Hydroxyurea? A complex, complicated relationship

All my sisters and I were diagnosed within the late 80s and early 90's.

At this time Sickle Cell Disease(SCD) was incredibly rare. Or at least not easily or routinely diagnosed.

Of course this also meant SCD management therapies and medicines were absent. Our family had to rely on research programs and 'a dime a dozen' doctors who knew of research programs to accurately diagnose us.

Magdalene however did not make it. She was diagnosed very late at the age of 3. Before her passing, she developed high fever from a suspected malaria infection, after travelling back to Mombasa from Taveta. She was rushed to the hospital where the doctors did everything they could to manage her fever. Her condition worsened as she developed seizures and later fell into a coma before passing.

Mary and I, also had different experiences growing up. She looked healthier but was more severe and prone to crisis. I, on the other hand exhibited many physical SCD symptoms but had less frequent crises. Even so, we had the same doctors, the same frequency of appointments and were on similar management therapies.

Folic acid, blood transfusion, malaria prophylaxis ( the 2week protocol) and infection prophylaxis i.e. penicillin. But no Hydroxyurea.

This was the first 10 years.

When we moved to Nairobi, we also moved doctors. We were still seen by a paediatrician until the age of 18. Up to this time my sister had approximately 30 transfusions, and I had 10. In addition to a paediatric haematologist we also saw a paediatric cardiologist and paediatric gastroenterologist.

This was possible because my parents were open to advise. They did their research and followed doctors recommendations on our specific health related needs, making sure they made our life as pain free as possible.

At any given time my sister was in the hospital. I was admitted less frequently but never at the same time. Our adolescents were most trying. Every 10 days, crisis would occur at night (10pm onwards) and wailing would ensue. At this point, everyone in the house is up wondering how long it would take this time until there's a form of resolution and no wailing. My parents would use all tools at their disposal to manage the crisis at home. Anti-inflammatories, hot/cold packs, ointments, honey milk, intake of warm water etc. Until finally it subsides or they resolve to rush to the ER.

Please note; I have come to understand this decision making was weighed against available resources, severity of crisis, and availability of off/leave days at work.

It was only until we transitioned to an adult haematologist when Hydroxyurea(HU) came up.

This was the early 2000s i.e 2007.

Hydroxyurea was not yet approved for use for paediatric patients; only adults.

Remember when I said my sister and I were on similar therapies?! Well this is another good example. She was older and was prescribed HU. Despite being hard to come by, our doctor insisted, we take it.

It was precisely after our surgical procedures i.e. a clot removal, gall bladder removal and hip replacement, for my sibling. And my gall bladder removal.

After this period, the doctor prescribed HU, indefinitely.

My sisters health immediately stabilised. Reduced hospitalisation, reduced crisis and SCD related complications. She was consistent on her intake and refills and managed to pursue studies in the US, far away from a support system.

This was significant because no one could imagine a person with sickle cell attaining this level of independence. She was independent and continued to maintain positive health outcomes.

She became incredibly successful to allow her to see the best doctors. It was years later when she had to go through chelation therapy due to iron overload from the many blood transfusions she had since birth.

However, years later, she was discontinued from HU. Her bone marrow stopped producing red cells optimally.

For me, I was not as consistent and diligent with intake of HU. I was the kind to be reminded. ALOT. I attended boarding school, like all my siblings but I was home every weekend. I don't remember ever taking HU, at least not as consistently or as prescribed.

I didn't like having to go to the nurses office daily. I did't like the size of the capsules and I didn't really understand why I had to take them in the first place. I had a deep desire to fit in and look normal.

So unlike my sister whose health stabilised. Mine seemed to deteriorate.

After high school and in university, I had more frequent and severe crises. I was in the emergency room atleast every month with crisis. It was also during this time that my monthly cycle became unbearable.

Between the years of 2013 to 2018 I was completely off HU. I had convinced myself it did more harm than good. It caused cancer and if I continued taking it, I would never forgive myself for intentionally poisoning myself.

It was also during this time that I started my advocacy journey.

This was precipitated by my frustration with the health system in Kenya. It was compounded by the incessant assumption by doctors and decision makers that SCD was not a problem in Kenya. I was not happy.

The doctors asked me questions they should have the answers to and everything was bloody expensive. I had aged out of my parents insurance cover which meant going to the hospital cost me between KES 15000 - 25000 a clinic visit. This included the consultation, labs and tests, medicines.

This cost quadrupled whenever I fell into crisis and had to be hospitalised. And ballooned by 10000% when I was admitted. It was unsustainable and I could not afford it.

So I stopped going, entirely.

I stopped going to clinic visits. I stopped taking hydroxyurea and I essentially, mentally blocked out the sickle cell side of my life and all its associations.,for as long as I could.

Eventually in 2018, these series of choices eventually built up to the mother of all crises.

My heart, my lungs, my kidneys and my liver were all compromised. It started with a UTI and developed into multiple sepsis and my kidneys had to be dialysed. My lungs filled with water as did my legs, early signs of pulmonary hypertension.

