Current Insights

A Systemic Review of Therapeutic Options for Peanut Allergy

Eimear O'Rourke; Hilary Tang; Andrew Chin; Andrew Long; Sayantani Sindher; R. Sharon Chinthrajah

Disclosures

Curr Opin Allergy Clin Immunol. 2022;22(3):188-193. 

In This Article

Immunotherapy

PA is a potentially life-threatening and lifelong disorder, in which treatment has been limited to complete avoidance of the allergen. Immunotherapy has the potential to improve the management, psychosocial impacts, and socio-economic impacts of this condition, therefore increasing QoL for the individual. Oral immunotherapy (OIT) is based on desensitisation, a treatment where individuals are exposed to increasing doses of an allergen to encourage tolerance and raise the threshold that triggers an allergic reaction.[55] In the PALISADE phase 3 trial, participants were fed daily doses of AR101, a PP-derived biologic OIT drug that delivers a daily maintenance dose of 300 mg of PP, and were screened for doselimiting symptoms at 100 mg PP or less. 67% tolerated 500 mg of PP, versus 4% with placebo, demonstrating that dosing with AR101 PP allowed for a higher tolerance of PP than placebo.[56] This study demonstrated that consistent OIT treatment with PP could lead to decreased sensitivity to peanut allergen exposure. This led to the US Food and Drug Administration (FDA) approval of the first peanut- derived OIT treatment: Palforzia.[57] With the adoption of the first and only FDA-approved PP in the USA for OIT treatment, Palforzia will next become available for treatment in the UK. An increasing number of clinical trials have reported similar conclusions of ability to tolerate gradual maintenance doses of 300 mg to 4000 mg of PP through OIT,[56,58,59] increasing to higher doses of 5000 mg, which is equal to 16–20 whole peanuts.[60]

Recent clinical trials indicate that early OIT is well tolerated and safe showing high completion rate,[61,62] however the long-term efficacy of sustained unresponsiveness to PP beyond short-term studies had not yet been fully understood. The sustained outcomes in OIT for peanut allergy (POISED) study, demonstrated that a 2-year buildup of peanut OIT could lead to desensitization to 4 grams of peanut, however, without continuous exposure to the protein, sustained unresponsiveness is rarer. The study found that at the 4000 mg PP level, there is an increased likelihood of redeveloping reactivity to peanut when peanut OIT was discontinued or decreased to 300 mg daily, demonstrating that the majority of patients require continued consumption of peanut to maintain tolerance.[63] Assessing beyond the short-term benefits of OIT, the novel POISED study provided better understanding on the durability of desensitization, indicating the need for consistent, high dose exposure to PP over time. At the end of the study, many patients tolerated higher PP thresholds after OIT compared to prior treatment, suggesting that each patient's optimal maintenance dose will ultimately depend on whether a patient's goal is protection against accidental ingestion or a desire to consume PP products. The randomized placebo-controlled trial IMPACT trial assessed the efficacy and safety of peanut OIT in children and the persistence of tolerance after a period of peanut avoidance. After 134 weeks of OFC, the median cumulative tolerated dose was 5005 mg for peanut OIT and 5 mg for placebo. However, after a period 26 weeks of peanut avoidance, this dose dropped to 755 mg for peanut OIT versus 0 mg for placebo, demonstrating that avoidance of peanut after OIT leads to remission in patients.[64] In addition to efficacy, the safety of OIT should be openly discussed with patients as adverse events during treatment are common, such as mild allergic reactions and in rare cases severe anaphylaxis.[65]

Epicutaneous Immunotherapy (EPIT) is an immunotherapy also under investigation for the treatment of PA and delivers allergens through intact skin to induce desensitization using an epicutaneous peanut patch.[66,67] In recent reports from the PEPTITES open-label extension trial (PEOPLE), continued clinical benefit was reported during 2 additional years of peanut EPIT in children aged 4 to 11 years.[67] Results from the phase 3 REALISE clinical trial confirmed that EPIT with Viaskin Peanut 250 μg as an immunotherapeutic agent for management is well tolerated and safe for children with PA.[68] With many immunotherapies for PA in various stages of development, peanut EPIT is not as potent in causing desensitization compared with OIT and sublingual immunotherapy,[67] however its high adherence level, long-term sustainability and reduced burden on the patient encourages further investigation in the area.[67]

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