Sarah Watts is a health and science writer based in Chicago. Follow her on Twitter at @swattswrites.
A few days before Christmas 2015, Paige Alexandria, a 28-year-old counselor at the Austin Women's Health Center in Texas, found out she was pregnant.
Alexandria had missed the cutoff for a medication abortion by three days.
"It was an unplanned pregnancy, and instantaneously I knew I needed an abortion," Alexandria recalls. Already a mother of two children, one with special needs, a third child was not something Alexandria and her husband felt prepared to take on. "Mentally, I knew my limit. I wasn't prepared for a third and I didn't want one," she says.
At an ultrasound appointment one week later, scans showed she was a little over eight weeks pregnant. Alexandria opted to have an abortion as soon as possible, and preferably with medication. "I really wanted to avoid a surgical abortion," she says. "It sounded a lot more invasive, and I'm already uncomfortable with pap smears and pelvic exams, so I initially went in wanting to do the pill."
But at the time, medication guidelines stipulated that one of the pills, called Mifepristone, could only be prescribed to end a pregnancy at eight weeks gestation or earlier – Alexandria had missed the cutoff by three days. If she wanted to end the pregnancy, she would need to undergo a surgical abortion, otherwise known as a vacuum aspiration abortion.
With a vacuum aspiration abortion, doctors dilate the cervix and manually aspirate out the contents of the uterus. Medication abortion, on the other hand, consists of the patient taking two pills – Mifepristone, which blocks the hormones that help the pregnancy develop, and Misoprostol, which empties the uterus over a period of days, identical to a miscarriage.
Alexandria was upset about the change of plans but resolute in her decision to end the pregnancy. "The fact that I didn't really have a choice in how my procedure was performed has made the experience just a little more sensitive for me," she says. She scheduled the earliest available appointment for a surgical abortion.
Paige Alexandria would have chosen to terminate her pregnancy with medication if the regulations were less stringent.
(Photo courtesy of Alexandria)
Like Alexandria, many people looking to terminate a pregnancy opt to do so with medication. According to research from the Guttmacher Institute, medication abortions accounted for nearly 40 percent of all abortions in the year 2017 – a marked increase from 2001, when medication abortions only accounted for roughly five percent of terminations. Taken 24-48 hours apart, Mifepristone and Misoprostol have a 95-99 percent success rate in terminating pregnancies up to 63 days – or nine weeks – of gestation, according to the American College of Obstetrics and Gynecology (ACOG).
But even though the World Health Organization (WHO) considers medical abortion to be highly safe and effective, the medication is still carefully guarded in the United States: Mifepristone is only available for terminating pregnancies up to 10 weeks gestation, per the FDA, even though limited research suggests that both are safe and effective at terminating pregnancies between 12 and 20 weeks.
Additionally, a separate set of regulations known as a Risk Evaluation and Mitigation Strategy (REMS) means that patients can only take Mifepristone under specific circumstances. Mifepristone must be distributed in person by a healthcare provider – usually interpreted in most states as a doctor or nurse practitioner – who has registered with the drug's manufacturer. The medication cannot be distributed through a pharmacy, so doctors who wish to provide the drug must stock the medication in-office, and both the provider and the patient must sign a form that warns them of the "risk of serious complications associated with Mifepristone," according to the FDA.
"REMS is a set of restrictions that the FDA puts on the distribution of drugs it considers dangerous or risky in some way," says Dr. Elizabeth Raymond, an OB-GYN and senior medical associate at Gynuity Health Projects. Although not always called REMS, these restrictions have been imposed on Mifepristone since the medication was approved by the FDA in 2000, Raymond says.
Raymond is part of a growing number of physicians and researchers who want to eliminate the REMS requirements for Mifepristone, also known by its brand name Mifeprex. In 2017, Raymond and several other physicians authored a paper in the New England Journal of Medicine (NEJM) arguing that Mifepristone is extremely safe and needlessly over-regulated.
