Patient Preference and Treatment Satisfaction With a Port Delivery System for Ranibizumab vs Intravitreal Injections in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Importance: The port delivery system (PDS) with ranibizumab has demonstrated noninferior and equivalent efficacy compared with monthly intravitreal injections of ranibizumab, an anti-vascular endothelial growth factor (VEGF) agent, in patients with neovascular age-related macular degeneration (nAMD), but evaluating patient preference is important to help inform clinical decision-making. Objective: Evaluate treatment satisfaction for ranibizumab delivered via PDS vs intravitreal injections as well as patient preference among those assigned to PDS. Design, Setting, and Participants: Archway was a phase 3 randomized active-comparator open-label clinical trial conducted at 78 sites in the US. Patients 50 years and older with nAMD diagnosed within 9 months of screening with a documented response to anti-VEGF therapy were included. Of 619 patients screened, 418 were enrolled; 415 were included in the primary analysis and 234 were included in the secondary exploratory analysis. The Archway study ran from September 12, 2019, through primary readout on May 22, 2020. Interventions: Patients were randomized 3:2 to PDS with ranibizumab, 100 mg/mL, with fixed refill exchanges every 24 weeks or intravitreal ranibizumab injections, 0.5 mg, every 4 weeks. Main Outcomes and Measures: Treatment satisfaction was measured using the Macular Disease Treatment Satisfaction Questionnaire in the PDS and intravitreal injection arms at week 40. Patient preference was assessed using the content-validated PDS Patient Preference Questionnaire (PPPQ), which measured the proportion of patients in the PDS arm with monthly monitoring who preferred treatment with the PDS at week 40 over previous intravitreal injections or concurrent fellow-eye injections. Both outcomes were exploratory end points. Results: The mean (SD) age of participants at baseline was 75.0 (7.9) years; 234 participants (59%) were women and 162 (41%) were men. At week 40, differences in overall treatment satisfaction scores were minimal for the PDS and intravitreal injection arms (mean, 68.0; 95% CI, 67.4-68.6; n = 237 and mean, 66.1; 95% CI, 64.9-67.3; n = 159, respectively; difference, 1.9; 95% CI, 0.7-3.1). A total of 234 of 248 patients (94.4%) in the PDS arm were included in the PPPQ analysis. At week 40, almost all patients in the PDS arm preferred treatment via PDS (218 of 234 [93.2%]) vs previous intravitreal injections (3 of 234 [1.3%]), including 172 of 234 (73.5%) with a very strong preference for the PDS. In patients who received concurrent fellow-eye injections (n = 78), 72 (92.3%) preferred the PDS. Conclusions and Relevance: Although PDS treatment was preferred by almost all patients assigned to PDS over previous intravitreal injections, both delivery methods have high treatment satisfaction. These findings provide further evidence for the PDS as a meaningful alternative treatment option for patients with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT03677934.

Rituximab versus Mycophenolate Mofetil in Patients with Pemphigus Vulgaris.

BACKGROUND: Rituximab and mycophenolate mofetil are used to treat pemphigus vulgaris, but they have not been adequately compared in clinical trials. METHODS: In a randomized, controlled trial, we assigned patients with moderate-to-severe pemphigus vulgaris in a 1:1 ratio to receive intravenous rituximab (1000 mg on days 1, 15, 168, and 182) or oral mycophenolate mofetil (2 g per day), in addition to an oral glucocorticoid administered on the same tapering schedule in the two groups. The primary end point was sustained complete remission at week 52, defined as the healing of lesions with no new active lesions, as reflected by a Pemphigus Disease Area Index (PDAI) activity score of 0 (on a scale of 0 to 250, with higher scores indicating greater disease severity), for at least 16 weeks without the use of glucocorticoids. Secondary end points were the cumulative dose of glucocorticoids, the number of disease flares, and the change from baseline in the score on the Dermatology Life Quality Index (DLQI; scores range from 0 to 30, with higher scores indicating greater impairment). RESULTS: Of the 135 patients who underwent randomization, 67 were assigned to receive rituximab and 68 to receive mycophenolate mofetil. The primary outcome was assessed in the modified intention-to-treat population: 62 patients in the rituximab group and 63 in the mycophenolate mofetil group. The median PDAI activity scores at baseline were 22.7 in the rituximab group and 18.3 in the mycophenolate mofetil group. At week 52, sustained complete remission was observed in 25 patients (40%) in the rituximab group and in 6 (10%) in the mycophenolate mofetil group (difference, 31 percentage points; 95% confidence interval [CI], 15 to 45; P<0.001). The mean cumulative glucocorticoid dose during the 52-week treatment period was 3545 mg in the rituximab group and 5140 mg in the mycophenolate mofetil group (difference, -1595 mg; 95% CI, -2838 to -353; P<0.001). There were 6 disease flares in the rituximab group and 44 in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05 to 0.29; P<0.001). The mean change in DLQI score was -8.87 points and -6.00 points, respectively (difference, -2.87 points; 95% CI, -4.58 to -1.17; P = 0.001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group. CONCLUSIONS: Rituximab was superior to mycophenolate mofetil in producing sustained complete remission at 52 weeks in patients with pemphigus vulgaris. Rituximab resulted in a greater reduction in glucocorticoid use than mycophenolate mofetil, but more patients in the rituximab group had serious adverse events. Further trials are needed to determine the comparative efficacy and safety of rituximab and mycophenolate mofetil beyond 52 weeks of treatment. (Funded by F. Hoffmann-La Roche; PEMPHIX ClinicalTrials.gov number, NCT02383589.).

