Factors predictive of the development of Levodopa-induced dyskinesia and wearing-off in Parkinson's disease.

The Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) study compared the initiation of levodopa (l-dopa) therapy with l-dopa/carbidopa (LC) versus l-dopa/carbidopa/entacapone (LCE) in patients with Parkinson's disease. In the current study, the STRIDE-PD study population was investigated to determine the effect of l-dopa dose and other risk factors on the development of dyskinesia and wearing-off. Patients were randomized to receive LCE (n=373) or LC (n=372). Blinded assessments for dyskinesia and wearing-off were performed at 3-month intervals for the 134- to 208-week duration of the study. The patients were divided into 4 dose groups based on nominal l-dopa dose at the time of onset of dyskinesia (or at study conclusion if there was no dyskinesia): group 1, <400 mg/day (n=157); group 2, 400 mg/day (n=310); group 3, 401 to 600 mg/day (n=201); and group 4, >600 mg/day (n=77). Similar analyses were performed with respect to wearing-off and any motor complication. The times to onset and frequency of dyskinesia, wearing-off, or any motor complication were compared using the log-rank test (overall trend test) and a Cox proportional hazards model (pairwise comparisons). A stepwise Cox proportional hazards model was used to screen predictive factors in a multivariate analysis. The risk of developing dyskinesia and wearing-off increased in an l-dopa dose-dependent manner (P<0.001 for both). Analyses using l-dopa equivalent doses produced comparable results. Factors that were predictive of dyskinesia, in rank order, were: young age at onset, higher l-dopa dose, low body weight, North American geographic region, LCE treatment group, female gender, and more severe Unified Parkinson's Disease Rating Scale (UPDRS) Part II. Multivariate analyses identified similar predictors for wearing-off but included baseline UPDRS Part III and excluded weight and treatment allocation. The risk of developing dyskinesia or wearing-off was closely linked to l-dopa dose. The current results suggest that physicians should use the lowest dose of l-dopa that provides satisfactory clinical control to minimize the risk of both dyskinesia and wearing-off.

Direct switch from levodopa/benserazide or levodopa/carbidopa to levodopa/carbidopa/entacapone in Parkinson's disease patients with wearing-off: efficacy, safety and feasibility--an open-label, 6-week study.

The study objective was to assess the efficacy, safety and feasibility of switching from levodopa/benserazide (LB) or levodopa/carbidopa (LC) to levodopa/carbidopa/entacapone (LCE) in Parkinson's disease (PD) patients with wearing-off. This was a multicenter, open-label, 6-week study; the primary outcome was success rate based on the patient-assessed Clinical Global Impression of Change (P-CGI-C). Secondary outcomes included investigator-assessed CGI-C (I-CGI-C), change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS), motor/non-motor wearing-off symptoms and quality of life-visual analog scale (QoL-VAS). After switching to LCE, 77% of patients reported an 'improvement' (p < 0.0001 vs. patients reporting 'no change or worsening'). Significant improvements were seen in I-CGI-C, UPDRS and QoL-VAS, regardless of prior therapy. Oral levodopa dosing was increased in 28% of patients; the primary outcome remained significant when these patients were excluded. The data suggest that switching from LB/LC to LCE provided a significant benefit in PD patients with wearing-off.

Burden of illness in multiple sclerosis (DEFENSE) study: the costs and quality-of-life of Finnish patients with multiple sclerosis.

OBJECTIVE: Although multiple sclerosis (MS) is one of the most common causes of non-traumatic disability among young adults, no published data on its economic and health-related quality-of-life (HRQoL) burden is available from Finland. The DEFENSE study aimed to estimate the costs and HRQoL of patients with MS (PwMS) in Finland and explore how these variables are influenced by disease severity and relapses. METHODS: Overall, 553 PwMS registered with the Finnish Neuro Society, a national patient association in Finland, completed a self-administered questionnaire capturing information on demographics, disease characteristics and severity (Expanded Disease Severity Scale [EDSS]), relapses, resource consumption and HRQoL. RESULTS: The PwMS had a mean EDSS score of 4.0. Overall, 44.1% had relapsing-remitting form of the disease (RRMS). The mean age was 53.8 years and 55.7% had retired prematurely due to MS. Disease-modifying therapies (DMTs) were used by 42.7% of the study population, and 21.5% across all disease types and severities had experienced relapses during the previous year. The mean total annual cost of MS was €46,994, which increased with advancing disease from €10,835 (EDSS score = 0) to €109,901 (EDSS score = 8-9). The mean utility was 0.644. HRQoL decreased with increasing disease severity. Relapses imposed an additional utility decrement among the PwMS with RRMS and EDSS ≤5 and had a trend-like effect on total costs. LIMITATIONS: The cross-sectional setting did not allow assessment of the significance of relapses in early MS or the use of DMTs on the prognosis of the disease. CONCLUSION: The study confirms previous findings from other countries regarding a significant disease burden associated with MS and provides, for the first time, published numerical estimates from Finland. Treatments that slow disease progression and help PwMS retain employment for a longer duration have the highest potential to reduce the disease burden associated with MS.

Five-year efficacy and safety of levodopa/DDCI and entacapone in patients with Parkinson's disease.

This was a retrospective pooled analysis of data from four comparably designed, double-blind, placebo-controlled, Phase III studies and their long-term open-label extensions. Patients on levodopa and a dopa decarboxylase inhibitor (DDCI) were randomized to entacapone or to placebo in the 6-month, double-blind phase, with all patients subsequently receiving entacapone in the extension phase. UPDRS III motor scores improved by -2.1 points during the first 6 months of levodopa/DDCI and entacapone therapy, and remained below baseline for up to 2 years. Increased daily 'ON' time, together with response duration to a single morning dose of levodopa and clinical global evaluation, also supported the long-term efficacy of levodopa/DDCI and entacapone. The mean daily dose of levodopa did not increase over the 5-year follow-up period. Long-term therapy with levodopa/DDCI and entacapone was well-tolerated.