Mariam Al-Attar, a 5th year medical student from Lancaster University, had never thought much about rare diseases until one day on her Rheumatology placement. A consultation between a young lady with a rare disease and a dedicated consultant taught Mariam about the challenges faced by patients with rare diseases and how their doctors can make all the difference by being their advocates.
This blog is adapted from her full winning essay entitled “TRAPPED – an insight into two sisters’ struggle to access treatment for a rare genetic disease” which was published in Orphanet Journal of Rare Diseases 2018 13:37. The Student Voice Essay Competition 2018 is now open for submissions so check it out here!
History, Examination, Investigation, Diagnosis…?Treatment
I must admit that, until recently, I hadn’t really given much thought to the issues surrounding rare diseases. When studying for exams, I dutifully learnt what I thought were all the steps in managing various conditions. Check the airway, breathing, circulation. Give oxygen. Give pain relief. With no thought about what happens when there’s a drug available, but it can’t be given for licensing or funding reasons. That is, until I observed one particular consultation during my rheumatology attachment.
My consultant informed me that the next patient we were seeing had a disease called TRAPS. I had never heard of it. She explained to me that it is incredibly rare, and that managing this patient had been extremely difficult. I presumed this must be because no treatment had been discovered. The patient, a young lady called Sophia, was called in. It became immediately clear to me that this was not a ‘normal’ clinic appointment. Instead of discussing symptoms, they talked about funding applications. Listening carefully, I figured out that there is a treatment for TRAPS, and Sophia was being advised to “make it last”. I couldn’t understand why the consultant would say this.
I then found out that Sophia would soon have her treatment completely withdrawn, despite desperately needing it. This left me even more bewildered. This was not a side of medicine I had seen before. To make matters worse, she had a half-sister, Lucy, who was in the same situation. I decided to find out more about TRAPS to understand how this could be possible.
TRAPS: Tumour Necrosis Factor Associated Periodic Syndrome
Tumour Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is an autosomal dominant auto-inflammatory disorder. It is incredibly rare, with an estimated prevalence of one in a million. That means there are only around 60 TRAPS patients in the whole country. If left untreated, patients run the risk of amyloidosis and renal failure. In the case of Sophia and her sister, this is risk magnified by the particular TRAPS mutation that they have. The rarity of this condition, along with its vague and varying clinical presentation, meant that the two sisters suffered with TRAPS for years before they were diagnosed. Recurrent attacks of fever, joint pain and rash led to an initial misdiagnosis of Systemic Juvenile Idiopathic Arthritis. After years of unsuccessful treatment, the sisters felt disillusioned and stopped attending clinic appointments.
Challenge One: Getting an Accurate Diagnosis
The breakthrough moment came when Lucy was referred to the rheumatology department during a disease flare-up. This was the first time a rheumatologist had seen the symptoms in their active state, and finally, the nature of the rash became clear. The consultant was the first to consider a genetic cause and the sisters received the correct diagnosis, over a decade after their main symptoms began. However, in hindsight, the sisters had actually been suffering with TRAPS related problems since birth. This delay is a common story for TRAPS patients, who often remain ‘enigmas’ for years on end, being passed between clinicians at an unsettling rate. However, this was just the beginning for the two sisters, who had unfortunately received a diagnosis with an acronym well suited to their subsequent predicament regarding access to treatment.
Challenge Two: Access to Treatment
Unlike many rare diseases, TRAPS does have a licensed treatment. Studies have demonstrated that the Interleukin-1 receptor blocker, Anakinra, reliably induces and maintains disease remission. For Sophia and Lucy, Anakinra, can truly be described as a wonder drug. However, obtaining it has been an immense struggle for all involved, exposing fundamental flaws in resource allocation for rare diseases. From what I understand, funding for rare diseases falls within the remit of NHS England’s Specialised Services, who publish commissioning policies allowing specialist centres to prescribe drugs and receive reimbursement. Until recently, this meant that patients with TRAPS could receive Anakinra through the National Amyloidosis Centre. But after April 2016, just months before the sisters were diagnosed, this policy and funding were withdrawn. With no commissioning policy in place at the time the sisters were diagnosed, the National Amyloidosis Centre submitted several individual funding requests on their behalf. However these requests were rejected repeatedly by NHS England on seemingly random and inconsistent grounds, including one assertion that TRAPS is too rare, followed by another stating that it is not rare enough. Inadequate trial data was also cited as justification for rejection, despite the evidence base being strong enough for the drug to be licensed, and the rarity of the disease leaving little scope for randomised controlled trials. Aside from the inconsistency of the decisions being made, I was struck by how short-sighted this funding refusal was because Anakinra costs far less than the dialysis that the sisters will almost certainly require if untreated.
