Octreotide LAR for the treatment of Graves- orbitopathy

Topic: GRAVES- ORBITOPATHY

Title: Randomized, double-blind, placebo-controlled trial of long-acting release octreotide for treatment of Graves- ophthalmopathy

Authors: Stan MN, Garrity JA, Bradley EA, Woog JJ, Bahn MM, Brennan MD, Bryant SC, Achenbach SJ, & Bahn RS.

Reference: Journal of Clinical Endocrinology and Metabolism 91: 4817-4824, 2006

Summary

Background

Somatostatin analogs have been proposed as a possible treatment for Graves- orbitopathy (GO).

Purpose

The objective of the study was to assess in a randomized, double-blind, placebo-controlled trial, whether long-acting release (LAR) octreotide is effective for active GO.

Material and Methods

Twenty-nine patients with active GO (Clinical Activity Score, CAS: > 3) were treated either with four 20-mg monthly doses of LAR octreotide (N = 14) or placebo (N = 11); 4 patients were lost to follow-up. Primary outcome measure was CAS change. Secondary outcome measures included changes in retro-bulbar tissue volume, proptosis, lid fissure width, range of motion, and diplopia fields.

Results

A slightly greater change in CAS was observed in the LAR octreotide-treated patients, but this group had a slightly more active GO to start with. A slightly significant reduction in the width of lid fissure was also noted with LAR octreotide administration. No other differences between the two groups were found.

Conclusions

The only clinically relevant effect of LAR octreotide treatment was a slight reduction in lid fissure width. This might be exploited, in the authors- view, in patients with significant lid retraction.

Commentary

The management of GO remains a difficult challenge. Patients who have severe and active orbitopathy are treated by glucocorticoids (in general by the intravenous route), orbital radiotherapy (alone or in combination), or orbital decompression. Unfortunately, about one third of treated patients are eventually unsatisfied with the treatment outcome, with a deep negative impact on their quality of life. Thus, it is easily understandable why novel treatments are regarded favourably, particularly if there is a sound rationale for their use. This is the case for somatostatin analogs such as octreotide & lanreotide. To use these drugs in GO appears justified by the demonstration of somatostatin receptors in orbital cells, both in fibroblasts and lymphocytes. Positive somatostatin receptor-based orbit scans (octreoscan) were reported to predict the subsequent response to immunosuppressive therapy for GO.

The initial studies (usually small and often uncontrolled) provided encouraging results using octreotide or lanreotide, although their effectiveness appeared lower than that of glucocorticoids. Over the last two years, four well-performed randomized controlled trials have unfortunately tempered the initial enthusiasm. Two large trials have evaluated the effects of LAR octreotide, but failed to detect significant differences between a LAR octreotide-treated group and a placebo-treated group, with the exception of a marginal (and surprising) reduction in proptosis observed in one study. A third, randomized, controlled study on the use of slow-release lanreotide did not reveal substantial differences between patients and controls, with the exception of an improvement in the downward gaze in lanreotide-treated patients. Likewise, the present report using LAR octreotide showed a slightly greater reduction in the Clinical Activity Score in the patients compared with the controls, but it should be noted that the patients had a more active GO than the controls to start with. In addition, a modest, although significant, decrease in lid fissure width was noted in LAR octreotide-treated patients. Although the authors claimed that this finding might be exploited in patients with relevant lid retraction, the real advantage of using such an expensive drug in this limited clinical setting remains (to say the least) uncertain.

The present report reinforces the notion that the currently available somatostatin analogs are of limited usefulness for the management of GO and should probably not be used (also when considering their high cost). Whether novel somatostatin analogs (such as SOM-230, currently under investigation) may prove more effective than octreotide and lanreotide remains to be ascertained. ( Summary and commentary prepared by Luigi Bartalena ) Present summary and commentary are related to Chapter N- 12 (Section 2) of TDM Full paper obtainable at http://jcem.endojournals.org/cgi/reprint/91/12/4817