in 2/8 patients with 10 sessions and 4/8 patients with 20 sessions. Clinical, endoscopic, symptomatic, biochemical, histological parameters all improved over time in both HBOT cohorts with a trend towards greater improvement after 20 sessions (Table). At W12, clinical responders demonstrated a significant increase in peak enhancement on CEUS compared to baseline (12.1 dB, 95% CI: 0.8 to 34.3), while non-responders showed a numerical decrease (–5.4 dB, 95% CI: –20.9 to 4.0). This divergent trajectory (Figure) was consistent across perfusion parameters related to both wash-in and wash-out, suggesting a treatment-related vascular response. In contrast, early gains in non-responders had waned by W12. This effect was larger after 20 sessions, supporting a potential dose–response effect. HBOT was well tolerated with no dose-limiting toxicity. Conclusion HBOT is a feasible adjunctive therapy in treatment-refractory moderate-severe UC. CEUS showed increased intestinal perfusion in HBOT responders, suggesting a useful non-invasive marker. References: 1. Dulai PS, et al. Am J Gastroenterol 2018;113:1516-1523. 2. Dulai PS, et al. Aliment Pharmacol Ther 2020;52:955-963. 3. Singh AK, et al. Eur J Gastroenterol Hepatol 2021;33:e564-e573 Conflict of interest: Mr. Pruijt, Maarten: Nothing to declare Mulders, Lieven: No conflicts Van Oostrom, Joep: Other: Speaker fees from Tillott’s and Takeda Van Der Zanden, Esmerij: No conflict of interest Neefjes-Borst, Andra: No conflict of interest Koelink, Pim: No conflict of interest Wildenberg, Manon: Received research grant support from Hoffman-La Roche, Boehringer-Ingelheim De Jonge, Wouter: No conflict of interest Ridderikhof, Milan: No conflict of interest Van Hulst, Rob: No conflict of interest D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Personal Fees: Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, AstraZeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Glaxo Smith Kline, Dr Falk Pharma, Pfizer, Johnson and Johnson, Merck, Mirador, Polpharma, Procise Diagnostics, Prometheus Biosciences, Sorriso Pharma, Spyre, Takeda, Ventyx Gecse, Krisztina B.: Grant: Abbvie, Pfizer Inc, Celltrion and Galapagos/Alfasigma Personal Fees: Consultancy fees from AbbVie, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Pfizer Inc., and Takeda and speaker’s honoraria from Celltrion, Eli Lilly, Janssen Pharmaceuticals, Pfizer Inc. and Takeda.
Pruijt et al. (Thu,) studied this question.