E4 EZ EE THE WASHINGTON POST.TUESDAY, NOVEMBER 5 , 2019
Foundation, a national nonprofit
group representing patients with
immune disorders, many of
whom receive immune globulin.
“It is the one thing, if you have an
antibody deficiency, that gives
you gas in the tank. It is necessary
to live.”
Made from human blood dona-
tions, immune globulin contains
infection-fighting antibodies de-
rived from blood plasma, and it is
typically administered to patients
intravenously in a hospital or an
infusion center. The medicine is
highly effective and has become
popular in recent years among
doctors who routinely prescribe it
for off-label conditions.
Jerry Siegel, a clinical associate
professor at Ohio State University
College of Pharmacy, said doctors
are using the treatment, known as
IG therapy, as a medicine for ail-
ments such as strep infections
that have crossed the blood-brain
barrier, infertility and even toe
fungus.
“We don’t always know why it
works, but it works,” Siegel said.
“When it was taking off in the
’80s, we would see patients come
into the hospital on a gurney so
flaccid they were unable to walk.
The next day, after their IG thera-
py, they were able to get up and
walk out the door. When you see
some really profound results like
that, it is really convincing to
prescribers.”
Shortages of immune globulin
have become more frequent in the
past few years, spurred by de-
mand for the medicine. Neverthe-
less, manufacturers say the cur-
rent shortage is among the worst
they have experienced since the
treatment has been on the mar-
ket.
In a statement in August, the
Food and Drug Administration
said that “despite increased sup-
ply of immune globulin products
in recent years, the demand for IG
products has also increased over
the same time and there is an
ongoing shortage.”
While the agency does not have
the authority to force an increase
in production, FDA officials said
they are trying to help mitigate
the shortage by working with
drug companies to boost supply.
Even so, the shortage is depriv-
ing patients of crucial treatment,
and some have resorted to desper-
ate measures. In Orlando, Laurel
Smith gave the hospital bottles of
immune globulin so that they
could continue treating her son,
Lowry, 7, who suffers from a rare
form of autoimmune encephali-
tis, called GAD-65, which means
his immune system attacks his
brain.
Lowry is treated with aggres-
sive medicines that dampen his
body’s immune response and
leave him with no natural defens-
es against invading germs that
can lead to illnesses and infec-
tions. As a result, Lowry gets in-
travenous immune globulin
(IVIG) treatments every month.
Without the treatments, exposure
to the outside world could send
him into a coma.
“Lowry needs triple immune
suppression to beat his disease,
but he has become a bubble boy
where a single infection could kill
him without IVIG to give protec-
tion from day-to-day germs,” his
mom said.
In 2017, just after Lowry was
diagnosed with limbic encephali-
tis, his doctor ordered home
health IVIG infusions. But doc-
tors soon decided to give the infu-
sions in a hospital as opposed to in
the home along with other treat-
ments, leaving his mother with
two bottles of the immune globu-
lin. Knowing its value, she held on
to it for over two years, assuring it
was always kept properly in case
of an emergency. To everyone’s
surprise, two years later, that
emergency came when they were
told that there were no more im-
mune globulin supplies, the hos-
pital could not obtain it, and Low-
ry’s infusion was canceled.
Michael Ganio, director of
pharmacy practice and quality at
the American Society of Health-SHORTAGE FROM E1 System Pharmacists, a trade
group, said that doctors are re-
sponding to the shortage by re-
ducing doses and lengthening the
time between treatments. He
pointed out that, in the past few
weeks, many medical offices have
been calling patients to tell them
that their infusion appointments
were canceled. “People are taking
a hard look at who is receiving the
medicine, and really, is it the right
treatment,” Ganio said.
This is where a tension point
has been created among the dif-
ferent communities who use im-
mune globulin. Some say that,
given the shortage, certain ill-
nesses should get priority. And
the Immune Deficiency Founda-
tion put out a statement in July
saying doctors should find suit-
able alternative medicines.
“For our population, there is no
substitute,” said Boyle, the IDF
president.
Many experts say that it will not
be easy to prevent immune globu-
lin shortages from continuing to
be a problem. According to the
Plasma Protein Therapeutic Asso-
ciation, which represents makers
of plasma-based medicines, while
collections continue to rise in the
United States, supply is failing to
meet the steady increase in de-
mand. Manufacturers operate
collection centers throughout the
country that pay people about
$30 for donated plasma.
Among the companies that
manufacture the medicine are
Takeda Pharmaceuticals, CSL
Behring, Grifols and ADMA Bio-
logics. Siegel said it can take seven
to 12 months to produce and sup-
ply plasma-based medicines to
customers. It can take more than
1,000 plasma donations to make a
one-year supply for a patient.
Katie Joyce, a spokeswoman
for Takeda, said the company was
making “efforts to optimize both
plasma collecting and manufac-
turing capacity, opening more col-
lection centers and more recently
investing in a new manufacturing
facility in the U.S.”
