A few years ago, Renea Molden’s doctors told her they wanted to take her off her opioid pills. It did not sound like good idea to her.

“I was mad, I’ll be honest. I was mad. I was frustrated,” said Molden, 40, of Kansas City, Mo. She struggles with fibromyalgia, bulging discs and degenerative disc disease. Her doctors were concerned about her potentially taking hydrocodone for the rest of her life, but to her, the three pills she took each day seemed to be the only way she could make it through work, go shopping or even fix dinner.

“It felt like they were taking a part of my life away from me,” she said.

For many people with chronic pain, opioids can seem like the difference between a full life or one lived in agony. Over the past few decades, they have become go-to drugs for acute pain, but Dr. Erin Krebs, with the Minneapolis Veterans Affairs Health Care System and the University of Minnesota, said research about the effectiveness of opioids for chronic pain was lacking. Even though millions of people take the drugs for long periods of time, there is little evidence to support that use.

“The studies that we had out there were short-term studies and mostly compared opioids to placebo medications,” Krebs said. “From those studies, we knew that opioids can improve pain a little bit more than a placebo, or sugar pill, in the short term, but that’s all we knew.”

But that’s changing. Krebs is the lead author of a new study that looks at the effectiveness of opioids for treating chronic pain over 12 months published Tuesday in the Journal of the American Medical Association.

The study involved 240 veterans with chronic back pain or osteoarthritis of the knee or hip who had pain that was ongoing and intense. Half were treated with opioids and half with non-opioid medications — either common over-the-counter drugs like acetaminophen or naproxen, or prescription drugs like topical lidocaine or meloxicam. Doctors and patients knew what group they were in, said Krebs, and that was deliberate because people’s expectations can influence how they feel.

“We found at the beginning of the study that patients who were enrolled really thought that opioids were far more effective than non-opioid medications,” she said.

But after as little as six months, the non-opioid group reported their pain was slightly less severe than the opioid group’s collective assessment. By the end of the year, Krebs said, “there was really no difference between the groups in terms of pain interference with activities. And over time, the non-opioid group had less pain intensity, and the opioid group had more side effects,” such as constipation, fatigue and nausea.

The study didn’t explore why, but Krebs has a theory: opioid tolerance.

“Within a few weeks or months of taking an opioid on a daily basis, your body gets used to that level of opioid, and you need more and more to get the same level of effect,” she said.

Opioids, of course, also carry the risk of dependence, addiction and overdose. Coming off of opioids gives patients who have developed a dependence flu-like symptoms that can last for days or weeks.

“This study adds the long-term evidence that shows that opioids really don’t have any advantages in terms of pain relief that might outweigh the known harms that they cause,” she said. “The bottom line for people who have chronic back pain or arthritis pain is just that you shouldn’t start opioids.”

But what about patients like Molden who had already been using opioids for a long time? Dr. Muhammed Farhan, medical director of the University of Missouri-Kansas City’s multidisciplinary pain management program, said diplomatic conversations with patients like Molden are part of his daily routine. Farhan also is the medical director of the University Health Pain Management Clinic at Truman Medical Centers, which doesn’t prescribe opioids.

He said he meets patients every day with problems like back pain who’ve reached the end of the line with the drugs.

“Most of the time what I see is that they are taking high doses of opioids and that they are in bed all the time or sleeping and still in pain,” he said.

Farhan said he starts by helping them adjust to the idea that they cannot eliminate pain entirely. He said this expectation can be especially dangerous for people who rely on increasing doses of opioids.

“Our idea of being completely pain-free can lead us to a place when they end up with more pain, no improvement in their quality of life after being on high doses of opioid medications, which can be harmful to the point that they may die,” Farhan said.

He said he tries to help his patients taper off opioids slowly and use alternative drugs and therapies.

Krebs agrees with this approach. “Medications have some role, but they really shouldn’t be the primary way we are treating chronic pain,” she said. “For osteoarthritis pain, the strongly recommended treatments are exercise treatments,” she said, and it’s important to maintain a healthy weight. “The same thing goes for back pain,” she said, where experts recommend exercise, rehabilitation treatments, yoga and cognitive therapies, among others.

Renea Molden said it’s been hard to leave hydrocodone behind, but she’s working at it.

“I know if I can just get through that day — there’s good days and there’s bad days, and you just kind of have to make it through the bad days,” she said.

But even on the worst days, Molden feels good that she’s facing her pain without opioids.

This story is part of a reporting partnership with NPR, KCUR and Kaiser Health News.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

A few years ago, Renea Molden’s doctors told her they wanted to take her off her opioid pills. It did not sound like good idea to her.

