Two more groups reported here that the anti-IgE biologic drug omalizumab (Xolair) was helpful in speeding immunotherapy for allergies, suggesting that the approach may be gaining momentum.
Omalizumab eliminates IgE from circulation and is approved as an adjunctive treatment for allergic asthma. Previous reports had indicated that the drug was helpful in preventing anaphylaxis during “rush” desensitization treatments for severe allergies.
Researchers at Duke University, testing omalizumab in teens undergoing oral immunotherapy for peanut allergy, said here that the strategy shortened the time needed to achieve a reasonable degree of peanut tolerance.
And clinicians in Boston found that omalizumab helped stave off anaphylactic reactions in a colon cancer patient who needed oxaliplatin but was severely allergic to the drug and had to undergo desensitization therapy with it.
Both reports were presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology (AAAAI). At last year’s AAAAI meeting, Kari Nadeau, MD, of Stanford University, reported that starting omalizumab in milk-allergic children nine weeks before starting oral immunotherapy allowed most of them to complete the entire first phase in just one day, such that they could tolerate two grams of powdered milk. The Duke study reported this year involved nine adolescents (age 12 to 19) with longstanding peanut allergies. Michele Henson, MD, said omalizumab was started four months before initiating the desensitization therapy in a modified rush protocol. The immunotherapy was a two-day process with a target of 475 mg of peanut powder. In comparison, the regular oral immunotherapy procedure at Duke is a one-day protocol that seeks to work patients up to ingesting 6 mg. Following these initial procedures, patients then take peanut powder daily with dose escalations every two weeks as tolerated. The ultimate target is 4,000 mg, equivalent to about 13 peanuts. The omalizumab was continued for one month after the maintenance dose was reached, then stopped. One of the nine patients stopped the therapy prematurely, and three others are still in the buildup phase, Henson said. For the five that have reached the maintenance dose of 4,000 mg/day, the time needed to reach it ranged from 233 to 276 days. In contrast, the median time to reach maintenance dosing for 28 patients undergoing the regular oral immunotherapy program at Duke has been 350 days (P<0.01), she reported. Reactive symptoms such as hives and chest tightness during the rush procedure and on dose escalation days also were less common and less severe than with the regular protocol. Henson said the group was interested next in pursuing a larger, randomized, double-blinded trial with omalizumab in peanut allergy therapy. Nadeau told MedPage Today that she was now aware of seven different reports of omalizumab used successfully in oral immunotherapy programs. "It's something that should be thought about in the future, either for the subset of the population that needs omalizumab, but also just in general for [the allergic] population to see if they can have a better therapy while they're going through oral immunotherapy," she said. The oxaliplatin case was handled by Katherine Cahill, MD, and colleagues at Brigham and Women's Hospital in Boston. It involved a 72-year-old man with stage IV colon cancer with liver and lung metastases, for whom an oxaliplatin-containing regimen was considered medically necessary despite serious allergic reactions. These involved severe itching, chills, low back and muscle pain, and coughing. A standard 12-step desensitization protocol was thwarted by repeated reactions even at oxaliplatin doses below 1 mg. Twice the man needed epinephrine to clear up the symptoms. His team then gave him two 150-mg doses of omalizumab two weeks apart and reattempted the desensitization, with omalizumab continued on a two-week dosing schedule. No reactions occurred during a 16-step desensitization protocol at Brigham and Women's Hospital. Four additional desensitizations with 12-step protocols were undertaken at another Boston hospital, Cahill and colleagues reported. Three relatively mild reactions occurred - two cases of bronchospasm that resolved with albuterol treatment, and an episode of severe back pain treated successfully with solumedrol and diphenhydramine. One potential worry about omalizumab is that it might itself cause anaphylaxis. The drug carries a boxed warning to that effect, following case reports of anaphylactic reactions occurring after omalizumab dosing. However, Nadeau said she was not aware of any anaphylactic reactions occurring in the oral immunotherapy studies, and it was well-tolerated in her own study. She noted that the drug has now been available for about 10 years "and there is a good safety database." Clinicians might be tempted to try omalizumab off-label in their own allergy patients undergoing desensitization, but one of Nadeau's collaborators, Dale Umetsu, MD, of Children's Hospital in Boston, told MedPage Today that the drug's retail price - more than $400 per 150-mg dose - would be a major obstacle. Nevertheless, the AAAAI meeting this year featured several other reports of omalizumab used off-label and without commercial support to treat various conditions successfully - chronic urticaria, eczema, and short stature related to severe atopy.