High-dose adrenomedullin effective against steroid-resistant ulcerative colitis
Adults with steroid-resistant ulcerative colitis (UC) may fare well with the vasodilatory peptide adrenomedullin at a high dose, which has been shown to induce complete remission within 8 weeks in a phase IIa trial.
The multicentre, double-blind trial randomly assigned 28 Japanese patients to one of the four groups given an infusion of 5, 10, or 15 ng/kg/min of adrenomedullin or placebo, respectively, for 8 hours per day for 14 days.
Only 21 patients completed treatment—four, five, six, and six in the respective groups—and made it to the final analysis. The average age of these patients was 45.2 years, and there were 13 men. There were no significant differences among the four groups except for the C-reactive protein (CRP) level. None of the patients received any biologics (infliximab or adalimumab) and immunosuppressants (cyclosporine or tacrolimus) for at least 3 months prior to enrolment.
At week 2, Mayo scores were comparable across all treatment groups. The same was true for the rate of clinical remission (defined as a Mayo score of 0).
Meanwhile, at week 8, the Mayo score was significantly lower in the high-dose adrenomedullin group (15 ng/kg/min) than in the placebo group (change, −9.3 vs −3.0; p=0.035), with the proportion of patients achieving clinical remission being higher (3/3, 100 percent vs 0/2, 0 percent; p=0.025).
After 2 weeks of treatment, steroid doses decreased in all patients who received the study drug. The corresponding changes in steroid doses between 0 and 8 weeks in the 5-, 10-, and 15-ng/kg/min adrenomedullin and placebo groups were −18.3, −6.7, and −23.3, and −8.7 mg.
Symptoms related to the vasodilatory effect of adrenomedullin, including headache, palpitation, blood pressure dip, and flushes, were more frequently observed in the active treatment groups than the placebo group. However, these symptoms were mild and tolerable.
The present data suggest that adrenomedullin is a promising therapeutic agent for inducing complete remission in refractory UC.