Occurrence and effects of octreotide antibodies during nasal, subcutaneousand slow release intramuscular treatment

Objective: Previous studies have indicated that antibody formation against octreotide is extremely rare. We examined the occurrence of octreotide anti body formation after treatment with three administration forms in large pop ulations of patients with acromegaly or carcinoid syndrome. Design: (i) Nasally administered octreotide: 70 previously untreated patien ts and 81 previously s.c, octreotide-treated patients participated. (ii) Su bcutaneously administered octreotide: 172 acromegalic patients and 59 patie nts with carcinoid syndrome treated for up to 12 years participated. (iii) Intramuscularly administered depot octreotide (Sandostatin LAR): 62 acromeg alic patients participated. Methods: Presence of antibodies is defined as increased precipitation by po lyethylene glycol of I-125- octreotide after incubation with serum; this wa s also used for screening of cross-reaction with somatostatin and lanreotid e (Somatuline). Results: In patients who received nasal octreotide for at least 9 and up To 12 months (n = 42), the occurrence of octreotide antibodies was 77% and 81 % for previously untreated and treated patients respectively. In subcutaneo usly treated patients it was 63/231 (27%) after a mean exposure of 3 years. In patients treated for more than 5 years (n = 53) it was 57% and after 8 years (n = 18) 72%. In contrast, no patient could with certainty be identif ied to be antibody-positive after a mean of 2.5 years intramuscular Sandost atin LAR treatment (n = 47). In all populations, the antibody-positive pati ents were as well controlled as the antibody-negative patients. Octreotide antibodies did not cross-react with native somatostatin (n = 141), while ab out 25% of the antibody-positive sera did cross-react with the somatostatin analogue, lanreotide (Somatuline, Ipstyl, Angiopeptin). Conclusions: Antibody formation against octreotide is much more frequent th an previously believed. It depends primarily on drug exposure time and rout e of administration. It does not alter the GH/IGF-I status in treated acrom egalic patients and induces only mild local reactions in some patients.