Results from a new randomized controlled trial show that sublingual immunotherapy (SLIT) for peanut allergy induces a moderate level of desensitization with minimal adverse effects compared with placebo. Results of the study were published in the January 2013 issue of the Journal of Allergy and Clinical Immunology.
"This is the first multicenter, randomized, placebo-controlled trial of peanut SLIT," write David M. Fleischer, MD, from the Department of Pediatrics, National Jewish Health, Denver, Colorado, and colleagues. "The study achieved its primary efficacy end point, demonstrating that treatment with peanut SLIT induces a statistically significant degree of desensitization in a majority of subjects compared with placebo."
After a baseline oral food challenge (OFC) of up to 2 g of peanut powder, 40 participants between the ages of 12 and 37 years were randomly assigned to receive either placebo or peanut SLIT. After 44 weeks, a 5-g OFC was performed, the study was unblinded, and placebo-treated participants were crossed-over to a higher-dose peanut SLIT. Another 5-g OFC was performed 44 weeks later. The researchers compared OFC results for both groups, with responders defined as those participants who successfully consumed either 5 g or at least 10-fold more peanut powder than the baseline OFC threshold.
Seventy percent (14/20) of the participants receiving peanut SLIT showed a positive response after 44 weeks of immunotherapy compared with 15% (3/20) of those receiving placebo (P < .001). Responders in the peanut SLIT group had an increase in the median successfully consumed dose (SCD) of peanut powder from 3.5 to 496 mg. The median SCD increased further to 996 mg at week 68 (P = .05 compared with week 44). Among the participants who crossed over from placebo to peanut SLIT, 44% (7/16) were responders and had an increase in the median SCD from 21 to 496 mg.
A total of 11,854 doses of SLIT (placebo and peanut) were administered throughout the study, and approximately 1.1% of these required treatment for adverse events. Most of the events (125/127) were mild in severity and treated primarily with oral antihistamines. In addition, 1 participant required 1 (0.01%) albuterol only and 1 (0.01%) required epinephrine and oral antihistamine.
Overall, the investigators identified 240 adverse events, though they judged that most (97.5%) of the events were unrelated to the study drug, including upper respiratory infections, gastrointestinal disorders, and headaches. Among the patients receiving peanut SLIT, 36% reported adverse events compared with 31% in the placebo group and 33% in the crossover high-dose group.
New but Not Unexpected
In addition to clinical response to OFC, the researchers evaluated peanut-specific immunoglobulin E (PN-IgE) levels in both groups and noted a statistically significant increase among peanut SLIT participants at week 44 (P = 0.035). This increase was not significant, however, between weeks 44 and 68 (P = .21). The change from baseline in PN-IgE levels among the participants receiving placebo or those in the crossover high-dose group was not significant (P= .43 and P = .07, respectively).
Researchers also noted a significant increase from baseline in peanut-specific IgG4 (PN-IgG4) levels at week 44 among participants treated with peanut SLIT (P = .001) but not between weeks 44 and 68 (P = .42). Among those in the high-dose crossover group, there was a statistically significant increase in PN-IgG4 levels at week 44 (P < .001), whereas no significant change from baseline was noted in PN-IgG4 levels among participants in the placebo group at this time (P = .99).
Despite these immunologic changes, the investigators saw no statistically significant differences in median change from baseline to week 44 in either PN-IgE or PN-IgG4 between peanut SLIT responders and nonresponders (P = .33). Nor was there was a significant difference between crossover high-dose responders and nonresponders noted (P = .07). In addition, the investigators found no difference in median antibody levels at week 44 between participants in the crossover high-dose group and those in the peanut SLIT group.
The participants also underwent peanut end point titration skin prick tests at baseline and week 68. Again, there was no significant difference between peanut SLIT responders and nonresponders.
The authors note that none of the patients treated with peanut SLIT for 44 weeks were able to undergo the desensitization challenge without symptoms. However, a subset of participants who were treated for 68 weeks and rechallenged did demonstrate increases in the SCD with fewer symptoms. "These data suggest continued long-term therapy with peanut SLIT might confer reduced reactivity to peanut after further desensitization, allowing for protection against accidental ingestions, which are reactions to less than 100 mg of peanut protein in general," the authors write.
The researchers acknowledge some study limitations, such as the limited dosing options available for SLIT compared with oral immunotherapy as well as the criteria used to define responders, which may not accurately predict clinical response. In addition, as only desensitization was evaluated, long-term tolerance data or dietary recommendations are lacking.
"These are not unexpected findings, but new, since traditional immunotherapy is not done orally but rather subcutaneously and does not include food allergens." said Rohit Katial, MD, program director, Allergy & Immunology, National Jewish Health, Denver, Colorado, who was not associated with the study.
"Further work is necessary, but [this is] a nice first step in moving towards a treatment option for those with food allergy, since currently the only option is avoiding the food one is allergic to," Dr. Katial told Medscape Medical News.
Funding for this study was provided by the National Institutes of Health, National Institute of Allergy and Infectious Disease, National Center for Research Resources, and National Center for Advancing Translational Sciences. Dr. Fleischer has received grants from the National Institutes of Health/National Institutes of Allergy and Infectious Diseases, has consultant arrangements with sanofi-aventis, is employed by National Jewish Health, and receives royalties from UpToDate. Full conflict-of-interest information is available in the article.
J Allergy Clin Immunol. 2013;131:119-127. Full text