"When the FDA first approved [Mifepristone] and imposed these requirements, they might have made sense 19 years ago when there was limited information about the use of this treatment in the United States," says Dr. Daniel Grossman, director at Advancing New Standards in Reproductive Health at UCSF and co-author of the 2017 report in the NEJM. "Now, after 19 years, it's clear that this medication is very safe, and safer than a lot of others available in a pharmacy."
Since 2000, Mifepristone has been implicated in 19 deaths, making its mortality rate 0.00063 percent.
According to their research, over three million people have taken Mifepristone since it was approved in 2000. Since then, Mifepristone has been implicated in 19 deaths, making its mortality rate 0.00063 percent. Even then, the risk is inflated, Grossman says.
"The requirement is that practitioners need to report any deaths that occur after taking these medications, and so you'll see deaths included in that figure which are homicides or suicides or something unrelated to taking Mifepristone," says Grossman. In contrast, Acetaminophen – better known as Tylenol – was associated with 458 overdose deaths between 1990 and 1998, as well as 56,000 emergency room visits and 26,000 hospitalizations. Sildenafil, better known as Viagra, was linked to 762 deaths in the first twenty months after it was approved by the FDA. Yet neither Tylenol nor Viagra have been burdened with the same REMS restrictions as Mifepristone.
"It's clearly about more than just the safety of the medication at this point," says Grossman. "It's more about stigma related to abortion and politics."
For people who want a medication abortion, the REMS requirements mean they often need to take off work to schedule a doctor's appointment, arrange for transportation and childcare, and then arrange an additional doctor's appointment days afterward to take the second dose of medication. While surgical abortion procedures are quicker (usually a one-day outpatient procedure, depending on gestation), many people prefer having the abortion in the comfort of their home or surrounded by family instead.
Paige Alexandria, who counsels people seeking abortions at her job, says that survivors of sexual violence often prefer medical abortions to surgical ones. "A lot of time survivors have a trauma associated with medical instruments or having pelvic exams, and so they're more comfortable taking a pill," she says.
But REMS also creates a barrier for healthcare providers, Grossman says. Stocking the medication in-office is "a hassle" and "expensive," while others are reluctant to register their name with the drug manufacturer, fearing harassment or violence from anti-choice protestors. As a result, the number of practitioners willing to provide medical abortions nationwide is severely limited. According to Grossman's own research published in the journal Obstetrics and Gynecology, 28 percent of OBGYNs admitted they would administer medication abortions if it were possible to write a prescription for Mifepristone rather than stock it in-office.
Amazingly, the restrictions on Mifepristone have loosened since it first came on the market. In 2016, the FDA updated the guidelines on Mifepristone to allow its use until 10 weeks gestation, up from eight weeks. But doctors say the REMS restrictions should be eliminated completely so that people can obtain abortions as early as possible.
"REMS restrictions inhibit people from being able to get a timely abortion," says Raymond, who stresses that abortion is generally more comfortable, more affordable, and safer for women the earlier it's done. "Abortion is very safe no matter when you get it, but it's also easier because there's less risk for bleeding, infections, or other complications," Raymond says. Abortions that occur earlier than eight weeks of gestation have a complication rate of less than one percent, while an abortion done at 12 or 13 weeks has a three to six percent chance of complications.
And even for people who want a medication abortion early on in their pregnancy, REMS restrictions make it so that they may not have time to obtain it before the 10-week period lapses, Raymond says.
"If you're seven weeks pregnant but it takes you three weeks to figure out travel and childcare arrangements to go into the doctor and take this medication, now you're at the cutoff date," she says. "Even if you manage to get an abortion at nine weeks, that's still a later gestational age, and so the risks are increased."
In 2016, at a little over nine weeks gestation, Alexandria completed her abortion by having a D&E. But because she didn't have anyone to drive her home after the procedure, she wasn't able to have sedation throughout, something she describes as "traumatic."
"I had the abortion completely aware and coherent, and paired with the fact that I hadn't even wanted a surgical abortion in the first place made it harder to deal with," Alexandria says.
"When you're just a day or two past eight weeks and you want an abortion – why is medication not immediately available?"
