Signal-to-noise ratio to assess magnitude, kinetics and impact on pharmacokinetics of the immune response to an adalimumab biosimilar.

Background: The antidrug antibody (ADA) signal-to-noise (S/N) ratio was explored as a novel immunogenicity measure to evaluate the immune response of healthy subjects to a single dose of GP2017, an adalimumab biosimilar. Methodology/results: Bioanalytical methods used for the analysis of ADA S/N ratios and ADA titers were validated for sensitivity, precision and drug interference. ADA S/N ratios strongly correlated with ADA titers. Correlations between ADA area under the curve and ADAmax and pharmacokinetics (PK) were stronger for ADA S/N ratio than for ADA titers. Conclusion: ADA S/N ratio allowed for a more sensitive evaluation of the magnitude and kinetics of the immune response, was better correlated with adalimumab PK and was superior to ADA titers in assessing the impact of the immune response on PK.

GP2017-HCF, a high concentration formulation, demonstrates similar pharmacokinetics, immunogenicity and safety to GP2017, an approved adalimumab biosimilar.

BACKGROUND: GP2017 is an adalimumab biosimilar. The objective of this study is to compare the pharmacokinetics (PK) of GP2017 in its approved formulation and GP2017-high concentration formulation (HCF) in a randomized, double-blind, two-arm PK bridging study. RESEARCH DESIGN AND METHODS: Healthy male subjects received a single 40 mg subcutaneous injection of either GP2017-HCF (n = 162) or GP2017 (n = 168). PK, safety, and immunogenicity were assessed over 72 days post-injection. RESULTS: The 90% confidence intervals [CIs] of geometric mean ratios between GP2017-HCF and GP2017 for Cmax, AUC0-inf, AUC0-360 and AUC0-last were within the pre-defined margin of 0.80 to 1.25; thus, PK comparability between GP2017-HCF and GP2017 was demonstrated. Subgroup analysis of PK comparability by anti-drug antibody (ADA) subpopulation showed that the 90% CIs of geometric mean ratios between GP2017-HCF and GP2017 for Cmax, AUC0-inf, AUC0-360 and AUC0-last were within the margin of 0.80 to 1.25 in ADA-positive and ADA-negative subjects. The proportions of subjects with positive ADA responses and with neutralizing antibodies were comparable between the GP2017-HCF and GP2017 groups. GP2017-HCF and GP2017 were well tolerated, and there were no reports of deaths or other serious adverse events. CONCLUSION: Results show PK comparability between GP2017-HCF and GP2017 and comparable safety and tolerability.

Use of Telemedicine to Screen Patients in the Emergency Department: Matched Cohort Study Evaluating Efficiency and Patient Safety of Telemedicine.

BACKGROUND: Early efforts to incorporate telemedicine into Emergency Medicine focused on connecting remote treatment clinics to larger emergency departments (EDs) and providing remote consultation services to EDs with limited resources. Owing to continued ED overcrowding, some EDs have used telemedicine to increase the number of providers during surges of patient visits and offer scheduled "home" face-to-face, on-screen encounters. In this study, we used remote on-screen telemedicine providers in the "screening-in-triage" role. OBJECTIVE: This study aimed to compare the efficiency and patient safety of in-person screening and telescreening. METHODS: This cohort study, matched for days and proximate hours, compared the performance of real-time remote telescreening and in-person screening at a single urban academic ED over 22 weeks in the spring and summer of 2016. The study involved 337 standard screening hours and 315 telescreening hours. The primary outcome measure was patients screened per hour. Additional outcomes were rates of patients who left without being seen, rates of analgesia ordered by the screener, and proportion of patients with chest pain receiving or prescribed a standard set of tests and medications. RESULTS: In-person screeners evaluated 1933 patients over 337 hours (5.7 patients per hour), whereas telescreeners evaluated 1497 patients over 315 hours (4.9 patients per hour; difference=0.8; 95% CI 0.5-1.2). Split analysis revealed that for the final 3 weeks of the evaluation, the patient-per-hour rate differential was neither clinically relevant nor statistically discernable (difference=0.2; 95% CI -0.7 to 1.2). There were fewer patients who left without being seen during in-person screening than during telescreening (2.6% vs 3.8%; difference=-1.2; 95% CI -2.4 to 0.0). However, compared to prior year-, date-, and time-matched data on weekdays from 1 am to 3 am, a period previously void of provider screening, telescreening decreased the rate of patients LWBS from 25.1% to 4.5% (difference=20.7%; 95% CI 10.1-31.2). Analgesia was ordered more frequently by telescreeners than by in-person screeners (51.2% vs 31.6%; difference=19.6%; 95% CI 12.1-27.1). There was no difference in standard care received by patients with chest pain between telescreening and in-person screening (29.4% vs 22.4%; difference=7.0%; 95% CI -3.4 to 17.4). CONCLUSIONS: Although the efficiency of telescreening, as measured by the rate of patients seen per hour, was lower early in the study period, telescreening achieved the same level of efficiency as in-person screening by the end of the pilot study. Adding telescreening during 1-3 am on weekdays dramatically decreased the number of patients who left without being seen compared to historic data. Telescreening was an effective and safe way for this ED to expand the hours in which patients were screened by a health care provider in triage.