Statins improve Graves' orbitopathy in active eye disease with hypercholesterolemia: Lancet

Italy: A recent study has pointed that oral atorvastatin addition to an intravenous glucocorticoids (ivGC) regimen improves the outcomes of Graves' orbitopathy in patients with moderate-to-severe, active eye disease who are hypercholesterolemia. The study appears in The Lancet Diabetes & Endocrinology.

However, according to the researchers, there is a need to confirm this association by conducting phase 3 studies in the future that could potentially recruit patients regardless of low-density lipoprotein cholesterol concentration. 

Statins are known to play a protective role in the development of Graves' orbitopathy suggesting that statin might be used for the disease treatment. To determine its use in the treatment, Giulia Lanzolla, University of Pisa and University Hospital of Pisa, Pisa, Italy, and colleagues aimed to assess the efficacy of the addition of a statin, atorvastatin, to ivGCs on Graves' orbitopathy outcomes in patients with hypercholesterolemia.

For achieving their objective, the researchers designed a randomized, open-label, phase 2, adaptive, clinical trial at a single, tertiary, referral hospital in Pisa, Italy. The study included patients with moderate-to-severe, active Graves' orbitopathy, with a low-density lipoprotein cholesterol concentration between 2·97 and 4·88 mmol/L. Thye were randomly assigned in the ratio of 1:1 in 11 blocks of eight to the ST group or the NST group. The ST group received ivGCs (methylprednisolone 500 mg once a week for 6 weeks followed by 250 mg once a week for an additional six weeks) for 12 weeks and oral atorvastatin (20 mg once a day) for 24 weeks. The NST group only received the ivGC regimen.

The primary endpoint was the Graves' orbitopathy outcome (composite evaluation of exophthalmos, clinical activity score, eyelid aperture, and diplopia) at 24 weeks in the modified intention-to-treat (ITT) population (patients who attended the week 12 visit).

Patients were considered responders when at least two of the following criteria were fulfilled in the most affected eye, without worsening in any of the same measures in both eyes: (1) reduction in exophthalmos of 2 mm or more, with no increase by 2 mm or more in the other eye; (2) reduction of clinical activity score by two or more points; (3) reduction in eyelid aperture by 2 mm or more, with no increase by 2 mm or more in the other eye; and (4) disappearance or improvement (change from constant to inconstant, intermittent, or absent, or from inconstant to intermittent or absent) of diplopia, and (5) improvement in visual acuity by 0·2 decimals or more. 

 88 (74%) patients were enrolled and randomly assigned to one of the two treatment groups (44 [50%] to the ST group and 44 [50%] to the NST group. 

"Addition of oral atorvastatin to an ivGC regimen improved Graves' orbitopathy outcomes in patients with moderate-to-severe, active eye disease who were hypercholesterolemia," the researchers wrote.

"Future phase 3 studies, which could potentially recruit patients regardless of low-density lipoprotein cholesterol concentration, are required to confirm this association," they concluded.

Reference:

The study titled, "Statins for Graves' orbitopathy (STAGO): a phase 2, open-label, adaptive, single centre, randomised clinical trial," is published in The Lancet Diabetes & Endocrinology.

DOI: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00238-2/fulltext