Yuhwen Soo

Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration.

OBJECTIVE Two similarly designed, phase-3 studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW 1, VIEW 2]) of neovascular age-related macular degeneration (AMD) compared monthly and every-2-month dosing of intravitreal aflibercept injection (VEGF Trap-Eye; Regeneron, Tarrytown, NY, and Bayer HealthCare, Berlin, Germany) with monthly ranibizumab. DESIGN Double-masked, multicenter, parallel-group, active-controlled, randomized trials. PARTICIPANTS Patients (n = 2419) with active, subfoveal, choroidal neovascularization (CNV) lesions (or juxtafoveal lesions with leakage affecting the fovea) secondary to AMD. INTERVENTION Patients were randomized to intravitreal aflibercept 0.5 mg monthly (0.5q4), 2 mg monthly (2q4), 2 mg every 2 months after 3 initial monthly doses (2q8), or ranibizumab 0.5 mg monthly (Rq4). MAIN OUTCOME MEASURES The primary end point was noninferiority (margin of 10%) of the aflibercept regimens to ranibizumab in the proportion of patients maintaining vision at week 52 (losing <15 letters on Early Treatment Diabetic Retinopathy Study [ETDRS] chart). Other key end points included change in best-corrected visual acuity (BCVA) and anatomic measures. RESULTS All aflibercept groups were noninferior and clinically equivalent to monthly ranibizumab for the primary end point (the 2q4, 0.5q4, and 2q8 regimens were 95.1%, 95.9%, and 95.1%, respectively, for VIEW 1, and 95.6%, 96.3%, and 95.6%, respectively, for VIEW 2, whereas monthly ranibizumab was 94.4% in both studies). In a prespecified integrated analysis of the 2 studies, all aflibercept regimens were within 0.5 letters of the reference ranibizumab for mean change in BCVA; all aflibercept regimens also produced similar improvements in anatomic measures. Ocular and systemic adverse events were similar across treatment groups. CONCLUSIONS Intravitreal aflibercept dosed monthly or every 2 months after 3 initial monthly doses produced similar efficacy and safety outcomes as monthly ranibizumab. These studies demonstrate that aflibercept is an effective treatment for AMD, with the every-2-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies

PURPOSE To compare efficacy and safety of 2 dosing regimens of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for diabetic macular edema (DME). DESIGN Two similarly designed, randomized, phase 3 trials, VISTA(DME) and VIVID(DME). PARTICIPANTS Patients (eyes; n=872) with type 1 or 2 diabetes mellitus who had DME with central involvement. METHODS Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser control. MAIN OUTCOME MEASURES The primary end point was mean change from baseline in best-corrected visual acuity (BCVA) at week 52. This report presents the 100-week results including mean change from baseline in BCVA, proportion of eyes that gained ≥15 letters, and proportion of eyes with a ≥2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. RESULTS Mean BCVA gain from baseline to week 100 with IAI 2q4, IAI 2q8, and laser control was 11.5, 11.1, and 0.9 letters (P < 0.0001) in VISTA and 11.4, 9.4, and 0.7 letters (P < 0.0001) in VIVID, respectively. The proportion of eyes that gained ≥15 letters from baseline at week 100 was 38.3%, 33.1%, and 13.0% (P < 0.0001) in VISTA and 38.2%, 31.1%, and 12.1% (P ≤ 0.0001) in VIVID. The proportion of eyes that lost ≥15 letters at week 100 was 3.2%, 0.7%, and 9.7% (P ≤ 0.0220) in VISTA and 2.2%, 1.5%, and 12.9% (P ≤ 0.0008) in VIVID. Significantly more eyes in the IAI 2q4 and 2q8 groups versus those in the laser control group had a ≥2 step improvement in the DRSS score in both VISTA (37.0% and 37.1% vs. 15.6%; P < 0.0001) and VIVID (29.3% and 32.6% vs. 8.2%; P ≤ 0.0004). In an integrated safety analysis, the most frequent serious ocular adverse event was cataract (2.4%, 1.0%, and 0.3% for 2q4, 2q8, and control). CONCLUSIONS In both VISTA and VIVID, the 52-week visual and anatomic superiority of IAI over laser control was sustained through week 100, with similar efficacy in the 2q4 and 2q8 groups. Safety in these studies was consistent with the known safety profile of IAI.

Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a phase II randomized, double-blind, placebo-controlled trial.

OBJECTIVE To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy. METHODS In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained. RESULTS Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015). CONCLUSION The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile.

Long-Term Efficacy and Safety Profile of Rilonacept in the Treatment of Cryopryin-Associated Periodic Syndromes: Results of a 72-Week Open-Label Extension Study

BACKGROUND Cryopyrin-associated periodic syndromes (CAPS) are rare, inherited autoinflammatory disorders associated with considerable hardship to patients. The interleukin-1 inhibitor rilonacept has been shown to be well-tolerated and effective in preventing CAPS symptoms in 2 pivotal studies. OBJECTIVE In this study, the long-term effects of rilonacept for improvement in CAPS symptoms and its safety and tolerability were evaluated during extended treatment. METHODS Patients with CAPS entered a 72-week open-label extension (OLE) following 2 sequential placebo-controlled Phase III studies (n = 44), or entered directly into the OLE (n = 57). Adults received weekly subcutaneous rilonacept 160 mg, and pediatric patients received subcutaneous rilonacept 2.2 mg/kg, up to 160 mg/week. Safety was evaluated in all patients, and efficacy was evaluated using a validated composite key symptom score in 56 patients. RESULTS After rilonacept treatment for 72 to 96 weeks mean key symptom score at OLE Week 72 was reduced from 2.6 to 0, and the mean number of multisymptom flare days was reduced from 7.3 (34.8% of days) at baseline to 0.6 (2.9% of days) at end point. Elevated levels of inflammatory markers (eg, high sensitivity-C reactive protein and serum amyloid A, were normalized. Adverse events were generally mild to moderate, the most common being injection site reactions and upper respiratory tract infections. The incidence of these events was similar to or lower than the rate reported in the pivotal studies. CONCLUSIONS Long-term treatment with rilonacept of up to 96 weeks resulted in improvements in clinical signs and symptoms of CAPS and normalized biomarkers of inflammation. Rilonacept exhibited a generally favorable safety and tolerability profile in adult and pediatric patients with CAPS throughout the extended treatment period. ClinicalTrials.gov identifier: NCT 00288704.

Intravitreal Aflibercept Injection in Diabetic Macular Edema Patients with and without Prior Anti-Vascular Endothelial Growth Factor Treatment: Outcomes from the Phase 3 Program.

PURPOSE To evaluate visual and anatomic outcomes after intravitreal aflibercept injection (IAI) versus laser in diabetic macular edema (DME) patients with and without prior anti-vascular endothelial growth factor (VEGF) treatment for DME. DESIGN Post hoc analysis of eyes from 2 similarly designed, phase 3 trials, VISTA and VIVID. PARTICIPANTS Patients (eyes) with DME with central involvement from VISTA (n = 461) and VIVID (n = 404). METHODS Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or macular laser photocoagulation. MAIN OUTCOME MEASURES This study reports exploratory outcomes through week 100. Analyses focused on VISTA because more patients received prior anti-VEGF therapy in VISTA (42.9%) versus VIVID (8.9%). RESULTS Of 42.9% of patients in VISTA who received prior anti-VEGF treatment, 83.3% to 92.6% received ≥ 1 prior injections of bevacizumab, and 71.4% to 82.4% received bevacizumab only as prior anti-VEGF treatment for a duration ranging from 28 days to 3.9 years. In patients with prior anti-VEGF treatment, mean best-corrected visual acuity (BCVA) changes from baseline in the IAI 2q4, IAI 2q8, and laser groups were +10.4 letters, +10.5 letters, and -0.7 letters at week 52 and +10.9 letters, +10.8 letters, and -0.8 letters at week 100, respectively. Corresponding changes in patients without prior anti-VEGF treatment were +14.1 letters, +11.0 letters, and +0.9 letters at week 52 and +12.0 letters, +11.3 letters, and +2.1 letters at week 100. In patients with prior anti-VEGF treatment, mean reductions in central retinal thickness were 180.2 μm, 192.2 μm, and 90.9 μm at week 52 and 180.1 μm, 196.4 μm, and 94.1 μm at week 100. Corresponding reductions in patients without prior anti-VEGF treatment were 190.3 μm, 175.7 μm, and 61.0 μm at week 52 and 200.0 μm, 186.7 μm, and 76.9 μm at week 100. The most frequent serious ocular adverse event was vitreous hemorrhage (1.3%, 0.7%, and 1.9%, respectively). CONCLUSIONS Visual and anatomic improvements over laser with both IAI regimens were significant and similar through week 100 in subgroups of patients in VISTA with and without prior anti-VEGF treatment for DME.

