Prospective, Observational, Multicenter, Real-World Study of the Efficacy, Safety, and Pattern of Use of the Dexamethasone Intravitreal Implant in Diabetic Macular Edema in France: Short-Term Outcomes of LOUVRE 3.

INTRODUCTION: To evaluate real-world efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in diabetic macular edema (DME) in France. METHODS: In this prospective, multicenter, observational, noncomparative, post-reimbursement study, consecutively enrolled patients with DME had a baseline evaluation on day 0. Those treated with DEX on day 0 were to be reevaluated at week 6 and months 6, 12, 18, and 24. DEX retreatment and/or alternative therapies were allowed during follow-up. The primary outcome measure was the maximum best corrected visual acuity (BCVA) gain from baseline during follow-up. Secondary outcome measures included time to maximum BCVA gain, patients (%) with prespecified BCVA gains from baseline at each visit, maximum central retinal thickness (CRT) reduction from baseline, patients (%) with CRT reduction ≥ 20% from baseline at each visit, patients (%) with DME resolution (per investigator judgement), and adverse events (AEs). RESULTS: Of 112 patients/eyes with DME for 3.5 years (mean) at baseline, 80 (including 86.1% previously treated) received DEX on day 0 and were analyzed for efficacy. Early study termination precluded collection of ≥ 12-month efficacy data. Patients received 1.4 DEX injections over 8.3 months (averages). The maximum BCVA gain from baseline was 3.6 letters, reached after 77.2 days (averages); 24.6% (week 6) and 15.0% (month 6) of patients experienced ≥ 10-letter BCVA gains from baseline. The mean maximum CRT reduction from baseline was -146.4 µm; 61.4% (week 6) and 36.0% (month 6) of patients had CRT reductions ≥ 20% from baseline, and 68.1% reported DME resolution at least once during follow-up. Ocular hypertension (n = 8, 12.1%) was the most frequent treatment-related AE. CONCLUSIONS: LOUVRE 3 confirmed that DEX improves BCVA and CRT, even in a patient population that had predominantly received DEX before enrollment in the study, and showed that DME resolution was observed during follow-up. DEX tolerability was consistent with published data, supporting treatment benefits in DME. GOV IDENTIFIER: NCT03003416.

Real-Life Efficacy, Safety, and Use of Dexamethasone Intravitreal Implant in Posterior Segment Inflammation Due to Non-infectious Uveitis (LOUVRE 2 Study).

INTRODUCTION: To evaluate real-life efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in posterior segment inflammation due to non-infectious uveitis (treatment-naïve or not) in French clinics. METHODS: In this prospective, multicenter, observational, non-comparative, post-reimbursement study, consecutive patients with posterior segment inflammation due to non-infectious uveitis were enrolled and evaluated at baseline (day 0). Those who received DEX on day 0 were re-evaluated at months 2, 6, and 18. Retreatment with DEX and/or alternative therapies was allowed during follow-up. PRIMARY OUTCOME: patients (%) with at least a 15-letter gain in best corrected visual acuity (BCVA) at 2 months. Secondary outcomes included patients (%) with at least 15-letter BCVA gains at 6 and 18 months; mean BCVA change from baseline at 2, 6, and 18 months; and patients (%) retreated, mean central retinal thickness (CRT), and adverse events (AEs) at all post-baseline visits. RESULTS: Ninety-seven of 245 enrolled patients with posterior segment inflammation due to non-infectious uveitis (80% previously treated) and disease duration of 5 years (average) received DEX on day 0 and were included in efficacy analyses. At month 2 (n = 91), 20.5% of patients (95% CI 12.0-28.9) gained at least 15 letters from a baseline mean of 60.9 letters; the mean gain was 6.2 letters (95% CI 3.5-8.9). At month 6, 50.0% (n = 38/76) of patients did not receive alternative treatment or DEX retreatment, mostly because inflammation had sufficiently subsided (n = 27/38, 71.1%). Although early study termination prevented efficacy analysis at 18 months (n = 12), CRT reductions persisted throughout follow-up. From baseline to month 18, 21/245 (8.6%) patients had DEX-related AEs; 17/245 (6.9%) had ocular hypertension (most common AE). CONCLUSION: LOUVRE 2 confirms DEX efficacy on visual acuity and CRT in predominantly DEX-pretreated patients with relatively old/stabilized uveitis. DEX tolerability was consistent with known/published data, confirming treatment benefits in posterior segment inflammation due to non-infectious uveitis. GOV IDENTIFIER: NCT02951975.

