WEAK ALLERGENICITY OF RECOMBINANT HIRUDIN CGP-39393 ((TM)REVASC) IN IMMUNOCOMPETENT VOLUNTEERS

Background: As a result of their polypeptidic nature, hirudins could t heoretically elicit an immunologic response in humans. Methods: The pr esent open survey evaluates the allergenic potential of recombinant hi rudin CGP 39393 (TMREVASC) after repeated intravenous or subcutaneous exposures in immunocompetent volunteers with no known previous exposur e to hirudins. Clinical signs and symptoms of allergic manifestations and surrogate markers of allergy (i.e. response to skin tests) were co llected before and after each administration of CGP 39393. Hirudin-spe cific immunoglobulin (Ig)G or IgE antibodies were measured. Results: T wo hundred and sixty-three healthy volunteers were eligible, of whom 1 2.2% had a history of allergy and 18.3% had a high level of total IgE. No signs or symptoms of allergy directly attributable to CGP 39393 we re reported, either during or immediately after a first challenge. Irr itative skin reactions, to either the prick or the intradermal skin te st, were observed in eight volunteers 28-56 days after the challenge. Three out of 200 volunteers exposed to a second course of CGP 39393 sh owed signs and symptoms of an allergic reaction. In all but one subjec t with a pruritic erythema it was possible to rule out a causative rol e for CGP 39393 (0.50%, 95% confidence limits [CL] 0.01-2.75). Three o ther volunteers displayed a suspect or a positive immediate-type skin reaction to the follow-up intradermal skin test without any signs or s ymptoms of allergy. Another asymptomatic volunteer (0.80%, 95% CL: 0.0 2-4.41) developed a low [i.e. 1+ on the radio-allergosorbent test (RAS T) scale] but measurable titre of hirudin-specific IgE antibodies afte r the second exposure to CGP 39393. A third exposure in five volunteer s was clinically uneventful. A positive reaction to the prick test and to the intradermal skin test was observed in one individual. Conclusi ons: Recombinant hirudin CGP 39393 appears to be a weak allergen. Repe ated exposures are safe in fully immunocompetent subjects, including t hose with a history of previous allergies and high levels of total IgE . Type I allergic reactions are rare (i.e. less than 1%) after a secon d exposure and are limited to the skin. Routine skin tests are not nee ded to identify patients at risk of developing type I allergic reactio ns. Hirudin-specific IgE antibodies are rarely seen and then at very l ow titres.