Mirapexin®/Sifrol® (pramipexole)

Mirapexin®/Sifrol® (pramipexole):
>five million patient-years of experience in Parkinson's disease

Clinical evidence: ongoing research

  • Results from a long-term clinical trial with Mirapexin®/Sifrol® (pramipexole) - CALM-PD* - have shown that initial treatment with Mirapexin®/Sifrol® in the early stages of the disease can significantly delay motor complications as compared to levodopa.1 These results played a pivotal role in recent guidelines by the American Academy of Neurology which support the advantages of starting treatment with a dopamine agonist.2
  • In the CALM-PD* trial, 301 patients were randomised to double-blind therapy with Mirapexin®/Sifrol® or levodopa; adjuvant therapy was allowed as rescue if necessary. After four years it was observed that initial treatment with Mirapexin®/Sifrol® reduced the risk of developing dyskinesias (involuntary jerking movements, themselves very disabling) by more than 50% versus initial treatment with levodopa.1,3,4 A further analysis of the CALM-PD* study has confirmed the potential benefits of treatment with Mirapexin®/Sifrol®, particularly in younger adult PD patients, where the lower incidences of dyskinesias and wearing off compared to levodopa are an advantage in the early stages of the disease. The study also highlights that PD patients need an individualised, tailored treatment approach that takes into account the disease stage, co-morbidities (e.g. depressive symptoms) and co-medication (e.g. their metabolism).5
  • Although there is significant ongoing research in this area, at present there are no therapies that have clearly been demonstrated to have a neuroprotective effect by preventing further dopaminergic cell death, thus slowing or postponing PD progression.
  • Important data from the CALM-PD* study using single-photon emission computed tomography (SPECT) show that patients receiving pramipexole demonstrated a significantly slower rate of decline in dopaminergic functioning than patients who received initial treatment with levodopa.6 This is of particular significance in view of the fact that patients are believed to have already lost an estimated 50 to 80% of dopaminergic neuronal functioning before symptoms or abnormal signs of functioning are detected.7
  • These CALM-PD* findings have been further substantiated by the INSPECT** study. Initial results from this study show that neither levodopa nor pramipexole had a short-term effect on the pharmacological mechanisms that regulate dopamine transporters (DAT)8 which are the markers used in single-photon emission computed tomography (SPECT) imaging. This imaging method was used for the CALM-PD* study. By ruling out short-term interference of levodopa and pramipexole with DATs, the INSPECT** study strengthened the earlier findings of the CALM-PD* study.
  • While previous studies with Mirapexin®/Sifrol®, such as the CALM-PD* study6,8 and in vitro studies, have suggested potential clinical benefits of early treatment, the PROUD***9 study presents a further approach to investigating the potential clinical benefits of early treatment of patients with PD by comparing imaging and clinical endpoints of PD progression, a key focus of current research. The PROUD*** study is the first to combine measurements of clinical outcomes in a PD patient with measurements of dopamine transporter density of certain brain areas (basal ganglia), through a SPECT imaging arm of the study.
* Comparison of the Agonist pramipexole with Levodopa on Motor Complications of Parkinson's Disease
** INvestigating the effect of short-term treatment with pramipexole or levodopa on [123]ß-CIT and SPECT imaging
*** Assessment of Potential ImPact of PRamipexole On Underlying Disease

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View references

  1. Parkinson Study Group, Holloway RG et al. Pramipexole vs levodopa as initial treatment for Parkinson's disease. Arch Neurol 2004; 61(7): 1044-1053.
  2. Miyasaki JM et al. Practice parameter: Initiation of treatment for Parkinson's disease: An evidence-based review. Neurology 2002; 58; 11-17.
  3. Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: A randomized controlled trial. JAMA 2000: 284:1931-38
  4. Corbin A et al. Maintained pramipexole monotherapy treatment results in significantly lower dyskinesia rates in early Parkinson's disease: A result of the CALM-PD study after 4 years. Poster Presentation P-04 / 2.231 11 December 2007 XVII WFN World Congress of Parkinson's Disease and Related Disorders.
  5. Parkinson's Study Group CALM Cohort Investigators. Long-term Effect of Initiating Pramipexole vs Levodopa in Early Parkinson Disease. Arch Neurol 2009;66(5): 563-570.
  6. Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 2002; 287(13): 1653-1661.
  7. Hirsch E et al. Melanised dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease, Nature 1988; 334: 345–348.
  8. Jennings DL, Tabamo RT, Seibyl JS, Marek KM. InSPECT: Investigating the effect of short-term treatment with pramipexole or levodopa on [123I]ß-CIT and SPECT imaging. Abstract 465 at 11th International Congress of Parkinson's Disease and Movement Disorders, Istanbul 2007.
  9. Schapira A et al. PROUD: The impact of early vs. delayed treatment with pramipexole on new onset Parkinson's disease. Poster P1366 presented at the 12th EFNS Congress 2008, Madrid, Spain.

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