Efficacy and safety of non‐ergot dopamine‐receptor agonists as an adjunct to levodopa in advanced Parkinson's disease: A network meta‐analysis

Abstract

Background and purpose Non‐ergot dopamine agonists (NEDAs) have been used as an adjunct therapy to levodopa in advanced Parkinson's disease (PD) for many years. However, there is no strong evidence that a given NEDA is more potent than another. To compare and rank the efficacy, tolerability, and safety of six commonly used NEDAs as an adjunct to levodopa in advanced PD, which includes long‐acting and standard formulations, a network meta‐analysis was performed. Methods The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases were searched from January 1996 to June 2022 for eligible randomized controlled trials (RCTs). Six NEDAs, including rotigotine transdermal patch, ropinirole immediate‐release (IR)/prolonged‐release (PR), pramipexole IR/extended‐release (ER), and piribedil, were investigated. Results A total of 34 RCTs (7868 patients) were included in the current study. The surface under the cumulative ranking curve indicated that ropinirole PR was associated with the best improvement in Unified Parkinson's Disease Rating Scale (UPDRS)‐II, UPDRS‐III, and UPDRS‐II + III (0.811, 0.742, and 0.827). For OFF time reduction, pramipexole IR ranked first (0.979), and ropinirole PR ranked first in OFF time responder rate (0.927). Pramipexole ER ranked first in overall withdrawals, and rotigotine transdermal patch ranked first in the incidence of adverse events (≥1 AEs). Conclusions This network meta‐analysis suggests six commonly used NEDAs are effective as an adjunct to levodopa in advanced PD. In comprehensive consideration of better symptomatic management, ropinirole PR may be a better choice than other NEDAs in advanced PD. Six NEDAs showed different profiles of AEs.

Comparative efficacy and safety of adjunctive drugs to levodopa for fluctuating Parkinson’s disease - network meta-analysis

“…The low ranking of pramipexole ER might be resulted from the fact that our analysis included only one relevant RCT, which showed that pramipexole ER had lower efficacy than pramipexole 52 . For rotigotine transdermal patch, our result was inconsistent with previous NMA studies in terms of relative efficacy ranking to ropinirole 10 , 13 . The discrepancy may be caused by SP511 study, which was included only in the present study (Supplementary Fig.…”

“…This study showed great improvement in the active arms and in the placebo arm, so there were no significant differences between the drugs and placebo. Some other included studies were different between the present and previous studies 10 , 13 ; nevertheless, in all three NMA studies, pramipexole and ropinirole ER ranked higher, suggesting the robustness of the findings of the present analysis.…”

“…A network meta-analysis (NMA) allows for the comparison of outcomes among two or more active treatments in a network of studies, even if there is no direct comparison between each treatment 4 . Previously, some reports applying NMAs have demonstrated comparative results among anti-PD drugs 5 – 13 . Many of them included intra-drug class comparisons, and NMAs that compared anti-PD drugs from different drug classes are limited.…”

Ropinirole patch treatment of nocturnal violent tremor in Parkinson's disease

“…A comparison of the efficacy between ropinirole and rotigotine patches has not yet been conducted. A more recent systematic review and network meta‐analysis evaluating the comparative efficacy of non‐ergot dopamine agonists showed that the improvement rate of UPDRS part II + III was higher with immediate‐ or prolonged‐release ropinirole tablets than with rotigotine 6 . Moreover, a comparative study of ropinirole transdermal patches versus tablets revealed no significant differences in motor or sleep scores 7 .…”

“…A more recent systematic review and network meta-analysis evaluating the comparative efficacy of non-ergot dopamine agonists showed that the improvement rate of UPDRS part II + III was higher with immediate-or prolonged-release ropinirole tablets than with rotigotine. 6 Moreover, a comparative study of ropinirole transdermal patches versus tablets revealed no significant differences in motor or sleep scores. 7 In our patient, the dosage of rotigotine was low and other anti-parkinsonian medications were not consistent when each using ropinirole patch and rotigotine.…”