Search

Background We studied the comparative effectiveness of biosimilar filgrastim vs original filgrastim in patients with chemotherapy-induced neutropenia. Patients and methods This multicenter, observational study was conducted at 14 centers. The study included 337 patients experiencing neutropenia under chemotherapy. Patients were given either filgrastim 30 MIU or 48 MIU (Neupogen®) or biosimilar filgrastim 30 MIU (Leucostim®). Data regarding age, chemotherapeutic agents used, number of chemotherapy courses, previous diagnosis of neutropenia, neutrophil count of patients after treatment, medications used for the treatment of neutropenia, and duration of neutropenia were collected. Time to absolute neutrophil count (ANC) recovery was the primary efficacy measure. Results Ambulatory and hospitalized patients comprised 11.3% and 45.1% of the enrolled patients, respectively, and a previous diagnosis of neutropenia was reported in 49.3% of the patients, as well. Neutropenia occurred in 13.7% (n=41), 45.5% (n=136), 27.4% (n=82), 11.4% (n=34), and 2.0% (n=6) of the patients during the first, second, third, fourth, and fifth cycles of chemotherapy, respectively. While the mean neutrophil count was 0.53±0.48 before treatment, a significant increase to 2.44±0.66 was observed after treatment (p=0.0001). While 90.3% of patients had a neutrophil count, Video abstract

Background Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease. Materials and methods This was a prospective single-center observational study in patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey–Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study. Results A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey–Bradshaw score showed a significant change at 12 months (P=0.007) but no significant change was observed in median CRP at this timepoint (P=0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P=0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients. Conclusion Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months.

The use of biosimilar drugs for multiple sclerosis (MS) has become widespread in Latin America, with the goal of reducing costs of treatments, promoting the sustainability of healthcare systems, and improving patient access to these therapies. There is currently a need to define and comply with requirements to guarantee the efficacy, safety, and quality of these drugs. Thus, the objective of the present study was to compile up-to-date information from each Latin American country assessed on (a) approval of biosimilar drugs by regulatory agencies; (b) use of biosimilar drugs, pharmacovigilance plans, risk management; and (c) update in the knowledge on different molecules. To do so, a group of experts from Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Panama, Peru, Uruguay, and Venezuela met to discuss the current situation regarding good practices and risks associated with the use of biosimilar drugs in their respective countries. Regulation, risk management plans, and pharmacovigilance in the whole continent must guide the strategies on the commercialization and access of biosimilar drugs and copies of complex molecules. Current regulations must be implemented for the registration of biosimilar drug products and complex molecules. It is paramount to ensure that new products follow the best quality standards at all stages beyond being safe and efficient. Uncontrolled interchangeability between original biological and biosimilar should be avoided. Latin America requires the implementation and full use of strong pharmacovigilance programs. National and multinational clinical studies are required to demonstrate the similarity in safety, efficacy, and immunogenicity profiles of complex molecules, as well as biological and biosimilar products. Plain Language Summary Plain language summary available for this article.

Background Biosimilars could be a promising option to help decrease healthcare costs and expand access to treatment. There is no previous evidence of a global bibliometric analysis on biosimilars. Therefore, we aimed to assess the quantity and quality of worldwide biosimilars research. Methods We performed a bibliometric analysis using documents about biosimilars published until December 2016 in journals indexed in Scopus. We extracted the annual research, languages, countries, journals, authors, institutions, citation frequency, and the metrics of journals. The data were quantitatively and qualitatively analyzed using Microsoft Excel 2013. Additional information about authors' participation was obtained using the R-package Bibliometrix. Publication activity was adjusted for the countries by population size. Also, author co-citation analysis and a term co-occurrence analysis with the terms included in the title and abstract of publications was presented as network visualization maps using VOSviewer. Results A total of 2330 biosimilar-related documents identified in the Scopus database, most of them were articles (1452; 62.32%). The number of documents published had an exponential increased between 2004 and 2016 (p

Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient.

BACKGROUND Infliximab original has changed the natural history of inflammatory bowel diseases (IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited. AIM To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD. METHODS An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar (CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar. RESULTS 98 patients (CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar (P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar (P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar. CONCLUSION The overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.

Background CT-P13 is a biosimilar of Remicade®, an agent approved in some countries for use in inflammatory bowel disease (IBD). Controlled clinical trials have demonstrated the efficacy and safety of CT-P13 in rheumatic diseases, but not in IBD. Aims To assess the effectiveness and safety of CT-P13 in IBD patients in real clinical practice. Methods This is a prospective observational study in patients with moderate to severe Crohn’s disease or ulcerative colitis treated with CT-P13. The study was performed in one single center. Patients included were naive or switched to anti-TNF treatment from the reference infliximab (Remicade®) to CT-P13. Efficacy and safety were assessed in naive and switched patients who were in remission at the time of the switch at months 3 and 6 of therapy. Results 87.5 and 83.9% of switched CD patients who were in remission at the time of the switch continued in remission, and 66.7 and 50% of naive CD patients reached remission, at months 3 and 6. In UC switched cases, 92 and 91.3% of patients in remission at the time of the switch continued in remission, at 3 and 6 months. In naive UC patients, the remission rates were 44.4 and 66.7%, at months 3 and 6. Adverse events occurred in 7.5% of patients during 6 months of study. Conclusions CT-P13 was efficacious and well tolerated in patients with CD or UC.