My liver required a hepatic and jaundice specialist, my whole body was the colour of turmeric. My lips, my palms, my eyes, my feet., all so so yellow with very swollen legs.

I had a very good doctor who brought me back from a very dire place.

I recall we had to pay a cumulative of USD 15000 of a larger bill at The Aga Khan, the rest of which was waived.

Lol., advocacy ;)

My doctor was obviously disappointed and asked me a simple question I couldn't answer. "Lea why don't you take your hydroxyurea?"

"You need to take your hydroxyurea or your life will be very difficult."

So I have been taking hydroxyurea since.

The HU Reality Among Persons with SCD in sub-Saharan Africa

1 out of 3 sickle cell warriors do not take hydroxyurea.

This of course is anecdotal. What many don't know is that people with sickle cell talk to each other and many do not take hydroxyurea.

There are many reasons for this.

But they don't matter if the people who need to take these medicines are incapable of accessing and affording these medications.

Here are some reasons I think HU isn't taken as it should:

Fragmented education through the patient continuum of care

Upon diagnosis an educational package should be given to let parents and caregivers know the what and why of hydroxyurea. This should be done upon diagnosis or at least the first visit to establish a foundation of care. For the initial years, doctors should emphasise, re-educate and readily prescribe HU to persons with SCD, to ensure adherence. This can look like routine caregiver education, individually or ideally within a support group to have a shared understanding and accountability mechanism. It is easier to be consistent if one has a support system and health providers who continue to educate and inform.

Sub-optimal health transitions

SCD is age specific. Persons with sickle cell have unique physiological, neurobiological, and psychosocial challenges faced through the different development stages.??From childhood, through adolescents, young and mature adulthood and geriatric stages, SCD has specific needs. The lack of education, support and responsiveness through these stages affects clinical adherence, HU dosage and subsequent efficacy. In addition the changing needs as we mature i.e. sexual and reproductive health, nutrition, psychosocial and economic needs are a backdrop giving perspective for continuous social support programs to improve health outcomes at all ages.

Poor HU Branding

When we begin taking HU, the first thing we are told is HU is a cancer drug that is effective for sickle cell. This automatically changes from a manageable condition to a terminal illness. The side effects then go to proof the point., this medicine is indeed toxic. However, instead of enhanced support, we are left to deal with our thoughts and biases., "Why is SCD so neglected we can't find medication specifically for SCD? Or at least do a better job at branding HU for SCD and only SCD?"

HU Side effects

HU has severe side effects especially when it is not dosed or monitored properly. Any side effects visibly affecting our physical appearance affect our self esteem and confidence. Having visibly darkened skin and nails, thinning/loss of hair, nausea, ulceration etc happen to us or a close third party, is off putting leading to discontinuation of HU. In many cases, if one is not attending clinics routinely, this effects persist. A negative perception of HU may develop, shaping adherence for years to come.

Erratic supplies

If we are unable to get these medicines at public health facilities where we have our clinics, we will not attend clinics. Having HU is a key factor enabling adherence to routine clinics. However majority of public health facilities do not stock these in adequate amounts or entirely. These allows pharmacies and drug providers to charge exploitative prices while providing HU of questionable quality.

Drug fatigue

This is when you get tired of routinely taking oral medication. This is so real that I had to fact check with fellow warriors. And truth be told, some of us take routine breaks of up to a month or two each year. This keeps us sane I think. My reason, reduce the HU saturation and allow my body to return to baseline. Not sure how scientific this is but it allows me agency and control.

Cost

Over the years HU has become much more affordable, yet a majority of patients are still unable to afford them. The Social determinants of health are a big factor in one's ability to access care consistently. Working in rural resource poor communities we find low income homes pay dearly for the cost of care. I believe HU can still be made available at a lower cost. If our supply chains are streamlined to allow for collective (government or organisational) procurement as well as have manufacturing done locally, we can still have lower prices. My sweet spot, $5 for a pack of 100.

...

Finally,

This article is not to convince you HU is good or bad. We need to equip ourselves with the right information and make informed decisions.

HU is not a silver bullet for sickle cell. It is one of the few therapies which have led to the best health outcomes for people with sickle cell.

It is generally well tolerated with some possible side effects.

It is the best therapy out there for sickle cell, yet not universally accessible early enough and continuously to gain optimal outcomes for all.

Access, affordability and availability to persons with SCD everywhere should be the main priority for decision makers, policy makers and pharma.

Yes, new therapies are welcome and needed. But not at the expense of a vulnerable population making do with unresponsive health systems, limited policy and financing priorities, and huge out-of-pocket expenditures.

I encourage patients to exercise personal agency by improving lifestyle choices, nutrition, exercise and rest behaviours. The best and/or most optimal outcomes for SCD happen when HU is complemented with a wholistic nurturing lifestyle.

Sincerely,

Lea