The entry of adalimumab biosimilars in Europe : an overview of price evolution and country responses

Background: From October 2018, adalimumab biosimilars could enter the European market. However, some countries, such as the Netherlands, report high discounts for the originator product that influence biosimilar entry. Consequently, we researched European (list) prices and reimbursement status of originator adalimumab, before and after the entry of biosimilars, and discuss relevant policy measures. Methods: Survey distributed via email to national experts consisting of three parts: i) general financing/co-payment of medicines, ii) reimbursement status and prices of originator adalimumab and availability of biosimilars, and iii) policy measures related to the use of adalimumab. Results: In the 27 surveyed countries, originator adalimumab is reimbursed (fully or only partial, and sometimes with restrictions in use), except for Kosovo, where it is not marketed. Following adalimumab biosimilars, a few countries have made changes to the reimbursement status/level or setting where adalimumab is available. Overall, a decrease in list prices of originator adalimumab was seen after loss of exclusivity rights. Some countries (Bulgaria, Germany, Greece, Italy, Latvia, the Netherlands and Romania) reported that list prices have not changed up to May 2019, although confidential discounts may exist. Adalimumab biosimilars were available in 23 of the 27 surveyed countries. Countries adopted various approaches to leverage competition from the use of (biosimilar) adalimumab. In some countries, a strategy was implemented even before patent expiry (Scotland), while others did not report specific measures. Conclusion: This study documented how European countries responded differently to patent expiry of originator adalimumab and biosimilar market entry, with implications for pricing and reimbursement

The impact of policy interventions to promote the uptake of biosimilar medicines in Belgium:a nationwide interrupted time series analysis

Background: The Belgian government has taken several measures to increase the uptake of biosimilars in past years. However, no formal evaluation of the impact of these measures has been made yet. This study aimed to investigate the impact of the implemented measures on biosimilar uptake. Methods: An interrupted time series analysis was performed using an autoregressive integrated moving average (ARIMA) model with the Box-Jenkins method. All data were expressed as defined daily doses (DDD) per month/quarter and obtained from the Belgian National Institute for Health and Disability Insurance (NIHDI). Three molecules were included in the analysis: etanercept (ambulatory), filgrastim (hospital), and epoetin (hospital). A significance level of 5% was used for all analyses. Results: In the ambulatory care, the effect of a financial prescriber incentive of 2019 was investigated. After this intervention, 44.504 (95% CI −61.61 to −14.812; P < 0.001) fewer etanercept biosimilar DDDs were dispensed monthly than expected in the absence of the intervention. Two interventions were modelled for biosimilars in the hospital setting. The first intervention of 2016 includes prescription targets for biosimilars and monitoring of hospitals on adequate tendering. The second intervention involves an information campaign on biosimilars. After the first intervention, a small decrease in quarterly epoetin biosimilar uptake of 449.820 DDD (95% CI −880.113 to −19.527; P = 0.05) was observed. The second intervention led to a larger increase in quarterly epoetin biosimilar uptake of 2733.692 DDD (95% CI 1648.648–3818.736; P < 0.001). For filgrastim, 1809.833 DDD (95% CI 1354.797–2264.869; P < 0.001) more biosimilars were dispensed immediately after the first intervention and 151.639 DDD (95% CI −203.128 to −100.150; P < 0.001) fewer biosimilars each quarter after the first intervention. An immediate and sustained increase of 700.932 DDD (95% CI 180.536–1221.328; P = 0.016) in quarterly biosimilar volume was observed after the second intervention. All other parameter estimates were not statistically significant. Conclusions: The results of this study suggest that the impact of past policy interventions to increase the uptake of biosimilars has been variable and limited. A holistic policy framework is required to develop a competitive and sustainable off-patent biologicals market in Belgium.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Adoption of biosimilar infliximab for rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel diseases in the EU5: A budget impact analysis using a Delphi panel

