Article In Brief
Headache experts agree that home oxygen therapy could alleviate cluster headache symptoms, but the Centers for Medicare and Medicaid Services has denied reimbursement for the therapy.
For nearly a decade, people who experience cluster headaches—cycles of brief, excruciatingly severe headaches on one side of the head—and the neurologists and other clinicians who treat them have been fighting to convince the Centers for Medicare and Medicaid Services (CMS) to provide coverage for one of the least complicated, most effective treatments for these headaches: high-flow oxygen therapy delivered in the home setting.
In 2011, CMS issued a National Coverage Determination (NCD) on the use of home oxygen therapy for cluster headaches, stating that “CMS believes that the evidence does not demonstrate that the home use of oxygen to treat CH improves health outcomes in Medicare beneficiaries with CH. Therefore, the home use of oxygen to treat CH is not reasonable and necessary...unless provided in the context of an approved clinical study.”
The NCD dismissed a randomized controlled trial, published in JAMA in 2009, that found that 78 percent of patients with cluster headache were pain-free after administration of oxygen in more than 150 attacks and called for a large prospective clinical trial limited to patients 65 and older with cluster headache.
(Clusterbusters, a non-profit research and educational organization dedicated to finding effective cluster headache treatments, estimates that between 200,000 and one million people in the United States live with cluster headache, but notes that high-quality research has not been done to determine an accurate number, nor is there a good estimate of how many cluster patients are over the age of 65.)
Since the 2011 NCD, leaders of the AAN, the American Headache Society (AHS), the Alliance for Headache Disorders Advocacy (AHDA), and Clusterbusters have submitted multiple appeals of the decision to the CMS, which have each been rejected. In 2014, then-CMS administrator Marilyn Tavenner denied a formal reconsideration request that was supported by a bipartisan group of more than a dozen US Senators. Since then, new research has been published to support the safety and efficacy of high-flow oxygen therapy for these headaches, which have been called “suicide” and “alarm clock” headaches because of their intensity and regularity.
A report published earlier this year in the journal Headache found that among 139 participants in a retrospective single-interaction national survey who were 65 years of age or older (Medicare eligible), 77 percent reported oxygen therapy to be effective: 18 percent “completely,” 38 percent “very,” and 21 percent “somewhat.” By comparison, 67 percent of subjects 65 years or older found triptan therapy, the current primary first-line therapy for cluster headache, to be effective: 11 percent “completely,” 42 percent “very,” and 13 percent “somewhat.”
In January 2019, a coalition of experts from the AHDA submitted another formal request for reconsideration of the NCD. “In addition to the study in Headache, 13 peer-reviewed research studies or topic reviews...have been published since issuance of CAG-00296R [the CMS NCD on the therapy] that support the efficacy/effectiveness, tolerability, and safety of oxygen for the acute treatment of cluster headache attacks,” they wrote.
Including the 2009 study in JAMA, they noted that there are now three published prospective randomized controlled trials that report efficacy, tolerability, and safety of acute oxygen treatment for cluster headache attacks, and that included subjects 65 years or older. “Though these studies were not powered to report subgroup analyses limited only to such older subjects, none of these studies reported serious adverse events for oxygen therapy for subjects of any age,” they wrote.
But on July 16, 2019, in a letter to Representative Andy Harris, MD, (Rep-MD) who is the former chief of obstetric anesthesiology at Johns Hopkins and who experiences cluster headaches, CMS administrator Seema Verma indicated that the agency is “unable to open the NCD reconsideration and conduct the NCD analysis,” although “we intend to do so in the future.”
“It's one of the most remarkable instances of public policy that's inexplicable, harmful and immovable,” said Robert E. Shapiro, MD, PhD, FAAN, past president of the AHDA, and professor of neurological sciences at the University of Vermont. “There is no justification in terms of the science, in terms of empathy, in terms of cost, for their bureaucratic obstinacy on this issue.”
The coverage denial doesn't just affect Medicare patients, noted AHS President Kathleen B. Digre, MD, FAAN, professor of neurology and ophthalmology at the John A. Moran Eye Center and chief of the division of headache and neuro-ophthalmology at the University of Utah in Salt Lake City.
“If CMS doesn't approve home oxygen therapy for cluster headache, many private insurance carriers won't approve it either. That means that some of these patients won't get access to the treatments they need. It's particularly absurd because delivering this therapy in the home setting is not that expensive. The costs vary regionally and even from one medical supply house to another, but a tank of oxygen typically costs about $50-100. If you use two or three tanks a month, plus tubing, it would cost less than $200-300 a month. Or you could purchase an in-home oxygen concentrator, a one-time expense which means you don't have to refill tanks, for anywhere from $595 to $2000. That's not that great of a cost to CMS, but to an older person on a fixed income, it certainly can be.”
