Fluocinolone Acetonide Intravitreal Implant for Treating Recurrent Non-infectious Uveitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

The National Institute for Health and Care Excellence (NICE) invited Alimera Sciences, the company manufacturing fluocinolone acetonide intravitreal implant (FAc) 0.19 mg (tradename ILUVIEN ®), to submit evidence on the clinical and costeffectiveness of FAc for treating recurrent non-infectious uveitis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre + , was commissioned to act as the independent Evidence Review Group (ERG). This paper contains a summary of the clinical and cost-effectiveness evidence submitted by the company, the ERG's critique on the submitted evidence, and the guidance issued by the NICE Appraisal Committee (AC). The company submission (CS) was mainly informed by the PSV-FAI-001 trial in which FAc was compared with (limited) current practice [(L)CP], which was not considered to be representative of UK clinical practice by the ERG. There was no comparison of FAc to any treatment listed in the final scope, and especially to the dexamethasone intravitreal implant (dexamethasone), which was considered to be a relevant comparator by the AC. The primary outcome of the PSV-FAI-001 was recurrence of uveitis in the treated eye. Most of the events for the primary outcome were imputed during the PSV-FAI-001 trial, which probably led to an overestimation of the number of recurrences of disease, and a biased estimate of the relative effectiveness of FAc versus (L)CP. Finally, the place of FAc in the treatment pathway was not clearly defined by the company. Substantial uncertainty surrounded the cost-effectiveness results due to the shortcomings of the clinical evidence. Additionally, the quality of life of patients was not measured during the PSV-FAI-001 trial and long-term effectiveness data of FAc were lacking. The ERG adjusted several issues identified in the CS and added dexamethasone as a comparator in the decision analytic model. The ERG presented multiple analyses as base-cases because several elements of the assessment remained uncertain. The fully incremental ERG results ranged from dexamethasone (extendedly) dominating FAc (when assuming a hazard ratio of 1 or 0.7 for dexamethasone versus FAc) to an incremental cost-effectiveness ratio (ICER) of £30,153 per quality-adjusted lifeyear (QALY) gained for FAc versus (L)CP [when assuming a hazard ratio of 0.456 for dexamethasone versus (L)CP]. The ICER of FAc versus (L)CP ranged from £12,325 to £30,153 per QALY gained. After a second AC meeting where alternative company scenarios comparing FAc with dexamethasone were considered by the AC, the AC concluded that "the results of the company's analyses ranged from the fluocinolone acetonide implant being dominant (that is, it was more effective and costs less), to an ICER of £29,461 per QALY gained, and most of the ICERs were below £20,000 per QALY gained". Therefore, the AC recommended FAc as a cost-effective use of National Health Service (NHS) resources for treating recurrent non-infectious uveitis affecting the posterior segment of the eye in the final TA590 ...

Efficacy of 0.19 mg Fluocinolone Acetonide Implant in Non-infectious Posterior Uveitis Evaluated as Area Under the Curve

“…We hypothesize that the purely inflammatory nature of uveitic macular edema responds better to intravitreal corticosteroids than DME, where other molecular pathways unrelated to inflammatory cytokines are involved. This study may come in support of cost-effectiveness analyses of FAc implant in NIU-PS [16]. No concerning IOPrelated adverse event was observed through the follow-up period.…”

Evaluation of fluocinolone acetonide 0.19 mg intravitreal implant in the management of birdshot retinochoroiditis

“…Our results show the efficacy of FAc implant in the management of vascular leakage, CMO and retinal dysfunction, as previously reported [25][26][27][28]. In our study, baseline full-field ERGs showed a high incidence of generalised cone system dysfunction, consistent with previous studies, [9,10,18] with additional inner retinal rod system dysfunction in a minority.…”

“…The therapeutic role of local ocular corticosteroids in non-infectious posterior uveitis is well established [19][20][21][22][23][24][25][26][27]. Slow-release, sustained-delivery intravitreal corticosteroid implants are approved for non-infectious uveitis, including the FAc 0.19 mg intravitreal implant (Iluvien®; Alimera Sciences Limited, Aldershot, UK).…”

“…Implants have demonstrated efficacy in controlling intraocular inflammation, and can reduce the need for systemic therapy. Local therapy is attractive in BRC as the disease is eye-limited [20][21][22][23][24][25][26][27]. This study evaluated the use of the FAc intravitreal implant in the management of BRC patients.…”

Lipid Nanoparticles for the Posterior Eye Segment

“…In the treatment of the posterior uveitis, intravitreal injections of corticoids are used (triamcinolone acetonide and dexamethasone phosphate). Furthermore, there are two fluocinolone acetonide intravitreal implants, and a biodegradable dexamethasone drug delivery system of poly(lactic-co-glycolic acid) (PLGA) approved [140][141][142]. As a biological therapy, efalizumab, a humanized monoclonal antibody against CD11, is used in a complication of the posterior uveitis, the macular edema.…”