Current state of biologic pharmacovigilance in the European Union: improvements are needed

Introduction: Pharmacovigilance is essential to monitoring the safety profiles of authorized medicines. Compared with small-molecule drugs, biological drugs are more complex, more susceptible to structural variability due to manufacturing processes, and have the potential to induce immune-related reactions, underscoring the importance of safety monitoring for these products. Although highly similar to reference products, biosimilars are not expected to be structurally identical. For these reasons, proper reporting of potential adverse drug reactions (ADRs) using distinguishable names and batch numbers is essential for accurate tracing of all biological drugs. To address the need for robust pharmacovigilance, the European Parliament and Council of the European Union provided legislation regarding pharmacovigilance of biologics in 2010.

Areas covered: This narrative review examines the current state of pharmacovigilance for biologics in the European Union (EU) and discusses relevant information on pharmacovigilance of biosimilars, the current EU pharmacovigilance system, and areas that could be improved.

Expert opinion: Although steps have been taken to improve pharmacovigilance of biologics in the EU, several enhancements can still be made, including additional training for healthcare professionals on ADR reporting, the use of 2D barcodes that enhance traceability, and an open discussion of potentially missed opportunities in the pharmacovigilance of biosimilars.     

Current challenges and emerging drug delivery strategies for the treatment of psoriasis

ABSTRACT

Introduction: Psoriasis is a common skin disorder associated with physical, social, psychological and financial burden. Over the past two decades, advances in our understanding of pathogenesis and increased appreciation for the multifaceted burden of psoriasis has led to new treatment development and better patient outcomes. Yet, surveys demonstrate that many psoriasis patients are either undertreated or are dissatisfied with treatment. There are many barriers that need be overcome to optimize patient outcomes and satisfaction.

Areas covered: This review covers the current challenges associated with each major psoriasis treatment strategy (topical, phototherapy, oral medications and biologics). It also reviews the challenges associated with the psychosocial aspects of the disease and how they affect treatment outcomes. Patient adherence, inconvenience, high costs, and drug toxicities are all discussed. Then, we review the emerging drug delivery strategies in topical, oral, and biologic therapy.

Expert opinion: By outlining current treatment challenges and emerging drug delivery strategies, we hope to highlight the deficits in psoriasis treatment and strategies for how to overcome them. Regardless of disease severity, clinicians should use a patient-centered approach. In all cases, we need to balance patients’ psychosocial needs, treatment costs, convenience, and effectiveness with patients’ preferences in order to optimize treatment outcomes.     

Interchangeability of biosimilar and biological reference product: updated regulatory positions and pre- and post-marketing evidence

Introduction: Since 2006, biosimilars have been available in several countries worldwide, thus allowing for potential savings in pharmaceutical expenditure. However, there have been numerous debates about the interchangeability of biosimilars and reference products based on concerns of immunogenicity by switching between biological products, which may cause lack of effect and toxicity.

Areas covered: The authors provide the reader with an overview of the different positions of regulatory authorities on the interchangeability and automatic substitution of biosimilars and reference products. Presently, the FDA allows automatic substitution without prescriber intervention if the biosimilar is interchangeable with reference products, while the European Medicines Agency delegate to each single EU member state.

Expert opinion: Different approaches in defining interchangeability and automatic substitution call for harmonization to increase confidence of healthcare professionals and patients about the clinical impact of switching. Networks of electronic healthcare records and administrative databases, potentially linkable to clinical charts and registries may rapidly assess frequency and benefit-risk profile of different switching patterns in routine care at different levels, thus integrating and strengthening pre-marketing evidence.     

Biologics for treating axial spondyloarthritis

Introduction: Spondyloarthritis (SpA) encompasses a heterogeneous group of diseases sharing genetic, immunological, clinical and imaging features. Axial spondyloarthritis (axSpA) refers to a subgroup characterised predominately by inflammation of the axial skeleton with subsequent symptoms of chronic (often inflammatory) back pain and sacroiliitis. There is a strong association with the major histocompatibility complex (MHC) class I allele human leukocyte antigen (HLA) B27. In the last decade, there has been significant progress in earlier detection of the disease and the molecular mechanisms involved in its pathogenesis. The subsequent introduction of anti-tumour necrosis factor (TNF) has revolutionised the treatment of patients with axSpA.

Areas covered: In this article, we review the current biologic therapies for axSpA, the emergence of biosimilars, predictors of response, primary and secondary failure and new biologics on the horizon.

Expert opinion: There have been significant advances in the treatment of axSpA. Beyond the clear efficacy of anti-TNF inhibition, IL-17 offers an alternative therapeutic target and there is promise from inhibition of the IL-17/IL-23 pathway and small molecules, such as Janus kinase (JAK) inhibitors. Biosimilars have offered greater affordability and choice within this increasingly growing field of therapeutics.     

Monoclonal Antibody Biosimilars in Oncology: Critical Appraisal of Available Data on Switching

Purpose

With the introduction of biosimilars of anticancer monoclonal antibodies (mAbs) in oncology, physicians are potentially confronted with the question whether it is clinically adequate to switch patients who are clinically stable on treatment with the reference product to a newly available biosimilar (or vice versa/from 1 biosimilar to another). For a proper impact assessment of switching, robust, product-specific, and clinically relevant evidence should be required, ideally including data from appropriately designed switching studies. In this article, we assess the current body of switching data available for approved or proposed biosimilars of anticancer mAbs.