Neurology Today reached out to James Rollins, MD, PhD, director of the CMS division of items and devices, for comment. No response had been received by press time.
“Just Go to the ED”
CMS representatives have insisted to the AAN representatives and other advocates that if Medicare beneficiaries want to receive oxygen therapy for their cluster headaches, they can do so in the “controlled setting” of an emergency department (ED) or their doctor's office, where high-flow oxygen therapy for cluster is covered.
“That completely misunderstands the clinical problem,” Dr. Shapiro said. “The nature of these attacks is that while they are excruciatingly severe, they are typically over within an hour. It's absurd to expect that a Medicare beneficiary—someone older than 65 and often with mobility issues—can get transported to their doctor's office or an emergency room, get checked in, and get therapy in a timely way. Furthermore, CMS expects them to treat these attacks in this way up to eight times per day, every single day. And it's also much more expensive to receive this kind of treatment in an ED rather than in the home setting.”
Patients who visit the emergency department for cluster headache are often in such extreme pain that they are treated with opioids—which are much less effective than oxygen therapy and pose the added risk of addiction. In a cluster headache cohort, for example, 41 percent of subjects were actively prescribed opioids and the cohort had an associated 3.4-fold higher incidence of opioid dependence, researchers reported in a 2017 study in Headache.
Sumatriptan and injectable dihydroergotamine (DHE), the only acute therapies approved by the US Food and Drug Administration (FDA) for cluster headache, are both contraindicated in those with significant cardiovascular risk factors—commonly found in many Medicare patients. [The FDA approved galcanezumab for episodic cluster headache in June.]
“Sumatriptan becomes problematic in those with frequent attacks of cluster headache,” said Vincent Martin, MD, professor of clinical medicine at the University of Cincinnati College of Medicine and president of the National Headache Foundation.
“You are not supposed to use sumatriptan more than a couple of times a day, and many cluster patients have up to eight cluster headaches per day. Some patients end up trying therapies that aren't even FDA-approved, such as anti-inflammatory shots like Toradol or narcotic medications, which have never been studied in cluster—but you can't leave these people with no other options.”
That is because the headaches cause unremitting pain and distress. In a recent case series in Cephalalgia, 175 cluster headache patients were polled about suicidal ideation, planning, and acts. More than 35 percent reported active suicidal ideation during attacks, 5.8 percent reported suicidal planning, and 2.3 percent reported actually attempting suicide.
“Cluster is one of the most severe forms of pain that anyone can possibly go through, and to withhold a therapy that's been shown in randomized controlled trials to be effective for these people is inhumane, and frankly, I would say unethical,” said Dr. Martin.
The Impossible Trial
The additional trial that CMS has requested is just not feasible, experts said. In their formal request to CMS Administrator Verma for reconsideration of the NCD, the AHDA noted that prevalence estimates suggest that fewer than 50,000 people over 65 have cluster headaches, rendering it effectively an orphan disease in this population. And because of the cardiovascular risks of sumatriptan and DHE, all enrolled subjects would need to be free of significant cardiovascular risk factors, so that they could either be randomized to an active comparator arm (sumatriptan or DHE) or receive rescue therapy.
“This cardiovascular exclusion would likely significantly limit trial enrollment. Cluster headache patients have a significantly higher prevalence of smoking which magnifies cardiovascular risks. Furthermore, 19 percent of Medicare beneficiaries have diagnosed heart disease, 42 percent self-report at least one heart condition, and > 69 percent have some form of cardiovascular disease,” they wrote.
“You could never recruit enough subjects aged 65 or older lacking cardiovascular issues, who were sufficiently in cycle where they were experiencing these attacks, for a sufficiently long duration, who had never had oxygen therapy before,” said Dr. Shapiro. “It's just not feasible. And from the 14 peer-reviewed research studies or topic reviews on oxygen therapy for cluster headache, several of which enrolled a number of Medicare-eligible patients, none reported serious adverse events in any age group, and no significant differences in efficacy, tolerability, or safety for patients 65 and older emerged in subgroup analyses.”
“I don't understand what the problem is,” Dr. Digre said. “This seems like a pretty straightforward thing to cover. The evidence we've put forward in our most recent appeal is strong, and I would certainly hope they would consider that evidence and put the coverage through.”
“It's an extraordinary situation,” said Dr. Shapiro. “It's a devastating condition with a simple remedy and the government is getting in the way, harming elderly Americans needlessly.”