Oral immunotherapy can desensitize peanut-allergic patients, but at a cost of more adverse events

Reference

The PALISADE Group of Clinical Investigators, Vickery BP, Vereda A, et al. AR101 oral immunotherapy for peanut allergy. N Engl J Med 2018;379(21):1991-2001.

Synopsis

Food allergy is an important and growing problem in industrialized nations. A strict elimination diet is recommended, but accidental exposures to small "doses" of peanut allergens are relatively common. Several recent trials have shown that oral desensitization is effective, but it is not widely available or recommended in routine clinical settings. Therefore, a drug has been developed that provides a 300-mg daily dose of peanut protein, with the idea that it can allow patients to avoid reactions to small exposures. The investigators recruited 551 patients aged 4 years to 55 years with a history of peanut allergy, an abnormal skin test result, and an allergic reaction when exposed to the equivalent of one-third of a peanut kernel. This report focuses primarily on the results in the 496 participants aged 4 years to 17 years. The 499 participants in that age group were randomized in a 3:1 manner to receive immunotherapy or placebo. The groups were fairly evenly matched, with 43% of participants female, 66% aged 4 to 11 years, and 72% with a previous episode of anaphylaxis. Children in the intervention group were given increasing doses of peanut protein from 0.5 mg to 6 mg in a single day, followed by a 40-week dose-escalation phase in which the dose was increased every 2 weeks from 3 mg to 300 mg, followed by a maintenance phase in which the the patients received 300 mg peanut protein daily or matching placebo for 24 weeks. At the end of the study period, the patients underwent a food challenge in which they were given 300 mg, 600 mg, and 1000 mg peanut protein in successive doses, if tolerated, and their reaction was assessed by a physician masked to treatment assignment. At the end of the study, patients in the immunotherapy group were more likely to be able to ingest peanut protein without developing moderate or worse symptoms (for the 600-mg dose: 67.2% vs 4.0%; P < .001; NNT = 2). A somewhat smaller number were able to tolerate the 1000-mg dose, equivalent to approximately 3 peanut kernels (50.3% vs 2.4%; P < .001; NNT = 2). Results were similar for older and younger children. For participants aged 18 years to 55 years, the difference in the ability to tolerate the 600-mg dose was not statistically significant (41.5% vs 14.3%), but was limited by small sample size (n = 55). Regarding safety, serious or severe adverse events were more common in the immunotherapy group (5.6% vs 1.6%; statistical significance not reported, but P = .06 by my calculation). Withdrawals due to adverse events were more common in the immunotherapy group (11.6% vs 2.4%; P = .002 by my calculation; NNTH = 11). Systemic allergic reactions were much more common in the active drug group than in the placebo group (53 vs 4). Of the 53 participants in the immunotherapy group who had a systemic allergic reaction, 1 was severe, 29 were moderate, and 23 were mild.