Current Issue : July-September Volume : 2025 Issue Number : 3 Articles : 5 Articles
Background: The advent of biosimilars has revolutionized the management of conditions like rheumatoid arthritis by offering cost-effective alternatives to expensive biologics. Objectives: This study aims to compare the post-marketing safety profiles of biosimilars used in rheumatology with their respective reference products (RPs). Methods: Data were retrieved from EudraVigilance for biosimilars of adalimumab, etanercept, infliximab, and rituximab, and compared with their RPs. Our analysis focused on biosimilars authorized before 2021, using data from January 2021 to December 2023. We conducted a descriptive analysis of suspected adverse events, categorized using the Medical Dictionary for Regulatory Activities, and performed a comparative analysis using the reporting odds ratio to identify potential safety signals of disproportionate reporting. Results: We analyzed 75,327 reports, identifying 566,249 drug–event pairs. The results indicate that biosimilars have safety profiles largely comparable to their RPs. Female patients predominated in the reports, representing 69.4% of RPs and 56.9% of biosimilars. Notably, biosimilars demonstrated higher reporting rates for non-serious suspected adverse drug events (AEs), such as injection site pain, arthralgia, and fatigue. Specific AEs, including drug ineffectiveness and off-label use, were more frequent for infliximab and etanercept biosimilars, possibly reflecting real-world usage patterns and nocebo effects. Serious AEs, including malignancies and immunological reactions, were also noted, underscoring the necessity for ongoing monitoring. Conclusions: Our findings suggest that biosimilars are safe alternatives to RPs, contributing to significant healthcare cost savings in the EU. This study underscores the need for ongoing pharmacovigilance and long-term safety research to validate the clinical use of biosimilars in rheumatology....
Purpose: This study aimed to evaluate the efficacy and safety of intravitreal injection of aflibercept biosimilar in the treatment of diabetic macular edema (DME). Methods: Clinical data were collected from 33 patients (40 eyes) newly diagnosed with DME in the ophthalmology department of our hospital between February and April 2024, all of whom were treated with the aflibercept biosimilar. Patients were managed according to the 3+ Pro re nata (PRN) regimen and completed a minimum follow-up period of 6 months. The best-corrected visual acuity (BCVA) testing, optical coherence tomography, optical coherence tomography angiography, and multifocal electroretinography were performed before and after treatment. BCVA and central retinal thickness (CRT) were compared at baseline and 1-, 3-, and 6-months post-treatment. Additionally, the changes in the foveal avascular zone area, vascular density (VD) of superficial and deep retinal capillaries in the macular region, and the first positive peak amplitude density in ring 1 were analyzed 6 months post-treatment. Results: BCVA improved significantly from 0.53 ± 0.12 logMAR at baseline to 0.31 ± 0.12, 0.26 ± 0.10, and 0.26 ± 0.08 logMAR at 1-, 3-, and 6-months post-treatment, respectively, (p < 0.05). CRT decreased significantly from 422.4 ± 63.04 μm at baseline to 294.7 ± 47.89, 272.1 ± 47.43, and 281.0 ± 40.72 μm at 1-, 3-, and 6-months post-treatment, respectively, (p < 0.05). The foveal avascular zone area significantly reduced from 0.40 ± 0.08 mm2 at baseline to 0.35 ± 0.07 mm2 at 6 months post-treatment. Superficial VD increased significantly from 38.90 ± 7.88% at baseline to 41.21 ± 7.98% at 6 months post-treatment, while deep VD significantly increased from 35.67 ± 7.50% at baseline to 38.72 ± 6.90% (p < 0.05). The first positive peak amplitude improved significantly from 55.30 ± 9.45 to 72.90 ± 7.44 nv/deg2 at 6 months post-treatment (p < 0.05). Conclusion: Intravitreal injections of aflibercept biosimilar can significantly reduce DME, improve BCVA, enhance macular perfusion, and restore macular function....
