OBJECTIVE: To demonstrate the therapeutic similarity of CT-P42 compared with reference aflibercept (Eylea) in adult patients with diabetic macular edema (DME). DESIGN: Randomized, active-controlled, double-masked, phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus with DME involving the center of the macula. METHODS: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 ml) by intravitreal injection every 4 weeks (5 doses), then every 8 weeks (4 doses), in the main study period. Results up to week 24 are reported herein. MAIN OUTCOME MEASURES: The primary end point was mean change from baseline at week 8 in best-corrected visual acuity (BCVA) using the ETDRS chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the 2-sided 95% confidence interval (CI) (global assumptions) and 2-sided 90% CI (United States Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set. RESULTS: Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). Best-corrected visual acuity improved from baseline to week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the predefined equivalence margin of ±3 letters (95% CI, -0.73 to 1.88 [global]; 90% CI, -0.52 to 1.67 [FDA]). Through week 24, other efficacy results for the 2 groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing ≥1 treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups. CONCLUSIONS: This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 ml) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
- MeSH
- biosimilární léčivé přípravky aplikace a dávkování MeSH
- časové faktory MeSH
- diabetická retinopatie * farmakoterapie diagnóza komplikace MeSH
- dvojitá slepá metoda MeSH
- inhibitory angiogeneze * aplikace a dávkování MeSH
- injekce intravitreální MeSH
- lidé středního věku MeSH
- lidé MeSH
- macula lutea patologie diagnostické zobrazování MeSH
- makulární edém * farmakoterapie diagnóza etiologie MeSH
- následné studie MeSH
- optická koherentní tomografie metody MeSH
- receptory vaskulárního endoteliálního růstového faktoru * aplikace a dávkování antagonisté a inhibitory MeSH
- rekombinantní fúzní proteiny aplikace a dávkování MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zraková ostrost MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- MeSH
- lidé MeSH
- macula lutea diagnostické zobrazování patologie MeSH
- neuromyelitis optica * diagnostické zobrazování patologie MeSH
- optická koherentní tomografie * MeSH
- retina diagnostické zobrazování patologie MeSH
- zánět zrakového nervu diagnostické zobrazování patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
PURPOSE: To assess the intraday repeatability of macular architecture measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography (SD-OCT) and to evaluate the independence from intraindividual intraocular pressure (IOP) fluctuations. METHODS: In this single-center, time-point comparison study, 88 eyes with glaucoma, 53 eyes with ocular hypertension (OHT), and 253 healthy eyes underwent two standardized SD-OCT and intraocular pressure (IOP) measurements on the same day with a 5-h time gap. Bland-Altman plots, intraclass correlation coefficients (ICC), and random-effects model were used to analyze repeatability of entire retinal thickness, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer measurements. RESULTS: Intraday measurements were highly reproducible in all 3 groups. ICC were greater than 0.90, respectively. The pairwise comparisons of morphometric parameters showed a statistically significant difference (P < 0.001, respectively) between groups (glaucoma vs. control, glaucoma vs. OHT) and a significant influence of time points. No correlation was found between IOP fluctuations and morphometric parameters (P > 0.05, respectively), except for a weak positive correlation with GCL (rho = 0.109, P = 0.031). CONCLUSIONS: The evaluation of macular morphometric parameters of SD-OCT showed a high intraday repeatability and an excellent degree of agreement in glaucoma, ocular hypertension, and healthy groups. The fixed effects of time points were statistically significant. Except for a weak positive correlation of ganglion cell layer, variability did not appear to be affected by intraday IOP changes. Additional research is required to fully understand the impact of IOP fluctuations on macular morphometric parameters, considering the small observed IOP changes.
