Hymenoptera Venom Immunotherapy

Beatrice M Bilò; Floriano Bonifazi


Immunotherapy. 2011;3(2):229-246. 

In This Article

Treatment Protocol

Many treatment protocols for the VIT induction phase have been designed.[10] They vary with respect to the number of injections, venom doses and time needed to reach the final dose (Table 2). A conventional regimen means increasing doses at weekly intervals for outpatients, the induction phase of rush regimens lasts 4–7 days for in-patients, and the ultrarush protocol maintenance dose is reached within 1–2 days or within a few hours. The cluster regimen is a modified rush approach schedule that involves administering several injections at 15–30 min intervals during the first visit, taking approximately 6 weeks to reach the maintenance dose. Rush and ultrarush protocols are particularly efficient in highly exposed subjects (e.g., beekeepers) or in patients referred to the specialist just prior to the start of the insect season, so that the protective dosage can be reached as quickly as possible. In addition, the cost of administering ultrarush VIT is lower than that of the slower protocols. These fast protocols are currently used in most, but not all,[46] European countries and it is not a readily available technique at most American medical centers.[47]

The starting dose of VIT is between 0.001 and 0.1 µg (Table 2). However, in a recent paper, the authors demonstrated that initiating VIT at the 1 µg dose can be applied safely in rush protocols, both in adults and in children.[76] They performed two different protocols, a rush protocol in 62 inpatients, and a modified rush protocol in 670 outpatients, thereby demonstrating that by starting with 1 µg of venom there was no SR.[76]

If two or more venoms are required, they should be administered in separate protocols a few days apart. While the build-up phase of VIT should be performed by an allergist, in some countries, maintenance treatment is eventually continued by the general practitioners.

In Europe, VIT may be performed with nonpurified aqueous (NPA), purified aqueous (PA) extracts and purified aluminium hydroxide adsorbed (PAHA) preparations (so-called 'depot' extracts) of yellow jacket and honeybee venoms, administered by subcutaneous injection. Purified venom extracts do not contain vasoactive amines (e.g., dopamine, histamine and serotonin) and have a reduced presence of small peptides (e.g., apamine, kinins and mast-cell degranulating peptide in the final product).[77] Polistes species and P. dominulus PA and PAHA extracts for diagnostic and therapeutic purposes are not currently commercially available in Europe. The efficacy of PA and depot extracts is supported by studies using both sting challenge and in-field stings, and is comparable to that of nonpurified preparations.[77] In the USA, neither PA nor PAHA preparations are commercially available.[31]

The NPA and PA extracts can be used for ultrarush, rush, clustered and maintenance phases, while PAHA preparations are only administered for the conventional build-up and maintenance schedule. Many European specialists switch to depot preparations following the up-dosing phase.[77]

The general consensus is that the maintenance interval should be kept at 4 weeks for the first year, extended to 6 weeks in the second year, and then to 8 weeks if VIT is continued for more than 5 years, provided that the treatment is tolerated.[4,10] It is recommended that the dose of 200 µg venom as a depot extract should not be exceeded over a 4-week period if possible.[45] If a depot extract is used, extending the injection interval to 8 weeks is possible without compromising the effectiveness of the therapy.[77] A longer interval is not recommended for honeybee allergic patients since beekeepers with less than ten stings a year were those who developed SRs most frequently.[78] Moreover, the number of studies assessing the feasibility of extending the maintenance interval for up to 12 weeks included too small a sample of patients with mainly vespid allergy, in which efficacy was evaluated mostly by in-field stings.[10,79] Recently, two studies evaluating the safety and efficacy of a further prolonged interval between injections of 6 months yielded contrasting data that can mainly be accounted for by the different selection criteria that was applied in each of them.[80,81] It is desirable that within the next few years, multicenter clinical trials will produce results that enable clinicians to select patients so that extending the interval between injections becomes risk free.


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