Introduction: Introducing biosimilar infliximab for the treatment in rheumatology (rheumatoid arthritis and ankylosing spondylitis) and inflammatory bowel disease (Crohn's disease and ulcerative colitis) may reduce treatment costs associated with biologics. This study aimed to investigate the budget impact of adopting biosimilar infliximab in five European countries, considering that the budget impact includes the adoption of biosimilar infliximab and the availability of biologic alternatives such as vedolizumab, biosimilar etanercept, biosimilar rituximab, and other relevant factors. Methods: An existing budget impact model was adapted to forecast the budget impact in the UK, Germany, France, Spain, and Italy. Epidemiological parameters were derived from published literature reviewed in July 2015. Current market shares of biologics were derived from Therapy Watch (2012/2013 data). Respondents in a Delphi panel, conducted in 2015 and consisting of several leading rheumatologists and gastroenterologists from different nationalities, were asked to forecast uptake of biosimilar infliximab and estimate the proportion of patients eligible for a particular type of biological treatment, including biosimilar infliximab. Scenario analyses assessed the influence of various factors, including price reductions, on the budget. Results: Uptake of biosimilar infliximab was particularly expected for naïve patients; switching patients that already received other biologics was not expected much. Market shares after 5 years of biosimilar infliximab were ~2% in rheumatology in all five countries and in gastroenterology ranged from 4% in France to over 30% in Italy. Except for France, budgets were expected to decrease for rheumatologic diseases. For gastroenterology, budgets were expected to decrease in Spain and Italy. Budgets were expected to increase substantially in the UK and Germany, due to the introduction of vedolizumab in the studied period. In France, budget was expected to slightly increase for ankylosing spondylitis, Crohn's Disease, and ulcerative collitis. Savings in budget were expected in all countries, for all diseases, when larger price discounts on biosimilar infliximab were used. Discussion and Conclusion: This study has shown that only when price reductions are large en

Intoxication with therapeutic and illicit drug substances and hospital admission to a Dutch university hospital

BACKGROUND: This article describes the retrospective analysis of the patients who presented with a drug-related intoxication to the emergency department of the Erasmus Medical Centre in 2000. METHODS: Data were collected from the emergency department's electronic database and the medical charts of the patients. RESULTS: A total of 243 patients were seen with a drug-related intoxication caused by ingestion of one or more medical substances, drugs of abuse (DOA) or combinations with alcohol. Mono-intoxication occurred in 58% of the patients, predominantly caused by DOA (56 patients), analgesics (17 patients) or benzodiazepines (14 patients). Benzodiazepines (55 patients), analgesics (42 patients), alcohol (42 patients), DOA (40 patients) and antidepressants (23 patients) were predominant in combined intoxications. More than half of the patients (142) were discharged after being treated in the emergency department and 80 patients were admitted to the wards. Eighteen patients were admitted elsewhere and three patients were lost to follow-up. Eve

Physicians' acceptance of pharmacists' interventions in daily hospital practice

Background The physicians' acceptance rate of pharmacists' interventions to improve pharmacotherapy can vary depending on the setting. The acceptance rate of interventions proposed by pharmacists located in the hospital pharmacy over the telephone and factors associated with acceptance are largely unknown. Objective To determine the physicians' acceptance rate of pharmacists' interventions proposed over the telephone in daily hospital practice and to identify factors associated with acceptance. Setting A retrospective case-control study was performed concerning adult patients admitted to a university hospital in the Netherlands. Method Pharmacists' interventions, based on alerts for drug-drug interactions and drug dosing in patients with renal impairment, recorded between January 2012 and June 2013 that were communicated over the telephone were included. Factors associated with physicians' acceptance were identified with the use of a mixed-effects logistic model. Main outcome measure The primary outcome was the proportion of accepted interventions. Results A total of 841 interventions were included. Physicians accepted 599 interventions, resulting in an acceptance rate of 71.2%. The mixed-effects logistic model showed that acceptance was significantly associated with the number of prescribed drugs (16 to ≤ 20 drugs ORadj 1.88; 95% CI 1.05-3.35, > 20 drugs ORadj 2.90; 95% CI 1.41-5.96, compared to ≤ 10 drugs) and the severity of the drug-related problem (problem without potential harm ORadj 6.36; 95% CI 1.89-21.38; problem with potential harm OR 6.78; 95% CI 2.09-21.99, compared to clinically irrelevant problems), and inversely associated with continuation of pre-admission treatment (ORadj 0.55; 95% CI 0.35-0.87). Conclusion Over the study period, the majority of pharmacists' interventions proposed over the telephone were accepted by physicians. The probability for acceptance increased for patients with an increasing number of medication orders, for clinically relevant problems and for problems related to treatment initiated during admission

