دانلود مقاله بهره وری و ایمنی رازاگیلین و پرامی پکسول در درمان بیماری پارکینسون
خلاصه
معرفی
مواد و روش ها
نتایج
بحث
در دسترس بودن داده ها
افشای
تضاد علاقه
مواد تکمیلی
منابع
Abstract
Introduction
Materials and Methods
Results
Discussion
Data Availability
Disclosure
Conflicts of Interest
Supplementary Materials
References
چکیده
زمینه. تک درمانی راساگیلین یا پرامیپکسول برای مدیریت بیماری پارکینسون اولیه (PD) پیشنهاد شده است. هدف از این تحقیق بررسی سیستماتیک اثربخشی و ایمنی بالینی رازاگیلین یا پرامی پکسول در PD اولیه (با طول مدت بیماری ≤5 سال و مرحله Hoehn و Yahr ≤3) بود. مواد و روش ها. کارآزمایی‌های تصادفی‌سازی و کنترل‌شده (RCTs) رازاگیلین یا پرامیپکسول برای PD اولیه منتشر شده تا سپتامبر 2021 بازیابی شد. نتایج مورد علاقه شامل تغییرات در مقیاس رتبه بندی بیماری پارکینسون واحد (UPDRS) قسمت های II و III و بروز عوارض جانبی بود. تفاوت میانگین استاندارد شده (SMD)، نسبت شانس (OR) و فاصله اطمینان 95% (CI) محاسبه شد و ناهمگنی با آزمون I 2 اندازه‌گیری شد. نتایج. نه رازاگیلین و یازده RCT پرامیپکسول وارد شدند. یک تجزیه و تحلیل تعقیبی از یک مطالعه رازاگیلین گنجانده شد. پنج مطالعه برای هر دارو در متاآنالیز امتیازات UPDRS گنجانده شد. متاآنالیز رازاگیلین بر روی بیمارانی که 1 میلی گرم در روز دریافت می کردند متمرکز شد. راساگیلین و پرامی پکسول به طور قابل توجهی نمرات UPDRS قسمت II و III را در مقایسه با دارونما بهبود بخشیدند. ناهمگونی قابل توجهی در بین مطالعات وجود داشت (I 2 > 70٪). نه رازاگیلین و نه پرامیپکسول در مقایسه با دارونما، خطر نسبی عوارض جانبی، عوارض جانبی جدی، یا عوارض جانبی منجر به قطع مصرف را افزایش ندادند. نتیجه. با استفاده از رویکرد درجه بندی توصیه ها، ارزیابی، توسعه و ارزیابی ها (GRADE) برای خلاصه کردن شواهد، ما اطمینان متوسطی را در مجموعه شواهد برای اثربخشی رازاگیلین یا پرامی پکسول در PD اولیه یافتیم که نشان دهنده RCT های مقایسه ای چند مرکزی با طراحی خوب بیشتر است. مورد نیاز باقی بماند.
Abstract
Background. Rasagiline or pramipexole monotherapy has been suggested for the management of early Parkinson’s disease (PD). The aim of this research was to systematically review the clinical efficacy and safety of rasagiline or pramipexole in early PD (defined as disease duration ≤5 years and Hoehn and Yahr stage of ≤3). Methods. Randomized controlled trials (RCTs) of rasagiline or pramipexole for early PD published up to September 2021 were retrieved. Outcomes of interest included changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III and the incidence of adverse events. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated, and heterogeneity was measured with the I2 test. Results. Nine rasagiline and eleven pramipexole RCTs were included. One post hoc analysis of one rasagiline study was included. Five studies for each drug were included in meta-analyses of the UPDRS scores. The rasagiline meta-analysis focused on patients receiving 1 mg/day. Rasagiline and pramipexole significantly improved UPDRS Part II and III scores when compared to placebo. Significant heterogeneity among the studies was present (I2 > 70%). Neither rasagiline nor pramipexole increased the relative risk for any adverse events, serious adverse events, or adverse events leading to withdrawal when compared with placebo. Conclusion. Applying a Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to summarize the evidence, we found moderate confidence in the body of evidence for the efficacy of rasagiline or pramipexole in early PD, suggesting further well-designed, multicenter comparative RCTs remain needed.
Introduction
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized clinically by bradykinesia, tremor, rigidity, and postural instability and histologically by neuronal inclusions composed of α-synuclein. Nonmotor symptoms including olfactory dysfunction, rapid eye movement, sleep behavior disorder, mood disorders, and autonomic dysfunction often precede the appearance of motor symptoms by several months or years [1, 2]. These motor and nonmotor symptoms can adversely affect a patient’s quality of life [3]. The incidence of PD is rising and increases with age [4, 5].
Early management of PD could prolong the ability of a patient to stay in working life and improve their overall quality of life [6, 7]. Levodopa is widely considered one of the most effective treatments for PD, but its use is often delayed because of drug-induced dyskinesias and wearing-off and on-off fluctuations [8, 9]. Alternatives to levodopa in early pharmacologic treatment of PD are dopamine agonists and monoamine oxidase B (MAO-B) inhibitors [10, 11]. A meta-analysis by Chang and coworkers (2017) [12] showed the irreversible inhibitor of MAO-B inhibitor rasagiline to have benefits both as a monotherapy and in combination with another intervention. The safety profile of rasagiline was similar to that of placebo in a systematic review of its use in PD patients [13]. Pramipexole, a nonergoline, D3-preferring dopamine agonist, is another treatment option for the management of motor symptoms associated with PD [14]. A recent systematic review showed that combined pramipexole and levodopa therapy was superior to levodopa monotherapy for the improvement of clinical symptoms in PD patients [15].
Prior systematic reviews evaluating the efficacy and safety of either rasagiline or pramipexole have evaluated patient populations at all stages of the disease. The goal of this study was to focus on the safety and efficacy of these drugs in early PD. Defining early PD in our review was based on the duration of PD in affected patients (five years or less) as well as the presence of mild to moderate symptoms based on the Hoehn and Yahr scale. The Hoehn and Yahr scale is commonly used in clinical studies to stage the level of functional disability and impairment seen in PD patients [16].
Results
4.1. Description of the Included Rasagiline Studies
The key characteristics of the nine rasagiline studies are reported in Table 1. One study [21] compared pramipexole and rasagiline as interventions and is included in this portion of the analysis. One post hoc analysis of a randomized controlled trial [22] met the inclusion criteria and was included in the systematic review. There were a total of 2121 patients in the studies, and 1059 patients were on rasagiline: 738 patients had a dose of 1 mg/day, 307 had a dose of 2 mg/day, and 14 had a dose of 4 mg/day. The mean age of study populations ranged from 59.3 to 70.2 years. The mean duration of PD ranged from 2.5 months to 4.8 years. The proportion of the study population who were males in the intervention groups ranged from 42.9 to 76.9%. There were four studies where other PD medications were either discontinued before the study or patients were PD-drug naïve [21, 23–25]. The rest of the studies allowed other PD medications with stable dosage for more than 4 weeks before the start of the study [26–29]. Rescue LD was accepted in one rasagiline study if PD symptoms worsened, and the current therapy did not relieve the symptoms [28]. Hoehn and Yahr stage was ≤3 in every study. The overall discontinuation rates were 7.3% and 10.7% in the rasagiline and placebo groups, respectively. One study reported seven discontinued patients without indicating which intervention the patients were using [27].