Efficacy, Safety, and Tolerability of Switching from Oral Cholinesterase Inhibitors to Rivastigmine Transdermal Patch with 1-Step Titration in Patients with Mild to Moderate Alzheimer’s Disease: A 24-Week, Open-Label, Multicenter Study in Japan

• Published in: Dementia and geriatric cognitive disorders extra 2019-05, Vol.9 (2), p.302-318
• Main Authors: Ueda, Kengo, Katayama, Sadao, Arai, Tetsuaki, Furuta, Nobuo, Ikebe, Shinichiro, Ishida, Yoshinori, Kanaya, Kiyoshi, Ouma, Shinji, Sakurai, Hirofumi, Sugitani, Masato, Takahashi, Makio, Tanaka, Toshihisa, Tsuno, Norifumi, Wakutani, Yosuke, Shekhawat, Ankita, Das Gupta, Ayan, Kiyose, Kazuki, Toriyama, Kazuhiro, Nakamura, Yu
• Format: Article
• Language: English
• Subjects: Activities of daily living; Algorithms; Alzheimer's disease; Caregivers; Cholinesterase inhibitors; Clinical trials; Cognitive ability; Dementia; Family medical history; Patients; Psychiatry; Research Article; Rivastigmine transdermal patch; Studies; Switching; Transdermal medication
• ISSN: 1664-5464; 1664-5464
• DOI: 10.1159/000501364

Background: Few studies have investigated treatment options for patients with Alzheimer’s disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. Objective: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. Methods: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm 2 ; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm 2 ; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. Results: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of −0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. Conclusion: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.