Healio
Healio
ByRichard Gawel

Read more

May 12, 2022
3 min read
Save

Editorial questions costs, effectiveness of peanut oral immunotherapy

ByRichard Gawel
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Peanut oral immunotherapy presents clinical and economic concerns and may not be necessary for children with good quality of life, according to an editorial by Michael R. Perkin, MB BS (Hons), PhD.

Perspective from Stephen A. Tilles, MD

“Significantly, children age 8 to 12 years and caregivers with low quality of life as reported by their FAQL-CF were more likely to pursue therapy with Palforzia,” Perkin, reader with the Population Health Research Institute and consultant pediatric allergist at St. George’s Hospital, University of London, wrote in the editorial, published in Clinical & Experimental Allergy. “So potentially what improvements are being presented as occurring after successful peanut immunotherapy reflect a selection bias of those with significantly reduced quality of life at baseline. The question, therefore, is whether for the majority with higher baseline quality-of-life scores, is consideration of peanut immunotherapy even necessary?”

Peanuts in a bowl
Source: Adobe Stock

Peanut (Arachis hypogaea) Allergen Powder-dnfp (Palforzia, Aimmune Therapeutics Inc.) — which has been approved for use by the National Institute for Health and Care Excellence in the U.K. and by the FDA in the U.S. — requires an initial dose escalation day followed by 11 more updosing visits every 2 weeks. The National Health Service in the U.K. expects to offer treatment to 600 patients in its first year, with a goal of 2,000 patients each subsequent year.

This annual total would require 24,000 day case visits, Perkin wrote. Current food challenge capacity in the U.K. is 30,076 per year, he continued, requiring 80% of all challenges to cease and switch to day case visits for oral immunotherapy.

However, Perkin cautioned that these updosing visits would need to be conducted in environments appropriate for managing anaphylaxis and administering adrenaline autoinjectors (AAIs), with one fatality resulting from treatment already recorded.

In fact, Perkin said, 14% of patients in the PALISADE trial required an AAI during treatment, with one patient receiving medication three times during a single visit. Perkin also cited three cases of life-threatening anaphylaxis during real-world treatment in Spain.

Perkin additionally expressed concern that 21% of the children in the PALISADE trial did not complete their immunotherapy regimen, with potential negative effects on their quality of life due to feeling they missed the opportunity to improve their lives.

During the ARTEMIS trial, Perkin continued, there were no statistically significant improvements in quality of life for children aged 13 to 17 years, although there were statistically significant improvements in three out of four saw for children aged 8 to 12 years.

Plus, 21% of patients who completed 134 weeks of peanut immunotherapy followed by 26 weeks of avoidance in the Immune Tolerance Network IMPACT trial remained tolerant, leading Perkin to question the treatment’s efficacy.

Perkin also noted that the prescribing information does not indicate how long maintenance should continue, which consists of 300 mg of peanut protein or two full peanuts, or when patients should switch from the medication to actual peanuts.

The medication in this maintenance therapy, meanwhile, would cost the NHS £10.12 each day per patient, or £3,693.80 per year. Providing challenge capacity and training staff to conduct updosing and food challenges would be a considerable cost as well, Perkin wrote.

Perkin further pointed out that up to 20% of children with peanut allergy spontaneously outgrow their allergy by age 10 years, prompting him to question whether starting younger children on treatment is even necessary.

Finally, Perkin cited a study where only 22 of 237 individuals with peanut allergy (9.3%) chose to pursue peanut immunotherapy. The leading reasons for declining therapy included concerns over adverse effects and concerns over the degree of commitment.

Perkin concluded that there needs to be a thorough discussion of the many issues, such as adverse events, side effects, quality of life, the need for sustained treatment, additional peanut consumption and cofactor restrictions related to peanut oral immunotherapy.

Perspective

Back to Top Stephen A. Tilles, MD)

Stephen A. Tilles, MD

The editorial by Perkin focuses on a historical comparison of a 1908 case report of an unapproved OIT to egg with the first FDA- and European Medicines Agency-approved OIT treatment, Palforzia [Peanut (Arachis hypgaea) Allergen Powder-dnfp], for the mitigation of allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanut in children aged 4 through 17 years. (See Palforzia’s Full Prescribing Information and Medication Guide for more information.)

An important feature not addressed in the editorial is both the importance and complexity of the drug development process, including the fact that food, when used as a treatment of a food allergy, is considered by regulatory authorities to be a biologic drug subject to strict chemistry, manufacturing and control regulations. There is good reason for this.

As evidenced by the 1908 case report, immunotherapeutic principles are not new. But the rigor required to ensure that commercially available therapeutics are safe and effective has been well chronicled by FDA guidance documents over the years. In recent decades, we have learned about the importance of maintaining consistent quality and standardized potency of component allergens when treating allergic patients with immunotherapy for respiratory diseases or stinging insect allergy.

To date, this has not been the case for unapproved food OIT. Instead, an approved food OIT must undergo strict processing and testing regulations and controls. For example, the process of starting with raw peanuts and ending with peanut flour suitable for use as Palforzia drug product is an exacting process, resulting in rejection of most lots of peanut flour source material, most commonly due to the failure to meet potency acceptance criteria for the immunodominant component peanut allergens Ara h 1, Ara h 2 and Ara h 6.

This process involves potency testing using both enzyme-linked immunosorbent assay and reversed-phase high-performance liquid chromatography such that the relative expression of these component allergens is consistent across every lot of drug substance. Furthermore, other lots of peanut flour source material have been rejected due to unacceptable levels of contamination with a carcinogenic toxin called aflatoxin.

Aside from the historical comparison of the 1908 case report, Perkin cites several suboptimal outcomes with unapproved food OIT use, including one tragic fatality that occurred in a patient treated with unapproved milk OIT. We share his concern for safety, and it is precisely for this reason that it was important to include more than 1,000 participants in Palforzia’s safety database prior to its approval, while continuing to monitor real world risk as part of a risk evaluation and mitigation strategy in the U.S. and a risk management plan in the E.U. In addition, there is an ongoing long-term open-label study, as well as planned real-world observational studies, that will continue to study safety, tolerability and efficacy through participant-reported outcomes. This level of scientific rigor is warranted to ensure an accurate safety and efficacy profile.

References:

Stephen A. Tilles, MD
Senior Medical Director and Global Head of Medical Affairs, Allergy, at Aimmune Therapeutics Inc.
Disclosures: Tilles reports being an employee of Aimmune Therapeutics Inc.
Sources/Disclosures

Collapse
Source:

Perkin MR. Clin Exp Allergy. 2022;doi:10.1111/cea.14145.



Disclosures: Perkin reports no relevant financial disclosures.

Read more about

oral immunotherapy
peanut allergy
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

 

Related Content