CSL Behring also noted that it
was working hard to manufacture
more product “with ongoing in-
vestment in state-of-the-art man-
ufacturing facilities around the
world to increase manufacturing
efficiency.”
Brad Pick, a Grifols spokesman,
said the company has plans to
open more infusion centers for
collecting plasma for the immune
globulin. The company is building
a new plant in Clayton, N.C. When
it’s operational in 2021, the com-
pany will have increased its pro-
duction capacity by more than
35 percent compared with today,
he said.
For patients, the shortage is
frustrating because there is not a
lot they can do to fix the problem.
Families can’t organize a blood
drive to help collect plasma. The
collected plasma is processed at a
central manufacturing plant and
then distributed, so donation
rates at a collection center do not
tie directly to availability of medi-
cines for local patients.
“We just don’t know when the
supply will increase,” Ganio said.
One manufacturer, he said, is
waiting on FDA approval to build
a new plant. But he said there is
“not a lot of transparency” from
the manufacturers.
In Massachusetts and other ar-
eas, some hospitals have notified
patients that immune globulin
will not be available to them until
next year.
Juli Hunt, whose son, Colton, 8,
was airlifted to Children’s Nation-
al Hospital from Fredericksburg
four years ago during an attack of
anti-NMDA receptor encephali-
tis, has been traveling to the hos-
pital in the District for monthly
intravenous immune globulin.
Last month, she received a notice
that he would no longer be receiv-
ing the IVIG treatments, and that
the subcutaneous version is a sol-
id option.
“I get that they are saving what
they have for those who are criti-
cal,” Hunt said. “But I am very
worried about how we are going
to do without it.”
[email protected]Drop in supplies of
plasma-based medicine
leaves patients at risk
ISTOCK“Presumably, it’s more than
just the check-in,” said health
sciences researcher Lisa Barbera
at the University of Calgary dur-
ing a phone interview in August.
“Maybe there’s something
about managing the symptoms
themselves that is directly benefi-
cial,” she said. “Maybe the man-
agement of the symptoms has
indirect benefits, like maybe you
can stay on chemotherapy longer,
or don’t have dose reduction be-
cause your side effects are being
monitored better.”
Barbera recently led an analy-
sis of data from patients treated
for cancer between 2007 and 2015
at Cancer Care Ontario. During
check-in, patients are directed to
a touch screen where they can
answer a short, 16-question sur-
vey about their symptoms. Their
answers are used and addressed
by providers during the visit;
they’re also stored and trended
over time.
Barbera and her colleagues
wanted to know whether routine
reporting on symptoms made a
difference in outcomes.
In health systems around the
world — not just in Canada — this
information isn’t usually docu-
mented or analyzed. It’s also of-
ten not stored with patient’s re-
cords, she said.
The researchers compared sur-
vival rates among people who had
never answered a survey to those
who had answered at least one
during treatment. They matched
patients in each group by age, sex,
cancer type and date of diagnosis,
ultimately studying more than
120,000 matched pairs.
The results, published in May,
were startling. Patients who an-
swered the survey were less than
half as likely to have died during
the study period than people who
never answered the questions.
“There is a strong argument to
be made for using these measures
in routine care,” said Barbera,
who presented the results at the
2019 meeting of the American
Society of Clinical Oncology. “But
this idea, that we have to change
how we do our assessments with
patients, is paradigm-shifting.”
Until the past few years, the
idea that a patient’s experience
could be measured and then in-
CANCER FROM E1 form treatment decisions was
seen as being too nebulous to be
useful in treating cancer. After all,
symptoms seem like a subjective
experience.
“Even if we thought [patient-
reported outcomes] were impor-
tant, they were too soft and sub-
jective to do anything useful
with,” said Andrea Pusic, chief of
plastic surgery and reconstruc-
tion at Brigham and Women’s
Hospital in Boston, in August.
She has used PROs to study pa-
tient satisfaction with breast re-
construction after mastectomies.
Broadly, oncology has under-
gone a general shift toward pa-
tient-centered care over the past
two decades. In the past two
years, research into the use of
PROs has surged in oncology.
That’s partly because researchers
have developed sophisticated
new tools to use that information,
and partly because of two recent
randomized clinical trials, both
published in 2017, that suggest
PROs have untapped benefits.
One, published in JAMA, was
carried out between 2007 and
2011 and led by oncologist Ethan
Basch. It involved more than 750
people treated for a range of
advanced cancers at Memorial
Sloan Kettering Cancer Center in
New York City. (Basch is now at
the University of North Carolina
at Chapel Hill.)
During their treatment, half
the patients were asked to answer
an online survey every week with
12 questions about their symp-
toms. (The delivery method is
crucial, as some studies estimate
that up to half of patients don’t
report symptoms to their doctors
during visits.)
