Seizure freedom as an outcome in epilepsy treatment clinical trials

Seizure freedom is recognized as the goal of epilepsy treatment by patients, families, and in treatment guidelines and is associated with notably improved quality of life. However, many studies of epilepsy treatments (including antiseizure medications/antiepileptic drugs, neurostimulation, and dietary therapies) fail to report data on seizure freedom. Even among studies that include this outcome, methods for defining and analyzing seizure freedom vary considerably. Thus, the available data are often difficult to interpret and comparisons between studies are particularly challenging. Although these issues had been identified over a decade ago, there remains a lack of clarity and standardized methods used in analyzing and reporting seizure freedom outcomes in studies of epilepsy treatments. In addition, it remains unclear whether short-term seizure freedom outcomes from pivotal clinical trials are predictive of longer-term seizure freedom outcomes for patients with treatment-refractory epilepsy. Ultimately, the limitations of the available data lead to the potential for misinterpretation and misunderstanding of seizure freedom outcomes associated with the spectrum of available treatments when examining treatment options for patients. Clearly defined outcome analyses of seizure freedom attainment and duration are essential in future clinical studies of treatment for seizures to guide treatment selection and modification for patients.     

How to implement guidelines and models of care

In subjects older than 50 years, the presence of clinical risk factors (CRFs) for fractures or a recent fracture is the cornerstone for case finding. In patients who are clinically at high short- and long-term risk of fractures (those with a recent clinical fracture or with multiple CRFs), further assessment with bone mineral density (BMD) measurement using dual-energy absorptiometry (DXA), imaging of the spine, fall risk evaluation and laboratory examination contributes to treatment decisions according to the height and modifiability of fracture risk. Treatment is available with anti-resorptive and anabolic drugs, and from the start of treatment a lifelong strategy is needed to decide about continuous, intermittent, and sequential therapy. Implementation of guidelines requires further initiatives for improving case finding, public awareness about osteoporosis and national policies on reimbursement of assessment and therapy.     

Opioid use frequency in early axial spondyloarthritis in Finland – a pharmacoepidemic register study

ObjectivesTo evaluate opioid use among incident axial spondyloarthritis (axSpA) patients compared to general population.MethodsFrom the national register, we identified all adult patients with axSpA (ICD-10 codes M45-46), who between 2010 and 2014 (index date, ID) were for the first time granted special reimbursement for any disease-modifying antirheumatic drugs (DMARDs). Three matched population controls were identified for each patient. Drug purchases were evaluated between 2009–2015, and opioid use was analyzed for one year before and after the ID. The Defined Daily Dose (DDD) was used as a tool to assess the opioid consumption before and after the biological (b) DMARD initiation.ResultsWe identified 3577 axSpA patients and 10,573 controls. Of these patients, 97.2% started a conventional synthetic (cs) DMARD during a year after ID and 23.4% switched later to a self-injected bDMARD between the ID and 31 Dec 2015 (median follow-up 3.4 years). Opioids were purchased at least once by 29.8% and 21.7% of the patients in the years before and after the ID, respectively, compared to 8.1% and 7.8% of the controls. The proportion of opioid-using patients was greatest during the last quarter before the ID [relative risk (RR) 4.72 (95% CI 4.14 to 5.39)] compared to controls, and it remained higher [RR 2.84 (2.59 to 3.11)] also after the start of csDMARDs. DDD of opioid consumption decreased from 7.7 to 1.6/1000 inhabitants after bDMARD initiation.ConclusionConsiderably more axSpA patients than population controls used opioids. The opioid consumption by dose decreased clearly after bDMARD initiation.     

Modern immunosuppression

Organ transplantation provides both life-saving and life-enhancing function for patients suffering from end-stage organ failure. Transplantation has only been possible due to the advances in immunosuppression. The viability of a transplanted organ depends on modulation of the human immune system to avoid rejection in response to foreign antigens. Modern immunosuppression consists of multi-modal therapy (chemical drugs and biological agents) acting on different parts of the immune response. Three phases of immunosuppression can be recognized: induction, maintenance and withdrawal. All patients must continue to take at least some immunosuppression to prevent rejection. Developments in immunosuppressant regimens have dramatically improved transplant success rates and experience over the years has helped to understand the side-effects and long-term complications of immunosuppression. Research continues to identify both novel compounds and ways of optimizing the use of current drugs.     

Volatile molecules for COVID-19: A possible pharmacological strategy?

COVID-19 is a novel coronavirus disease with a higher incidence of bilateral pneumonia and pleural effusion. The high pulmonary tropism and contagiousness of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have stimulated new approaches to combat its widespread diffusion. In developing new pharmacological strategies, the chemical characteristic of volatility can add therapeutic value to the hypothetical drug candidate. Volatile molecules are characterized by a high vapor pressure and are consequently easily exhaled by the lungs after ingestion. This feature could be exploited from a pharmacological point of view, reaching the site of action in an uncommon way but allowing for drug delivery. In this way, a hypothetical molecule for COVID-19 should have a balance between its lung exhalation characteristics and both antiviral and anti-inflammatory pharmacological action. Here, the feasibility, advantages, and disadvantages of a therapy based on oral administration of possible volatile drugs for COVID-19 will be discussed. Both aerosolized antiviral therapy and oral intake of volatile molecules are briefly reviewed, and an evaluation of 1,8-cineole is provided in view of a possible clinical use and also for asymptomatic COVID-19.     

抗体药物的药学监护

近年来，抗体药物在自身免疫性疾病及肿瘤治疗领域表现非凡，成为当前药物研发的热点之一。与传统小分子药物相比，抗体药物具有结构功能复杂、药动学特殊及免疫原性等特点，使其对临床合理用药提出了新的挑战。本文以抗体药物的结构和药动学特征为基础，从抗体药物的有效性、安全性、经济性、免疫原性和药物警戒五个方面，阐述如何将药学监护手段应用于抗体药物，旨在为抗体药物的临床合理使用提供参考。