Living with Geographic Atrophy: An Ethnographic Study.

INTRODUCTION: The specific impact from the patient's perspective of geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), is not well understood. METHODS: An ethnographic study was conducted to understand the impact of bilateral GA secondary to AMD on daily functioning by observing regular activities performed at home and through semi-structured interviews. Eligible subjects had a definitive GA diagnosis, including presence of drusen, GA lesion size of at least one disc area in the better-seeing eye, and no other confounding ophthalmologic diagnosis. Data were collected via video recordings and field notes, and analyzed by coding video transcripts. RESULTS: Functional impact domains affecting more than two of the 16 subjects from the United Kingdom, United States, or Germany were activities of daily living (difficulty reading, n = 16; driving, n = 12; and watching movies, television, or theater, n = 11), emotional (frustration, and fear of blindness, n = 7 each), social/leisure (interference with hobbies, n = 8, and diminished social activities, n = 4), physical (n = 4), and financial (n = 10). Subjects with a best-corrected visual acuity (BCVA) of 20/100 or better in the better-seeing eye (n = 10) reported similar functional impacts to those with a BCVA of worse than 20/100 in their better-seeing eye (n = 5). CONCLUSION: This study helps address gaps in patient-focused research into GA, which negatively impacts the day-to-day functioning of patients. Larger qualitative and quantitative studies are needed to quantify patient experiences and assess the correlation between BCVA score and impact of GA. FUNDING: F. Hoffmann-La Roche Ltd.

Reliability and Construct Validity of the NEI VFQ-25 in a Subset of Patients With Geographic Atrophy From the Phase 2 Mahalo Study.

PURPOSE: Geographic atrophy (GA) is an advanced form of age-related macular degeneration characterized by progressive, irreversible visual function loss. This analysis evaluates the psychometric properties of the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) composite, near activity, and distance activity scores in patients with GA. DESIGN: Reliability and validity study. METHODS: Reliability and validity were tested with NEI VFQ-25 data collected from 100 subjects with GA from United States' sites of the phase 2 Mahalo study of lampalizumab (ClinicalTrials.gov identifier: NCT01229215). RESULTS: Strong internal consistency and reproducibility were demonstrated for the NEI VFQ-25 composite (Cronbach's α, 0.95; intraclass correlation coefficient [ICC], 0.86), near activity (Cronbach's α, 0.84; ICC, 0.80), and distance activity (Cronbach's α, 0.84; ICC, 0.84) scores. Convergent validity with the binocular measures, Minnesota Low-Vision Reading Test (MNRead) reading speed and Functional Reading Independence (FRI) index score, was demonstrated for baseline NEI VFQ-25 composite (Pearson correlation [r] = 0.61 and 0.69, respectively), near activities (r = 0.69 and 0.73), and distance activities (r = 0.57 and 0.64) scores. Known-group validity testing for baseline mean NEI VFQ-25 scores (composite, near activities, and distance activities) showed differences between patients with mean maximum MNRead reading speed ≥ 80 vs < 80 words per minute, and between mean FRI index score ≥ 2.5 vs < 2.5 (all P < .0001). CONCLUSIONS: Psychometric evidence supports the NEI VFQ-25 as a reliable and valid cross-sectional measure of the impact of GA on patient visual function and vision-related quality of life.