Learnings from Regional Market Dynamics of Originator and Biosimilar Infliximab and Etanercept in Germany

Drug budget and prescription control measures are implemented regionally in Germany, meaning that the uptake of pharmaceuticals, including biosimilars, can vary by region. We examine regional market dynamics of tumor necrosis factor alpha (TNFα) inhibitor originators and biosimilars in Germany and studied the influence of biosimilar policies on these dynamics. This study is based on: (1) a literature review in which German biosimilar policies are identified, (2) the analysis of dispensing data (2010–2018) for the class of TNFα inhibitors, and (3) ten semi-structured interviews investigating prescribers’ and insurers’ views on factors potentially influencing biosimilar uptake. The analysis of biosimilar market shares of infliximab and etanercept revealed wide variation

Reporting of quality attributes in scientific publications presenting biosimilarity assessments of (intended) biosimilars: a systematic literature review

Publisher's version (útgefin grein)Last years, more than 46 unique biosimilars were approved by EMA and/or US-FDA following patent expiration of reference products. Biosimilars are not identical like generics, but highly similar versions where demonstrating biosimilarity of quality attributes (QAs) to a reference product is the basis of development and regulatory approval. Information on QAs assessed to establish biosimilarity may not always be publicly available, although this information is imperative to understand better the science behind biosimilars approval. This study aims to identify QA types reported in publications presenting biosimilarity assessments of (intended) biosimilars over time. English full-text publications presenting biosimilarity assessments of QAs for (intended) biosimilars between 2000 and 2019 identified from PubMed and EMBASE. Publication characteristics and QAs classified into: structural (physicochemical properties, primary structure, higher-order structures (HOSs), post-translational modifications (PTMs), and purity and impurities) and functional (biological and immunochemical activities) were extracted from publications. Seventy-nine publications were identified (79% open-access, 75% industry-sponsored, 62% including unapproved biosimilars, and 66% involving antibodies). Reporting frequencies varied for QA types: biological activity (94%), physicochemical properties (81%), PTMs (79%), primary structure (77%) purity and impurities (73%), HOSs (58%), and immunochemical activity (41%). The number of publications increased from 6 (7%) during 2009–2011 to 62 (79%) during 2015–2019. Eighteen (28%) publications reported all QA types relevant to an active-biological-substance. Reporting of most QA types increased over time that most evidenced by immunochemical activity (from 0% to 47%) which occured after EMA monoclonal antibody (mAbs) guidline in 2012 and more publications on mAbs later on when compared to earlier period. Biosimilarity assessments of QAs have been published in peer-reviewed publications for about 60% of approved biosimilars. Publishing biosimilarity assessments and reporting QAs over time appears to be affected by regulatory actions that occurred in 2012-2015, including regulatory approval and development of regulatory guidelines for biosimilars. Availability of a complete, publicly accessible and unbiased biosimilarity assessment of QAs, as part of a trusted and transparent regulatory process, will contribute to increased confidence and acceptance of biosimilars in clinical practice.This study was funded by the Saudi Food and Drug Authority(SFDA) through the Saudi Arabian cultural mission (SACM), the Hague,Netherlands as a part of a Doctor of Philosophy (Ph.D.) project for AMA.The SFDA has no role in any aspect of the study, including the pre-paration, review, the approval of the manuscript, nor the decision topublish the manuscript.Peer Reviewe