Sickle Cell Patients Have Even Fewer Choices for Pain Relief

By Crystal Lindell

Pfizer is voluntarily taking its sickle cell disease medication Oxbryta (voxelotor) off the market, amid concerns that it could be causing deaths and other complications. Doctors are being told to stop prescribing Oxybryta and to start sickle cell patients on other medications. 

Pfizer said its decision was based on clinical data showing the overall benefits of Oxbryta no longer outweighs the risks. In postmarketing studies, patients taking Oxbryta had higher rates of a vaso-occlusive crisis, a condition that causes severe pain when mis-shaped red blood cells block the flow of blood to tissues and organs. Patients taking the medication also had higher death rates. 

The company said it was also discontinuing all clinical trials of Oxbryta and expanded access programs worldwide. Oxbryta has been on the market since 2019. The medication works by preventing red blood cells from becoming C-shaped and breaking down too quickly.

Pfizer’s announcement delivers another setback to sickle cell patients, who already lack treatment options and face discrimination in the healthcare system. There aren’t many treatments for sickle cell disease (SCD), a lifelong inherited blood disorder that can cause complications starting in early childhood and lead to shortened life expectancy.

The lack of treatments is due in part to the fact that SCD is relatively rare in wealthier countries. It primarily impacts those whose ancestors are from sub-Saharan Africa, an under-served patient population. About 100,000 Americans have SCD, a number so low it discourages drug makers from developing medications to treat it. Over 8 million people worldwide have SCD.

Many sickle cell patients have also borne the brunt of opioid phobia in the United States. They often end up having to go to the ER during pain flares, where many are treated as drug seekers. 

‘This Is a Step Backward’

The National Alliance of Sickle Cell Centers released a statement saying the Pfizer recall was disappointing. But they were glad that Pfizer was re-evaluating Oxbryta to see which SCD patients may still benefit from it..

"At this time, the risks are too great but there may be an opportunity in the future to better understand how to optimize this medication (and all) medications in sickle cell disease,” the organization said. 

It urged sickle cell patients currently taking Oxbryta to make an appointment with their doctor and emphasized that patients should not stop taking the drug abruptly. Instead, they should work out a weaning plan with their care team. 

“Don’t lose faith,” they said. “This is a step backward but we will stay on the path to better outcomes for everyone.”

The organization added that these types of issues highlight the importance of long-term follow-up with a sickle cell center and of clinical registries like GRNDaD, an international registry developed to track the effectiveness of SCD treatments.

“We encourage everyone to see a sickle cell specialist annually to review what is and what is not working for them,” the organization said. “We all know that sickle cell disease is highly variable, many people are different and respond differently to medications. We need to better understand these differences to identify which medication will work best for which people."

An article in MedScape explained that Pfizer’s decision to recall Oxbryta (voxelotor) came amid increased scrutiny of the drug by the European Medicines Agency (EMA). 

EMA began a review of voxelotor in July after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo. Another trial showed a higher  number of deaths than expected. 

Pfizer’s Aida Habtezion, Pfizer’s Chief Medical Officer, said the recall was in the best interest of patients. 

“Our primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options,” Habtezion said. “We advise patients to contact their physicians to discuss alternative treatment while we continue to investigate the findings from our review of the data.”

Patients, physicians, pharmacists, or other healthcare professionals with questions about Oxbryta should contact Pfizer at 1-800-438-1985.

Steroids Raise Risk of Hospitalization for Sickle Cell Patients

By Pat Anson, PNN Editor

People with sickle cell disease who are prescribed a corticosteroid – an anti-inflammatory medicine often used to treat pain – are significantly more likely to be hospitalized with a severe pain episode, according to a new study.

Sickle cell disease (SCD) is a genetic disorder that causes red blood cells to form in a crescent or sickle shape, which creates painful blockages in blood vessels known as vaso-occlusive episodes (VOE), which can lead to infections, strokes and organ failure. About 100,000 Americans live with SCD, primarily people of African or Hispanic descent.

“Individuals living with SCD often suffer crippling episodes of pain, which can greatly impair their quality of life,” said Ondine Walter, MD, of Toulouse University Hospital in France, lead author of the study published in the journal Blood.

Walter and her colleagues looked at medical data for over 5,100 patients with SCD in the French National Health Insurance Database between 2010 and 2018. Patients had to have at least one hospitalization for VOE to be included, and their corticosteroid exposure was identified using outpatient prescribing records.

