Discontinuation of venom immunotherapy
Authors: David B.K. Golden
Journal: Journal of Allergy and Clinical Immunology (1998)

The report of van Halteren et al (J Allergy Clin Immunol 1997;100:767-70) is a welcome addition to the literature on discontinuation of venom immunotherapy (VIT), but many of the conclusions are not supported by the data. They conclude that the risk of sting reaction after stopping therapy was not related to the duration of VIT because the mean duration of treatment did not differ between reactors and nonreactors. However, they do not present the actual distribution of the data, which is critical to the analysis (ie, the number of patients who were treated for less than 5 years or more than 5 years). Moreover, they fail to point out that 5 of the 6 reactors had less than 5 years of VIT. To illustrate this point, we note the more astute analysis of Keating et al1Keating MU Kagey-Sobotka A Hamilton RG Yunginger JW Clinical and immunologic follow-up of patients who stop venom immunotherapy.J Allergy Clin Immunol. 1991; 88: 339-348Abstract Full Text PDF PubMed Scopus (94) Google Scholar who also found that the mean duration of therapy in reactors and nonreactors was similar, but who found a very different reaction rate in patients who had VIT for less than 5 years (10%) than in those who had 5 years or more (no reactions at all). On the basis of the insufficient data and analysis presented by van Halteren et al, their conclusion cannot be accepted. The authors do not provide sufficient data on the chronology of the challenge (or field) stings, which occurred over a 3-year period, especially for the 11 patients who had a single sting. It has been previously noted by several investigators that the reaction rate is virtually zero after just 1 year off therapy.1Keating MU Kagey-Sobotka A Hamilton RG Yunginger JW Clinical and immunologic follow-up of patients who stop venom immunotherapy.J Allergy Clin Immunol. 1991; 88: 339-348Abstract Full Text PDF PubMed Scopus (94) Google Scholar, 2Golden DBK Addison BI Gadde J Kagey-Sobotka A Valentine MD Lichtenstein LM Prospective observations on patients who discontinue venom immunotherapy.J Allergy Clin Immunol. 1989; 84: 162-167Abstract Full Text PDF PubMed Scopus (63) Google Scholar, 3Muller U Berchtold E Helbling A Honeybee venom allergy: results of a sting challenge 1 year after stopping venom immunotherapy in 86 patients.J Allergy Clin Immunol. 1991; 87: 702-709Abstract Full Text PDF PubMed Scopus (130) Google Scholar A higher reaction rate would result if one analyzed only the data for stings occurring 2 or 3 years after VIT. In fact, it has been reported that additional patients are likely to react to stings after 4 or more years off VIT even if they had no reaction to a sting after 2 years off VIT.1Keating MU Kagey-Sobotka A Hamilton RG Yunginger JW Clinical and immunologic follow-up of patients who stop venom immunotherapy.J Allergy Clin Immunol. 1991; 88: 339-348Abstract Full Text PDF PubMed Scopus (94) Google Scholar, 4Golden DBK Kagey-Sobotka A Lichtenstein LM Discontinuing venom immunotherapy: long-term outcome.J Allergy Clin Immunol. 1997; 99: S377Google Scholar More detailed data on the number of patients stung after 1 year, 2 years, and 3 years off therapy would be helpful. In the discussion, the authors fail to present adequate comparisons with the existing literature. They state that the reaction rate of 8% is “relatively high” when it is actually very consistent with the many reports of reaction rates of 7% to 14% in the first 3 years after discontinuing VIT.1Keating MU Kagey-Sobotka A Hamilton RG Yunginger JW Clinical and immunologic follow-up of patients who stop venom immunotherapy.J Allergy Clin Immunol. 1991; 88: 339-348Abstract Full Text PDF PubMed Scopus (94) Google Scholar, 5Golden DBK Kwiterovich KA Kagey-Sobotka A Valentine MD Lichtenstein LM Discontinuing venom immunotherapy: outcome after five years.J Allergy Clin Immunol. 1996; 97: 579-587Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar, 6Haugaard L Norregaard OFH Dahl R In-hospital sting challenge in insect venom–allergic patients after stopping venom immunotherapy.J Allergy Clin Immunol. 1991; 87: 699-702Abstract Full Text PDF PubMed Scopus (73) Google Scholar, 7Urbanek R Forster J Kuhn W Discontinuation of bee venom immunotherapy in children and adolescents.J Pediatr. 1985; 107: 367Abstract Full Text PDF PubMed Scopus (68) Google Scholar They also state that other studies are necessary to confirm their conclusion that treatment can be safely discontinued when the venom-IgE antibodies disappear during therapy. This observation has been reported by several other investigators over the past 15 years,3Muller U Berchtold E Helbling A Honeybee venom allergy: results of a sting challenge 1 year after stopping venom immunotherapy in 86 patients.J Allergy Clin Immunol. 1991; 87: 702-709Abstract Full Text PDF PubMed Scopus (130) Google Scholar, 6Haugaard L Norregaard OFH Dahl R In-hospital sting challenge in insect venom–allergic patients after stopping venom immunotherapy.J Allergy Clin Immunol. 1991; 87: 699-702Abstract Full Text PDF PubMed Scopus (73) Google Scholar, 8Reisman RE Duration of venom immunotherapy: relationship to the severity of symptoms of initial insect sting anaphylaxis.J Allergy Clin Immunol. 1993; 92: 831-836Abstract Full Text PDF PubMed Scopus (83) Google Scholar but these reports are not cited. The authors twice state that they did not find the same results as other investigators when they should actually say that their data are insufficient to make such conclusions. They state that they did not find that patients who had more severe pretreatment reactions were at higher risk for posttreatment reactions, when in fact they go on to say that they did not have enough patients with less severe reactions to perform any meaningful comparison. They also state that their results do not support the findings of others that systemic reactions during VIT are associated with a higher risk of posttreatment reactions, when in fact they had no such patients in their study and should therefore state that they are unable to reach any conclusion in this regard. All in all, I must take issue with the authors’ conclusions that VIT can be safely stopped after 3 years or that sting challenge can reliably identify those at risk for relapse.