Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy

Several uncontrolled studies suggest octreotide is beneficial in thyroid-associated ophthalmopathy (TAO); however, the natural tendency of TAO to improve mandates randomized, controlled trials. We report results of a double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR). Fifty euthyroid patients (11 males, 39 females; age 22 - 74 yr, median 50 yr) with active TAO [ clinical activity score ( CAS) greater than or equal to 3, NOSPECS( no signs or symptoms; only signs, no symptoms; signs only; proptosis; eye muscle involvement; corneal involvement; sight visual acuity reduction) 2a-5a] of median duration 0.9 yr received either 30 mg LAR or placebo every 4 wk for 16 wk; both groups then received 30 mg LAR for wk 16 - 32 and were followed up without treatment for a further 24 wk. Objective assessments included all individual parameters of TAO, CAS, and derived scores for soft tissue inflammation STI) and ophthalmopathy index (OI). During wk 0 - 16 there was significant reduction in STI, subjective diplopia, and CAS in LAR-treated patients; STI and CAS were also reduced with placebo. The OI reduced by - 1.12 in LAR ( P = 0.0017) vs. - 0.23 in placebo ( P = 0.33), giving a barely significant treatment effect by Wilcoxon ( P = 0.043), but analysis of covariance failed to confirm this ( P = 0.16). During wk 16 - 32 there was no significant change in OI in either group. The overall results ( wk 0 - 32) showed reduction in STI and CAS in both groups. In this double-blind, placebo-controlled trial, no significant therapeutic effect of octreotide LAR was seen in patients with moderately severe TAO. The improvements in both treated and placebo groups emphasize that the results of open studies must be viewed with caution.