Occurrence and effects of octreotide antibodies during nasal, subcutaneous and slow release intramuscular treatment.
OBJECTIVE
Previous studies have indicated that antibody formation against octreotide is extremely rare. We examined the occurrence of octreotide antibody formation after treatment with three administration forms in large populations of patients with acromegaly or carcinoid syndrome.


METHODS
(i) Nasally administered octreotide: 70 previously untreated patients and 81 previously s.c. octreotide-treated patients participated. (ii) Subcutaneously administered octreotide: 172 acromegalic patients and 59 patients with carcinoid syndrome treated for up to 12 years participated. (iii) Intramuscularly administered depot octreotide (Sandostatin LAR): 62 acromegalic patients participated.


METHODS
Presence of antibodies is defined as increased precipitation by polyethylene glycol of (125)I-octreotide after incubation with serum; this was also used for screening of cross-reaction with somatostatin and lanreotide (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 subcutaneously 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 identified to be antibody-positive after a mean of 2.5 years intramuscular Sandostatin LAR treatment (n=47). In all populations, the antibody-positive patients were as well controlled as the antibody-negative patients. Octreotide antibodies did not cross-react with native somatostatin (n=141), while about 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 than previously believed. It depends primarily on drug exposure time and route of administration. It does not alter the GH/IGF-I status in treated acromegalic patients and induces only mild local reactions in some patients.
Kaal
A
A
Institute of Experimental Clinical Research, University of Aarhus, Denmark. AA@AFDM.au.dk
Orskov
H
H
Nielsen
S
S
Pedroncelli
A M
AM
Lancranjan
I
I
Marbach
P
P
Weeke
J
J
D000172:Acromegaly / Q000188:drug therapy; D000281:Administration, Intranasal; D000906:Antibodies / Q000032:analysis*; D003429:Cross Reactions; D003692:Delayed-Action Preparations; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007700:Kinetics; D008303:Malignant Carcinoid Syndrome / Q000188:drug therapy; D015282:Octreotide / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000276:immunology; D013004:Somatostatin / Q000031:analogs & derivatives / Q000276:immunology
D000906:Antibodies; D003692:Delayed-Action Preparations; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D015282:Octreotide