Economic impact of onabotulinumtoxinA for overactive bladder with urinary incontinence in Europe.

BACKGROUND: Overactive bladder (OAB) is a common condition that has a significant impact on patients' health-related quality-of-life and is associated with a substantial economic burden to healthcare systems. OnabotulinumtoxinA has a well-established efficacy and safety profile as a treatment for OAB; however, the economic impact of using onabotulinumtoxinA has not been well described. METHODS: An economic model was developed to assess the budget impact associated with OAB treatment in France, Germany, Italy, Spain and the UK, using onabotulinumtoxinA alongside best supportive care (BSC)-comprising incontinence pads and/or anticholinergic use and/or clean intermittent catheterisation (CIC)-vs BSC alone. The model time horizon spanned 5 years, and included direct costs associated with treatment, BSC, and adverse events. RESULTS: Per 100,000 patients in each country, the use of onabotulinumtoxinA resulted in estimated cost savings of €97,200 (Italy), €71,580 (Spain), and €19,710 (UK), and cost increases of €23,840 in France and €284,760 in Germany, largely due to day-case and inpatient administration, respectively. Projecting these results to the population of individuals aged 18 years and above gave national budget saving estimates of €9,924,790, €27,458,290, and €48,270,760, for the UK, Spain, and Italy, respectively, compared to cost increases of €12,160,020 and €196,086,530 for France and Germany, respectively. Anticholinergic treatment and incontinence pads were the largest contributors to overall spending on OAB management when onabotulinumtoxinA use was not increased, and remained so in four of five scenarios where onabotulinumtoxinA use was increased. This decreased resource use was equivalent to cost offsets ranging from €106,110 to €176,600 per 100,000 population. CONCLUSIONS: In three of five countries investigated, the use of onabotulinumtoxinA, in addition to BSC, was shown to result in healthcare budget cost savings over 5 years. Scenario analyses showed increased costs in Germany and France were largely attributable to the treatment setting rather than onabotulinumtoxinA acquisition costs.

Two-year, prospective, multicenter study of the use of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in the clinical setting in France.

PURPOSE: To evaluate patterns of use and long-term efficacy and safety of dexamethasone intravitreal implant (DEX implant) in the treatment of macular edema secondary to branch or central retinal vein occlusion (BRVO, CRVO) in French clinical practice. METHODS: A 24-month, prospective, multicenter, longitudinal, observational study (LOUVRE) conducted at 48 randomly selected sites in metropolitan France enrolled consecutive adult patients with macular edema following retinal vein occlusion (RVO) who were treated with DEX implant at baseline. Re-treatment with DEX implant and use of other RVO treatments was at the physician's discretion. The primary endpoint was the change in best-corrected visual acuity (BCVA) from baseline to month 6. Secondary endpoints included change in BCVA, intraocular pressure (IOP), adverse events, and RVO treatments administered through month 24. RESULTS: The analysis population of 375 patients (53.9 % BRVO, 46.1 % CRVO) received a mean of 2.6 DEX implant injections over 2 years; mean time between injections was 6.6 months. Mean (SD) change in BCVA from baseline was 5.1 (19.0) letters at month 6 (p < 0.001) and 4.6 (22.3) letters at month 24 (p < 0.001). During the study, 208 patients (55.5 %) received treatment other than DEX implant for RVO, usually laser or ranibizumab therapy, with first use of other therapy occurring at a mean of 8.7 months. Mean change from baseline BCVA at month 6 was 5.5 letters (p < 0.001, N = 254) in patients who had received only DEX implant and 4.2 letters (p = 0.006, N = 121) in patients who had received additional other RVO treatment during the first 6 months. At month 24, mean change from baseline BCVA was +20.7 letters in patients treated with a single DEX implant only (p < 0.001), +4.9 letters in patients treated with ≥2 DEX implants only (p = 0.029), and +2.3 letters in patients treated with DEX implant and other RVO treatment (p = 0.143). The most common adverse events (incidence) were cataract progression (39.7 %) and increased IOP (34.4 %). No glaucoma incisional surgeries were required. CONCLUSIONS: Efficacy and safety of DEX implant in the treatment of RVO-associated macular edema were demonstrated in the French clinical setting. Patients who switched from DEX implant to other RVO treatments did not have improved outcomes. The study is registered at ClinicalTrials.gov with the identifier NCT01618266.