title: Efficacy and safety of three different cumulative doses of intravenous methylprednisolone for moderate to severe and active Graves' orbitopathy.
abstract: BACKGROUND
  Optimal doses of i.v. glucocorticoids for Graves' orbitopathy (GO) are undefined.
  
  
  METHODS
  We carried out a multicenter, randomized, double-blind trial to determine efficacy and safety of three doses of i.v. methylprednisolone in 159 patients with moderate to severe and active GO. Patients were randomized to receive a cumulative dose of 2.25, 4.98, or 7.47 g in 12 weekly infusions. Efficacy was evaluated objectively at 12 wk by blinded ophthalmologists and subjectively by blinded patients (using a GO specific quality of life questionnaire). Adverse events were recorded at each visit.
  
  
  RESULTS
  Overall ophthalmic improvement was more common using 7.47 g (52%) than 4.98 g (35%; P = 0.03) or 2.25 g (28%; P = 0.01). Compared with lower doses, the high-dose regimen led to the most improvement in objective measurement of ocular motility and in the Clinical Activity Score. The Clinical Activity Score decreased in all groups and to the least extent with 2.25 g. Quality of life improved most in the 7.47-g group, although not reaching statistical significance. No significant differences occurred in exophthalmos, palpebral aperture, soft tissue changes, and subjective diplopia score. Dysthyroid optic neuropathy developed in several patients in all groups. Because of this, differences among the three groups were no longer apparent at the exploratory 24-wk visit. Major adverse events were slightly more frequent using the highest dose but occurred also using the lowest dose. Among patients whose GO improved at 12 wk, 33% in the 7.47-group, 21% in the 4.98-group, and 40% in the 2.25-group had relapsing orbitopathy after glucocorticoid withdrawal at the exploratory 24-wk visit.
  
  
  CONCLUSIONS
  The 7.47-g dose provides short-term advantages over lower doses. However, this benefit is transient and associated with slightly greater toxicity. The use of a cumulative dose of 7.47 g of methylprednisolone provides short-term advantage over lower doses. This may suggest that an intermediate-dose regimen be used in most cases and the high-dose regimen be reserved to most severe cases of GO.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Endocrine Unit, Ospedale di Circolo, 21100 Varese, Italy. luigi.bartalena@uninsubria.it
authors.forename: L
authors.initials: L
authors.lastname: Bartalena
authors.forename: G E
authors.initials: GE
authors.lastname: Krassas
authors.forename: W
authors.initials: W
authors.lastname: Wiersinga
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
authors.forename: M
authors.initials: M
authors.lastname: Salvi
authors.forename: C
authors.initials: C
authors.lastname: Daumerie
authors.forename: C
authors.initials: C
authors.lastname: Bournaud
authors.forename: M
authors.initials: M
authors.lastname: Stahl
authors.forename: L
authors.initials: L
authors.lastname: Sassi
authors.forename: G
authors.initials: G
authors.lastname: Veronesi
authors.forename: C
authors.initials: C
authors.lastname: Azzolini
authors.forename: K G
authors.initials: KG
authors.lastname: Boboridis
authors.forename: M P
authors.initials: MP
authors.lastname: Mourits
authors.forename: M R
authors.initials: MR
authors.lastname: Soeters
authors.forename: L
authors.initials: L
authors.lastname: Baldeschi
authors.forename: M
authors.initials: M
authors.lastname: Nardi
authors.forename: N
authors.initials: N
authors.lastname: Currò
authors.forename: A
authors.initials: A
authors.lastname: Boschi
authors.forename: M
authors.initials: M
authors.lastname: Bernard
authors.forename: G
authors.initials: G
authors.lastname: von Arx
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D009915:Orbit / Q000187:drug effects / Q000473:pathology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D008775:Methylprednisolone