If a patient’s answers suggest-ed discomfort or another new
problem, a provider followed up.
The other patients were assigned
to a standard care, which meant
regular visits with an oncologist.
Basch’s group found that peo-
ple who reported their symptoms
via the online program lived, on
average, five months longer than
people who didn’t. In the context
of cancer treatments, that’s a big
deal.
For a new therapy, it would be
considered a rousing success: The
clinical trial that led to the ap-
proval of Yervoy (ipilimumab) to
treat metastatic or unresectable
melanoma reported a survival
benefit of four months associated
with the drug. (Yervoy has an
estimated cost of more than
$250,000 per year.)
The other study, published in
the Journal of the National Can-
cer Institute, involved more than
100 patients treated for advanced
lung cancer and was led by oncol-
ogist Fabrice Denis at Jean Ber-
nard Center in Le Mans, France.
Roughly half of the study par-
ticipants tracked symptoms us-
ing a Web-based program; the
rest did not. Denis and his collab-
orators reported in their prelimi-
nary analysis that patients who
monitored symptoms lived, on
average, seven months longer
than patients who didn’t. Earlier
this year, their final analysis con-
firmed that survival benefit.
Basch hypothesizes that PROs
provide a way to detect remis-
sions or treat side effects quickly,
without waiting for an appoint-
ment or even having to call the
doctor.
“People lived longer with PRO
monitoring. Relapses were iden-
tified earlier. And when they were
found early, and intervened on
earlier, people lived longer and
did better,” he said during an
interview in August.
And a longer life isn’t the only
benefit researchers have found
since then.
“Monitoring PROs improved
people’s symptoms and quality of
life,” he said. “It decreased use of
the emergency room.”
To Basch, the evidence is clear.
These technologies pick up symp-
toms that clinicians will miss, not
because of a lack of empathy but
because of the limitations of hu-
man communication within thelarge-scale health system.
The challenge, he said, is im-
plementing good PRO tools in
practice. “The truth is that it’s
hard to do, and can easily be done
poorly,” he said
“It’s frustrating that it takes so
long to get this into routine prac-
tice,” said Sandra Wong, chief of
surgery at Dartmouth-Hitchcock
Health in New Hampshire. “And
practice totally lags behind evi-
dence right now. We have all this
great data about how it works,
and we know it will take years and
years before people put it into
practice.”
The gold standard of medical
evidence is the randomized clini-
cal trial, like the ones carried out
by Basch and Denis. But both of
those studies analyzed patient
data within a single institution.
Achieving similar results in mess-
ier, everyday clinical practice can
be difficult. Barbera, in Calgary,
launched her recent retrospective
study as a way to measure the
impact of PROs in a real-world
setting.
Barbera points to interactions
between doctors and patients as a
potential challenge to reaping the
benefits of PROs.
“Clinicians may underestimate
what’s happening, or miss what’s
happening, and patients don’t
want to volunteer what’s happen-
ing,” she said. “They want to be
seen as well-behaved patients,
good patients.”
Wong agrees. “We rely on the
patient to call us when some-
thing’s wrong,” she said. “A lot of
patients wait too long.”
Pusic, in Boston, notes that
doctors aren’t taught how to col-
lect and use information about
symptoms from patients. “We un-
derestimate the difficulty of put-
ting that information in the
hands of clinicians in a way that
they would find useful,” she said.
“It’s data they’re not used to deal-
ing with.”
Wong said many institutions
around the world have launched
new programs to capture patient-
symptom data with varied suc-
cess. And they’re not just in can-
cer: A range of fields have begun
to investigate the best ways to use
PROs. “We’re seeing it done a
million different ways,” Wong
said.
[email protected]Reporting symptoms aids cancer care
Patients who answered
the survey were less
than half as likely to
have died during the
study period than
people who never
answered the questions.
BY KARIN BRULLIARDThe video of Cinder-Block the
obese cat went viral recently, a few
days after her veterinarian posted
it to Facebook: Sitting still at the
edge of an underwater treadmill,
the 22-pound feline moves one
wet gray paw with the belt and
meows plaintively to an off-screen
vet tech encouraging her feeble
workout.
Cinder-Block’s instant fan base
had a word for her: relatable.
Veterinarians had another: typ-
ical.
“We see cats that fat every day.
Every day,” said Brita Kiffney, an
associate veterinarian at North-
shore Veterinary Hospital in Bell-
ingham, Wash., where Cinder —
the cat’s name before the clinic
added “Block” in a nod to her
stoutness — has resided since be-
ing relinquished by her owner
several weeks ago.
“Twenty years ago, we didn’t
see 25 pound cats,” said Ernie
Ward, a veterinarian who found-
ed the Association for Pet Obesity
Prevention, adding that the
Cinder-Block video keeps pop-
ping up in his text messages.
