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.     

2017年安徽省某三甲医院细菌耐药性监测

目的 了解铜陵市人民医院2017年临床分离细菌对抗菌药物的耐药状况。方法 对2017年1-12月临床分离菌采用纸片扩散法(KB)进行药敏试验，按CLSI 2017年版标准判读药敏试验结果，采用WHONET 5.6软件进行数据分析。结果 临床分离细菌共3436株，其中革兰阳性菌719株，占20.9%；革兰阴性菌2717株，占79.1%。耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为23.8%和72.3%，耐甲氧西林株对β-内酰胺类抗生素和其他测试抗菌药物的耐药率显著高于甲氧西林敏感株，未发现对万古霉素和替考拉宁耐药的葡萄球菌。粪肠球菌对青霉素、氨苄西林和呋喃妥因的耐药率较低，屎肠球菌对氯霉素的耐药率较低，5.3%屎肠球菌对万古霉素耐药。大肠埃希菌、克雷伯菌属(肺炎克雷伯菌和产酸克雷伯菌)和奇异变形菌中ESBLs的检出率分别为41.4%、50.7%和19.4%。肠杆菌科细菌中克雷伯菌属和沙雷菌属对碳青霉烯类抗生素耐药率较高，分别为37.5%和36.0%，其他菌属的耐药率低于3%。鲍曼不动杆菌对亚胺培南和美罗培南的耐药率分别80.3%和79.1%；铜绿假单胞菌对亚胺培南和美罗培南的耐药率分别为29.7%和28.4%。肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌中广泛耐药株的检出率分别为31.3%(171/546)、0.6%(3/508)和0.7%(3/416)。结论 本院革兰阴性菌呈增多趋势，尤其广泛耐药的肺炎克雷伯菌应引起高度关注，做好细菌耐药性监测，加强临床抗菌药物的合理使用和医院感染控制。     

The theory of Rational Addiction

The Theory of Rational Addictions, by Gary Becker & Kevin Murphy (1988), was a rational choice model that became a standard tool for economists modeling addictive behavior. The approach differs from other theories of addiction by modeling addictive behavior as the gradual implementation of a rational, forward‐looking plan, where consumption at any point in time is partly motivated by the immediate payoff of consumption and partly by the effects this consumption has on the individual in the future. This makes addictive behavior a subset of rational behavior, requiring no more specific government policies or attention than any other consumption choice. Later work by economists extended the theory in different ways, allowing it to match an increasing number of consumption patterns, and searched for ways to test the forward‐looking assumption in different types of market data. While the work was successful as a contribution to rational choice theory, with possible statistical applications, there are several reasons to dismiss its usefulness as an explanation of real‐world addictive behavior and its ability to assess the welfare effects of addictions.     

Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From the KEYNOTE-028 and KEYNOTE-158 Studies

IntroductionPembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC.MethodsEligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)–positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review.ResultsEighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5–48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4–29.4); two patients had complete response (one with a PD-L1–positive tumor), and 14 patients had partial response (13 with PD-L1–positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events.ConclusionsPembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.     

干扰素在恶性淋巴瘤自体移植后早期干预的应用

目的:观察非霍奇金淋巴瘤（non-Hodgkin's lymphoma，NHL）患者自体造血干细胞移植（autologous hematopoietic stem cell transplantation，ASCT）术后应用重组人α-2b干扰素（α-2b IFN）进行早期干预治疗的临床疗效。方法:选取18例行ASCT的NHL患者为研究对象，移植前疾病评估均未达到完全缓解（complete remission，CR），试验组血象恢复后给予IFN 3 000 000 U次/隔日干预治疗，3个月后停用；对照组未行干扰素干预治疗，分析总体疗效及两组对比的生存情况。结果:随访中位时间为34（10~50）个月，患者中位生存时间为37（31~45）个月，3年总体无进展生存（progressive free survival，PFS）、总生存（overall survivial，OS）分别为54.7%、66.8%。ASCT后试验组1年内无疾病复发，2年内复发率为12.5%；对照组1年内复发率为20%，2年内复发率为30%。结论:NHL患者在ASCT后给予重组人α-2b IFN早期干预治疗，患者耐受性好，可能降低移植后早期复发率。