Background: Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease. Materials and methods: This was a prospective single-center observational study in patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey–Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study. Results: A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey–Bradshaw score showed a significant change at 12 months (P =0.007) but no significant change was observed in median CRP at this timepoint (P= 0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P =0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients. Conclusion: Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months.

OBJECTIVES: Erythropoietin has been widely adapted into clinical practice in orthopedic surgery to prevent anemia and ultimately lower the use of allogeneic blood transfusions. Its safety and efficacy has been shown in various randomized clinical trials. Questions regarding the cost-effectiveness of this treatment, however, have yet to be answered conclusively. Notably, current indication guidelines are based on preoperative hemoglobin levels, but do not differentiate between total hip arthroplasty (THA) and total knee arthroplasty (TKA). This literature review aims at analyzing the cost-effectiveness of preoperative erythropoietin as blood sparing measure in patients undergoing elective orthopedic surgery, specifically THA and TKA. Additionally, patient inclusion criteria are analyzed in order to identify the potentially most cost-effective patient subgroups, e.g. based on preoperative hemoglobin levels, primary or revisional surgery and THA versus TKA. METHODS: Systematic literature review. RESULTS: A MEDLINE database search and subsequent exclusion of irrelevant or inaccessible papers resulted in the inclusion of 8 research articles that at least partially performed a cost-effectiveness or cost-benefit analysis of erythropoietin in orthopedic surgery. Four of the studies concluded erythropoietin is not cost-effective, three studies were not able to draw a conclusion based on their data, and one study found erythropoietin cost-effective. CONCLUSIONS: We found that studies were difficult to compare, with inclusion criteria and comparators varying among studies. Notably, most economic evaluations were substantially lacking depth and did not comply with common guidelines for pharmacoeconomic research. Although some articles found erythropoietin generally not cost-effective, their data did suggest otherwise within certain patient subgroups. Patients with lower preoperative hemoglobin levels, primary surgery and THA benefitted the most from erythropoietin. Additionally, most studies seemed to overestimate treatment costs, using outdated prices or neglecting competitively priced biosimilars. Therefore, a more differentiated approach is required to elucidate the costeffectiveness of erythropoietin in orthopedic surgery, discriminating between total hip and knee arthroplasty.

Treatment issues of multiple sclerosis (MS) in Latin America (LA) have recently been addressed. Some particular features of the health systems, patients and medical providers are scarcely described. Moreover, LA patients are rarely included in clinical trials; therefore, data collected from key opinion leaders (KOL) from LA, although unofficial, remain as a needed source of information. In a stand-alone gathering, organized by a pharmaceutical company, in Brazil 2014, according to ‘Compliance Program Guidance for Pharmaceutical Manufacturers', we surveyed the opinion of KOL in MS from 6 LA countries. Neurologists were selected and invited to the gathering based on their academic, research and clinical experience with MS patients and involvement as participants and speakers on regional events. A voluntary anonymous electronic survey was proposed in an interactive lecture (table 1). Important definitions were given previously without further discussion on the topic to avoid biased answers.

Biotherapeutic products (BPs) have revolutionized medicine, changing the way we treat several pathologies such as autoimmune diseases and cancer, among others. Herein, we present an overview of similar BPs (SBPs), also called biosimilars, including the manufacturing process and regulatory aspects involved. The objective of developing an SBP is to manufacture a molecule that is highly similar to a reference BP by conducting a comparability exercise (CE) that can demonstrate similar safety and efficacy. This CE consists of quality, as well as nonclinical and clinical evaluation. A case-by-case analysis approach guided by scientific and objective standards must be the foundation for the SBP approval process. The establishment of a balance between a comprehensive CE for SBPs and their reference BPs, and the design of costeffective strategies to provide better access to BPs, should be the key goal for national regulatory authorities.

