Fabio is a patient with hereditary amyloidosis (ATTRv). Here he explains his struggle to get a diagnosis and treatment in Brazil, illustrating the unmet needs for Brazilians with the disease

When Fabio Almeida started to have pain in his legs in 2012, he recognised the symptoms as the same as those experienced by his father, who had died of hereditary amyloidosis (ATTRv, also known as hATTR) 12 years before. Fabio knew from genetic testing in 2008 that he was carrying the same disease-causing gene variant that his father had, but he hoped his emerging symptoms might have another cause.

“It felt like I had pins in my legs, and they felt heavy as if I’d been running a marathon. I was also very tired.”

Fabio went to see a doctor in Sao Paulo, who dismissed his concerns, telling a family member that the symptoms had a psychological cause. Later, Fabio learned that this doctor was not a specialist in amyloidosis, as Fabio had initially thought, so he started to search for someone who was better qualified to help. 

He sent an e-mail to the amyloidosis patient organisation in Portugal (he has dual citizenship of Brazil and Portugal), hoping to arrange a meeting with a specialist there. Instead, the patient organisation put him in touch with a specialist in Rio de Janeiro. “In our first conversation, she said it was about 90% certain that I was seeing the start of symptoms related to ATTRv.”

It took three months after that to confirm ATTRv through further testing. As Fabio had suspected, his symptoms were being caused by the disease. The delay he experienced shows the great importance of disease awareness and of access to specialists, he says. “The first doctor was not capable of making a diagnosis, but the second doctor knew what was wrong in the first meeting. This is why it’s so important to have doctors who specialise in this disease.”

“I knew about my family history and I suspected I had the disease. But even for me, it was not possible to get a diagnosis quickly. You can imagine how difficult it is for people that have no idea of what is going on.”

In 2013, the only treatment available to people in Brazil with ATTRv was a liver transplant. But Fabio knew that two people in his family had died following their liver transplant operations, so he was “very afraid” of what the outcome of a transplant might be.

There were treatments for ATTRv at that time, but they had not been approved in Brazil. To get access, Fabio would need to pay for treatment himself, which was impossible because of the cost, or move to Portugal (where he has dual citizenship), which would mean heart-wrenching upheaval for him and his family, or start legal action against the government to force them to give him access. 

Fabio decided to begin legal action on the basis that the government was acting unconstitutionally: it was not fulfilling its obligation to provide its citizens with healthcare, he argued. It would be up to a judge to decide if Fabio’s life was at risk, in which case he would be granted access to the treatment.

“These types of diseases progress quickly and we cannot wait for the ministry of health to eventually approve the treatment. That can take years. My only choice at that moment was to sue the government.”

Fabio’s younger brother had started showing symptoms of ATTRv six months before he had, so they struggled together; first to have access to consultations and then to medicine. It was a “nightmare” of a time for the two of them that was filled with challenge, stress and expense. 

Fabio knew exactly how high the stakes were for the two of them.

“When my father’s first symptoms started, I was 12 years old. And when my father died, I was 22. Between 12 and 22 was a terrible time.”

As the legal process continued, Fabio’s symptoms were worsening. He lost temperature sensation in his legs and feet, and he started having diarrhoea. With having to visit the doctors so regularly and with his legal battle ongoing, he accepted that he would have to work part-time rather than full time and accept the reduction to his income. “I had to enter survival mode,” he says. “It was all or nothing. Because I knew the history of the disease in my family, I was totally focused on either getting this treatment or getting another treatment through a clinical trial.” 

In late 2013, Fabio and his brother won the right to have their treatment reimbursed by the healthcare system, but three months later, the government appealed against the court’s decision, making the continuation of the treatment uncertain. The whole process had already been psychologically difficult and as the legal action continued Fabio’s mental health worsened. “I started to have anxiety crises, because it was too much for me.”

When a clinical trial for a new treatment started in Brazil in 2015 Fabio and his brother looked carefully at the possibility of enrolling. They believed there was a good chance of the treatment being successful, and they knew that enrolling would give them access to the treatment after the trial finished. On the other hand, the clinical trial was a double-blind study in which some patients would be receiving a placebo rather than the active drug. “We took the risk because we were not comfortable with the risk of losing access to the treatment because of the legal action.”

Six months into the 15-month-long clinical trial, Fabio started to suspect that he and his brother were in the placebo arm of the trial because their symptoms were progressing. In his brother’s case, the progression was worse—he lost more than 20 pounds of weight and started having difficulty walking—which made it difficult to decide whether to continue.

