08 May Study Compares Systemic Therapy vs Ocular Implant For Uveitis
MedicalResearch.com Interview with:
Dr. Kempen
John H Kempen, MD, PhD
Protocol Chair, MUST Trial Follow-up Study; Vice Chair, MUST Research Group
Director of Epidemiology for Ophthalmology, Massachusetts Eye and Ear
Harvard Medical School
Editor-in-Chief, Ophthalmic Epidemiology
President, Sight for Souls
MedicalResearch.com: What is the background for this study?
Response: Uveitis is about the fifth leading cause of blindness in the united states. Among types of uveitis, intermediate, posterior and panuveitis are the leading causes of blindness. Before 2005, systemic therapy with corticosteroids—supplemented when indicated with immunosuppressive drugs (most of the time)—was the primary treatment recommended for these conditions. With approval of the fluocinolone acetonide implant in 2005 for intermediate, posterior and panuveitis, it became unclear which of the alternative treatment approaches should be the treatment of choice.
The multicenter uveitis steroid treatment (must) trial was initiated in 2005 to directly compare the alternative treatments. Systemic therapy was administered using high dose prednisone followed by tapering of corticosteroids to maintenance doses of 10 mg/day or less (generally 7.5 mg/day or less) or to zero; this was supplemented by immunosuppressive corticosteroid-sparing drugs in 88% of participants. Implant therapy was done by initial quieting of the anterior chamber of the eye with topical, injected or systemic corticosteroids followed by surgical implant placement within 28 days (first eye) and 56 days (second eye if it was indicated). After this, systemic corticosteroids and immunosuppressive drugs were tapered off.
MedicalResearch.com: What are the main findings?
Response: Control of inflammation was clearly superior in the implant group through five years, but after that a considerable number of reactivations of uveitis activity occurred in the implant group, such that the proportion controlled in the two groups was similar after that. The expected duration of implant effect in controlling uveitis had been expected to be about three years; we observed a considerably longer period of uveitis inactivity after implant treatment on average. The period when implant-randomized eyes began to have reactivations was when the visual acuity results began to diverge. Because implant-treated eyes tended to have strong and sudden relapses whereas systemic-treated eyes tended to have less dramatic relapses as corticosteroids and immunosuppressive drugs were tapered slowly.
The implant group continued to have an approximately 3- to 5-fold higher risk of elevated intraocular pressure, need for medical or surgical treatment of elevated intraocular pressure, glaucoma (as diagnosed by an outcomes committee) and cataract/need for cataract surgery (among those initially at risk).
Regarding systemic adverse outcomes, the only statistically significant difference between groups was that the systemic group was more likely than the implant group to be prescribed antibiotics for an infection (72% vs 57%), although hospitalization for infection did not differ significantly (6 vs 9 hospitalizations for infection respectively). Among a large array of other pre-specified potential problems that might have been related to corticosteroid or immunosuppressive treatment, no other statistically significant differences were observed. Need for treatment for hypertension and hyperlipidemia was a little more frequent in the systemic group but not to a statistically significant degree.
Quality of life results generally tended to be similar in the two groups by seven years, with favorable scores in both groups, and improvement from baseline in vision-related quality of life.
MedicalResearch.com: What should readers take away from your report?
Response: Given that systemic therapy was better at preserving visual acuity, had fewer side effects, and generally would cost less, these results suggest that systemic therapy is the preferred initial therapy for these conditions unless special circumstances dictate local therapy. Given that implant was superior in controlling uveitis activity for the first five years, the results support use thereof if systemic therapy is failing to control uveitis activity adequately. The occurrence of visual acuity loss at about the same time point that uveitis activity relapsed in the implant arm suggests that it may be desirable to replace implants before uveitis relapse occurs, although this practice pattern has not been widely used given the high local side effect risks with this treatment and the difficulty in predicting when relapse would occur. (Relapse of uveitis activity occurred over a broad range of time).
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response:
- Whether alternative local therapies can be developed which have fewer side effects and better visual outcomes.
- Whether long-term highly important adverse systemic outcomes occur with long-term systemic therapy with low-dose corticosteroids and/or immunosuppressive drugs.
Disclosures: Bausch & lomb (Rochester, NY) supplied implants to patients randomized to implant who were unable to purchase them within the trial.
The study was funded primarily by the National Eye Institute/National Institutes of Health.
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Last Updated on May 8, 2017 by Marie Benz MD FAAD