Dr Jason Raw outlines key findings from the SYNPASES trial, which explored the tolerability of safinamide used as an adjunct therapy in patients with Parkinson's disease
Zambon has officially presented the results from SYNAPSES, its multinational, multicentre, retrospective/prospective cohort observational study that explored the tolerability of safinamide used as an adjunct therapy in 1,610 patients followed up to 12 months. The study was designed to include potentially all patients treated with safinamide as per clinical practice1, and investigate the real-world use of safinamide in six European countries including the UK, particularly in patient populations not well represented in clinical trials such as those older than 75, those with psychiatric illnesses or those with relevant comorbidities.
Study primary and secondary objectives
The primary objective was to evaluate the occurrence of adverse events in patients treated with safinamide in real-life conditions during one year in the first post-commercialisation phase as reported by the investigators, following an analysis conducted in the overall population, and in the above-mentioned subgroups of interest.
Secondary objectives included the description of the characteristics of patients treated with safinamide according to clinical practice and the description of safinamide treatment patterns in real-life settings as well as motor evaluations, as measured by UPDRS III (Unified Parkinson’s Disease Rating Scale)1.
45.8% patients experienced adverse events (AE), 27.7% patients had adverse drug reactions (ADR) and 9.2% patients had serious adverse events (SAE). The AEs were those described in safinamide’s patient information leaflet. The majority of AEs were mild or moderate and resolved with no differences detected between the subgroup of patients. 47.3% patients older than 75 years had at least one AE, 26.1% at least one ADR, 13.6% at least one SAE and 2.3% at least SADR. The proportions of patients experiencing at least one AE, ADR or SADR were similar in the population of patients aged >75 compared to patients aged ≤75, while higher for SAE in patients aged >75 (13.6%) compared to patients aged ≤75 (7.7%).
Clinically significant improvements were seen in the UPDRS motor score and in the UPDRS total score in ≥40% of patients1. The percentage of patients experiencing AEs during one year of treatment with safinamide in real-life conditions was 30% lower compared to the percentage observed in six-months pivotal trials2,3. The monthly incidence rate of AEs was very low: 0.07 AEs per patient per month.
Safinamide was shown to reduce by about 40%-50% motor fluctuations with visible efficacy at four months, in particular on wearing-off and early morning fluctuations1 which affect the majority of patients with PD. This significant and rapid-onset effect of safinamide may be explained by its dual mechanism of action, which is dopaminergic and glutamatergic4. There is a significant association between motor fluctuations and the annual costs of PD: the mean cost of patients with motor fluctuations is generally two-three times greater than that for patients without5.
Dr Jason Raw, Fairfield General Hospital, Bury, Greater Manchester, UK, affirmed: “The majority of patients treated with levodopa experience motor fluctuations with a significant deterioration of their quality of life. The SYNAPSES study showed that safinamide was able to reduce motor fluctuations and wearing-off, and as a consequence may improve subjects’ QoL and hopefully reduce some of the economic burden of PD”.
The SYNAPSES study confirmed validity and tolerability of safinamide, as adjunct therapy, in fluctuating patients and in special groups of subjects. Motor complications and motor scores improved with clinically significant results in the UPDRS scale maintained in the long-term.
1 G. Abruzzese et al. /Safinamide in Routine Clinical Practice.
2 Borgohain R, Szasz J, et Al.; Study 016 Investigators (2014) Randomized trial of safinamide add-on to levodopa in Parkinson’s disease with motor fluctuations. Mov Disord 29, 229-237.
3 Schapira AH, Fox SH, et Al. (2017) Assessment of safety and efficacy of safinamide as a levodopa adjunct in patients with Parkinson’s disease and motor fluctuations. A randomized clinical trial. JAMA Neurol 74, 216-224.
4 Cattaneo C, Sardina M, Bonizzoni E (2016) Safinamide as add-on therapy to levodopa in mid- to late-stage Parkinson’s disease fluctuating patients: post-hoc analyses of studies 016 and SETTLE. J Parkinsons Dis 6, 165-173.
5 Keränen T, Kaakkola S, et Al. (2003) Economic burden and quality of life impairment increase with severity of PD. Parkinsonism Rel Disord 9, 163-168.