PD: Adverse Effects (MDS 2005)

Subject: PD: Adverse Effects (MDS 2005)

Date: 3/28/2005

PD: Adverse Effects (MDS 2005)

E-MOVE reports from the 9th International Congress of Parkinson’s Disease and Movement Disorders, New Orleans 5-8 March, 2005. Pages and abstract numbers are from Movement Disorders 2005;20(suppl 10).

Incidence of dyskinesias in a ten-year naturalistic follow-up of patients with early Parkinson’s disease (PD) receiving ropinirole compared with L-dopa
O Rascol, AD Korczyn, P De Deyn, A Lang

The dyskinesia-delaying effect of initial treatment with ropinirole is maintained for up to 10 years, according to this study.

Patients who completed the 056 study comparing ropinirole to levodopa as initial monotherapy were invited to enter this open-label, long-term follow-up study. Patients could receive any medication during follow-up regardless of initial assignment. Assessments continued every 6 months for 10 years after initial treatment.

Of 130 patients completing the 056 trial, 69 entered this study (42 ropinirole, 27 levodopa, reflecting the initial 2:1 randomization). After 10 years, 52.4% of ropinirole patients and 77.8% of levodopa patients had dyskinesias (p=0.0457). The mean time to development of dyskinesias was 8.6 vs. 7.0 years in favor of ropinirole (p=0.0065). Neither the frequency of disabling dyskinesias nor the total decline in UPDRS scores were significantly different between the groups.

Previous E-MOVE reports on the 056 study are archived at
http://www.mdvu.org/emove/article.asp?ID=582
http://www.mdvu.org/emove/article.asp?ID=366

Body weight determines levodopa associated dyskinesia in Parkinson’s disease
JC Sharma, M Vassallo
P228, S68

Lower body weight is associated with increased risk for dyskinesias, according to this retrospective study.

Two hundred sixty-eight PD patients were followed for up to 7 years. At final presentation (n=224), dyskinesias were more common in women than men (32% vs. 20%). Dyskinetic patients had been treated longer, and had received higher daily doses of levodopa. Dyskinetic patients also had lower body weight at initial presentation (67 vs. 75 kg, p<0.013) and at final presentation (65.3 kg vs. 76.8 kg, p<0.001). Levodopa dose per kilogram was higher in dyskinetic patients irrespective of gender. Only weight and higher levodopa dose were independently correlated with risk for dyskinesias.

The incidence of liver abnormalities in patients receiving tolcapone was assessed in these two studies.

1. Evaluation of liver-related adverse events with tolcapone: A review of 7 years of worldwide safety data
R Watts, G Kricorian
P400, S118

Watts and Kricorian analyzed data from spontaneous reporting and literature review worldwide between 1997 and 2004. From an estimated 180,000 patients receiving tolcapone during that period, 219 hepatobiliary adverse events were identified. Analysis of these events showed:
--Prior to commencement of rigorous liver function monitoring in June 1999, among 100,000 treated patients, there were 156 hepatobiliary events, including 3 deaths, 8 cases of massive hepatic injury, and 26 cases of hepatitis.
--After June 1999, among 80,000 treated patients, there were 63 events, including 1 case of massive hepatic injury and 5 cases of hepatitis, and no deaths.
--A total of 21 cases had elevation in AST or ALT more than 3x the upper limit of normal. The median time to elevation was 81 days, and duration to resolution was 21 days.

The authors note that “due to under-reporting of adverse events to the manufacturer, this figure may somewhat underestimate the true incidence of liver-related adverse events.” On the other hand, they note, the cases reported include all hepatobiliary events, “irrespective of a causal relationship to tolcapone. Many of these patients were taking several other medications including agents that are known to cause hepatic adverse events.”

2. Results from a 2-year centralized tolcapone liver enzyme monitoring program
M Lew, G Kricorian
P404, S119-120

Lew and Kricorian analyzed 11,883 blood samples from 1725 patients on tolcapone sent by 715 physicians to a central database between January 1999 and January 2001, after the commencement of rigorous liver function monitoring. Results showed:
--A total of 67 patients (3.9%) had an elevation of either AST or ALT above the upper limit of normal in at least one sample. Of these, 15 (22%) were greater than 2x the ULT.
--Of 8 patients with AST elevation >3x ULT, 5 resolved to normal while continuing tolcapone, 2 had returned to below 2x ULT at the end of the study, and 1 was dropped from therapy because of an abnormal value at baseline. A similar pattern was seen for those patients with elevated ALT.
--One patient had both the highest ALT (8-9x) and the highest AST (15-16x), which occurred at baseline. ALT resolved to normal and AST to below 2x normal while on tolcapone.

Both studies were supported by Valeant Pharmaceuticals.

E-MOVE Editor: Richard Robinson, NASW, WE MOVE

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