“This period was the most difficult of all for me. To have the right to access the treatment, we needed to complete the clinical trial. If we left the clinical trial, we’d have no right to access the treatment once the trial ended.” 

The brothers decided to continue with the trial, and when it ended they were allowed access to the treatment. That new treatment started in October 2016, and once they had started it their symptoms became more stable. Unfortunately, the pain in Fabio’s legs had already become chronic, with pain crises happening on some days. “It is impossible to work with this sort of pain, it’s very disabling,” he says. 

Diarrhoea is another challenge for him and his brother, and for many other patients he knows. “Some patients have diarrhoea all day. So they are afraid to leave their room, which affects their social lives and their work—it’s impossible to work.”

Despite the enormous challenges he has had to face, Fabio considers himself fortunate. “We are lucky because treatments are available now. The stories are very different between our time and my father’s time, 20 years ago.”

In 2013, Fabio reactivated a patient advocacy group for patients with amyloidosis that had been founded in 1989 but was no longer running. He would lead the group for the next eight years.

The organisation required a lot of time and dedication but for Fabio its work was a moral imperative: “When I received the treatment myself, I knew that other people would die without it. I thought about my father who’d died with no chance of treatment, and I couldn’t accept that for other people.”

“It took five years for the government to approve my treatment for other patients. It’s impossible for patients with this disease to wait that long… We are talking about a progressive neurological disease—it’s not possible to reverse its course.”

“A diagnosis can take years. If the patient has no family history of the disease, it is very complicated to navigate through the different levels of the healthcare system. Patients who have a family history are different: they will probably go directly to the reference centres who can make the diagnosis.”

In Fabio’s experience, patients who have a family history of hereditary amyloidosis are often reluctant to accept that they are becoming ill with the disease, and this can add further delay to patients’ diagnostic journeys. “People know about the symptoms, but when they start noticing them, they are in denial that they have started.” Even family members who have been caregivers to a patient with ATTRv, can be slow to respond to the onset of symptoms and don’t seek a diagnosis, so have worse outcomes, Fabio says.

Holistic care is another unmet need too, Fabio says. “Sometimes we have access to diagnosis and treatments, but we don’t have access to holistic healthcare. People only see the disease not the person, but it’s more complicated than that.” This type of approach is about how healthcare is organised, so it is a big challenge for us.” 

In particular, Fabio points to the need for more psychological support for patients. “Our reference centres don’t provide mental health care, so sometimes patients need to set up appointments with psychologists or psychiatrists elsewhere, who aren’t experienced in talking with patients about hereditary diseases. Doctors have to change their minds because they think only about physical healthcare, not mental healthcare.” He believes that doctors would benefit from training about how to talk to patients during appointments and when communicating the results of tests. 

There also needs to be support for families affected by the disease, as the hereditary nature of the disease creates an enormous burden, practically, financially and emotionally. 

“For my mother to have to take care of my grandfather, then to take care of my father, then to have children with the disease… that’s not easy. I didn’t talk with my mother about my diagnosis until I had access to treatment, because otherwise it would have been too much for her.”

Fabio’s greatest hope for the future is that Brazilian patients get early diagnosis of their ATTRv so they can get treatment during the early stages of their disease. There may be “thousands of people” in Brazil with a gene variant that causes ATTRv, but without a diagnosis, he says. 

Many, particularly those living in rural communities (perhaps one or two thousand kilometres away from the specialist centres in the cities) have difficulty getting not only diagnosis but also monitoring and treatment.

“The first step was getting the first treatments approved and the second step is getting people an early diagnosis—so we need healthcare systems capable of making an early diagnosis. Otherwise patients will have many consequences.”

Fabio also hopes that there will be equitable access to diagnosis and treatment across the globe. “I know that in Bolivia, Paraguay, Venezuela and many other countries, there is no treatment available to patients. And imagine, in Africa, for example, how many patients don’t have access to treatment, or even to diagnosis.”

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This digital spotlight has been made possible with financial support from Alnylam Pharmaceuticals. Interviews and writing included in these articles have been independently conducted by RARE Revolution Magazine. All opinions are those of the contributors. RARE Revolution Magazine retains all copyright. RARE Revolution Magazine and Alnylam Pharmaceuticals are not responsible for the content of external sites linked to within this article.

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