Providence Multiple Sclerosis Center, Portland, OR, USA.
Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, WA, USA.
Clin Ther. 2018 Dec;40(12):2077-2087. doi: 10.1016/j.clinthera.2018.10.011. Epub 2018 Nov 22.
The goal of this study was to evaluate clinical outcomes and patient-reported outcomes (PROs) over 12 months in patients with relapsing multiple sclerosis (RMS) who switched from glatiramer acetate (GA) to delayed-release dimethyl fumarate (DMF) 240 mg BID after suboptimal response to GA in real-world clinical practice.
The RESPOND (Effectiveness of DMF and Its Impact on PROs in Suboptimal GA Responders With RMS) study was a Phase IV, prospective, multicenter, open-label, single-arm, 12-month observational trial. The study was conducted in the United States at 63 sites between August 2013 and February 2016. Patients diagnosed with RMS who experienced a suboptimal response to GA (defined as perceived suboptimal efficacy, intolerance, or poor adherence to GA) were eligible for enrollment. DMF treatment was initiated within 60 days of enrollment. The primary objective was to estimate the annualized relapse rate (ARR) at 12 months based on data collected from medical records and compare it with the 12 months before DMF initiation. Secondary objectives of the study included assessing the change in PRO scores from baseline to 12 months; PROs were recorded before and at 6 and 12 months after DMF initiation.
Of the 318 patients included in the analysis population, 247 (78%) completed treatment. Mean (SD) time on GA treatment before switching to DMF was 51.3 months (49.1 months). The ARR (95% CI) reported for the 12 months before DMF initiation was 0.49 (0.42-0.57) compared with 0.11 (0.07-0.17) at 12 months after DMF initiation, representing a 78% reduction in ARR (P < 0.0001). Statistically significant improvements from baseline were observed for multiple PROs, including the 36-item Short Form Health Survey physical and mental component summaries (P = 0.0201 and P = 0.0014, respectively), the 5-item Modified Fatigue Impact Scale (P = 0.0002), the 14-item Treatment Satisfaction Questionnaire for Medication (P < 0.0001), and the 7-item Beck Depression Inventory (P = 0.0117).
DMF may be an effective treatment option in patients with RMS who experience a suboptimal response to GA. The results should be interpreted with caution due to the observational nature of the study and the lack of a control group. Other limitations of the study include a potential bias due to regression to the mean and lack of randomization. ClinicalTrials.gov identifier: NCT01903291.
本研究旨在评估在真实世界临床实践中，对于接受过培美曲塞二钠（GA）治疗但疗效欠佳的复发性多发性硬化症（RMS）患者，转换用延迟释放型富马酸二甲酯（DMF）240mg bid 治疗后 12 个月的临床结局和患者报告结局（PRO）。
RESPOND（DMF 在 GA 疗效欠佳的 RMS 患者中的有效性及其对 PRO 的影响）研究是一项为期 12 个月的前瞻性、多中心、开放标签、单臂、四期观察性试验。该研究于 2013 年 8 月至 2016 年 2 月在美国 63 个地点进行。符合以下条件的 RMS 患者有资格入组：GA 治疗疗效欠佳（定义为认为疗效欠佳、不耐受或对 GA 治疗依从性差），在入组后 60 天内开始 DMF 治疗。主要终点是根据病历记录的数据估计 12 个月时的年化复发率（ARR），并与 DMF 起始前的 12 个月进行比较。研究的次要终点包括评估从基线到 12 个月时 PRO 评分的变化；在 DMF 起始前和起始后 6 个月和 12 个月时记录 PRO。
在分析人群中，318 例患者中，247 例（78%）完成了治疗。转换用 DMF 前接受 GA 治疗的平均（SD）时间为 51.3 个月（49.1 个月）。DMF 起始前 12 个月的 ARR（95%CI）为 0.49（0.42-0.57），而 DMF 起始后 12 个月的 ARR 为 0.11（0.07-0.17），ARR 降低 78%（P＜0.0001）。与基线相比，多项 PRO 均有显著改善，包括 36 项简明健康调查量表的身体和心理成分总结（P=0.0201 和 P=0.0014）、5 项简化疲劳影响量表（P=0.0002）、14 项治疗满意度问卷（P＜0.0001）和 7 项贝克抑郁量表（P=0.0117）。
对于 GA 治疗疗效欠佳的 RMS 患者，DMF 可能是一种有效的治疗选择。由于研究的观察性质和缺乏对照组，结果应谨慎解释。研究的其他局限性包括由于向均数回归和缺乏随机化而导致的潜在偏倚。ClinicalTrials.gov 标识符：NCT01903291。