Background/Objectives: To derive the equivalence margin (EQM), typically, a “classical” meta-analysis on direct within-trial estimation of the effect size of the reference drug compared to the placebo or standard of care is performed: a certain factor of the 95% confidence interval for the pooled treatment effect compared to placebo is used. However, treatment regimens in many indications are becoming more complex (e.g., combination treatments), and for most of these clinical study data, direct comparisons are not available. On the other hand, data for the comparison of the common treatment to the reference treatment in one study and to the placebo in another study are available in some situations. Methods: In such situations, an anchor-based indirect comparison can be applied to estimate the treatment effect of Reference vs. Placebo. This treatment effect (Reference vs. Placebo) can be estimated by calculating the difference of the two treatment effects and the variance as the sum of both variances. The 95% confidence interval of this estimated treatment effect can then be used to derive the EQM. To alleviate any concerns about the underlying assumptions of transitivity and consistency, multiple sensitivity analyses can be performed. Results: We present a case study for deriving the EQM using the anchor-based indirect comparison along with sensitivity analyses (i.e., direct comparison against similar reference drug, the impact of variation of treatment effect on Comparator, and effect size Reference vs. Placebo, including trial data with slightly different population characteristics) for a planned efficacy trial in the biosimilar setting. Conclusions: An anchor-based indirect comparison for EQM derivation is an approach health authorities can agree to if sufficiently supported through other means, e.g., relevant sensitivity analyses....
Background: Biosimilars are designed to closely resemble their reference biologics in terms of quality, safety, and efficacy, with only minor variations in clinically inactive components and manufacturing methods. Evaluating the safety of switching between these products is critical for healthcare providers and patients. Concerns may arise when transitioning patients from a reference biologic to a biosimilar or between different biosimilars. Objective: This systematic review and meta-analysis aims to evaluate the frequency of adverse events associated with switching from a reference biologic to its biosimilar, using data derived from randomized controlled trials (RCTs). Methods: A comprehensive search was conducted in MEDLINE and Cochrane Central databases from their inception to December 2024. Studies included RCTs that reported adverse reactions related to switching between reference-to-reference biologics and reference-to-biosimilar biologics. Record screening, data extraction, and risk of bias assessment were performed independently by two reviewers. Random effects models were applied to pool crude outcome data. Results: The search identified 668 abstracts, with an additional 14 studies found through hand-searching review articles. Of these, 12 trials involving 1326 participants in the reference–reference group and 1176 participants in the reference–biosimilar group met the inclusion criteria. The frequency of adverse events, serious adverse events, and treatment-related adverse events did not differ significantly between the reference–reference and reference–biosimilar groups: relative risk (RR) = 0.96 (95% confidence interval [CI], 0.85–1.08), RR = 1.06 (95% CI, 0.68–1.65), and RR = 1.03 (95% CI, 0.66–1.59), respectively. Heterogeneity was generally low to moderate across outcomes, and subgroup analyses based on disease type and reference product showed no differences. Conclusions: Switching between reference biologics and biosimilars demonstrates a comparable safety profile, suggesting that both options are viable. However, the findings are limited by the small number of trials and the scope of patient populations and products studied. PROSPERO registration number: CRD42021267205....
Background/Objectives: Biosimilar studies use overall response rate to assess clinical similarity. Sample size and power depend on the equivalence margin, defined in either risk difference or risk ratio scale. This manuscript investigates how different evaluation metrics and varying response rates affect study power. Methods: Two numerical simulations are conducted. The first is designed to test in the risk difference scale, while the second tests in the risk ratio scale. Both simulations consider no difference between the biosimilar and reference product. Response rates vary from 0.1 to 0.9, and all scenarios are repeated 10,000 times. Results: The study shows inconsistent results in testing the equivalence of overall response rate across the risk difference and risk ratio scales, even when the hypotheses are mathematically equivalent. Consequently, the study is often under powered for testing in both scales. Additionally, study power is sensitive to outcome response rate deviation, with different directions of change in the two different evaluation metrics. Conclusions: Biosimilar study design should avoid the concept of converting equivalence margins between risk difference and risk ratio scales, assuming no change in study power. Careful strategies should be planned for estimating overall response rates for sample size assessments....
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