Question

• Can patients with known peanut allergy treated with an anti-IgE medication once per week for four week tolerate increased doses of ingested peanut?

Clinical Bottom Lines

1. 450 mg of the anti-IgE medication TNX-901, given subcutaneously every 4 weeks for 4 injections, seems to confer a level of protection to 50% to 75% of test subjects for amounts of peanut flour that would be typical of an "accidental" ingestion (325-650 mg, or 1 to 2 peanuts).
2. However, in practice, it would be impossible to know which patients would actually develop protection from the anti-IgE therapy.
3. Anti-IgE therapy is very promising, and will undoubtedly show efficacy with a wide spectrum of atopic disease, but for certain conditions, like with peanut or other food allergies, it will never replace the mainstays of treatment (avoidance, epinephrine, antihistamines).
   

Summary of Key Evidence

1. Threshold of sensitivity to peanut consumption increased from baseline to final challenge in a dose dependent manner.
2. Of the three different doses of TNX-901 tested (150 mg, 300 mg, and 450 mg), only the 450 mg dose showed statistical significance (P<0.001) for allowing an increase in the threshold of sensitivity to an oral peanut challenge, although all treatment groups did demonstrate increases from baseline.
3. Proportion of patients with a successful study (defined as being able to tolerate 0.9 log more peanut flour compared to threshold) was greater in all treatment groups compared to placebo.
4. Impressive reductions in serum free IgE for all treatment groups were seen (93.2% decrease in the 450 mg group after 4 weeks), which was sustained even after the study was completed.
5. A substantial placebo effect was seen in the study (estimated at 20%).
   

Additional Comments

• TNX-901 is a humanized IgG1 monoclonal antibody that binds to IgE, thereby blocking binding to high affinity Fce receptors on the mast cells and basophils, which prevents allergy-mediator release.
• TNX-901 is well tolerated, with local injection site reactions being the biggest complaint. No lab abnormalities were reported with the study.
• Unfortunately, there were no objective measures to the oral food challenges. It is difficult to account for the amount of anxiety seen in the subjects, which may have contributed to premature cessation of the oral food challenges, and may also account for the notable placebo effect.
• TNX-901 is no longer available due to an agreement between a consortium of drug companies, but a very similar compound, Omalizumab (Xolair), is available. Omalizumab is currently approved for use with severe persistent asthma, and is in phase II clinical trials for use with peanut allergies.
  

Citation

1. Leung D, Sampson H, et al. Effect of Anti-IgE Therapy in Patients with Peanut Allergy. N Engl J Med 2003; 348: 986-93.
2. Merz B. Studying Peanut Anaphylaxis. N Engl J Med 2003; 348: 975-76.
3. Metzger H. Two Approaches to Peanut Allergy. N Engl J Med 2003; 348: 1046-48.
4. Sampson HJ. Update on food allergy. J Allergy Clin Immunol 2004; 113: 805-19.
5. www.foodallergy.org
6. "Omalizumab." Physicians' Desk Reference, 2005 ed.

CAT Author: Miguel Wolbert, MD

CAT Appraisers: Jonathan Fliegel, MD

Date appraised: December 1, 2004