“I was mad, I’ll be honest. I was mad. I was frustrated,” said Molden, 40, of Kansas City, Mo. She struggles with fibromyalgia, bulging discs and degenerative disc disease. Her doctors were concerned about her potentially taking hydrocodone for the rest of her life, but to her, the three pills she took each day seemed to be the only way she could make it through work, go shopping or even fix dinner.

“It felt like they were taking a part of my life away from me,” she said.

For many people with chronic pain, opioids can seem like the difference between a full life or one lived in agony. Over the past few decades, they have become go-to drugs for acute pain, but Dr. Erin Krebs, with the Minneapolis Veterans Affairs Health Care System and the University of Minnesota, said research about the effectiveness of opioids for chronic pain was lacking. Even though millions of people take the drugs for long periods of time, there is little evidence to support that use.

“The studies that we had out there were short-term studies and mostly compared opioids to placebo medications,” Krebs said. “From those studies, we knew that opioids can improve pain a little bit more than a placebo, or sugar pill, in the short term, but that’s all we knew.”

But that’s changing. Krebs is the lead author of a new study that looks at the effectiveness of opioids for treating chronic pain over 12 months published Tuesday in the Journal of the American Medical Association.

The study involved 240 veterans with chronic back pain or osteoarthritis of the knee or hip who had pain that was ongoing and intense. Half were treated with opioids and half with non-opioid medications — either common over-the-counter drugs like acetaminophen or naproxen, or prescription drugs like topical lidocaine or meloxicam. Doctors and patients knew what group they were in, said Krebs, and that was deliberate because people’s expectations can influence how they feel.

“We found at the beginning of the study that patients who were enrolled really thought that opioids were far more effective than non-opioid medications,” she said.

But after as little as six months, the non-opioid group reported their pain was slightly less severe than the opioid group’s collective assessment. By the end of the year, Krebs said, “there was really no difference between the groups in terms of pain interference with activities. And over time, the non-opioid group had less pain intensity, and the opioid group had more side effects,” such as constipation, fatigue and nausea.

The study didn’t explore why, but Krebs has a theory: opioid tolerance.

“Within a few weeks or months of taking an opioid on a daily basis, your body gets used to that level of opioid, and you need more and more to get the same level of effect,” she said.

Opioids, of course, also carry the risk of dependence, addiction and overdose. Coming off of opioids gives patients who have developed a dependence flu-like symptoms that can last for days or weeks.

“This study adds the long-term evidence that shows that opioids really don’t have any advantages in terms of pain relief that might outweigh the known harms that they cause,” she said. “The bottom line for people who have chronic back pain or arthritis pain is just that you shouldn’t start opioids.”

But what about patients like Molden who had already been using opioids for a long time? Dr. Muhammed Farhan, medical director of the University of Missouri-Kansas City’s multidisciplinary pain management program, said diplomatic conversations with patients like Molden are part of his daily routine. Farhan also is the medical director of the University Health Pain Management Clinic at Truman Medical Centers, which doesn’t prescribe opioids.

He said he meets patients every day with problems like back pain who’ve reached the end of the line with the drugs.

“Most of the time what I see is that they are taking high doses of opioids and that they are in bed all the time or sleeping and still in pain,” he said.

Farhan said he starts by helping them adjust to the idea that they cannot eliminate pain entirely. He said this expectation can be especially dangerous for people who rely on increasing doses of opioids.

“Our idea of being completely pain-free can lead us to a place when they end up with more pain, no improvement in their quality of life after being on high doses of opioid medications, which can be harmful to the point that they may die,” Farhan said.

He said he tries to help his patients taper off opioids slowly and use alternative drugs and therapies.

Krebs agrees with this approach. “Medications have some role, but they really shouldn’t be the primary way we are treating chronic pain,” she said. “For osteoarthritis pain, the strongly recommended treatments are exercise treatments,” she said, and it’s important to maintain a healthy weight. “The same thing goes for back pain,” she said, where experts recommend exercise, rehabilitation treatments, yoga and cognitive therapies, among others.

Renea Molden said it’s been hard to leave hydrocodone behind, but she’s working at it.

“I know if I can just get through that day — there’s good days and there’s bad days, and you just kind of have to make it through the bad days,” she said.

But even on the worst days, Molden feels good that she’s facing her pain without opioids.

This story is part of a reporting partnership with NPR, KCUR and Kaiser Health News.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

A few years ago, Renea Molden’s doctors told her they wanted to take her off her opioid pills. It did not sound like good idea to her.

“I was mad, I’ll be honest. I was mad. I was frustrated,” said Molden, 40, of Kansas City, Mo. She struggles with fibromyalgia, bulging discs and degenerative disc disease. Her doctors were concerned about her potentially taking hydrocodone for the rest of her life, but to her, the three pills she took each day seemed to be the only way she could make it through work, go shopping or even fix dinner.

“It felt like they were taking a part of my life away from me,” she said.

