Microencapsulated Ragweed Pollen Extract Safe, Effective for Seasonal Allergic Rhinitis

Nov. 8, 2005 (Anaheim) - A microencapsulated ragweed pollen extract (MRPE) administered by mouth significantly reduces allergic rhinitis symptoms compared with placebo, according to a presentation here by Peter Creticos, MD, at the annual meeting of the American College of Allergy, Asthma & Immunology.

"There's a lot of interest in looking at alternatives to standard immunotherapy, which is encumbered by requiring weekly shots during the build-up phase and one to two shots per month for several years of maintenance," Dr. Creticos told Medscape. "Compliance is a real issue; shots hurt and can be fraught with systemic reactions that can be serious or life threatening." Dr. Creticos, the principal investigator of the study, is from the Division of Allergy and Clinical Immunology at Johns Hopkins University School of Medicine in Baltimore, Maryland.

In this study, the oral immunotherapy was delivered via microencapsulated beads put into a capsule, which "enables the antigen to be delivered more efficiently to the Peyer's patches in the jejunum and duodenum, where the antigen can be presented and processed and not destroyed by stomach acid," according to Dr. Creticos.

He and his colleagues conducted a double-blind, placebo-controlled clinical trial of MRPE in 607 patients with ragweed-allergic rhinitis. The aims of the study were to determine if this method of oral administration would improve compliance, and be safe and effective. Eligibility criteria included at least a two-year history of ragweed allergic rhinitis; positive skin prick tests; and positive CAP IgE assay.

The patients were randomized to MRPE (40 amphotericin B [Amb], 1 unit once daily); MRPE 40 Amb, 1 unit once weekly; or placebo. Patients were treated for up to 24 weeks with doses starting eight to 12 weeks before the start of the ragweed season. Primary outcome measure was mean daily total symptom score (TSS). Of the 522 patients who received at least one dose of the study medication, mean ages were similar among the groups (range, 36.6 - 37.8 years).

There was no significant difference in efficacy between the treatment groups overall (P = .19). However, several subsets of patients benefited significantly from MRPE compared with placebo when dose and duration of treatment were accounted for. When initiated 10 weeks before the ragweed pollen season, MRPE given to 86 patients at a dose of 40 Amb a 1 units/day reduced TSS by 36% compared with placebo (MRPE TSS, 7 vs placebo TSS, 11; P = .007).

There were also significant differences in TSS when dosing began nine weeks (n = 166; P = .004) or 11 weeks (n = 55; P = .037) before the ragweed pollen season. In addition, MRPE at 40 Amb once daily suppressed production of IgE. Treatment duration was a critical determinant of efficacy.

Patients treated with the orally administered MRPE tolerated the drug well in general, with mild to moderate gastrointestinal adverse effects being most common. Diarrhea occurred in 11.2% (MRPE once daily), 7.6% (MRPE once weekly), and 5.4% (placebo). Upper abdominal pain occurred in 7.8% (MRPE once daily), 2.5% (MRPE once weekly), and 2.0% (placebo). There were no severe adverse events (SAEs) attributable to treatment; SAEs occurred in 12.2% of the MRPE once-daily group, 8.6% of the MRPE once-weekly group, and in 8.8% of patients in the placebo group.

Ragweed allergen MRPE delivery is both efficacious and safe when dosed appropriately, according to Dr. Creticos. He told Medscape, "We're really interested in learning what we can about immunologic markers that could make it easier to select appropriate patients and predict how long you need to treat them.

He added, "There's a tremendous amount of interest in whether you can use oral [immunotherapy] not just during the season, but whether it can be disease-modifying; a long-term, continuous regimen may be more important for its disease-modifying ability."

New safety trials of this oral immunotherapy delivery system in ragweed-allergic patients will start in the winter of 2005-2006 in anticipation of a multicenter efficacy trial to take place during the 2007 ragweed season, Dr. Creticos said. Physicians with ragweed-allergic patients who live in the Baltimore area and may be interested in participating should contact Dr. Creticos' research coordinator by phone at 1-410-550-2111.

The study was sponsored by Curalogic A/S in Copenhagen, Denmark. Dr. Creticos disclosed that he serves as a consultant for Curalogic A/S, as well as for multiple pharmaceutical companies.

ACAAI 2005 Annual Meeting: Abstract 52. Presented Nov. 7, 2005.

Reviewed by Helen Fosam, PhD