Background: The nature of adverse events (AEs) observed post authorization for biopharmaceuticals differs from chemically synthesized, small molecules. It remains unclear if this observed difference can be attributed to differences in authorized indications between the groups. Objectives: To investigate if the nature of AEs identified post-authorization for biopharmaceuticals differs from AEs of small molecules within the same Anatomical Therapeutic Chemical (ATC) class. Methods: All biopharmaceutical and small molecule products centrally approved in the European Union classified in the ATC class of “antineoplastic and immunomodulating agents” (“L”) were included. Generics and biosimilars were excluded. All safety related changes to the Summary of Product Characteristics during 2004- 2011 were analyzed; individual AEs were identified and coded according to MedDRA 14.1. Proportions of AEs within therapeutic subgroups were compared and tested using two-sided Fisher's exact tests. Results: A total of 747 AEs were identified; 361 for biopharmaceuticals and 386 for small molecules. For biopharmaceuticals, 171 (47.4%) AEs were reported for immunosuppressants, 128 (35.5%) for immunostimulants and 62 (17.2%) for antineoplastic agents. For small molecules the most AEs, 288 (74.6%), were reported for antineoplastic agents, 92 (23.8%) for immunosuppressants and 6 (1.6%) for endocrine therapies. Within the ATC subgroup of immunosuppressants, neoplasms, 20% vs. 2% (p

OBJECTIVES: Erythropoietin has been widely adapted into clinical practice in orthopedic surgery to prevent anemia and ultimately lower the use of allogeneic blood transfusions. Its safety and efficacy has been shown in various randomized clinical trials. Questions regarding the cost-effectiveness of this treatment, however, have yet to be answered conclusively. Notably, current indication guidelines are based on preoperative hemoglobin levels, but do not differentiate between total hip arthroplasty (THA) and total knee arthroplasty (TKA). This literature review aims at analyzing the cost-effectiveness of preoperative erythropoietin as blood sparing measure in patients undergoing elective orthopedic surgery, specifically THA and TKA. Additionally, patient inclusion criteria are analyzed in order to identify the potentially most cost-effective patient subgroups, e.g. based on preoperative hemoglobin levels, primary or revisional surgery and THA versus TKA. METHODS: Systematic literature review. RESULTS: A MEDLINE database search and subsequent exclusion of irrelevant or inaccessible papers resulted in the inclusion of 8 research articles that at least partially performed a cost-effectiveness or cost-benefit analysis of erythropoietin in orthopedic surgery. Four of the studies concluded erythropoietin is not cost-effective, three studies were not able to draw a conclusion based on their data, and one study found erythropoietin cost-effective. CONCLUSIONS: We found that studies were difficult to compare, with inclusion criteria and comparators varying among studies. Notably, most economic evaluations were substantially lacking depth and did not comply with common guidelines for pharmacoeconomic research. Although some articles found erythropoietin generally not cost-effective, their data did suggest otherwise within certain patient subgroups. Patients with lower preoperative hemoglobin levels, primary surgery and THA benefitted the most from erythropoietin. Additionally, most studies seemed to overestimate treatment costs, using outdated prices or neglecting competitively priced biosimilars. Therefore, a more differentiated approach is required to elucidate the costeffectiveness of erythropoietin in orthopedic surgery, discriminating between total hip and knee arthroplasty.

OBJECTIVES: Erythropoietin has been widely adapted into clinical practice in orthopedic surgery to prevent anemia and ultimately lower the use of allogeneic blood transfusions. Its safety and efficacy has been shown in various randomized clinical trials. Questions regarding the cost-effectiveness of this treatment, however, have yet to be answered conclusively. Notably, current indication guidelines are based on preoperative hemoglobin levels, but do not differentiate between total hip arthroplasty (THA) and total knee arthroplasty (TKA). This literature review aims at analyzing the cost-effectiveness of preoperative erythropoietin as blood sparing measure in patients undergoing elective orthopedic surgery, specifically THA and TKA. Additionally, patient inclusion criteria are analyzed in order to identify the potentially most cost-effective patient subgroups, e.g. based on preoperative hemoglobin levels, primary or revisional surgery and THA versus TKA. METHODS: Systematic literature review. RESULTS: A MEDLINE database search and subsequent exclusion of irrelevant or inaccessible papers resulted in the inclusion of 8 research articles that at least partially performed a cost-effectiveness or cost-benefit analysis of erythropoietin in orthopedic surgery. Four of the studies concluded erythropoietin is not cost-effective, three studies were not able to draw a conclusion based on their data, and one study found erythropoietin cost-effective. CONCLUSIONS: We found that studies were difficult to compare, with inclusion criteria and comparators varying among studies. Notably, most economic evaluations were substantially lacking depth and did not comply with common guidelines for pharmacoeconomic research. Although some articles found erythropoietin generally not cost-effective, their data did suggest otherwise within certain patient subgroups. Patients with lower preoperative hemoglobin levels, primary surgery and THA benefitted the most from erythropoietin. Additionally, most studies seemed to overestimate treatment costs, using outdated prices or neglecting competitively priced biosimilars. Therefore, a more differentiated approach is required to elucidate the costeffectiveness of erythropoietin in orthopedic surgery, discriminating between total hip and knee arthroplasty.