A Diagnosis But No Access to Treatment
Repeated rejections from NHS England left the sisters and their doctors feeling helpless. Although their nearly lifelong mystery had been solved, there appeared to be nothing anybody could do about it, simply because of the rarity of the diagnosis. Had they been diagnosed with Rheumatoid Arthritis, Anakinra would have been funded without question. I could scarcely imagine the sisters’ frustration.
One Doctor’s Refusal to Give Up
However, the consultant’s refusal to give up and inspiring dedication to helping the sisters did lead to a small breakthrough. She approached the producers of Anakinra directly at a conference and convinced them to provide a ‘compassionate supply’ of 6 months’ worth of treatment for free. For Sophia and Lucy this was life-changing. For the first time they were finally able to have a taste of a normal life, previously denied to them by TRAPS. With treatment their disease went into complete remission. However, the sisters continued to live with uncertainty, knowing that their lifeline would soon be taken away. Adding a more sinister dimension to the situation was the knowledge of the potentially lethal consequences of discontinuing Anakinra once it had been initiated. It was towards the end of these six months that the consultation I saw took place, and it was for this reason that the sisters were being advised to take their medication sparingly.
A Fortunate Turn of Events
In this 6-month remission period Sophia was well enough to become pregnant. She had been unsuccessfully trying to conceive for over seven years due to her active disease. This wonderful turn of events led to a flurry of requests to the hospital trust for continuation of the treatment. They eventually agreed to fund the drug temporarily – until the end of Sophia’s pregnancy and until January for Lucy. However, it is now March, as I write this, and the prescriptions of Anakinra appear to be continuing despite the arbitrary deadlines given for stopping the drug.
With untiring commitment, the professor at the National Amyloidosis Centre has personally worked on a commissioning policy for TRAPS, hoping to get it approved in time to prevent any need for treatment discontinuation. It is looking like this may possibly happen around May – but for now, the sisters’ futures remain uncertain.
Common Challenges Faced by Patients with Rare Diseases
This story highlights two barriers to treatment for patients with TRAPS which can be broadly applied to many rare diseases. The first is the challenge of getting an accurate diagnosis. The second is access to treatment.
Doctors as Advocates
However, this story also highlights the significant impact that clinicians can have on an individual level. The commitment of dedicated doctors is the only reason the sisters were ever able to obtain treatment. Until policies are changed nationally, this case should encourage doctors to persevere for their patients, however time-consuming and frustrating it may be. For the two sisters, it has resulted in some months of much needed relief and a much-wanted pregnancy. Although their futures are uncertain, the relentless work of the clinicians involved means that there is hope for future funding. I may be a lot less naïve now, but I still struggle to comprehend the idea of telling a patient that I cannot help them simply because their disease is too rare. Denying treatment to one in a million is denying one patient too many. I have been inspired by the outstanding level of dedication shown by the doctors involved in the sisters’ case, and have realised that being a good doctor is so much more than diagnosing and prescribing. We should be advocates for our patients. This is particularly relevant for those with rare diseases, who often face greater barriers to accessing treatment, in a system making tough decisions with limited resources. Sophia and Lucy’s story has empowered me to go above and beyond to help my future patients, because no one should ever be trapped.
Mariam Al-Attar won Findacure’s Student Voice Essay Competition 2017. She graduated in 2018 and is currently an FY1 doctor. Mariam first became interested in rare diseases during a rheumatology placement at medical school, and this is one of the things that has inspired her to pursue a career in rheumatology. She is also passionate about medical education as well as academics and research.
This blog is an adaptation of the essay published in the OJRD – visit their website for the full article.
M4RD work with Findacure on the Student Voice Competition and this year’s competition is now open! The winner will have their essay published in Orphanet Journal of Rare Diseases! There are also cash prizes and the opportunity to speak at the M4RD annual symposium at The Royal Society of Medicine in Feb 2019! Deadline for submission is 12th November so check out full details here. And don’t forget to sign up to receive the latest news from M4RD about competitions and events.