Peanut immunotherapy

ICER report (US economic review) – showed that peanut immunotherapy led to more systemic reactions and more adrenaline use  – so just avoid?

2014 Andrew Clark Lancet STOP II study – 39 children 7-16yrs, peanut flour orally.  2 weekly up dosing,  starting with 2 mg, increasing to 800 mg of peanut protein then maintained for total of 26 weeks.  Tolerance then assessed with challenge.

91% achieved tolerance of 5 peanuts daily (although only 62% actually had negative challenge!).

Side effects mainly oral itching (6% of doses), nausea, vomiting.  1 patient needed IM adrenaline (twice) for wheeze. Even minor reactions are annoying especially GI, or if daily!  And not always predictable.  Tend to get less over time, of course.  Paul Turner feels adverse event reporting “massaged” somewhat (no international consensus on reporting) – the word anaphylaxis not used except to thank the Anaphylaxis campaign, yet 22% of patients had wheeze at some point, even though reported rate of wheeze is 0.4% of doses. Still, anaphylaxis in hospital when potential reaction expected not the same as unexpected reaction in community.

Peanut IgE significantly reduced but not SPT! So works as long as you keep taking your daily dose, definitely side effects incl anaphylaxis, but not a cure.

No data yet on rates of reactions after treatment. But using anxiety model, OIT helps with “perception of severity” (as lots of minor reactions), “perceived ability to cope” (as managed already) and “rescue factors” (as more used to carry medicines).  Note how experience of using AAI seen as positive (and kids often laugh at anticlimax of it!). 1/3 of benefit of OIT seen after initial confirmation challenge, particularly where anaphylaxis occurred (and in patients as well as parents)! [Sarah Burrell, ADC 2021]

Roughly 10-20% don’t desensitize at all. A further 10-20% don’t achieve full dose.  And another 10-20% the fail at the end tolerance challenge.  Benefit likely to be highest for those most at risk of anaphylaxis, yet tendency will be to cherry pick lowest risk cases…

AR101 Oral Immunotherapy trial (PALISADE) –  multiple authors including Jonathan Hourihane and George du Toit.  US, N=496 aged 4-17yrs.  Dose escalation then 24/52 maintenance (so about 12 months total) with peanut derived product, 67% passed 600mg peanut protein challenge (about 2 peanuts). [Some adult patients included initially but unsuccessful in all of them!]

Frequent mild/moderate events, but also in placebo group! 4.3% had severe events cf 0.8% of placebo group.  About 10% withdrew due to adverse events , mostly GI- interestingly another 10% were lost due to parents withdrawing consent, I wonder what their reasons were.

Michael Perkins NEJM editorial – possible risk of eosinophilic oesophagitis? Only 1 case confirmed.

Now that this is a commercial product (Palforzia), unlikely that using peanut flour acceptable in future? But Natasha trial currently looking at peanut flour in UK.

[N Engl J Med 2018]

Second trial, just in Europe (ARTEMIS), n=227, up dosing every 2 weeks, just 12 weeks maintenance (300mg), so about 9 months treatment total.  58% tolerated 1000mg peanut (about 3 peanuts).  Again, lots of mild/moderate adverse events but in the controls too! 1% rate of severe in treatment group (1 patient).  10% withdrew due to adverse effects.  No eosinophilic oesophagitis reported. “Clinically important” improvements seen at the time of final food challenge in QOL scores related to “Allergen avoidance and diet restrictions” and “Risk of accidental exposure”, and in FAIM domains relating to perceived likelihood and chance of dying (both self and parent/carer reported) in the future.

Follow up study of self selected group of those who successfully completed PALISADE, who then opted to continue treatment for total of 18 vs 24 months – 48% of former still able to tolerate 2000mg, cf 80.8% of latter. Less adverse events over time of treatment, improved quality of life scores (“clinically meaningful”). Still peanut SPT positive (IgE a bit less for the 24 month group)!  There were more accidental peanut exposures in this study than in the original trial, suggesting less vigilance, but the severity of these reactions and need for adrenaline was low, which might confirm an immunomodulatory effect.

Severe and uncontrolled asthma was an exclusion criterium, obviously. Similarly chronic/recurrent abdominal pain.

AR101 (Palforzia) has now received NICE approval for use in NHS England.

Future may be to combine different routes eg sublingual/patch.