Today, Alexandria shares her story publicly to advocate for abortion care. Although she doesn't regret her surgical abortion and acknowledges that not everyone experiences surgical abortion the same way she did, she does wish that she could have gone a different route.
"If I had to do it over, I would still try to do the pill, because [the surgical abortion] was such a terrifying experience," she says. "When you're just a day or two past eight weeks and you want an abortion – why is medication not immediately available? It just doesn't make sense."
Sarah Watts is a health and science writer based in Chicago. Follow her on Twitter at @swattswrites.
In late March, just as the COVID-19 pandemic was ramping up in the United States, David Fajgenbaum, a physician-scientist at the University of Pennsylvania, devised a 10-day challenge for his lab: they would sift through 1,000 recently published scientific papers documenting cases of the deadly virus from around the world, pluck out the names of any drugs used in an attempt to cure patients, and track the treatments and their outcomes in a database.
Before late 2019, no one had ever had to treat this exact disease before, which meant all treatments would be trial and error. Fajgenbaum, a pioneering researcher in the field of drug repurposing—which prioritizes finding novel uses for existing drugs, rather than arduously and expensively developing new ones for each new disease—knew that physicians around the world would be embarking on an experimental journey, the scale of which would be unprecedented. His intention was to briefly document the early days of this potentially illuminating free-for-all, as a sidebar to his primary field of research on a group of lymph node disorders called Castleman disease. But now, 11 months and 29,000 scientific papers later, he and his team of 22 are still going strong.
On a Personal Mission<p>In the science and medical world, Fajgenbaum lives a dual existence: he is both researcher and subject, physician and patient. In July 2010, when he was a healthy and physically fit 25-year-old finishing medical school, he began living through what would become a recurring, unprovoked, and overzealous immune response that repeatedly almost killed him.</p><p>His lymph nodes were inflamed; his liver, kidneys, and bone marrow were faltering; and he was dead tired all the time. At first his doctors mistook his mysterious illness for lymphoma, but his inflamed lymph nodes were merely a red herring. A month after his initial hospitalization, pathologists at Mayo Clinic finally diagnosed him with idiopathic multicentric Castleman disease—a particularly ruthless form of a class of lymph node disorders that doesn't just attack one part of the body, but many, and has no known cause. It's a rare diagnosis within an already rare set of disorders. Only about 1,500 Americans a year receive the same diagnosis. </p><p>Without many options for treatment, Fajgenbaum underwent recurring rounds of chemotherapy. Each time, the treatment would offer temporary respite from Castleman symptoms, but bring the full spate of chemotherapy side effects. And it wasn't a sustainable treatment for the long haul. Regularly dousing a person's cells in unmitigated toxicity was about as elegant a solution to Fajgenbaum's disease as bulldozing a house in response to a toaster fire. The fire might go out (though not necessarily), but the house would be destroyed.</p><p>A swirl of exasperation and doggedness finally propelled Fajgenbaum to take on a crucial question himself: Among all of the already FDA-approved drugs on the market, was there something out there, labeled for another use, that could beat back Castleman disease and that he could tolerate long-term? After months of research, he discovered the answer: sirolimus, a drug normally prescribed to patients receiving a kidney transplant, could be used to suppress his overactive immune system with few known side effects to boot.</p><p>Fajgenbaum became hellbent on devoting his practice and research to making similar breakthroughs for others. He founded the Castleman Disease Collaborative Network, to coordinate the research of others studying this bewildering disease, and directs a laboratory consumed with studying cytokine storms—out-of-control immune responses characterized by the body's release of cytokines, proteins that the immune system secretes and uses to communicate with and direct other cells. </p><p>In the spring of 2020, when cytokine storms emerged as a hallmark of the most severe and deadly cases of COVID-19, Fajgenbaum's ears perked up. Although SARS-CoV-2 itself was novel, Fajgenbaum already had almost a decade of experience battling the most severe biological forces it brought. Only this time, he thought, it might actually be easier to pinpoint a treatment—unlike Castleman disease, which has no known cause, at least here a virus was clearly the instigator. </p>
