AimsTo demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular oedema (DMO).MethodsA 24-month single-masked study with patients randomised 1:1:1 to T&E+laser (n=121), T&E (n=128) or PRN (control; n=123). All patients received monthly injections until BCVA stabilisation. The investigator decided on re-treatment in the PRN and treatment-interval adaptations in the T&E groups based on loss of BCVA stability due to DMO activity. Likewise, laser treatment was at investigator's discretion. Collectively, these features reflect a real-life scenario. Endpoints included mean average change in BCVA from baseline to months 1–12 (primary), mean BCVA change from baseline to months 12 and 24, treatment exposure and safety profile.ResultsBoth T&E regimens were non-inferior to PRN based on mean average BCVA change from baseline to months 1–12 (T&E+laser: +5.9 and T&E: +6.1 vs PRN: +6.2 letters; both p<0.0001). Mean BCVA change at month 24 was similar across groups (+8.3, +6.5 and +8.1 letters, respectively). The mean number of injections was 12.4 and 12.8 in the T&E+laser and T&E groups and 10.7 in the PRN group. The T&E regimens showed 46% reduction in the number of clinic visits. Over 70% of patients maintained their BCVA, with treatment intervals of ≥2 months over 24 months. Safety profile was consistent with that described in the product information.ConclusionsT&E is a feasible treatment option for patients with DMO, with a potential to reduce treatment burden. Slightly more injections were required versus PRN, likely due to the specifics of the T&E regimen applied here.Trial registration numberNCT01171976.

Signaling through the interleukin-4/interleukin-13 (IL-4/IL-13) receptor complex is a crucial mechanism in the development of bronchial asthma and chronic obstructive pulmonary disease (COPD). In bronchial epithelial cells, this signaling pathway leads to changes in the expression levels of several genes that are possibly involved in protection against and/or pathogenesis of these diseases. The expression of pendrin (SLC26A4), a candidate for the latter category, is upregulated by IL-4/IL-13 and leads to overproduction of mucus and increased viscosity of the airway surface liquid (ASL). Therefore, elucidating the transcriptional regulation of pendrin could aid in the development of new pharmacological leads for asthma and/or COPD therapy. Here we show that IL-4/IL-13 significantly increased human pendrin promoter activity in HEK-Blue cells but not in STAT6-deficient HEK293 Phoenix cells; that mutation of the STAT6 binding site (N(4) GAS motif) rendered the promoter insensitive to IL-4/IL-13; and that addition of the N(4) GAS motif to an IL-4/IL-13-unresponsive sequence of the human pendrin promoter conferred sensitivity to both ILs.

IMPORTANCE Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment. OBJECTIVE To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis. INTERVENTIONS Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48. MAIN OUTCOMES AND MEASURES Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of −3 letters to 3 letters for BCVA and −36 μm to 36 μm for CST. RESULTS Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of −0.8 letter (90% CI, −1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were −108 (5) μm in the SB11 group vs −100 (5) μm in the ranibizumab group, with an adjusted treatment difference of −8 μm (95% CI, −19 to 3 μm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group. CONCLUSIONS AND RELEVANCE These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration.

Background/AimsTo provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).MethodsSetting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one ‘study eye’. Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.ResultsBaseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was −0.6 letters (90% CI −2.1 to 0.9) and of change from baseline in central subfield thickness was −14.9 µm (95% CI –25.3 to –4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.ConclusionsLonger-term results of this study further support the biosimilarity established between SB11 and RBZ.

ABSTRACT.Purpose: To evaluate the influence of haemorheopheresis on anatomical and functional findings in patients with soft-drusen maculopathy. Methods: We investigated 29 eyes (16 patients) and randomized 25 eyes (16 controls) with soft-drusen maculopathy [soft, confluent and reticular drusen, drusenoid retinal pigment epithelium detachment (RPED)]. Each patient received a series of eight haemorheophereses (cascade filtration of 1.5 plasma volume) within 10 weeks. The patients were followed up using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, optical coherence tomography, fluorescein angiography, electroretinography and measurements of pulsed ocular blood flow. Results: After the procedures, there was a substantial reduction in rheologically active substances [lipoproteins, immunoglobulin M (IgM), fibrinogen], plasma and blood viscosity. At the 1.5-year follow-up, we noticed soft drusen absorption; reattachment of drusenoid RPED and stabilization or improvement of visual acuity occurred in 72% of patients in comparison to only 39% of patients in the control group. Full-field electroretinograms showed significantly higher scotopic activity of treated patients in comparison with the control group, and mainly insignificant differences in photopic activity between both groups. Despite the significant increase of activity in the paramacular retina in treated patients, the differences in amplitudes of multifocal electroretinography (mfERG) average responses were insignificant between groups. Conclusion: Haemorheopheresis seems to be capable of changing the activity of promoters of the natural course of soft-drusen maculopathy, its development and progression. Visual acuity and electrical activity of the retina can be stabilized or even improved. The therapy has been shown to be effective and safe.

No abstract

No abstract

COVID-19. 3 The FSH provided more than 14 000 beds and timely treatment for the mild cases, as well as breaking down transmission of the virus. It has been suggested that the FSH were a major reason for the successful control of COVID-19 in China. 3 In the FSH, due to social isolation, uncertainty, fear of virus transmission, and overwhelming negative news portrayals in mass media coverage, 4 the psychological unwellness of both COVID-19 patients and health-care workers (HCW) was prominent. Our baseline cross-sectional survey with 372 COVID-19 patients in FSH and 742 frontline HCW who were engaged in direct contact with COVID-19 patients observed a high proportion of psychological effects among them. We used three selfadministered instruments: the nine-item Patient Health Questionnaire (PHQ-9; cutoff point 5), the seven-item Generalized Anxiety Disorder (GAD-7; cutoff point 5), and the Insomnia Severity Index (ISI; cutoff point 8), to assess symptoms of depression, anxiety, and insomnia among participants. We found that 67.7%, 53.0%, and 48.7% of the COVID-19 patients, and 60.5%, 54.2%, and 42.6% of the frontline HCW suffered symptoms of depression, anxiety, and insomnia, respectively. Multiple psychological intervention measures were carried out in the FSH. First, we set up publicity and education exhibition board areas to convey psychological information, including common psychological problems, coping methods, and ways to obtain online and offline psychological services, to both COVID-19 patients and HCW. All the COVID-19 patients and HCW in the FSH had access to these areas. Second, 11 hospitals and institutions jointly developed a free online psychological support system that was loaded as a 'mini-program' into the most popular instant messenger (WeChat) in China. The system was first available on 11 February 2020 and consisted of three sections. The psychological information section presented popular science readings about common psychological unwellness that may occur during a public emergency, and the latest encouraging facts on COVID-19. The online assessment section provided several self-administrated tools to assess the psychological fitness, and could give an overall explanation and suggestions for users according to the results of the scales. The psychological intervention section provided an online behavioral and sleep cognitive therapy system, as well as a portal for online consulting through which psychologists and psychiatrists could be reserved for remote video consultations. Both patients and HCW had free access to use the system via WeChat. Third, nurses in the FSH were trained with basic psychological nursing skills in February, such as listening to the patient patiently, showing interest in the content of the conversation, and understanding the patient's situation and feelings. Fourth, at least one psychiatrist was assigned to each FSH. The psychiatrists participated in joint rounds and visits, provided timely monitoring of the psychological status of patients, and provided proper psychologi...