Researchers found that patients exposed to a corticosteroid in the month prior to a pain flare were nearly four times more likely to be hospitalized for VOE than those who did not get a steroid. The median time between filling a prescription for a corticosteroid and hospitalization was just five days.

Nearly half the patients (46%) were prescribed a corticosteroid during the study period, an indication of just how common steroid treatment is for SCD. Walter said the results demonstrate the need for better education of clinicians and patients about the potential risks of corticosteroids, especially when there isn’t a clear reason to use them.

“Based on our data, corticosteroids are commonly prescribed for conditions unrelated to their underlying SCD. Vaso-occlusive events and related hospitalization appear to follow corticosteroid prescription fairly quickly. This evidence suggests corticosteroids may be contributing to the events and should be avoided as much as possible in these patients,” Walter said. “Corticosteroids are mostly easy to avoid, and in circumstances when they are necessary, it’s important to start them in collaboration with an SCD expert and to take all appropriate precautionary measures to administer them safely.”

The American Society of Hematology’s Clinical Practice Guideline recommends against using corticosteroids for acute pain in SCD patients.

The French research team also found that SCD patients taking the drug hydroxyurea had about half the risk of being hospitalized for VOE than those not taking it, which may indicate the drug has a protective effect. Hydroxyurea is often prescribed to SCD patients to reduce the number of pain flares and the need for blood transfusions. Men benefited from hydroxyurea more than women and children.

It’s not uncommon for someone with SCD to visit an emergency room a few times each year due to acute pain or complications such as anemia. Many are disappointed by the experience. A 2021 survey of SCD patients in the U.S. found that nearly two-thirds felt ER staff were rude, ignorant or misinformed about sickle cell disease, didn’t take their pain seriously or believed they were drug seekers.

Most Sickle Cell Patients Face Stigma During ER Visits

By Pat Anson, PNN Editor

Nearly two-thirds of people with sickle cell disease in the U.S. feel judged and stigmatized when they visit an emergency department due to a pain flare, according to a new survey by Health Union.

About 100,000 Americans live with sickle cell disease (SCD), a genetic disorder that mainly affects people of African or Hispanic descent. SCD causes red blood cells to form in a crescent or sickle shape, which can create blockages in blood vessels that cause intense pain.  It’s not uncommon for someone with SCD to visit an ER a few times each year due to pain or complications such as anemia, stroke, infection and organ failure.

Health Union surveyed 111 people living with SCD to share their experiences dealing with the disease and how they are perceived by healthcare professionals, coworkers, teachers, friends and family members. Most said they did not feel judged or stigmatized by others – except when dealing with ER staff.

Many felt ER staff were rude, ignorant or misinformed about sickle cell disease, didn’t take their pain seriously, and believed they were drug seekers. Nearly half of those surveyed (43%) said they avoided going to the ER because they worried that people would judge them.

“A doctor judged me during a hospitalization. He stated I wasn’t in that much pain to be using Dilaudid. He also stated I was drug seeking because a sickle cell crisis can be managed with Motrin. His statement is not true!” one participant told Health Union.

Sickle cell patients had an entirely different take on their pharmacists, hematologists and primary care providers. Over half (53%) trusted their providers and felt their primary care doctors were friendly, understanding, easy to talk to, and provided excellent care.

"Navigating the healthcare system can already be complex, but undergoing such wildly different experiences can make access to reliable, timely, effective care even more difficult for people with sickle cell disease," said Olivier Chateau, Health Union's co-founder and CEO.

The finding that many people are not happy with their pain treatment in hospitals is not unique to sickle cell patients.  A 2016 PNN survey of over 1,250 hospitalized pain patients found that most felt they were labeled as addicts or drug seekers. Over 80% believed hospital staff were not adequately trained in pain management and over half rated the quality of pain care in hospitals as poor or very poor.  

A report last year by the National Academies of Sciences, Engineering, and Medicine found that sickle cell patients often face discrimination and stigma when navigating the healthcare system. The report found that SCD received little attention from the healthcare community compared to other chronic illnesses. To get proper treatment, many sickle cell patients have to educate themselves about their disease and become their own advocates.

The Health Union survey found that nearly three out of four sickle cell patients (73%) were currently using a prescription analgesic. Many others took prescription strength NSAIDs (35%), muscle relaxants (23%) or anti-anxiety/antidepressant drugs (16%). Only 5% said they experienced an issue with substance abuse.