Thinking Beyond COVID<p>The week of March 13, when the World Health Organization declared COVID-19 a pandemic, Fajgenbaum found himself hoping that someone would make the same connection and apply the research to COVID. "Then like a minute later I was like, 'Why am I hoping that someone, somewhere, either follows our footsteps, or has a similar background to us? Maybe we just need to do it," he says. And the CORONA Project was born—first as a 10-day exercise, and later as the robust, interactive tool it now is. </p><p>All of the 400 treatments in the CORONA database are examples of repurposed drugs, or off-label uses: physicians are prescribing drugs to treat COVID that have been approved for a different disease. There are no bonafide COVID treatments, only inferences. The goal for people like Fajgenbaum and Stone is to identify potential treatments for further study and eventual official approval, so that physicians can treat the disease with a playbook in hand. When it works, drug repurposing opens up a way to move quickly: A range of treatments could be available to patients within just a few years of a totally new virus entering our reality compared with the 12 - 19 years new drug development takes.</p><p>"Companies for many decades have explored the use of their products for not just a single indication but often for many indications," says Stone. "'Supplemental approvals' are all essentially examples of drug repurposing, we just didn't call it that. The challenge, I think, is to explore those opportunities more comprehensively and systematically to really try to understand the full breadth of potential activity of any drug or molecule."</p>
The left column shows the path of a repurposed drug, and on the right is the path of a newly discovered and developed drug.
Cures Within Reach
A Confounding Virus<p>The FDA declined to comment on what drugs it was fast-tracking for trials, but Fajgenbaum says that based on the CORONA Project's data, which includes data from smaller trials that have already taken place, he feels there are three drugs that seem the most clearly and broadly promising for large-scale studies. Among them are <a href="https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30503-8/fulltext" target="_blank" rel="noopener noreferrer"><u>dexamethasone</u></a>, which is a steroid with anti-inflammatory effects, and <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-combination-treatment-covid-19" target="_blank" rel="noopener noreferrer"><u>baricitinib</u></a>, a rheumatoid arthritis drug, both of which have enabled the sickest COVID-19 patients to bounce back by suppressing their immune systems. The third most clearly promising drug is <a href="https://www.nih.gov/news-events/news-releases/full-dose-blood-thinners-decreased-need-life-support-improved-outcome-hospitalized-covid-19-patients" target="_blank" rel="noopener noreferrer"><u>heparin</u></a>, a blood thinner, which a recent trial showed to be most helpful when administered at a full dose, more so than at a small, preventative dose. (On the flipside, Fajgenbaum says "it's a little sad" that in the database you can see hydroxychloroquine is still the most-prescribed drug being tried as a COVID treatment around the world, despite over the summer being <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2021801" target="_blank" rel="noopener noreferrer"><u>debunked</u></a> widely as an effective treatment, and continuously since then.)</p><p>One of the confounding attributes of SARS-CoV-2 is its ability to cause such a huge spectrum of outcomes. It's unlikely a silver bullet treatment will emerge under that reality, so the database also helps surface drugs that seem most promising for a specific population. <a href="https://jamanetwork.com/journals/jama/fullarticle/2773108" target="_blank" rel="noopener noreferrer"><u>Fluvoxamine</u></a>, a selective serotonin reuptake inhibitor used to treat obsessive compulsive disorder, showed promise in the recovery of outpatients—those who were sick, but not severely enough to be hospitalized. <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772185" target="_blank" rel="noopener noreferrer"><u>Tocilizumab</u></a>, which was actually developed for Castleman disease, the disease Fajgenbaum is managing, was initially written off as a COVID treatment because it failed to benefit large portions of hospitalized patients, but now seems to be effective if used on intensive care unit patients within 24 hours of admission—these are