PMID- 37853009 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231123 IS - 2373-8057 (Print) IS - 2373-8057 (Electronic) IS - 2373-8057 (Linking) VI - 9 IP - 1 DP - 2023 Oct 19 TI - Comparative efficacy and safety of adjunctive drugs to levodopa for fluctuating Parkinson's disease - network meta-analysis. PG - 143 LID - 10.1038/s41531-023-00589-8 [doi] LID - 143 AB - It remains unclear which adjunctive drug for Parkinson's disease (PD) in combination with levodopa is more effective, tolerable, and safe. We aimed to compare the efficacy, tolerability, and safety among anti-PD drugs from several classes in patients with fluctuating PD who received levodopa through network meta-analysis (NMA). Twelve anti-PD drugs belonging to 4 different drug classes (dopamine agonists, monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, and an adenosine A2A receptor antagonist) were selected. We systematically searched PubMed, Embase, and the Cochrane Library for eligible randomized controlled trials (RCTs) comparing placebo with anti-PD drug or among anti-PD drugs in patients with PD who experienced motor fluctuations or wearing-off and received levodopa. We included 54 RCTs in the analysis. The NMA was performed under a frequentist framework using a random-effects model. The efficacy outcome was change in daily off-time, and the tolerability outcome was discontinuation due to all causes. Safety outcomes included discontinuation due to adverse events (AEs) and the incidence of AEs, dyskinesia, hallucination, and orthostatic hypotension. According to the surface under the cumulative ranking curve (SUCRA) in the NMA, ropinirole transdermal patch (SUCRA, 0.861) ranked the highest in efficacy, followed by pramipexole (0.762), ropinirole extended release (ER) (0.750), and safinamide (0.691). In terms of tolerability, ropinirole (0.954) ranked the highest, followed by pramipexole (0.857), safinamide (0.717), and ropinirole ER (0.708). Each anti-PD drug had different SUCRA ranking profiles for the safety outcomes. These findings suggest that ropinirole, pramipexole, and safinamide are well-balanced anti-PD drugs that satisfy both efficacy and tolerability outcomes. CI - (c) 2023. Springer Nature Limited. FAU - Sako, Wataru AU - Sako W AUID- ORCID: 0000-0003-2009-2486 AD - Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan. w.sako.fn@juntendo.ac.jp. FAU - Kogo, Yuki AU - Kogo Y AUID- ORCID: 0000-0002-8120-3971 AD - Medical Headquarters, Eisai Co., Ltd., Tokyo, Japan. FAU - Koebis, Michinori AU - Koebis M AD - Medical Headquarters, Eisai Co., Ltd., Tokyo, Japan. FAU - Kita, Yoshiaki AU - Kita Y AUID- ORCID: 0000-0002-0642-4555 AD - Publication Business, Medical Professional Relations Inc., Osaka, Japan. FAU - Yamakage, Hajime AU - Yamakage H AD - Department of Medical Statistics, Satista Co., Ltd., Kyoto, Japan. FAU - Ishida, Takayuki AU - Ishida T AD - Medical Headquarters, Eisai Co., Ltd., Tokyo, Japan. FAU - Hattori, Nobutaka AU - Hattori N AUID- ORCID: 0000-0002-2034-2556 AD - Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20231019 PL - United States TA - NPJ Parkinsons Dis JT - NPJ Parkinson's disease JID - 101675390 PMC - PMC10584871 COIS- The authors declare no competing non-financial interests but the following competing financial interests; W.S. has received honoraria from Eisai Co. Ltd, Kyowa Kirin Co. Ltd, Sumitomo Pharma Co. Ltd, and Takeda Pharmaceutical Co. Ltd; has received research support from Mitsubishi Tanabe Pharma Co. and JSPS KAKENHI. Y.Kogo, M.K., T.I. are employees of Eisai Co., Ltd. Y.Kita provided medical writing support, funded by Eisai Co., Ltd. H.Y. performed statistical analysis, funded by Eisai Co., Ltd. N.H. received personal fees from Meiji Seika Pharma Co., Ltd. during the conduct of the submitted work; grants from Ono Pharmaceutical Co., Ltd., FP Corp., Eisai Co., Ltd., and Nihon Mediphysics Co., Ltd.; personal fees from Sumitomo Dainippon Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Hakko-Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., FP Corp., Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Nihon Medi-physics Co., Ltd., Novartis Pharma K.K., Biogen Idec Japan Ltd., AbbVie GK, Boston Scientific Japan K.K., Sanofi K.K., Alexion Pharmaceuticals, Inc., Mylan N.V., Daiichi Sankyo Co., Ltd., Hisamitsu Pharmaceuticals Co., Inc., and Kao Corp.; and reports donations to the department, endowed research departments and joint collaborative research departments from Sumitomo Dainippon Pharma Co., Ltd., Otsuka Pharmaceutical, Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Hakko-Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., GSK K.K., Kissei Pharmaceutical Co. Ltd., Novartis Pharma K.K., Nihon Medi-physics Co., Ltd., Biogen Idec Japan Ltd., AbbVie GK, Medtronic, Inc., Boston Scientific Japan K.K., Ono Pharmaceutical Co., Ltd., Hydrogen Health Medical Labo Co., ABIST Co., Ltd., Daiwa Co., Ltd., Bayer Yakuhin Ltd., Nihon Pharmaceutical Co., Ltd., Asahi Kasei Medical Co., Ltd., MiZ Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co. Ltd., and OHARA Pharmaceutical Co., Ltd. outside the submitted work. EDAT- 2023/10/19 00:43 MHDA- 2023/10/19 00:44 PMCR- 2023/10/19 CRDT- 2023/10/18 23:22 PHST- 2023/06/13 00:00 [received] PHST- 2023/10/06 00:00 [accepted] PHST- 2023/10/19 00:44 [medline] PHST- 2023/10/19 00:43 [pubmed] PHST- 2023/10/18 23:22 [entrez] PHST- 2023/10/19 00:00 [pmc-release] AID - 10.1038/s41531-023-00589-8 [pii] AID - 589 [pii] AID - 10.1038/s41531-023-00589-8 [doi] PST - epublish SO - NPJ Parkinsons Dis. 2023 Oct 19;9(1):143. doi: 10.1038/s41531-023-00589-8.