Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study

Abstract

BackgroundSince 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs.AimThis population-based study was aimed to compare the effects of biosimilars, reference product and other ESAs still covered by patent on hemoglobinemia in chronic kidney disease (CKD) and cancer patients in a Local Health Unit (LHU) from Northern Italy.MethodsA retrospective cohort study was conducted during the years 2009–2014 using data from Treviso LHU administrative database. Incident ESA users (no ESA dispensing within 6 months prior to treatment start, i.e. index date (ID)) with at least one hemoglobin measurement within one month prior to ID (baseline Hb value) and another measurement between 2nd and 3rd month after ID (follow-up Hb value) were identified. The strength of the consumption (as total number of defined daily dose (DDD) dispensed during the follow-up divided by days of follow-up) and the difference between follow-up and baseline Hb values [delta Hb (ΔHb)] were evaluated. Based on Hb changes, ESA users were classified as non-responders (ΔHb≤0 g/dl), responders (0<ΔHb≤2 g/dl), and highly responders (ΔHb>2 g/dl). A multivariate ordinal logistic regression model to identify predictors for responsiveness to treatment was performed. All analyses were stratified by indication for use and type of dispensed ESA at ID.ResultsOverall, 1,003 incident ESA users (reference product: 252, 25.1%; other ESAs covered by patent: 303, 30.2%; biosimilars: 448, 44.7%) with CKD or cancer were eligible for the study. No statistically significant difference in the amount of dose dispensed during the follow-up among biosimilars, reference product and other ESAs covered by patent was found in both CKD and cancer. After three months from treatment start, all ESAs increased Hb values on average by 2g/dl. No differences in ΔHb as well as in frequency of non-responders, responders and highly responders among different types of ESAs were observed in both indications of use. Overall, around 15–20% of ESA users were non-responders. Strength of treatment, but no type of dispensed ESAs was found to be predictor of responsiveness to treatment.ConclusionsNo difference on the effects on hemoglobinemia among users of either biosimilars or reference product or ESAs covered by patent was observed in a general population from Northern Italy, despite a comparable dispensed dose of the different ESAs during the first three months of treatment.

Prevalence of Use and Cost of Biological Drugs for Cancer Treatment: A 5-Year Picture from Southern Italy

“…For most of the monoclonal antibodies and other non-biological targeted therapies approved for cancer treatment, the Italian Drug Agency implemented drug-specific monitoring registries as tools to monitor the appropriate use, effectiveness, and safety of those drugs that may facilitate post-marketing monitoring, although so far these registries have not been systematically used for scientific purposes [ 19 ]. On the other hand, an Italian network of claims databases has been successfully built for the post-marketing assessment of benefit–risk profiles of biologics/biosimilars in other therapeutic areas, thus demonstrating that these sources may also offer greater opportunities for exploring the clinical and economic impact of biological drugs and related biosimilars in oncology in the real-world setting [ 15 , 16 , 20 ].…”

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

“…The only RCT in patients with cancer 30 had a high likelihood of bias based on inadequate sample size, lack of an intent-to-treat analysis, and industry funding and authorship. The quality of the four included cohort studies of biosimilars [31][32][33][34] in patients with cancer was not formally assessed.…”

Management of Cancer-Associated Anemia With Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update

“…These results were confirmed in another Italian retrospective cohort study, which did not find a difference in HgB response among new users of either biosimilars or reference product of epoetin alfa or other ESAs in either CKD or patients with cancer during the first 3 months of treatment. 34 Clinical interpretation. Based on limited evidence, it seems that compared with the originator, biosimilars of epoetin alfa are safe and effective.…”