Palforzia (Peanut)

Oral immunotherapy (OIT) is a treatment where an allergic individual takes increasing amounts of an allergen by mouth, according to a standardised protocol over time with the goal of being able to eat and tolerate higher amount of the allergen at the end of the treatment. This can then offer protection from accidental exposure to the allergen.

Immunotherapy has a long history for the treatment of pollen, pet dander, and bee and wasp venom allergies. Immunotherapy to these allergens is provided by the sublingual route and subcutaneous injections, whereas immunotherapy to food is usually done through eating. In 2020, following a series of large, multicentre trials, PALFORZIA became the first treatment to be licensed for peanut allergy. PALFORZIA is a series of capsules/sachets containing different doses of peanut protein which can be used to gradually increase exposure to peanut according to a carefully studied protocol.

The treatment itself would involve your child eating a small, measured amount of allergen under medical supervision. If this is tolerated, then you would give your child the same dose at home every day for 2 weeks before returning to try a higher dose. Each increase in dose is done under direct medical supervision at our centre. Once a top dose (which will vary depending on the allergen) has been reached, then this dose is continued daily, although this may be reduced to 3 times a week, to maintain the effect. There will be ongoing follow up throughout this period and depending on the course of the initial part of the process, the maintenance dose may be increased.

Over the past decade there has been a large increase in the number of research studies looking into desensitisation and these have included careful observation of how the treatment impacts on the immune system. It appears that regular exposure to the food causing allergy, but at a level below that which causes a reaction, causes the immune system to increase production of a specific antibody called IgG4. This has a blocking effect on the allergic antibody, known as IgE, and enhances tolerance to the food. As IgG4 levels increase, the effect is greater, allowing more of the food to be tolerated. We are still in the infancy of our understanding as to what is really happening at a molecular level but the science is advancing and we hope that soon there will be a simple blood test that will directly guide desensitisation. However, until we have such a ‘biomarker’ desensitisation is very much led by how well the patient is tolerating food and slowly increasing the level of exposure, rather than anything being gained by lots of blood tests.

It is anticipated that approximately 6-8 months will be required to reach a stable state, taking maintenance.

Peanut OIT is not without risk or side effects. Among the adverse events (AEs) that can occur, the most concerning is anaphylaxis, which in its worst form has the potential to be life-threatening.

Chu et al. recently published a meta-analysis that included 12 randomized, controlled peanut OIT trials with 1041 patients comparing peanut OIT versus no peanut OIT. It showed high-certainty evidence that peanut OIT increased the risk of anaphylaxis (RR 3.12; 95% CI 1.76–5.55), the frequency of anaphylaxis (IRR 2.72; 95% CI 1.57–4.72), and the use of epinephrine during build-up and maintenance phases (RR 2.21; 95% CI 1.27–3.83). Additionally, it showed moderate-certainty evidence that peanut OIT increased serious side effects (RR 1.92; 95% CI 1.00–3.66), although, in this analysis, all cases of anaphylaxis were considered to be serious, independent of whether they were considered as such by the original study team. The authors estimated that peanut oral immunotherapy was associated with 151 more episodes of anaphylaxis per 1000 patients than would be expected in patients practicing avoidance. A repost to this report is available online which further discusses risks associated with therapy.

It is of course important to be aware that the therapy can cause side effects, but likewise it is important to consider the context of these reactions. Reactions to treatment will be most likely to occur during up-dosing, under direct medical supervision in a controlled environment or at worst, at home but with immediate access to emergency medication. The key benefit of OIT is to reduce the risk of reactions that will occur unexpectedly and outside of controlled conditions and thus carrying more risk.

Patients have typically been excluded from studies if they have experienced a recent life-threatening allergic reaction, poorly controlled asthma, suspicion of eosinophilic gastrointestinal disease, or other factors that would hinder their ability to cooperate with the treatment, e.g., a high level of anxiety.

Even if your child is suitable for immunotherapy, it does not mean that it is the right treatment for them. For many patients, continuing to avoid peanut, coupled with an appropriate emergency action plan is the right way to manage the allergy. Desensitisation carries a risk and also has an impact on your day-to-day life during the updosing period and beyond. If your child is medically suitable, there is an important process of shared decision making, alongside detailed information about the treatment, to help you decide if it is the right thing to do. We will not consider your child for treatment without going through this process and you will be required to sign a consent form to confirm that you have discussed the pros and cons of each approach.

If your child is unable to tolerate the therapy a discussion will be had with the team with respect to continuing on therapy. There are many reasons for not being able to tolerate the therapy or the issue may be one of logistics. If allergic side effects are the issue then we will discuss reducing the dose and prolonging the up-dosing schedule, as well as the use of concomitant medications. If the difficulty is with taste, our expert dietitian and nursing team will have tips to assist with this. If the side effect is that of eosinophilic oesophagitis (EoE), therapy will be stopped. We will endeavour to circumvent logistical concerns by offering clinic visits on multiple days of the week running into the early evening.