Sustained-release anti-inflammatory therapy proves valuable in NIU

Supplements And Featured PublicationsModern Retina Europe Summer 2021
Volume 1
Issue 1

Long-term treatment helps chronic, vision-threatening disease.

Sustained-release anti-inflammatory therapy proves valuable in NIU

Noninfectious uveitis (NIU) comprises a group of diseases characterised by inflammation of the uvea and the surrounding tissue. NIU affects approximately 300,000 adults in the United States, with a majority being of working age.1 The goals of NIU treatment are to control inflammation, reduce tissue damage and potentially restore vision loss, while minimising adverse effects.2 Treatment of NIU is often challenging because of significant variability in the disease presentation and the presence of accompanying systemic disorders.

The current standard of care in NIU treatment includes corticosteroids, which can be delivered via local or systemic routes. Systemic therapy may be desirable in managing NIU with concomitant systemic disease and/or when both eyes are affected. However, systemic corticosteroid treatment is associated with the risk of steroid-related adverse effects. Systemic and local (intra/periocular) steroids also require frequent dosing.

Related: Uveitis: A leading and underestimated cause of visual morbidity in patients

Sustained-release intraocular corticosteroid implants provide an efficacious, long-lasting and local treatment option for NIU. The implants have particular advantages for the relatively young patient population affected by NIU, who may be challenged to return for frequent follow-up or wish to avoid systemic treatment because of concerns about fertility. In this category, Retisert (fluocinolone acetonide 0.59 mg; Bausch + Lomb) and Yutiq (fluocinolone acetonide 0.18 mg; EyePoint) both provide the drug for up to 3 years. Retisert is implanted via a procedure, whereas the smaller Yutiq implant is delivered by an in-office intravitreal injection. Both implants help reduce the recurrence of uveitis, improve or stabilise vision, and limit the need for concomitant anti-inflammatory medications.3,4

Although both implants are associated with risks of IOP elevation and cataract development, these risks are generally lower with the lower-dose Yutiq than Retisert3,4 and can be minimised by identifying steroid responders with a trial of sub-tenon/intraocular triamcinolone or intraocular dexamethasone.

Cost-effectiveness analysis

Treatment with the sustained-release Yutiq implant can reduce recurrence of uveitis and the need for additional adjunctive anti-inflammatory therapies and provide substantial improvement to patients’ vision and quality of life. Although it stands to reason that using a single-dose, sustained-release corticosteroid implant such as Yutiq would provide an overall benefit, formal cost-effectiveness analysis helps test this assumption and guide beneficiary decisions.

The largest payers in the United Kingdom and United States are the National Health Service and the Department of Health & Human Services, respectively. In the US, the Medicare programme cost was $644 billion in 2019, corresponding to 15% of federal spending, and Medicare spending has increased, on average, by 4.8% per year since 2010.5,6

Related: AAO: Study confirms Phase III results for uveitis treatment

To manage the challenge of increased healthcare costs, governments could increase taxes or divert tax dollars towards healthcare and away from other vital parts of society, such as education and transportation. As no such policy is easy to implement, cost-effectiveness analyses can be applied to help optimise the use of healthcare resources.

In cost-effectiveness analyses, costs are determined using historical data and/or mathematical models and are then assessed in the context of health outcomes to determine whether one intervention could be more favourable than an alternative (eg the standard of care). Incremental cost-effectiveness ratios (ICERs) describe the difference in mean costs of 2 interventions divided by differences in the mean outcomes.

In the context of NIU, a more desirable therapy may be one that offers cost savings while providing the same visual outcome and a longer duration. In addition to directly benefiting patients with NIU, a more cost-effective treatment allows scarce healthcare resources to be allocated elsewhere, thus indirectly benefiting all patients and society as a whole.

Cost-effectiveness study

The UK’s National Institute for Health and Care Excellence (NICE) recently initiated a cost-effectiveness analysis that compared the fluocinolone acetonide (FA) intravitreal implant 0.18 mg (Yutiq in the US) against the dexamethasone intravitreal implant 0.7 mg (Ozurdex) for treatment of recurrent NIU.7

The study used results from a 36-month parallel, randomised, double-blind trial that compared FA implant with sham injection3 and evaluated 3 scenario analyses, each assuming a different level of efficacy for the dexamethasone implant (HR, dexamethasone vs sham, 0.456 [derived from an earlier cost-effectiveness study]; HR, dexamethasone vs FA implant, 1 and 0.7). Additional assumptions also were incorporated into a de novo Markov model to carry out the cost-effectiveness assessment.

