PATH-HHT
Trial question
What is the role of pomalidomide for epistaxis in patients with HHT?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
48.0% female
52.0% male
N = 144
144 patients (69 female, 75 male).
Inclusion criteria: patients with HHT who had an Epistaxis Severity Score of at least 3 in the past 3 months.
Key exclusion criteria: renal insufficiency; hepatic insufficiency; treatment with thalidomide or other imid drugs in the past 6 months; treatment with bevacizumab or pazopanib in the past 6 weeks; peripheral neuropathy; known underlying hypoproliferative anemia.
Interventions
N=95 pomalidomide (at a dose of 4 mg daily for 24 weeks).
N=49 placebo (matching placebo daily for 24 weeks).
Primary outcome
Mean reduction in Epistaxis Severity Score at week 24
1.84 points
0.9 points
1.8 points
1.4 points
0.9 points
0.5 points
0.0 points
Pomalidomide
Placebo
Significant
increase ▲
Significantly greater reduction in mean Epistaxis Severity Score at week 24 (1.84 points vs. 0.9 points; MD 0.94, 95% CI 0.31 to 1.57).
Secondary outcomes
Significantly greater reduction in mean HHT-specific quality-of-life score at week 24 (2.7 points vs. 1.2 points; MD 1.4, 95% CI 0.3 to 2.6).
No significant difference in the rate of receipt of any RBC transfusions through 24 weeks (16% vs. 22%; RR 0.73, 95% CI 0.36 to 1.46).
Significantly greater reduction in mean daily epistaxis duration at week 24 (6.1 min/day vs. 3.7 min/day; MD 2.4, 95% CI 4.7 to 9.6).
Safety outcomes
No significant differences in serious adverse events, bleeding serious adverse events, fatigue, peripheral neuropathy.
Significant differences in neutropenia (44% vs. 10%), constipation (47% vs. 18%), rash (35% vs. 10%).
Conclusion
In patients with HHT who had an Epistaxis Severity Score of at least 3 in the past 3 months, pomalidomide was superior to placebo with respect to mean reduction in Epistaxis Severity Score at week 24.
Reference
Hanny Al-Samkari, Raj S Kasthuri, Vivek N Iyer et al. Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia. N Engl J Med. 2024 Sep 19;391(11):1015-1027.
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