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What Are the Implications of OFF Periods, Economic Burden in Parkinson Disease?


A recent webinar discussed what causes symptom recurrence in patients with Parkinson disease and what implications this has for health outcomes and health care cost.

Behind Alzheimer disease, Parkinson disease (PD) serves as the second-most common neurodegenerative condition worldwide, with more than 1 million cases in the US alone. More troubling, however, is the rate at which it is growing in the general population.

Daniel Kremens, MD, JD, co-director of the PD and Movement Disorders Center at Jefferson Medical College of Thomas Jefferson University, spoke about this topic recently in a webinar called, “Understanding Parkinson Disease: OFF Periods and Economic Burden.” Kicking off the discussion, Kremens pointed out that “the fascinating thing is that it is increasing at a faster rate than any other neurodegenerative disease and we don’t know why that is.”

At nearly 60,000 new cases of PD each year, many patients are being introduced to the physical and cost-related implications of the condition. Moreover, early-onset PD among those in their 20s, 30s, and 40s can further exacerbate cost as “it can hit people in their prime earning years.” Based on a study referenced in the webinar, 23% to 75% of patients with PD reported early retirement due to their condition, characterized as 4 to 7 years earlier than the general population.

The ability to continue working for those diagnosed with PD depends on a number of factors, such as management of OFF periods, which is the recurrence of symptoms after a period of symptom control. Based on prior studies, OFF periods have been shown to impede work productivity and employment in patients, as well as have a greater impact on the paid employment of respective caregivers when compared with those caring for patients without OFF periods.

So, what factors contribute to the prevalence of OFF periods?

As Kremens noted, “early in the disease, even though you have lost a lot of your dopaminergic neurons, you still have enough left that they can take the dopamine that you’re getting from your medicine, levodopa, convert it to dopamine in the brain and the cells in the brain can uptake that dopamine and store it to release it later in the day.”

However, as PD is a progressive disease, this ability changes as more dopaminergic neurons die and are then unable to buffer or release more dopamine. In fact, OFF periods are shown to occur in 40% of patients after 4-5 years of diagnosis, and in 70% within 9 years of using levodopa, he said.

Additionally, the gut plays a prominent role in the ability to manage OFF periods. “Most of PD medicines, including carbidopa/levodopa, are taken orally and if you have gastroparesis—slowness of the gut and problems with absorption, you may take medicine and it may be sitting in the gut when its supposed to be moving through and getting released,” explained Kremens. “As a result of that the patient may have delayed ON, or dose failures, and this results in OFF periods even when patients are taking their medicines as prescribed.”

Expanding the discussion on the financial burden of PD, Kremens referenced the annual economic impact of PD in the United States, which totalled $14.4 billion in 2010. For each patient, the direct cost was $12,800 and the indirect cost, such as early retirement, was $10,000. Furthermore, utilization was significantly high, attributing to 1.9 million inpatient days, 1.3 million physician office visits, and 30,000 emergency visits.

When factoring in OFF periods, a prior study referenced in the webinar indicated that patients experiencing OFF periods for ≥ 50% of their day reported more than 4 times higher health care costs ($8992) than those who experienced OFF periods < 10% of their day ($2131).

“We know that PD is much more than just a motor problem. Motor and non-motor problems can be significantly troublesome and disabling to patients, and that OFF periods, those periods when patient symptoms are re-emerging despite taking medications, translate into higher health care costs for patients,” concluded Kremens.

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