Microperimetric assessment of retinal sensitivity in eyes with diabetic macular edema from a phase 2 study of intravitreal aflibercept

Purpose: To evaluate retinal sensitivity in patients with diabetic macular edema who received intravitreal aflibercept injection (IAI) or laser. Methods: A substudy included 46 patients from DA VINCI (a randomized, double-masked Phase 2 study) receiving either laser, 0.5 mg IAI every 4 weeks, 2 mg IAI every 4 weeks, 2 mg IAI every 8 weeks after 3 monthly doses (2q8), or 2 mg IAI as-needed after 3 monthly doses for 52 weeks. Retinal sensitivity was measured in one (central), five (one central and four inner), and eight (four inner and four outer) optical coherence tomography subfields. Results: Mean best-corrected visual acuity improvement in the subgroup at Week 52 was 3.3 letters with laser and ranged from 5.4 to 16.3 letters in the IAI groups. Retinal sensitivity of laser patients at Week 52 was comparable with baseline in the central optical coherence tomography subfield but decreased in the five and eight optical coherence tomography subfields. Compared with laser, retinal sensitivity significantly increased with IAI in the 2q8 and pooled IAI groups in the 5 and 8 optical coherence tomography subfields at Week 52 (P < 0.05). Conclusion: Intravitreal aflibercept injection improved best-corrected visual acuity and retinal sensitivity in this subgroup of patients. Laser may cause a deterioration of macular function that is not detectable with best-corrected visual acuity testing.

Effect of Fluid Status at Week 12 on Visual and Anatomic Outcomes at Week 52 in the VIEW 1 and 2 Trials

BACKGROUND AND OBJECTIVE To evaluate effect of retinal fluid status at week 12 on visual and anatomic outcomes at week 52 in patients with neovascular age-related macular degeneration from the VIEW studies. PATIENTS AND METHODS Post-hoc analysis included 1,465 eyes treated with intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) 2 mg every 4 weeks (2q4) or every 8 weeks following three initial monthly injections (2q8) or ranibizumab (Lucentis; Genentech, South San Francisco, CA) 0.5 mg every 4 weeks (Rq4), which had known retinal fluid status at weeks 12 and 52. RESULTS At 12 weeks, 512 (35%) eyes had fluid and 953 (65%) were fluid-free. Two hundred three (41.5%), 148 (29.8%), and 161 (33.5%) eyes had fluid in Rq4, 2q4, and 2q8, respectively. Best-corrected visual acuity (BCVA) change at week 52 from baseline was independent of retinal fluid status at week 12 or treatment assignment. Eyes were more likely to remain fluid-free at week 52 if absent of fluid at week 12. CONCLUSION At week 52, 2q4, 2q8, and Rq4 improved BCVA independent of fluid status at week 12.

Efficacy and Safety of Sarilumab for Noninfectious Uveitis of Posterior Segment: Outcomes From the Phase 2 SATURN Trial

Posoudit ucinnost a bezpecnost sarilumabu, lidske protilatky proti receptoru interleukinu-6, pro lecbu neinfekcni uveitidy zadniho segmentu (NIU).Subkutanni sarilumab může poskytnout klinicke přinosy při lecbě NIU zadniho segmentu, zejmena u oci s uveitickým makularnim edemem.