Related: FDA accepts Bausch Health, Clearside Biomedical's resubmitted Xipere NDA

The study found that the FA implant extendedly dominated the dexamethasone implant in the first set of analyses, whereas dexamethasone dominated and extendedly dominated the FA implant in the second and third, respectively. Across all analyses, the ICER of the FA implant vs sham injection/standard of care ranged from £12,325 to £30,153 ($16,896 to $41,335) per quality-adjusted life-year (QALY).

Additional analyses found that the FA implant was dominant (more effective, lower cost) in some scenarios, with most ICERs below £20,000 ($27,417) per QALY gained. Based on these additional analyses, the NICE Appraisal Committee recommended the FA implant as a cost-effective use of NHS resources for recurrent NIU affecting the posterior segment.

Related: AAO: Fingolimod for MS offers disease control with no development of uveitis

The study had several limitations. First, it was unclear to the authors whether FA implants would be administered as a first, second or third treatment line in the treatment pathway, which would determine the most relevant comparator. Second, it was unclear whether subsequent FA implants should be considered, which would change the scope of the appraisal.

In addition, the model structure may not have adequately represented the natural course of the disease and the effect of treatment on visual acuity, and only accounted for a single, treated eye, whereas NIU may often develop into a bilateral disease. Finally, no quality-of-life data were captured in the clinical study of the FA implant on which the model was based.

Implication for practice

I have found the FA implant (Yutiq) to be an effective treatment for NIU, and I discuss the option with patients who have chronic and/or recurrent NIU affecting the posterior segment and have previously responded to shorter-duration intraocular steroid injections without associated IOP elevation. I prefer localised treatment over systemic therapy, especially in patients with unilateral disease and no extraocular inflammatory findings. In my experience, Yutiq offers long-term control of intraocular inflammation and macular oedema.

Related: Pearls for ocular surgical success in patients with chronic uveitis

One major drawback of modelling-based cost-effectiveness analyses is the reliance on assumptions that may not be truly representative of routine clinical practice. In the real world, treatment must be individualised. Cultural/geographical variations in clinical practice patterns also can alter the course of treatment. Still, although some assumptions and limitations are inherent in cost-effectiveness analyses, this research provides evidence on which to base decisions about the value of care.

1. Thorne JE, Suhler E, Skup M, et al. Prevalence of noninfectious uveitis in the United States: a claims-based analysis. JAMA Ophthalmol. 2016;134(11):1237-1245. doi:10.1001/jamaophthalmol.2016.3229
2. Valenzuela RA, Flores I, Urrutia B. New pharmacological strategies for the treatment of non-infectious uveitis. a minireview. Front Pharmacol. 2020;11:655. doi:10.3389/fphar.2020.006553
3. Jaffe GJ, Pavesio, CE; Study Investigators. Effect of a fluocinolone acetonide insert on recurrence rates in noninfectious intermediate, posterior, or panuveitis: three-year results. Ophthalmology. 2020;127(10):1395-1404. doi:10.1016/j.ophtha.2020.04.0014
4. Callanan DG, Jaffe GJ, Martin DF, Pearson PA, Comstock TL. Treatment of posterior uveitis with a fluocinolone acetonide implant: three-year clinical trial results. Arch Ophthalmol. 2008;126(9):1191-1201. doi:10.1001/archopht.126.9.11915.
5. National Health Expenditure Data. Centers for Medicare & Medicaid Services. December 17, 2019. Accessed July 1, 2021.
6. The federal budget in 2019: an infographic. Congressional Budget Office. April 15, 2020. Accessed 1 July 2021.
7. Pouwels XGLF, Petersohn S, Carrera VH, et al. Fluocinolone acetonide intravitreal implant for treating recurrent non-infectious uveitis: an evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics. 2020;38(5):431-441. doi:10.1007/s40273-019-00851-z

David R. Lally, MD
p: (413) 732-2333
Lally practices at New England Retina Consultants and is an attending surgeon at Baystate Medical Center in Springfield, Massachusetts. He is an assistant professor in the Department of Surgery at the University of Massachusetts Medical School-Baystate and an assistant professor of ophthalmology at the University of Massachusetts Medical School.

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