Efficacy and Safety for Ozurdex^® in the theatment of DME patients​¹

The efficacy and safety of Ozurdex^® DEX implant 0.7 and 0.35 mg in the treatment of Diabetic macular edema was evaluated in the study; Three-Year, Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema, also called MEAD-study, done by David S Boyer and his fellow scientists in two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.​

1048 patients with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 µm by optical coherence tomography were included in the clinical trial.​

The patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.​

The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).​

Anatomical and functional improvements after 3 years:^1​

• Significant reductions in CRT vs sham (p<0.001) (Ozurdex^® n=352, sham n=350)​.

• Improvements in BCVA with a low number of injections with Ozurdex over 3 years (mean 4.1 (0.7 mg) – 4.4 (0.35 mg)) (n=351)​.

• 22.2% of the patients had a ≥15 letter improvement in BCVA when treated with Ozurdex^®  vs 12.0% for Sham (p<0.018). ​

• The mean change in BCVA was +3.5 letter in the Ozurdex^® group vs +2.0 letters for Sham (p=0.023)​.

   

For the Ozurdex group, the mean baseline BCVA was 56.1 letters and mean baseline CRT was 463.0 µm. Rates of cataract-related AE were 67.9% in phakic eyes treated with Ozurdex^® (n=265). Increases in IOP were usually controlled with medication or no therapy; One patient (0.3%) in the Ozurdex group required trabeculectomy for steroid-induced increase in IOP (n=347)​.

For pseudophakic patients​

• 23.3% of the patients had a ≥15 letter improvements in BCVA when treated with Ozurdex vs 10.9% for sham. (p=0.024 vs sham)​.

• The mean change of letters in BCVA was +6.5 for the Ozurdex group vs 1.7 letters for the sham group (p<0.001)​.

IOP^​

As expected with ocular steroid treatment and intravitreal injections, increases in intraocular pressure (IOP) may be seen.​²

Approximately one-third of patients in each DEX implant treatment group had a clinically significant increase in IOP requiring treatment during the study. However no patient underwent removal of the implant to control the IOP, and only 0.3% of the patients in the Ozurdex treatment groups underwent glaucoma incisional surgery for steroid-induced increases in IOP. ​¹

The mean IOP peaked at a similar level and returned to baseline levels by 6 months after each injection.​¹

Furthermore, in comparison with the incidence of IOP AEs after the first treatment and during the first year of the study, the incidence of IOP AEs did not increase after subsequent treatments or in year 2 or 3, and the proportion of patients using IOP-lowering medications in the study eye remained similar from year to year. Together these results indicate that there was no cumulative effect of DEX implant on IOP.¹

Adopted from Boyer et al. by AbbVie.

87% of phakic OZURDEX^® patients had some degree of lens opacification/early cataract at baseline

In the 3-year DME clinical trial​

• 67.9% of phakic OZURDEX eyes (n=265) experienced cataract vs 20.4% phakic sham eyes (n=249)¹

• Over ¾ of cataract surgeries were performed between 18 and 30 months¹

Adapted from Boyer D et al 2014 by AbbVie.

Less frequently reported, but more serious adverse event reactions include endophthalmitis, necrotizing retinitis, retinal detachment and retinal tear.¹

All patients with posterior capsule tear, such as those with posterior lens (e.g. due to cataract surgery), and/or those who have an iris opening to the vitreous cavity (e.g. due to iridectomy) with or without a history of vitrectomy, are at risk of implant migration into the anterior chamber. Implant migration to the anterior chamber may lead to corneal oedema. Persistent severe corneal oedema could progress the need for corneal transplantation. Other than those patients contraindicated where OZURDEX should not be used. Ozurdex should be used with caution and only following a careful risk benefit assessment. These patients should be closely monitored to allow for early diagnosis and management of device migration.^1​

Safety and efficacy for Ozurdex^® in the treatment of RVO patients^​​3

The Geneva trial, conducted by Julia A. Haller and colleagues, focused on evaluating the safety and efficacy of the dexamethasone intravitreal implant (DEX implant; OZURDEX) for patients with vision loss due to macular edema (ME) associated with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). This research encompassed two identical, multicenter, masked, randomized, and sham-controlled clinical trials over a six-month period, involving a total of 1267 participants. Patients were divided into three groups, receiving either a 0.7 mg DEX implant, a 0.35 mg DEX implant, or a sham treatment. The primary outcome measure was the time taken to achieve a 15-letter or greater improvement in best-corrected visual acuity (BCVA). Secondary endpoints included assessments of BCVA, central retinal thickness, and safety profiles. This study aimed to provide robust data on the therapeutic efficacy and safety of the DEX implant in treating ME associated with RVO.​

