Current Issue : July-September Volume : 2023 Issue Number : 3 Articles : 5 Articles
Background: Although with the application of etanercept biosimilars in the field of rheumatoid arthritis, the evidences of their efficacy, safety, and immunogenicity are still limited. We conducted this meta-analysis to evaluate the efficacy, safety and immunogenicity of etanercept biosimilars for treating active rheumatoid arthritis compared to reference biologics (Enbrel®). Methods: PubMed, Embase, Central, and ClinicalTrials.gov were searched for randomized controlled trials of etanercept biosimilars treated in adult patients diagnosed with rheumatoid arthritis from their earliest records to 15 August 2022. The outcomes included ACR20, ACR50, and ACR70 response rate at different time points from FAS or PPS, adverse events, and proportion of patients developed anti-drug antibodies. The risk of bias of each included study was assessed using the revised Cochrane Risk of Bias in Randomised Trials tool, and the certainty of evidence was rated according to the Grading of Recommendation Assessment, Development, and Evaluation. Results: Six RCTs with 2432 patients were included in this meta-analysis. Etanercept biosimilars showed more benefits in ACR50 at 24 weeks from PPS [5 RCTs, OR = 1.22 (1.01, 1.47), p = 0.04, I2 = 49%, high certainty], ACR50 at 1 year from PPS [3 RCTs, OR = 1.43 (1.10, 1.86), p < 0.01, I2 = 0%, high certainty] or FAS [2 RCTs, OR = 1.36 (1.04, 1.78), p = 0.03, I2 = 0%, high certainty], and ACR70 at 1 year from PPS [3 RCTs, OR = 1.32 (1.01, 1.71), p = 0.04, I2 = 0%, high certainty]. In terms of other outcomes about efficacy, safety, and immunogenicity, the results showed that there was no significant difference between etanercept biosimilars and reference biologics, and the certainty of evidences ranged from low to moderate. Conclusion: Etanercept biosimilars showed more benefits in ACR50 response rate at 1 year than reference biologics (Enbrel®), other outcomes for clinical efficacy, safety, and immunogenicity of etanercept biosimilars were comparable with originator in patients with rheumatoid arthritis. Systematic Review Registration: PROSPERO, identifier CRD42022358709...
Background: This study aimed to investigate the pharmacokinetics, safety, and immunogenicity of recombinant humanized anti-human IL-6R monoclonal antibody injection, LZM008, and evaluate the pharmacokinetic similarity between LZM008 and tocilizumab (ACTEMRA®) in Chinese healthy male subjects. Research design and methods: In this randomized, double-blinded, paralleled, two-center Phase I clinical trial, 96 subjects were randomized with a 1:1 ratio to receive 4 mg/kg intravenous dose of LZM008 or ACTEMRA® and evaluated for 28 days. The pharmacokinetic bioequivalence was assessed by the maximum serum concentration (Cmax), the area under the serum concentration–time curve (AUC) from time 0 to the last detectable drug concentration (AUC0-t), and AUC0-∞. The statistical analysis was conducted using SAS Enterprise Guide statistical software. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Anti-drug antibodies (ADAs) were measured by a bridged electrochemiluminescence immunoassay. Results: LZM008 (N = 49) and ACTEMRA® (N = 47) groups showed similar pharmacokinetic properties. After a single intravenous infusion of 4 mg/kg LZM008, the Cmax and AUC0-∞ values of LZM008 reached 87.99 μg/mL and 11,526.70 h*μg/mL, respectively, with Tmax 1.98 h, and the half-life (t1/2) was 83.45 h. The 90% confidence intervals of ratios for Cmax, AUC0-t, and AUC0-∞ were within the range of 80.00%–125.00%. After infusion, one (2.0%) subject in the LZM008 group and three (6.4%) subjects in the ACTEMRA® group showed positive ADA test results. The incidence of treatment emergent adverse events (TEAEs) was comparable in LZM008 and ACTEMRA® groups (98.0% versus 100%), with the decrease in blood fibrinogen and neutrophil counts being the most common TEAEs. Conclusion: The pharmacokinetic characteristics and immunogenicity exhibited by LZM008 were similar to those of the reference product, ACTEMRA®. The safety profiles of LZM008 were similar in the two groups with mild–moderate adverse effects....
