For levodopa-responsive patients with Complex/Advanced Parkinson's disease
Consider DUODOPA when available combinations of Parkinson medicinal products have not given satisfactory results
Why is continuous dopaminergic stimulation, which can be an alternative to pulsatile, non-continuous stimulation, important?3,5-7
Over time, progressive neurodegeneration and the chronic use of oral dopaminergic therapy, such as levodopa, cause intermittent stimulation of dopamine receptors in the brain, which may lead to treatment-resistant motor complications5,6
Continuous infusion of DUODOPA can provide a smooth and consistent delivery of levodopa8
In a multicentre, multiple-dose, open-label study of 19 subjects with Complex/Advanced PD receiving DUODOPA over 30 days:8
- DUODOPA rapidly achieved therapeutic plasma levels of levodopa8
- DUODOPA maintained stable plasma levodopa levels over 16 hours8
- DUODOPA's continuous intestinal delivery allows rapid absorption, avoiding fluctuations in drug delivery that result from erratic gastric emptying1,8
Adapted from Nyholm D et al. 2013.
PD=Parkinson's disease; SD=standard deviation.
In a study, DUODOPA provided predictability of 'ON' time and 'OFF' time9
A 54-week, international, prospective, open-label study assessed the safety and efficacy of DUODOPA in Complex/Advanced PD patients with severe motor fluctuations (N=354). Safety was the primary endpoint; for the majority of patients AEs were mild or moderate and transient. Secondary endpoints included 'OFF' time, 'ON' time with/without troublesome dyskinesia, UPDRS and HRQoL outcomes.9
Complex/Advanced patients with severe motor fluctuations on DUODOPA had a significant increase in 'ON' time without troublesome dyskinesia and a significant decrease in 'OFF' time compared with baseline (both p<0.001), which was sustained throughout the study.9
Adapted from Fernandez HH et al. 2015.
AE=adverse event; HRQoL=health-related quality of life; PD=Parkinson's disease; UPDRS=Unified Parkinson's Disease Rating Scale.
In a study, benefits in non-motor symptoms were sustained over a period of two years with DUODOPA10
The GLORIA registry: A 24-month, non-interventional, observational registry study, evaluating the long-term efficacy of DUODOPA on motor and non-motor symptoms, QoL and safety in Complex/Advanced PD patients (N=375).10
Significant and sustained improvements in motor fluctuations and some associated non-motor symptoms were observed, particularly in:10*
- Sleep/fatigue (p<0.001)10
- Mood/cognition (p=0.004)10
- Gastrointestinal symptoms (p<0.001)10
Adapted from Antonini A et al. 2017.
*Improvement measured by reduction from baseline in the mean non-motor symptoms scale (NMSS) scores.
GI=gastrointestinal; NMSS=non-motor symptoms scale; PD=Parkinson's disease; QoL=quality of life.
Safety and tolerability9,10
A generally well-understood safety profile with years of experience9,10
- Levodopa therapy has been used in clinical practice for over 40 years and has an established and well-understood safety profile1,12
- DUODOPA can provide continuous infusion of levodopa, the gold standard treatment, for levodopa-responsive Parkinson's disease in Complex/Advanced patients1,4,13
- A safety analysis was performed for patients who received DUODOPA in all studies, to allow for a summary of the drug-related adverse reactions1,9,14
Drug-related undesirable effects that occur frequently with the DUODOPA system:1
*Adverse drug reactions observed in clinical trials. Frequencies assigned reflect adverse event frequencies and are regardless of causality assigned by the investigator.1
†Impulse control disorders: pathological gambling, increased libido and hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including DUODOPA.1
- Another analysis was performed for patients who received DUODOPA or placebo gel via PEG-J to allow for a summary of procedure- and device-related adverse reactions in all studies1,9,14
Device- and procedure-related undesirable effects that occur frequently with the DUODOPA system include:1
*Adverse drug reactions observed in clinical trials. Frequencies assigned reflect adverse event frequencies and are regardless of causality assigned by the investigator.1
†Complication of device insertion was a commonly reported adverse reaction for both the nasojejunal tube and the PEG-J. This adverse reaction was co-reported with 1 or more of the following adverse reactions for the nasojejunal tube: oropharyngeal pain, abdominal distention, abdominal pain, abdominal discomfort, pain, throat irritation, gastrointestinal injury, esophageal haemorrhage, anxiety, dysphagia, and vomiting. For the PEG-J, this adverse reaction was co-reported with 1 or more of the following adverse reactions: abdominal pain, abdominal discomfort, abdominal distension, flatulence, or pneumoperitoneum. Other non-serious adverse reactions that were co-reported with complication of device insertion included abdominal discomfort, abdominal pain upper, duodenal ulcer, duodenal ulcer haemorrhage, erosive duodenitis, gastritis erosive, gastrointestinal haemorrhage, peritonitis, pneumoperitoneum, small intestine ulcer.1
PEG-J=percutaneous endoscopic gastro-jejunostomy
- Most device and procedure related adverse reactions to DUODOPA occurred during the first 28 days after the PEG-J procedure1,9,14
- Serious side effects include: Anaphylactic reaction, leucopenia, thrombocytopenia, agranulocytosis, neuroleptic malignant syndrome, eye disorders, gastrointestinal bleeding and duodenal ulceration, malignant melanoma, and sepsis1
DUODOPA has a generally well-understood safety profile9
A 54-week, international, prospective, open-label study assessed the safety and efficacy of DUODOPA in Complex/Advanced PD patients with severe motor fluctuations (N=354).9
324 (91.5%) of the 354 enrolled patients completed the NJ phase and proceeded to PEG-J.9
Adapted from Fernandez HH et al. 2015.
*A single event could be coded to >1 preferred term.
AE=adverse event; NJ=nasojejunal; PEG-J=percutaneous endoscopic gastro-jejunostomy.
- For the majority of patients adverse events were mild (18.5%) or moderate (43.8%) and transient9
- Low withdrawal rate (7.6%) due to adverse events, most commonly due to complication of insertion of device9
For more detailed safety information, please refer to the Summary of Product Characteristics (SmPC).
References
- DUODOPA (levodopa/carbidopa intestinal gel) Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/medicine/20786. Accessed August 2022.
- Burack M, et al. Mov Disord Clin Pract 2018;5:383-93.
- Antonini A. J Mov Disord 2009;2:4-9.
- Slevin JT, et al. J Parkinsons Dis 2015;5:165-74
- Olanow CW, et al. Nat Clin Pract Neurol 2006;2(7):382-92.
- Thanvi BR and Lo TCN. Postgrad Med J 2004;80:452-8.
- Nyholm D. Parkinsonism Relat Disord 2007;13:S13-7.
- Nyholm D, et al. AAPS J 2013;15:316–23.
- Fernandez HH, et al. Mov Disord 2015;30(4):500–9.
- Antonini A, et al. Parkinsonism Relat Disord 2017;45:13–20 and Supplementary Data.
- Antonini A, et al. Neurodegener Dis Manag 2018;8:161-70.
- Poewe W, et al. Clin Interv Aging 2010;5:229-38.
- Boyd JT, et al. Clin Park Relat Disord 2020;2:25-34.
- Olanow, et al. Lancet Neurol. 2014;13:141-9.
Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.
Adverse events should also be reported to AbbVie on [email protected]
UK-DUOD-210223. Date of preparation: August 2022.