The results of the Geneva trial demonstrated that a single administration of the dexamethasone intravitreal implant significantly expedited the time required to achieve a 15-letter or greater improvement in best-corrected visual acuity (BCVA) compared to the sham group, with statistical significance noted at P<0.001. The proportion of eyes achieving this level of visual improvement was significantly higher in both DEX implant groups from days 30 to 90 post-administration (P<0.001). Additionally, the incidence of a 15-letter or greater loss in BCVA was significantly lower in the DEX implant 0.7 mg group across all follow-up visits compared to the sham group  (P≤0.036). Improvements in mean BCVA were consistently greater in both DEX implant groups at all follow-ups, and this effect was observed in patients with both BRVO and CRVO, though with different response patterns. Notably, the percentage of eyes with intraocular pressure (IOP) of 25 mmHg or higher peaked at 16% at day 60 for both doses (P<0.001) but aligned with sham group levels by day 180, with no significant between-group differences in cataract occurrence or cataract surgeries. The study concluded that the DEX implant effectively reduces the risk of vision loss, enhances the speed and likelihood of visual improvement, and represents a valuable therapeutic option for managing macular edema secondary to BRVO and CRVO.​

References and abbreviations

1. Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ et al; Ozurdex MEAD Study Group. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014 Oct;121(10):1904-14. 
2. Ozurdex SPC section 4.4, 28-06-2024
3. Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J et al; Ozurdex GENEVA Study Group; Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010 Jun;117(6):1134-1146.e3.

IOP Intraoccular pressure, BCVA Best Corrected Visual Acuity, DME Diabetic Macular Edema, CTR Central Retinal Thickness,

Obligatorisk informasjon

Ozurdex (deksametason) intravitrealt implantat i applikator.

Indikasjoner: Behandling av voksne med synssvekkelse pga. diabetisk makulaødem (DME) som er pseudofake, eller som anses å ikke oppnå tilstrekkelig respons med, eller er uegnet for ikke-kortikosteroid behandling, makulaødem etter okklusjon i netthinnens sidegrensvene (BRVO) eller okklusjon i netthinnens sentralvene (CRVO), betennelse i øyets bakre segment som fremstår som ikke-infeksiøs uveitt.

Dosering: 1 implantat gis intravitrealt. Administrering i begge øyne samtidig anbe­fales ikke. Pasienten skal selv administrere bredspektrede antimikrobielle dråper dag­lig, i 3 dager før og etter hver injeksjon. DME: Pasienter som responderte første gang bør vurderes for ny behand­ling. Ny behandling kan foretas etter ca. 6 måneder ved synssvekkelse og/eller økt netthinnetykkelse, sekundært til tilbakevendende eller forverret diabetisk makulaødem. Erfaring fra gjentatte administreringer >7 implantater mangler. RVO og uveitt: Gjentatte doser vurderes ved respons på behandling etterfulgt av gradvis reduksjon i synsskarphet. Erfaring fra gjentatt dosering med <6 måneders intervaller er svært begrenset.

Utvalgt sikkerhetsinformasjon:

Kontraindikasjoner: Aktiv eller mistanke om okulær eller periokulær infeksjon, inkl. de fleste virale sykdommer i hornhinnen og konjunktiva, herunder ak­tivt epitel, herpes simplex-keratitt (dendrittisk keratitt), kopper, vannkopper, mykobakterielle in­feksjoner og soppsykdommer. Fremskredet glaukom som ikke kan kontrolleres i tilstrekkelig grad bare med legemidler. Afakiske øyne med revnet bakre linsekapsel. Øyne med intraokulær linse i fremre kammer (ACIOL), irisfiksert eller transskleral fik­sert intraokulær linse og revnet bakre linsekapsel.

Forsiktighetsregler:

·       Administreres av kvalifisert øyelege med erfaring med intravitreale injeksjoner.

·       Anbefales ikke ved maculaødem sekundært til RVO med signifikant retinal iskemi.

·       Gjentatt administrering >2 implantater ved ikke-infeksiøs uveitt i øyets bakre segment og ved okklusjon i netthinnens vene gir økning i enkelte bivirkninger.

·       Hvis forbedret syn opprettholdes eller synet forverres og legemidlet ikke forsinker utviklingen, bør be­handling ikke skje på nytt.

·       Ved rift i bakre linsekapsel er det risiko for forskyvning av implantat inn i fremre kammer.

·       Brukes med forsiktighet ved samtidig bruk av antikoagulantia eller trombocytthemmende le­gemidler.

·       Bør ikke brukes under graviditet eller amming, vurder i så fall nytte/risiko.

Bivirkninger: Hyppigst sett er forhøyet intraokulært trykk, kataraktdannelse og konjunktival eller vitreal blødning. Endoftalmitt, nekrotiserende retinitt, netthinneløsning, netthinnerift, hodepine og migrene er rapportert. Kan indusere glaukom og sekundære okulære infeksjoner.

Pakninger og pris (AUP): 1 stk.: kr NOK 13 606,00. Dette er et avtaleprodukt, del av LIS 2201c, hvor det er inngått en egen prisavtale med Sykehusinnkjøp HF. Reseptgruppe: C.

For mer utfyllende informasjon om indikasjoner, dosering, kontraindikasjoner, forsiktighetsregler, bivirkninger, pris og refusjon, se Felleskatalogen.no.
For detaljerte instruksjoner/bilder mht. administrering, se pakningsvedlegg eller SPC.
Referanse: Ozurdex SPC, avsnitt 4.1, 4.2, 4.3, 4.4, 4.6, 4.8, sist oppdatert 28.06.2024.

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