some of the sickest patients with the highest risk of dying. </p><p>Other than fluvoxamine, most of the drugs labeled as promising do skew toward targeting hospitalized patients, more than outpatients. One reason, Fajgenbaum says, is that "if you're in a hospital it's very easy to give you a drug and to track you, and there are very objective measurements as to whether you die, you progress to a ventilator, etc." Tracking outpatients is far more difficult, especially when folks have been routinely asked to stay home, quarantine, and free up hospital resources if they're experiencing only mild symptoms. </p><p>But the other reason for the skew is because COVID is very unlike most other diseases in terms of the human immune response the virus triggers. For example, if oncology treatments show some benefit to people with the highest risk of dying, then they usually work extremely well if administered in the earlier stages of a cancer diagnosis. Across many diseases, this dialing backward is a standard approach to identifying promising treatments. With COVID, all of that reasoning has proven moot. </p><p>As we've seen over the last year, COVID cases often start as asymptomatic, and remain that way for days, indicating the body is mounting an incredibly weak immune response initially. Then, between days five and 14, as if trying to make up for lost time, the immune system overcompensates by launching a major inflammatory response, which in the sickest patient can lead to the type of cytokine storms that helped Fajgenbaum realize his years of Castleman research might be useful during this public health crisis. Because of this phased response, you can't apply the same treatment logic to all cases.</p><p>"In COVID, drugs that work late tend to not work if given early, and drugs that work early tend to not work if given late," says Fajgenbaum. "Generally this … is not a commonplace thing for a virus." </p>
Thursday, March 11th, 2021 at 12:30pm - 1:45pm EST
On the one-year anniversary of the global declaration of the pandemic, this virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the COVID-19 vaccines. Planned topics include the effect of the new circulating variants on the vaccines, what we know so far about transmission dynamics post-vaccination, how individuals can behave post-vaccination, the myths of "good" and "bad" vaccines as more alternatives come on board, and more. A public Q&A will follow the expert discussion.
SPEAKERS:<img lazy-loadable="true" data-runner-src="https://leaps.org/media-library/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTY3Mzc4NS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NjYwNjU4NX0.Tdrh5pze5P4XxgiJK3J4JFrsrijfabIzNJz-AATghDE/image.jpg?width=534&coordinates=365%2C3%2C299%2C559&height=462" id="87554" class="rm-shortcode" data-rm-shortcode-id="b6c7311be7aec25807f9af19b683bf1d" data-rm-shortcode-name="rebelmouse-image" data-width="534" data-height="462" />
Dr. Paul Offit speaking at Communicating Vaccine Science.commons.wikimedia.org<p><strong><a href="https://www.research.chop.edu/people/paul-a-offit" target="_blank" rel="noopener noreferrer">Dr. Paul Offit, M.D.</a>, is the director of the Vaccine Education Center and an attending physician in infectious diseases at the Children's Hospital of Philadelphia. He is a co-inventor of the rotavirus vaccine for infants, and he has lent his expertise to the advisory committees that review data on new vaccines for the CDC and FDA.</strong></p>
Dr. Monica Gandhi
UCSF Health<p><a href="https://profiles.ucsf.edu/monica.gandhi"></a><strong><a href="https://profiles.ucsf.edu/monica.gandhi" target="_blank">Dr. Monica Gandhi, M.D., MPH,</a> is Professor of Medicine and Associate Division Chief (Clinical Operations/ Education) of the Division of HIV, Infectious Diseases, and Global Medicine at UCSF/ San Francisco General Hospital.</strong></p>
Dr. Onyema Ogbuagu, MBBCh, FACP, FIDSA
Yale Medicine<p><strong><a href="https://medicine.yale.edu/profile/onyema_ogbuagu/" target="_blank" rel="noopener noreferrer">Dr. Onyema Ogbuagu, MBBCh</a>, is an infectious disease physician at Yale Medicine who treats COVID-19 patients and leads Yale's clinical studies around COVID-19. He ran Yale's trial of the Pfizer/BioNTech vaccine.</strong></p>
Dr. Eric Topol
Dr. Topol's Twitter<p><strong><a href="https://www.scripps.edu/faculty/topol/" target="_blank" rel="noopener noreferrer">Dr. Eric Topol, M.D.</a>, is a cardiologist, scientist, professor of molecular medicine, and the director and founder of Scripps Research Translational Institute. He has led clinical trials in over 40 countries with over 200,000 patients and pioneered the development of many routinely used medications.</strong></p>