Oedème maculaire etocclusionsveineuses:EtudeLOUVREetsonincidenceen pratique clinique

JeanFrançoisKOROBELNIK

Bordeaux,France

• Financialdisclosures:

– Consultant:Alcon,Alimera,Allergan,Bayer,

Horus,Novartis,Roche,Théa,Zeiss

– Investigator:Allergan,Bayer,Novartis,Roche,

SecondSight,Théa

3

4

INTERNAL USE ONLY

Design de l’étude

Allergan. Data on file.

Organisation de l’étude1ère inject.: Suivi sur 6 mois puis 2ème injection même suivi2ème inject. (par 700ug) si AV<10/10 et OCT>250µm199 patients è pas de necessité de 2ème injection

6 m

ois

5

INTERNAL USE ONLY

Variation moyenne de la MAVC: population retraitée

1. Allergan Data on File.

Variation moyenne de l’AV: population retraitéeRé-injection (700ug) (199 patients une seule injection)Même efficacité sur l’AV moyenne à la 2ème injectionLe sham répond aussi, (mais moins bien) à une injection retardée

6

INTERNAL USE ONLY

Variation de PIO à 12 mois: predictible, transitoire et gérable

Variations de la PIO (à 2 mois), population retraitée•Environ 3 % des patients ont une PIO>35mmHg•Environ 16 % des patients ont une PIO>25 mmHg

16% 16%

16% 16%

3% 3%

Two-year, Prospective, Multicenter Study of the Use of Dexamethasone Intravitreal Implant for Treatment of

Macular Edema Secondary toRetinal Vein Occlusion in France

Jean-François Korobelnik, MD2; Vincent Gualino, MD1; Laurent Kodjikian, MD, PhD3; Cécile Delcourt, MSc4;

Richard Leaback, MD5; Sybil Pinchinat, MSc6; Marie-Eve Velard, MSc7

1Clinique Honoré Cave, Montauban, France; 2Bordeaux University Hospital, Bordeaux, France; 3La Croix-Rousse Hospital, University Hospital of Lyon, Lyon,

France; 4University of Bordeaux, Centre de Recherche INSERM Bordeaux, Bordeaux, France; 5Allergan plc, Marlow, United Kingdom; 6Biostatem, Castries,

France; 7Allergan plc, Courbevoie, France

Background

¢ Dexamethasone intravitreal implant (DEX implant; Ozurdex®) was the first treatment reimbursed for macular edema (ME) due to branch or central retinal vein occlusion (RVO) in France

¢ The French National Authority for Health (HAS) required an additional study to inform on the patterns of use and long-term safety and efficacy of DEX implant treatment of RVO-associated ME in French clinical practice

¢ Study protocol (LOUVRE) was validated by an independent scientific committee and the HAS in 2011

9

LOUVRE Study Objective

¢ This prospective, observational, 24-month, longitudinal study characterized the patterns of use, and long-term efficacy and safety of DEX implant treatment for RVO-associated ME in the French clinical setting

10

Study Design

¢ 48 sites were randomly selected in metropolitan France● 27.6% public practice; 72.4% private practice

¢ Consecutive patients with ME due to RVO treated with DEX implant at baseline were enrolled

¢ Need for re-treatment with DEX implant and use of other treatments were at physician/patient discretion

¢ Assessments: best-corrected visual acuity (BCVA), central retinal thickness (CRT), adverse events (AEs), and intraocular pressure (IOP)

● At baseline, week 6, and months 4, 6, 12, 18, and 24

11

Outcome Measures

¢ Primary endpoint:● Change in BCVA at month 6

¢ Key secondary endpoints:● Patient characteristics ● All RVO-related treatments and procedures

● BCVA change (ETDRS letters) at all follow-up visits

● Patients (%) with ≥15-letter BCVA gain at all follow-up visits

● AEs during and after injection

12

¢ A total of 520 patients presented with ME secondary to RVO at the participating sites during the study enrollment period

¢ The analysis population consisted of 375 patients

¢ The 2-year study completion rate for the analysis population was 74.4% (279/375)

Patients screened (n=520)

Enrolled (n=375)

Completed month 24 (n=279)

Analysis population

Study conducted from October 2011 to October 2014

Patient Disposition

Patient Characteristics at BaselineCharacteristics Total analysis

population (N=375)Mean age, years (SD) 70.3 (11.2)Gender, n (%)

Male 206 (54.9)RVO subtype, n (%)

BranchCentral

202 (53.9)173 (46.1)

Treatment status, n (%)*NaïvePreviously treated, with DEX implantPreviously treated, no DEX implant

145 (38.9)149 (40.0)79 (21.1)

Mean time since onset of ME, months (SD) 10.8 (18.1) Mean BCVA in the study eye, letters (SD) 47.6 (21.2)Mean CRT in the study eye, µm (SD) 554 (180)* Data missing for 2 patients

14

Ocular Comorbidities at Baseline

Comorbidity Total analysispopulation (N=375)

Ocular hypertension 73 (19.5)Glaucoma 52 (13.9)Age-related macular degeneration 5 (1.3)Cataract 108 (28.8)Pseudophakic 101 (26.9)

15

¢ The second most common ocular comorbidity was ocular hypertension

Treatments received for ME n (%)DEX implant intravitreal injections

123456 or 7

124 (33.1)92 (29.3)59 (18.8)43 (13.7)38 (12.1)19 (6.1)

Other ocular treatmentsLaserRanibizumabBevacizumabAflibercept

106 (28.3)114 (30.4)12 (3.2)5 (1.3)

Other ophthalmic treatment n (%)IOP-lowering medication

Week 6Month 6Month 24

82 (21.9)43 (11.5)21 (5.6)