“Nowadays, 20 pounds is the new
normal.”
America has a fat cat problem.
A fat pet problem, really: More
than 50 percent of dogs are over-
weight or obese, according to esti-
mates by Ward’s group. But it’s
worse among cats. Ward, who
surveys vet clinics every year,
found that 60 percent of cats
qualified last year — and of those,
more than half are obese. Cinder
is just one among the masses, and
their numbers are rising.
Veterinarians have been talk-
ing about this for years, and they
say they cringe every time a roly-
poly cat becomes an Internet su-
perstar. Part of the problem, in
their view, is that we see Cinder-
Blocks as cute, or at least funny.
“When I see that cat, I don’t see
the excess fat. I don’t see the size. I
just see the disease,” Ward said.
Fat pets live shorter lives. A cat
as large as Cinder-Block is highly
likely to develop diabetes, Ward
said. Like many overweight pets,
she has arthritis, which can make
jumping to the floor or even walk-
ing painful.
How did we get here? Not
knowing what a healthy cat body
looks like is one way, veterinari-
ans say. Showing love through
treats — and a perpetually full
bowl — is another. In the United
States, cats are more likely to live
exclusively indoor lifestyles than
they used to, so they’re not pounc-
ing and chasing and climbing as
much. They are also skilled at
demanding food, often at dawn.Deborah Linder, a veterinarian
who heads the Tufts Obesity Clin-
ic for Animals, recalled working
with a personal trainer who
owned a 20 pound cat. She asked
what he would tell the cat if it
were a client.
“He said, ‘Oh, I’d make him do
kitty pushups and make him cut
out the calories. But, well, she
meows at me,’ ” Linder said. “That
really hit home for me that this is
much more about the relation-
ship people have with their pets.”
Other factors can contribute to
pet weight gain, veterinarians say.Genetics play a role. Hypothyroid-
ism, a rare ailment, can cause cats
to pack on pounds. Even an ani-
mal’s microbiome may be in-
volved, Ward said.
Incredibly, Cinder-Block is
slimmer than she used to be — at
one point, she waddled about at
25 pounds, Kiffney said. Her pre-
vious owner had multiple pets
and struggled to keep Cinder-
Block’s feedings separate from
those of her slimmer feline house-
mates.
Her girth eventually was chal-
lenging for the owner to manage.
“She’s so fat that she gets poop
stuck to her bottom,” requiring
frequent wiping, Kiffney said. The
cat was also getting regular uri-
nary tract infections, causing her
to urinate in the house.
Cinder-Block will stay for a
while at Northshore — in a room
“bigger than a bedroom,” all to
herself, Kiffney said — as she
works toward her goal weight of
12 pounds. She’ll eventually live
with the office manager.
Meanwhile, she’s getting more
famous as fans follow her weight-
loss journey. Northshore’s Face-
book page had just under 2,000
followers before the treadmill
vide. Now this animal hospital in
a small city has more than 15,000,
and its Instagram account has
42,000 — three times as many as
Cedars-Sinai, a large human hos-
pital in the megalopolis of LosAngeles.
Cinder-Block’s regimen in-
volves prescription weight-loss
food and low-key play. Kiffney
said they use the underwater
treadmill — one of only two in the
county — because it reduces the
weight on her joints. The clinic
has taken some flak on social
media for “torturing” a cat with
water, Kiffney said, but she said
she thinks Cinder-Block is the
rare kitty that can cope.
“She has a really placid atti-
tude,” she said. “She’s just easy
going, friendly, like a dog when
you talk to her. She’ll flop on her
side so you can pet her belly.”
The treadmill is typically used
for dogs, Kiffney said, though one
other feline patient, a cat named
Fatty, also relied on it to drop
pounds. (His video didn’t go viral.)
For cats, reducing food is much
more important than exercise,
Ward said. He warned that weight-
loss is slow-going — usually only a
half-pound a month at best.
At that rate, Cinder-Block will
need nearly two years to reach her
goal. So far, she’s lost three-tenths
of a pound, Kiffney said. A more
recent video shows the cat walk-
ing on the treadmill with a tad
more vigor. “We’re still working
on her enthusiasm for that,” Kiff-
ney said. More at washingtonpost.com/
scienceCat is a viral video star, but her obesity isn’t so cute
Veterinarians warn
that too many of our
pets are overweight
BRITA KIFFNEY
Cinder-Block, a 22-pound cat in Bellingham, Wash., is famous for expressing displeasure about a
treadmill workout in a video that went viral. America has a fat pet problem, especially with cats.
Cinder is just one among the masses, and their numbers are rising, veterinarians say.“When I see that cat, I
don’t see the excess fat.
I don’t see the size. I just
see the disease.”
Ernie Ward, a veterinarian who
founded the Association for Pet
Obesity Prevention