- MeSH
- dospělí MeSH
- glaukom * diagnóza patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- macula lutea * patologie diagnostické zobrazování MeSH
- následné studie MeSH
- nervová vlákna * patologie MeSH
- nitrooční tlak * fyziologie MeSH
- oční hypertenze diagnóza patofyziologie MeSH
- optická koherentní tomografie * metody MeSH
- reprodukovatelnost výsledků MeSH
- retinální gangliové buňky * patologie MeSH
- senioři MeSH
- tonometrie oční MeSH
- zraková pole fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Cíl: Idiopatická intrakraniální hypertenze (IIH) je charakterizována zvýšeným intrakraniálním tlakem (intracranial pressure; ICP), a to obvykle u mladých obézních žen bez patologie oběhového systému. Zkoumali jsme vztah mezi měřeními optické koherentní tomografie (optical coherence tomography; OCT) a otevíracím tlakem mozkomíšního moku (cerebrospinal fluid; CSF) u nově diagnostikovaných pacientů s IIH, kteří dosud nebyli léčeni. Materiál a metody: Do studie bylo zařazeno 19 osob s diagnózou IIH a 22 zdravých osob v kontrolní skupině. V obou skupinách jsme měřili tloušťku vrstvy nervových vláken sítnice (retinal nerve fibre layer; RNFL), fovey (F) a komplexu gangliových buněk (ganglion cell complex; GCC) a parametry terče zrakového nervu. Výsledky: Průměrné tloušťky RNFL a F byly výrazně vyšší ve skupině pacientů než v kontrolní skupině (p < 0,01). V průměrné hodnotě tloušťky GCC nebyl mezi pacienty a kontrolní skupinou žádný statistický rozdíl. Při porovnání tloušťky RNFL podle kvadrantů měli pacienti s IIH výrazně vyšší hodnoty ve všech kvadrantech. Ve skupině pacientů byly parametry pozitivně korelujícími s otevíracím tlakem CSF stupeň edému papily (rho=0,869, p < 0,01), doba trvání symptomů papily (rho=0,458, p=0,049) a index tělesné hmotnosti (rho=0,653, p=0,002). Závěr: Zvýšená tloušťka peripapilární RNFL a F naměřená pomocí OCT je u nově diagnostikovaných pacientů s IIH spojená se zvýšeným ICP. OCT tak může u pacientů s podezřením na IIH sloužit jako cenný doplněk při subjektivním hodnocení edému papily. Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy. Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.
Aim: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure (ICP), usually in young, obese women with no circulatory pathology. We investigated the relationship between optical coherence tomography (OCT) measurements and cerebrospinal fluid (CSF) opening pressure in newly diagnosed IIH patients who have not been treated yet. Material and methods: The study included 19 individuals diagnosed with IIH and 22 healthy individuals in the control group. We measured the retinal nerve fibre layer (RNFL), fovea (F) and ganglion cell complex (GCC) thickness as well as the optic nerve head parameters in both groups. Results: The mean RNFL and F thicknesses were significantly higher in the patient group compared to the control group (P < 0.01). There was no statistical difference in mean GCC thickness between the patient and control groups. When RNFL thickness was compared by quadrant, the IIH patients had significantly higher values in all quadrants. In the patient group, the parameters that correlated positively with CSF opening pressure were papilloedema grade (rho=0.869, P < 0.01), duration of symptoms (rho=0.458, P=0.049) and body mass index (rho=0.653, P=0.002). Conclusion: Increased peripapillary RNFL and F thickness measured by OCT is associated with elevated ICP in newly diagnosed IIH patients. OCT may thus serve as a valuable supplement to the subjective assessment of papilloedema in patients suspected of having IIH.
AIMS: To 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). METHODS: A 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. RESULTS: Both 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. CONCLUSIONS: T&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 NUMBER: NCT01171976.
- MeSH
- časové faktory MeSH
- diabetická retinopatie komplikace diagnóza MeSH
- inhibitory angiogeneze aplikace a dávkování MeSH
- injekce intravitreální MeSH
- jednoduchá slepá metoda MeSH
- lidé středního věku MeSH
- lidé MeSH
- macula lutea diagnostické zobrazování MeSH
- makulární edém diagnóza farmakoterapie etiologie MeSH
- následné studie MeSH
- optická koherentní tomografie MeSH
- ranibizumab aplikace a dávkování MeSH
- retrospektivní studie MeSH
- vaskulární endoteliální růstový faktor A antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zraková ostrost * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. METHODS: In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. FINDINGS: 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5-5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36-3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63-8·91; p=0·002). We did not identify meaningful associations for macular volume. INTERPRETATION: Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. FUNDING: Instituto de Salud Carlos III.
- MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- macula lutea diagnostické zobrazování MeSH
- následné studie MeSH
- nemoci retiny diagnostické zobrazování etiologie MeSH
- neurony sítnice patologie MeSH
- optická koherentní tomografie metody MeSH
- prognóza MeSH
- progrese nemoci * MeSH
- roztroušená skleróza komplikace patofyziologie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
