title: Double-blind, placebo-controlled trial of octreotide long-acting repeatable (LAR) in thyroid-associated ophthalmopathy.
abstract: 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) > or =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.
authors.affiliation: Department of Ophthalmology, Royal Victoria Infirmary, Newcastle on Tyne NE1 4LP, United Kingdom. Jane.Dickinson@nuth.northy.nhs.uk
authors.forename: A Jane
authors.initials: AJ
authors.lastname: Dickinson
authors.forename: Bijay
authors.initials: B
authors.lastname: Vaidya
authors.forename: Margaret
authors.initials: M
authors.lastname: Miller
authors.forename: Alan
authors.initials: A
authors.lastname: Coulthard
authors.forename: Petros
authors.initials: P
authors.lastname: Perros
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Baister
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Andrews
authors.forename: Lutz
authors.initials: L
authors.lastname: Hesse
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Heverhagen
authors.forename: Armin E
authors.initials: AE
authors.lastname: Heufelder
authors.forename: Pat
authors.initials: P
authors.lastname: Kendall-Taylor
mesh_terms: D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006111:Graves Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007205:Indium Radioisotopes; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D009801:Oculomotor Muscles / Q000473:pathology; D011379:Prognosis; D011788:Quality of Life; D012647:Self-Assessment; D012907:Smoking; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017211:Treatment Failure
chemical_list: D003692:Delayed-Action Preparations; D007205:Indium Radioisotopes; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C081788:pentetreotide; D015282:Octreotide