Background. On September 5, 2019, British Columbia announced a new policy (the Biosimilars Initiative) to switch from originator to biosimilar infliximab for patients with inflammatory bowel diseases. Objective. To monitor the impacts of the policy on the use of medications and health services during the first year of the policy. Methods. In this population-based cohort study, we used administrative health data to construct three historical cohorts and one policy cohort of patients with inflammatory bowel diseases who used the originator infliximab. We then monitored the cumulative incidence of medications and health services. Log-likelihood ratios were used to quantify differences between the policy cohort and the average of the historical cohorts. Results. The cohorts included 1839–2368 users of the originator infliximab, ages 4–90 years, mean age 43 years. During the first year of follow-up, we found: (1) a 0.9% increase in the first dispensation of infliximab, biosimilar, or originator; (2) a 16.2% increase in infliximab dose escalation; (3) a decrease of 2.4% in the dispensation of antibiotics and a 2.6% decrease in new use of prednison; (4) an anticipated increase in visits to physicians and gastroenterologists to manage switching to biosimilars (24.0%); (5) a 4.0% decrease in discharges from hospital; and (6) a 2.9% decrease in emergency admissions to hospital. Conclusion. British Columbia’s Biosimilars Initiative for nonmedical switching from originator to biosimilar infliximab for inflammatory bowel diseases was not associated with harmful impacts on medications and health services use. An increase in dose escalation was accompanied by an improvement in health status proxies....
Objectives: Bevacizumab was first marketed in 2005. Since then, its stability has been extensively studied. The arrival of numerous biosimilars on the market has called into question these stabilities and organisation within reconstitution units. To study the stability of the Bevacizumab biosimilar Alymsys® marketed by Zentiva laboratory in ready-to-use vials at a concentration of 25 mg/mL and following dilution to obtain final concentrations of 1.4 and 16.5 mg/mL and storage in polyolefin IV bags at 4 °C. In parallel, the impact of a storage temperature excursion at 25 °C for three days and storage of the vial before opening at room temperature (25 ± 2 °C) and after opening at 4 °C was studied. Methods: The vials were supplied by Zentiva laboratory. The vials (three batches) were diluted to the final concentrations of 1.4 or 16.5 mg/mL in 100 mL IV bags of NaCl. The IV bags and vials were stored at 4 °C and at room temperature throughout the duration of the study. The physico-chemical stability was tested using the following methods: turbidimetry, UV spectrometry and fluorescence, dynamic light scattering, ion exchange and steric exclusion chromatography, pH, osmolality and density. Results: Out of all the parameters studied, for the two concentrations and standard storage conditions (90 days at +4 °C) or after a three-day temperature excursion at +25 °C, no modification was detected for the three batches tested with respect to physical and chemical stability. Hence, no signs of physical instability were observed, with, in particular, the absence of formation of submicron or micron sized aggregates and particles. The steric exclusion chromatography profiles did not demonstrate any oligomer formation or molecular structure rupture. Ion exchange chromatography did not demonstrate any significant modification in the distribution of charge variants. Derivative UV and fluorescence spectral analysis did not demonstrate any modification. The thermal denaturation curves were identical, suggesting the absence of thermodynamic destabilisation. Identical results were observed for the vials stored for 60 days at 4 °C after opening. Finally, only ion exchange chromatography demonstrated a slight change after 45 days of storage at 25 °C for vials before opening. Conclusions: After dilution in sterile conditions with 0.9% NaCl in polyolefin IV bags, at the usual concentrations of 1.4 and 16.5 mg/mL, the Bevacizumab biosimilar Alymsys® is stable for at least three months at 4 °C protected from light and after a three-day temperature excursion at +25 °C. The same conclusions can be reached for the 25 mg/mL vials stored for 60 days at +4 °C after opening. However, the stability of vials stored at 25 °C before opening is no longer guaranteed beyond 15 days....
Background and Objectives: The ever-expanding entry of biosimilar drugs into the Israeli market requires doctors to decide whether to prescribe these medications. We aimed to assess the prevalence of biosimilar use and Israeli gastroenterologists’ knowledge, experience, and perception of biosimilar treatment. Materials and Methods: A cross-sectional survey was conducted among Israeli Gastroenterology Association (IGA) members between March and May 2022 using a structured 20-item questionnaire. Results: The questionnaire was completed by 108 gastroenterologists. Sixtytwo percent prescribed biosimilars to their patients in the past year. Most of the patients (81%) were biologically naïve and only 19% were switched to a biosimilar. Most gastroenterologists (75%) answered that the effectiveness is the same. The rates of resistance to switching were 19%, 36%, and 70% for patients in remission for over two years, pregnant women, and difficulty reaching remission, respectively. In cases seeing a lack of response after switching, most physicians chose to change the mechanism of action, with only a small percentage returning to the brand-name drug. Conclusions: Most Israeli gastroenterologists are not concerned about biosimilars’ safety and efficacy. Despite this, most physicians will prefer the brand-name drug, especially regarding adalimumab. The populations in which physicians most oppose switching are those who have had difficulty achieving remission and pregnant women....
Loading....