TOPLINE

Among patients with refractory ulcerative colitis, adjunctive hyperbaric oxygen therapy (HBOT) was well tolerated and associated with clinical, endoscopic, and mechanistic improvements, evidenced by increased bowel perfusion and preserved bowel wall thickness among responders.

METHODOLOGY

• HBOT involves inhalation of 100% oxygen under increased atmospheric pressure to enhance tissue oxygenation and promote neovascularization. For biologic-refractory ulcerative colitis, HBOT may reopen a therapeutic window for disease stabilization and avoidance of colectomy.
• Researchers conducted a phase 2a pilot trial in Netherlands, with patients enrolled between January 2023 and December 2024. The study aimed to evaluate the preliminary efficacy and safety of different HBOT regimens in treatment-refractory ulcerative colitis.
• The trial enrolled 16 patients (age ≥ 16 years) with moderate-to-severe disease activity (total Mayo score ≥ 5; Mayo endoscopic subscore [MES] ≥ 2) who had previously failed at least two classes of advanced therapies and were maintained on stable background medications for at least 8 weeks before enrollment.
• HBOT was administered using supervised, multiplace hyperbaric chambers. Participants were sequentially assigned to receive either 10, 20, or 30 HBOT sessions (2.4 atmospheres absolute; 120 min per session delivered on consecutive weekdays). Dose escalation to the 30‑session cohort was not undertaken after the 20‑session group met the prespecified response rate of at least 50%.
• The primary endpoint was composite clinical and endoscopic response at week 12, defined as a reduction of at least 3 points and 30% from baseline in total Mayo score, a rectal bleeding subscore of 0, and a decrease of at least 1 point in MES.

TAKEAWAY

• At week 12, composite clinical and endoscopic response was achieved in 38% of patients (95% CI, 18-61) overall, with a response rate of 25% (95% CI, 7-59) in the 10-session cohort and 50% (95% CI, 22-78) in the 20-session cohort.
• At 12 weeks, clinical response was seen in 56% of patients (95% CI, 33-77), symptomatic remission in 44% (95% CI, 20-70), histologic remission in 19% (95% CI, 7-43), with a mean reduction of 4.3 points in total Mayo score (95% CI, -5.6 to -3.0), alongside improvements in quality of life.
• Contrast-enhanced ultrasound and intestinal ultrasound demonstrated a clear divergence by week 12, with responders showing increased perfusion and preserved bowel wall thickness, while nonresponders showed declining perfusion and reduced bowel wall thickness.
• HBOT was well tolerated through week 26, with fatigue, worsening symptoms of ulcerative colitis, and nasopharyngitis as the most common treatment-emergent adverse events; no serious adverse events or treatment-related discontinuations were reported.

IN PRACTICE

“HBOT is a well-tolerated adjunctive treatment showing preliminary clinical and endoscopic benefit in refractory UC [ulcerative colitis] patients. The unique vascular response identified by CEUS [contrast-enhanced ultrasound] suggests a regenerative mechanism distinct from conventional anti-inflammatory therapies,” the authors of the study wrote.

SOURCE

The study was led by Lieven Mulders, MD, Amsterdam UMC, University of Amsterdam, Netherlands. It was published online in the Journal of Crohn’s and Colitis.

LIMITATIONS

The study was an open-label, single-center pilot study with modest sample size and no placebo group. Observed dose‑ranging signals may have been influenced by baseline differences between treatment groups introduced by the sequential cohort design. The need for specialized hyperbaric chamber facilities and technical expertise in contrast‑enhanced ultrasound analysis may have limited the broader applicability of the intervention. 

DISCLOSURES

This study received support from a research grant from the European Crohn’s and Colitis Organisation. Two authors disclosed serving as advisors and receiving speaker fees and honoraria from various pharmaceutical and biotech companies. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.