Treatment preferences of originator versus biosimilar drugs in Crohn’s disease; discrete choice experiment among gastroenterologists

Objective. To explore preferences of gastroenterologists for biosimilar drugs in Crohn’s disease. Material and methods. Discrete choice experiment was carried out involving 51 Hungarian gastroenterologists in May 2014. The following attributes were used to describe hypothetical choice sets: 1) type of the treatment (biosimilar/originator), 2) severity of disease, 3) availability of continuous medicine supply, 4) frequency of the efficacy check-ups. Multinomial logit model was used to differentiate between three attitude types: 1) always opting for the originator, 2) willing to consider biosimilar for biological-naïve patients only, 3) willing to consider biosimilar treatment for both types of patients. Conditional logit model was used to estimate the probabilities of choosing a given profile. Results. Men, senior consultants, working in inflammatory bowel disease center and treating more patients were more likely willing to consider biosimilar for biological-naïve patients only. Treatment type (originator/biosimilar) was the most important determinant of choice for patients already treated with biologicals, and the availability of continuous medicine supply in case of biological-naïve patients. The probabilities of choosing the biosimilar with all the benefits offered over the originator under current reimbursement conditions are 89% versus 11% for new patients, and 44% versus 56% for patients already treated with biological. Conclusions. For gastroenterologist, the continuous medical supply would be one of the major benefits of biosimilars. However, benefits offered in the scenarios do not compensate for the change from the originator to the biosimilar treatment of patients already treated with biologicals.     

Biosimilars in psoriasis: Clinical practice and regulatory perspectives in Latin America

Latin American countries view biosimilar agents as an effective approach to curtail health‐care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country‐specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health‐care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes.     

Oral rehydration therapy in diarrhea

Diarrhea in infants and children can lead rapidly to varying degrees of dehydration. In its worst form, dehydration must be treated by means of inpatient intravenous therapy. In most cases, however, oral rehydration therapy will suffice. Drs Swedberg and Steiner examine the composition of the fluids available for treatment and outline a treatment regimen. The information herein, “highly relevant to the developing world” according to one reviewer, also has practical import for industrialized areas.     

The challenge of biosimilars.

BACKGROUND: The purpose of this report was to review issues associated with the introduction of alternative versions of biosimilars used in the oncology setting. DESIGN: Data were obtained by searches of MEDLINE, PubMed, references from relevant English-language articles, and guidelines from the European Medicines Agency. RESULTS: When biosimilars are approved in EU, they will be considered 'comparable' to the reference product, but this does not ensure therapeutic equivalence. Inherent differences between biosimilars may produce dissimilarities in clinical efficacy, safety, and immunogenicity. Switching biosimilars should be considered a change in clinical management. Regulatory guidelines have been established for some biosimilar categories but, because of the limited clinical experience with biosimilars at approval, pharmacovigilance programs will be important to establish clinical databases. Guidelines also provide a mechanism for the extrapolation of clinical indications (approved indications for which the biosimilar has not been studied). This may be of concern where differences in biological activity can result in adverse outcomes or when safety is paramount (e.g. stem cell mobilization in healthy donors). These issues should be addressed in biosimilar labeling. CONCLUSIONS: Biosimilars should provide cost savings and greater accessibility to biopharmaceuticals. A thorough knowledge surrounding biosimilars will ensure the appropriate use of biopharmaceuticals.     

肿瘤专科医务人员对抗肿瘤生物类似药认知的调查分析

目的 调查肿瘤专科医务人员对抗肿瘤生物类似药的认知情况，为其临床合理使用提供保障。方法 采用问卷调查法，调查对象为我院40个科室的医师、护师和药师，使用自行设计的问卷对医务人员的一般资料、对生物类似药概念和特征的认知、抗肿瘤生物类似药临床使用的认知、抗肿瘤生物类似药相关药学服务的认知情况进行调查。结果 共发放问卷206份，有效回收201份，问卷有效回收率为97.57%。有79例（39.31%）知道生物类似药的定义，52例（25.87%）知道生物类似药的特征，53例（26.37%）知道抗肿瘤生物类似药适应证外推，其中内科知道生物类似药概念和特征的比例最高；有41例（20.40%）认为抗肿瘤生物类似药与参照药可以互换，41例（20.40%）认为抗肿瘤生物类似药之间可以互换，154例（76.62%）倾向于使用参照药，其原因主要是安全性（94例，46.77%）和有效性（113例，46.22%）；有193例（96.02%）认为制定“抗肿瘤药物超说明书用药管理制度”有必要，177例（88.06%）认为药师在抗肿瘤生物类似药临床应用中发挥了作用，并给出了开展抗肿瘤生物类似药相关药学服务的建议；有90例（44.78%）建议配置，137例（68.16%）建议处方审核，155例（77.11%）建议药学监护，120例（59.70%）建议处方点评，92例（45.77%）建议血药浓度监测。结论 我院肿瘤专科医务人员对抗肿瘤生物类似药的认知程度较低，药师应积极、准确地向医务人员传递抗肿瘤生物类似药相关信息，并提供全程化药学服务，以促进其安全、有效、经济、合理的使用。