Objective: To determine the rankings for efficacy and tolerability of levodopa adjuncts in patients with Parkinson’s disease (PD) and wearing-off by network meta-analysis.

Background: When the treatment of PD is oriented toward improving patient’s QOL, it is important to choose a drug that balances the improvement of motor symptoms and side effects. Over the past 2 decades, the choice of treatment has become more complex with the introduction of new anti-PD drugs including rasagiline, safinamide, opicapone, dopamine agonists with extended release, and istradefylline. Since there is no comparative study between these new anti-PD drugs, this study will create evidence that might help physician to make treatment choice.

Method: The network meta-analysis was conducted in accordance with the PRISMA guideline (PROSPERO No. CRD42021270256). Twelve drugs available in Japan for PD patients with wearing-off (pramipexole IR/ER, ropinirole IR/ER/transdermal patch, rotigotine transdermal patch, entacapone, opicapone, istradefylline, selegiline, rasagiline, and safinamide) were included in the study. We systematically searched PubMed, Embase, and the Cochrane Library for randomized, double-blind trials of these drugs. Data were supplemented from the Japanese Common Technical Documents. Change in daily Off-time from baseline to the last evaluation was defined as an efficacy outcome, and discontinuation rate (due to all causes or adverse events) and incidence of adverse events were defined as safety/tolerability outcomes. Surface under the cumulative ranking (SUCRA) curve was used to estimate the comparative efficacy and safety/tolerability of the individual drugs.

Results: Fifty-four trials met the eligibility criteria. For Off-time, 11 out of 12 active drugs were superior to placebo, and SUCRA was greater for ropinirole transdermal patch (86.1%), pramipexole IR (76.2%), ropinirole ER (75.0%), and safinamide (69.1%). Two out of 11 drugs were superior to placebo in discontinuation rate due to all cause, and SUCRA was greater for ropinirole IR (95.4%), pramipexole IR (85.7%), safinamide (71.7%), and ropinirole ER (70.8%).

Conclusion: We found balanced efficacy and tolerability in dopamine agonists and safinamide. Further studies will be needed since the number of head to head trials was limited.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparison-of-efficacy-and-safety-of-adjunct-treatments-to-levodopa-in-patients-with-parkinsons-disease-and-wearing-off-a-network-meta-analysis-of-randomized-double-blind-trials/