Upper limit IgE levels for Xolair use

[participant1]

With regards to Xolair use, has anyone heard of a clinical reason to institute an upper limit for IgE levels? For example, I have seen the lower limit of >30 IU/ml, and higher values corresponding to weight-based dosing, but was wondering what plans use for an absolute upper limit?

[chantell.reagan]

According to Xolair prescribing information, the patient’s baseline IgE level should be between 30 IU and 700 IU and baseline weight should be no more than 150 kg. In addition, the safety and effectiveness of Xolair at doses >750 mg/4 weeks has not been demonstrated in controlled clinical trials.

Originally, these restrictions were based on the dosing formula that used weight and free IgE levels (0.016mg/kg per IU of baseline serum IgE concentration). The dosing table was created to minimize dosing errors, but issues came up for patients who fell outside of the table, particularly those with IgE values > 700IU/ml. Using multiple vials for higher doses was discouraged for fear of the accumulation of small amounts of endotoxin, which are part of all biological products, and have the potential to cause local or systemic reactions. Technically this concern can be addressed by giving smaller doses more frequently than every 2 weeks; however, this approach may not be efficient because, as stated in one article, “only a modicum of the free IgE is relevant clinically.” Upon our request, Genentech identified several available case reports which document the use of Xolair (in doses up to 900mg/4 weeks) in patients with IgE levels up to 24,000IU/ml, with no explicit evidence of diminished efficacy. Most case reports showed no increase in adverse effects.

In a poll of 6 regional and national health plan Xolair policies (publicly available or contributed by our members):
•3/6 (50%) plans did not define an upper IgE limit
•3/6 (50%) plans cited the PI limits of up to 700IU/ml; also 1 plan allows IgE levels up to 1300IU/ml, if all other criteria are met (Excellus)

In conclusion, there may not be explicit clinical rationale to prohibit the use of Xolair for patients with IgE levels >700IU/ml; however, if use of higher doses in these patients is not efficient, there may be potential economic implications.

Sources:
Aetna Clinical Policy Bulletin: Xolair – baseline IgE between 30-700IU/ml
BCBS Florida Medical Policies – not defined
Cigna Xolair Coverage Policy – not defined
Excellus Xolair policy – levels between 30-700IU/ml, but up to 1300IU/ml, if all other criteria met
Regence Xolair policy <700IU/ml
Xolair prescribing information
Lanier B. Unanswered clinical questions and speculation about the role of anti-immunoglobulin E in atopic and nonatopic disease. Allergy Asthma Proc. 2006 Mar-Apr;27(2 Suppl 1):S37-42. (Pubmed abstract)