Al-Janabi, Ahmed;
Sharief, Lazha;
Al Qassimi, Noura;
Chen, Yi-Hsing;
Ding, Tao;
Ambler, Gareth;
Ladas, Dimitris;
... Tomkins-Netzer, Oren; + view all
(2023)
Can simvastatin reduce the need for immunomodulatory drugs to treat uveitis? A prospective, randomized, placebo-controlled trial.
Ophthalmology Science
, Article 100333. 10.1016/j.xops.2023.100333.
(In press).
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Abstract
Objective: To assess the efficacy of simvastatin 80mg/day versus placebo in patients with non-infectious non-anterior uveitis receiving prednisolone ≥10mg/day./ Design: Randomized, double-masked, controlled trial./ Subjects: Adult patients with non-infectious non-anterior uveitis on oral prednisolone dose of ≥10 mg/day./ Methods: Patients were randomly assigned at a 1:1 ratio to receive either simvastatin 80mg/day or placebo. 32 patients were enrolled (16 in each arm) all of whom completed the primary endpoint and 21 reached the two-year visit (secondary end points)./ Main outcome measures: The primary endpoint was mean reduction in the daily prednisolone dose at 12 months follow-up. Secondary end points were mean reduction in prednisolone dose at 24 months, percent of patients with a reduction in second-line immunomodulatory agents, time to disease relapse and adverse events./ Results: Our results show that simvastatin 80mg/day did not have a significant corticosteroid-sparing effect at 12 months (estimate: 3.62, 95% CI: -8.15 to 15.38; p=0.54). There was no significant difference between the groups with regards to prednisolone dose or change in dose at 12 and 24 months. There was no difference between the two groups in percent of patients with reduction in second-line agent by 24 months. Among patients who achieved disease quiescence the median time to first relapse was longer for those receiving simvastatin (8.7 months, 95% CI 3.2-14.19) than placebo (3.2 months, 95% CI 0.17-6.23), though this was not statistically significant. There was no significant difference in adverse events or serious adverse events between the two groups./ Conclusions: Simvastatin 80mg/day did not have an effect on the dose reduction of corticosteroids nor conventional immunomodulatory drugs at one and two years. The results suggest that it may extend the time to disease relapse among those that achieve disease quiescence./ Systemic corticosteroids represent the mainstay treatment for patients with uveitis, particularly those with systemic involvement or bilateral disease. While treatment is very effective in controlling the intra-ocular inflammation, long-term systemic side effects limit their use, so that ophthalmologists continually aim to reduce the dose to ≤10mg/d.1 To achieve this, other immunomodulatory agents can be added to enhance and maintain inflammatory control. While they are effective in the majority of cases,2, 3, 4, 5 they are not without their own risks of complications and can affect hepatic, renal and gastrointestinal function, as well as increase the risk for opportunistic infections./ Statins are routinely prescribed to reduce serum cholesterol levels and improve clinical outcomes in patients with cardiovascular diseases. They are considered an effective treatment with a low risk of systemic side effects, primarily myalgia and rhabdomyolysis. Studies have shown that they also have pleiotropic immunomodulatory effects, both in vitro and in vivo.6 In animal models of uveoretinitis statins reduced the clinical and histological scores of inflammation and inhibited T lymphocyte recruitment into the retina.7 Two large observational population-based studies also showed a protective effect of statins against the development of uveitis.8 9 Clinical studies in multiple sclerosis patients showed a positive effect from simvastatin on brain atrophy, suggesting these drugs cross the blood-brain barrier and can play a role in controlling disease activity.10 In rheumatoid arthritis, statins led to improvement in disease activity scores and reduced the numbers of tender and swollen joints.11 A study on the effect of statins among patients with sarcoidosis, demonstrated an increased time to disease flare among patients with mild-moderate disease.12 Given the relatively safe side effect profile of statins, they would be a suitable treatment option for patients with uveitis, as well as reducing serum cholesterol levels and improving the cardiovascular outcomes in patients on long-term corticosteroid therapy./ The aim of this study was to prospectively examine in a randomized double masked clinical trial the additional anti-inflammatory effect and safety of simvastatin in patients with uveitis and to determine if their addition could reduce the amount of corticosteroid or number/ dose of additional immunomodulatory agents required to keep the uveitis controlled.
| Type: | Article |
|---|---|
| Title: | Can simvastatin reduce the need for immunomodulatory drugs to treat uveitis? A prospective, randomized, placebo-controlled trial |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.xops.2023.100333 |
| Publisher version: | https://doi.org/10.1016/j.xops.2023.100333 |
| Language: | English |
| Additional information: | © The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CC-BY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Statistical Science |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10170534 |
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