Evaluating Benefit-risk Decision-making in Spinal Muscular Atrophy: A First-ever Study to Assess Risk Tolerance in the SMA Patient Community

PurposePatients’ perceptions of benefit–risk are essential to informing the regulatory process and the context in which potential therapies are evaluated. To bring this critical information to regulators, Cure SMA launched a first-ever Benefit-Risk Survey for spinal muscular atrophy (SMA) to characterize decision-making and benefit–risk trade-offs in SMA associated with a potential therapy. We hypothesized that risk tolerance would be correlated with SMA type/severity and disease progression. This article presents the results of a benefit–risk survey to enhance understanding of how patients with SMA and caregivers evaluate specific benefits and risks associated with potential therapies.MethodsAffected adults, representing all SMA types (I–IV) within the Cure SMA database, and caregivers of affected individuals of all ages/types were invited via e-mail to participate. Best–worst scaling (BWS) was used to assess participants’ priorities on benefit–risk trade-offs, as it provides higher discrimination and importance scaling among tested attributes. Twelve potentially clinically meaningful treatment benefits and 11 potential risks (ranging in severity and immediacy) were tested. Multiple factors were correlated with individual responses, including: SMA type/disease severity, stage of disease, respondent type, sex, and quality of life/level of independence (current and expected). Survey respondents were also evaluated for "risk-taking attitudes."FindingsA total of 298 responses were evaluated (28% affected adults and 72% caregivers, mostly parents). Most respondents were diagnosed >5 years ago (67.3%), with 22.1% SMA type I, 45.6% SMA type II, and 27.9% SMA type III. No strong correlation was found between risk tolerance and SMA type, stage of disease progression, respondent type, sex, quality of life assessment, or rated levels of independence. Irrespective of SMA type, respondents consistently rated the following risks, associated with a potential treatment, as "least tolerable": life-threatening allergic reactions; 1 in 1000 risk of life-threatening side effects leading to possible organ failure; or worsening quality of life. Furthermore, all SMA type respondents rated these risks as "most tolerable": invasive mode of treatment administration (including need for general anesthesia); side effect of dizziness; and other common side effects such as nausea, vomiting, loss of appetite, headaches, back pain, or fatigue.ImplicationsWith the approval of the first SMA treatment, these findings offer a unique opportunity to assess and characterize baseline risk-tolerance in SMA against which to evaluate future SMA treatment options. Although differences had been expected in risk tolerance among respondents based on disease baseline and certain patient attributes, this was not observed. Survey results should inform future SMA drug development and benefit–risk assessments.     

Sustainability and switching of biologics for psoriasis and psoriatic arthritis at Fukuoka University Psoriasis Registry

Biologics are efficacious for treating psoriasis vulgaris (PsV) and psoriatic arthritis (PsA), but sometimes must be terminated or changed for various reasons including ineffectiveness or adverse events. To find the optimal choice of biologics for treating psoriasis, we analyzed the real‐world data on drug survival and the reason for terminating or switching biologics. Medical records from patients with PsV or PsA, who visited the Department of Dermatology, Fukuoka University Hospital from 2010 to 2017, were analyzed. Two hundred and eleven patients received biologics, and 147 patients (69.7%) were treated with only one biologic, while 64 patients (30.3%) were switched to different products. Frequently used biologics in PsV were ustekinumab (UST), infliximab and adalimumab when calculated by patient‐year. Tumor necrosis factor inhibitor (TNFi) use decreased while UST and interleukin (IL)‐17 inhibitors increased in newly introduced patients. UST showed the highest survival rate as a first‐line drug, but the advantage was lost in the second reagent's group. The major reasons for terminating/switching biologics were as follows: primary ineffectiveness (26.4%), secondary loss of efficacy (36.5%), patient's preference, including referral to nearby hospital, or stopped visiting (22.6%), side‐effects (7.7%), comorbidities (3.4%) and economic burden (2.4%). In PsA patients, TNFi are more frequently employed than in PsV patients, although switching to UST or IL‐17 inhibitors showed an increasing trend. Biologic reagents were changed mostly because of primary or secondary loss of efficacy, which affected drug survival. Further research is needed to find the optimal choice of biologics with larger samples at multiple facilities.     

胶质细胞源性神经营养因子干预视网膜色素变性给药方式的研究进展

视网膜色素变性（retinitis pigmentosa，RP）的治疗目前仍处于探索阶段。胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor，GDNF）是目前研究中重要的神经营养因子，但其传统给药方式生物利用度相对较低。近年来GDNF安全有效的给药方式成为研究热点，包括经病毒载体或非病毒载体的基因工程法释药技术、经聚合物释放系统释药技术、经细胞移植释药技术、小分子触发器诱导产生GDNF等。本文就GDNF干预RP的给药方式进行综述。     

Isolated Anisocoria as a Presenting Stroke Code Symptom is Unlikely to Result in Alteplase Administration

Background

Acute stroke codes may be activated for anisocoria, but how often these codes lead to a final stroke diagnosis or alteplase treatment is unknown. The purpose of this study was to assess the frequency of anisocoria in stroke codes that ultimately resulted in alteplase administration.

冰片对黄芪甲苷和三七总皂苷配伍有效成分在脑缺血/再灌注模型大鼠脑组织分布的影响

目的探讨冰片是否具有促进黄芪甲苷(AST IV)和三七总皂苷(PNS)配伍时主要有效成分透过大脑中动脉栓塞(MCAO)再灌注模型大鼠血脑屏障的作用。方法大鼠随机分为假手术组、模型组、冰片组、AST IV组、PNS组、AST IV+PNS组、冰片+AST IV+PNS组,制备MCAO再灌注大鼠模型,以液相色谱-质谱联用法(LC-MS/MS)测定大鼠患侧与健侧大脑皮层、小脑中AST IV和PNS有效成分(人参皂苷Rg1、Rb1和三七皂苷R1)的含量。结果 AST IV无论是单用还是与PNS、冰片配伍,其口服后主要分布在大脑皮层,尤其是患侧大脑皮层。冰片+AST IV+PNS能使患侧与健侧大脑皮层中AST IV含量显著增加。PNS单用,其有效成分人参皂苷Rg1、Rb1和三七皂苷R1主要分布在患侧小脑。冰片+AST IV+PNS能使患侧大脑皮层中人参皂苷Rb1含量显著增加,使健侧和患侧大脑皮层中人参皂苷Rg1含量增加,使大脑皮层尤其是患侧大脑皮层及小脑中三七皂苷R1含量增加。结论大鼠脑缺血再灌注后,AST IV与PNS的有效成分人参皂苷Rb1、Rg1及三七皂苷R1在大脑皮层和小脑均有一定的分布。AST IV单用时,AST IV主要分布在大脑皮层;PNS单用时,人参皂苷Rb1、Rg1及三七皂苷R1主要分布在小脑。冰片与AST IV、PNS合用后,能促进AST IV及人参皂苷Rb1、Rg1及三七皂苷R1向大脑皮层富集,尤其是向缺血再灌注侧大脑皮层富集;而且能不同程度地促进AST IV,人参皂苷Rb1、Rg1及三七皂苷R1在大脑皮层的吸收,尤其是在患侧大脑皮层的吸收。