Treatments Received over 24 Months

167 patients received DEX implant only; 208 also received other RVO treatments

Mean: 2.6 DEX with a mean time of 6.9 ± 3.6 months

First use after a mean (SD) of 8.7 ±6.4 months

Primary Endpoint

¢ Change in BCVA at month 6 :● A mean change of +5.1 ± 19.0 letters

(P<.001 vs baseline)

¢ Mean interval between 1st and 2nd DEX injections in patients retreated during the first 6 months was 4.9 ± 1.1 months

17

At least 30% of patients had a BCVA gain of 15 letters or more at each visit between months 6 and 24 18

Patients with BCVA Gain ≥15 Letters

43,4

24,9

31,3 30,4 31,0

38,7

05

101520253035404550

W6 M4 M6 M12 M18 M24

Patie

nts

(%)

Total analysis population (N=375)

Treatment with DEX implant alone was effective in improving BCVA; moving to other treatments did not improve efficacy

Mean BCVA by Treatment Subgroup

19

47,3

58,3

47,9

52,3

49,350,9 51,5

40

45

50

55

60

65

47,9

59,6

53,6

56,9 56,855,3

57,9

40

45

50

55

60

65

Study visitD0 M6 M12 M18 M24

Mea

n B

CVA

(95%

CI),

lette

rs

≥1 DEX implant (N=167) DEX implant + other treatments (N=208)

36.5% of patients treated with DEX implant only received a single injection; mean BCVA gain was 9 letters at month 6 vs 20 letters at month 24

Follow-upVisit

≥1 DEX implant (N=167), mean letters (SD)

DEX implant + other treatments (N=208), mean letters (SD)

Week 6 11.8 (1.2)* 11.1 (1.1)†

Month 4 6.1 (1.5)* 0.8 (1.3)

Month 6 7.0 (1.6)* 3.7 (1.3)†

Month 12 7.3 (1.8)* -0.1 (1.5)

Month 18 5.9 (2.0)* 1.3 (1.6)

Month 24 8.3 (2.0)* 2.3 (1.6)

P value(vs baseline)

*≤.0031 †≤.0056

Mean BCVA Gain by Treatment Subgroup

Mean BCVA by Treatment Subgroup

21

Raisons des switch :

¢ Récidive de l’OM dans 36% des cas

¢ Présence d’une ischémie dans 27% des cas (laser)

¢ Sans aucune raison 22% des cas

¢ 15% autres

22

Follow-up Visit ≥1 DEX implant (N=167)

DEX implant + other treatments (N=208)

Month 6, % 30.9 31.6

Month 24, % 45.3 34.5

Patients with BCVA Gain ≥15 Letters by Treatment

Moving to other treatments did not result in a greater response rate

40,3

47,9

23,0

30,1

0

10

20

30

40

50

60

Month 6 Month 24

Patie

nts

with

a ≥

15-le

tter

gain

, %

<3 months (N=180)

≥3 months (N=183)

Mean BCVA gain: +8.5 +6.7+2.0 +3.0

Visit

BCVA Gain by ME Onset

¢ Significantly greater response rates and mean BCVA gains from baseline were seen at months 6 and 24 in patients with recent onset ME (P ≤.004)

¢ At month 6, patients with recent onset ME gained 10.7 ± 19.31 letters when treated with DEX implant only vs 4.1 ± 22.32 letters when moved to other treatments

23

Significant reductions in CRT from baseline were seen at all follow-up visits in each treatment subgroup (P <.001)

Mean CRT by Treatment Subgroup

24

523,8

292,4

396,1

341,2

377,9 371,6 364,2

250

300

350

400

450

500

550

600

650

579,1

308,6

479,7

384,0415,2 416,9

383,6

250

300

350

400

450

500

550

600

650

Study visitSc M6 M12 M18 M24

Mea

n C

RT

(95%

CI),

µm

≥1 DEX implant (N=167) DEX implant + other treatments (N=208)

Patients with Common Ocular Adverse Events

Adverse eventPatients with events,

N (%)Patients with drug-

related events, N (%)Any adverse event 261 (69.6) 162 (43.8)

Most commonly reported ocular adverse events

IOP increases 129 (34.4) 99 (26.4)*

Cataract 149 (39.7) 82 (21.9)*

* Related to the drug or injection procedure

25

Comorbidity Total analysispopulation (N=375)

Ocular hypertension 73 (19.5)Glaucoma 52 (13.9)Age-related macular degeneration 5 (1.3)Cataract 108 (28.8)Pseudophakic 101 (26.9)

Ocular Comorbidities at Baseline

Patients with Common Ocular Adverse Events

26

Adverse eventPatients with events,

N (%)Patients with drug-

related events, N (%)Any adverse event 261 (69.6) 162 (43.8)

Most commonly reported ocular adverse events

IOP increases 129 (34.4) 99 (26.4)*

Cataract 149 (39.7) 82 (21.9)*

* Related to the drug or injection procedure

¢ IOP increased ≤ 5 mmHg in 74.1% of patients¢ IOP increased ]5 – 9] mmHg in 17.1% of patients¢ IOP increased ≥ 10 mmHg in 8.8% of patients

¢ 5.6% (21/375) of patients were using IOP-lowering medication at month 24

¢ 110 eyes (40% of phakic eyes) underwent cataract surgery

Patients with Common Ocular Adverse Events

27

¢ No incisional glaucoma surgery

¢ No hypertonia surgery

¢ There were no reports of endophthalmitis

Conclusions

¢ In the French clinical setting, DEX implant demonstrated efficacy and safety similar to those of phase 3 trials

● BCVA significantly increased at all follow-up visits

● CRT was reduced at all follow-up visits

● DEX implant was well tolerated

§ The most frequently reported AEs were cataract and IOP increase, consistent with previous observations

28