For many people with chronic pain, opioids can seem like the difference between a full life or one lived in agony. Over the past few decades, they have become go-to drugs for acute pain, but Dr. Erin Krebs, with the Minneapolis Veterans Affairs Health Care System and the University of Minnesota, said research about the effectiveness of opioids for chronic pain was lacking. Even though millions of people take the drugs for long periods of time, there is little evidence to support that use.

“The studies that we had out there were short-term studies and mostly compared opioids to placebo medications,” Krebs said. “From those studies, we knew that opioids can improve pain a little bit more than a placebo, or sugar pill, in the short term, but that’s all we knew.”

But that’s changing. Krebs is the lead author of a new study that looks at the effectiveness of opioids for treating chronic pain over 12 months published Tuesday in the Journal of the American Medical Association.

The study involved 240 veterans with chronic back pain or osteoarthritis of the knee or hip who had pain that was ongoing and intense. Half were treated with opioids and half with non-opioid medications — either common over-the-counter drugs like acetaminophen or naproxen, or prescription drugs like topical lidocaine or meloxicam. Doctors and patients knew what group they were in, said Krebs, and that was deliberate because people’s expectations can influence how they feel.

“We found at the beginning of the study that patients who were enrolled really thought that opioids were far more effective than non-opioid medications,” she said.

But after as little as six months, the non-opioid group reported their pain was slightly less severe than the opioid group’s collective assessment. By the end of the year, Krebs said, “there was really no difference between the groups in terms of pain interference with activities. And over time, the non-opioid group had less pain intensity, and the opioid group had more side effects,” such as constipation, fatigue and nausea.

The study didn’t explore why, but Krebs has a theory: opioid tolerance.

“Within a few weeks or months of taking an opioid on a daily basis, your body gets used to that level of opioid, and you need more and more to get the same level of effect,” she said.

Opioids, of course, also carry the risk of dependence, addiction and overdose. Coming off of opioids gives patients who have developed a dependence flu-like symptoms that can last for days or weeks.

“This study adds the long-term evidence that shows that opioids really don’t have any advantages in terms of pain relief that might outweigh the known harms that they cause,” she said. “The bottom line for people who have chronic back pain or arthritis pain is just that you shouldn’t start opioids.”

But what about patients like Molden who had already been using opioids for a long time? Dr. Muhammed Farhan, medical director of the University of Missouri-Kansas City’s multidisciplinary pain management program, said diplomatic conversations with patients like Molden are part of his daily routine. Farhan also is the medical director of the University Health Pain Management Clinic at Truman Medical Centers, which doesn’t prescribe opioids.

He said he meets patients every day with problems like back pain who’ve reached the end of the line with the drugs.

“Most of the time what I see is that they are taking high doses of opioids and that they are in bed all the time or sleeping and still in pain,” he said.

Farhan said he starts by helping them adjust to the idea that they cannot eliminate pain entirely. He said this expectation can be especially dangerous for people who rely on increasing doses of opioids.

“Our idea of being completely pain-free can lead us to a place when they end up with more pain, no improvement in their quality of life after being on high doses of opioid medications, which can be harmful to the point that they may die,” Farhan said.

He said he tries to help his patients taper off opioids slowly and use alternative drugs and therapies.

Krebs agrees with this approach. “Medications have some role, but they really shouldn’t be the primary way we are treating chronic pain,” she said. “For osteoarthritis pain, the strongly recommended treatments are exercise treatments,” she said, and it’s important to maintain a healthy weight. “The same thing goes for back pain,” she said, where experts recommend exercise, rehabilitation treatments, yoga and cognitive therapies, among others.

Renea Molden said it’s been hard to leave hydrocodone behind, but she’s working at it.

“I know if I can just get through that day — there’s good days and there’s bad days, and you just kind of have to make it through the bad days,” she said.

But even on the worst days, Molden feels good that she’s facing her pain without opioids.

This story is part of a reporting partnership with NPR, KCUR and Kaiser Health News.

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.

That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.

So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.

But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.

Courtesy UAB Photo

The ABCs of TTT

In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.

Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.

Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.

It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA_1c [hemoglobin A_1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”

Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.

The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.

Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.

Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.

But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.

Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.

In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).

The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.

Slow on the uptake

Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.

Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.

Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.

“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”

The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”

Technology, or the lack of it

Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.

TTT challenges patients, too

Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.

“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”

Researchers have explored these questions.

Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).

“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”

The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”

Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”

A patient’s story: Overcoming fear and self-image

Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.

As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.

But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.

“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”

“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.

The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.

Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.

“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”

She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.

“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”

As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”

With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.

“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”

Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.

Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.

“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”

She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.

“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”

The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”

Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.

“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”

[email protected]

It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.

That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.

So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.

But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.

Courtesy UAB Photo

The ABCs of TTT

In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.

Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.

Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.

It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA_1c [hemoglobin A_1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”

Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.

The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.

Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.

Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.

But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.

Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.

In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).

The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.

Slow on the uptake

Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.

Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.

Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.

“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”

The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”

Technology, or the lack of it

Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.

TTT challenges patients, too

Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.

“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”

Researchers have explored these questions.

Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).

“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”

The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”

Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”

A patient’s story: Overcoming fear and self-image

Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.

As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.

But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.

“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”

“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.

The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.

Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.

“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”

She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.

“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”

As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”

With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.

“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”

Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.

Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.

“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”

She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.

“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”

The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”

Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.

“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”

[email protected]

It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.

That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.

So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.

But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.

Courtesy UAB Photo

The ABCs of TTT

In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.

Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.

Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.

It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA_1c [hemoglobin A_1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”

Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.

The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.

Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.

Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.

But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.

Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.

In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).

The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.

Slow on the uptake

Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.

Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.

Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.

“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”

The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”

Technology, or the lack of it

Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.

TTT challenges patients, too

Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.

“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”

Researchers have explored these questions.

Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).

“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”

The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”

Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”

A patient’s story: Overcoming fear and self-image

Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.

As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.

But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.

“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”

“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.

The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.

Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.

“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”

She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.

“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”

As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”

With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.

“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”

Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.

Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.

“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”

She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.

“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”

The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”

Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.

“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”

[email protected]

Mild cognitive impairment rises in heart patients with comorbidities. Allergies? There’s an app for that. Why nongastroenterologists should know SIBO. And tuberculosis prevention in HIV is about to speed up.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Mild cognitive impairment rises in heart patients with comorbidities. Allergies? There’s an app for that. Why nongastroenterologists should know SIBO. And tuberculosis prevention in HIV is about to speed up.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Mild cognitive impairment rises in heart patients with comorbidities. Allergies? There’s an app for that. Why nongastroenterologists should know SIBO. And tuberculosis prevention in HIV is about to speed up.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

National Institute of Health’s researchers conducted a diagnostic assay of 60 cerebral spinal fluid samples: 12 from people with Parkinson disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 with Alzheimer disease. The test correctly excluded all the 31 controls and diagnosed both Parkinson disease and dementia with Lewy bodies with 93% accuracy.

Moreover, test results were available within 2 days compared with 13 days for related assays.

Like prion diseases, Parkinson disease and dementia with Lewy bodies cause progressive deterioration of brain functions. The diseases typically progress for years before symptoms appear; once they do, distinguishing one from another can be difficult. The NIH says early, accurate diagnoses are essential for developing treatments and identifying patients eligible for clinical trials.

National Institute of Health’s researchers conducted a diagnostic assay of 60 cerebral spinal fluid samples: 12 from people with Parkinson disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 with Alzheimer disease. The test correctly excluded all the 31 controls and diagnosed both Parkinson disease and dementia with Lewy bodies with 93% accuracy.

Moreover, test results were available within 2 days compared with 13 days for related assays.

Like prion diseases, Parkinson disease and dementia with Lewy bodies cause progressive deterioration of brain functions. The diseases typically progress for years before symptoms appear; once they do, distinguishing one from another can be difficult. The NIH says early, accurate diagnoses are essential for developing treatments and identifying patients eligible for clinical trials.

National Institute of Health’s researchers conducted a diagnostic assay of 60 cerebral spinal fluid samples: 12 from people with Parkinson disease, 17 from people with dementia with Lewy bodies, and 31 controls, including 16 with Alzheimer disease. The test correctly excluded all the 31 controls and diagnosed both Parkinson disease and dementia with Lewy bodies with 93% accuracy.

Moreover, test results were available within 2 days compared with 13 days for related assays.

Like prion diseases, Parkinson disease and dementia with Lewy bodies cause progressive deterioration of brain functions. The diseases typically progress for years before symptoms appear; once they do, distinguishing one from another can be difficult. The NIH says early, accurate diagnoses are essential for developing treatments and identifying patients eligible for clinical trials.

Lab mouse

A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.

The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).

Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”

“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.

“Miristen could be the drug that sends the disease into permanent remission.”

For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.

The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.

The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.

The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.

The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.

“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.

“Our current study showed these findings may also apply to other types of leukemia.”

Lab mouse

A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.

The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).

Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”

“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.

“Miristen could be the drug that sends the disease into permanent remission.”

For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.

The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.

The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.

The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.

The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.

“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.

“Our current study showed these findings may also apply to other types of leukemia.”

Lab mouse

A microRNA-targeting drug could improve the effectiveness of tyrosine kinase inhibitors (TKIs) against chronic myelogenous leukemia (CML), according to preclinical research published in Nature Medicine.

The drug, miristen, targets miR-126, a microRNA expressed in leukemia stem cells (LSCs).

Researchers found that miristen “enhanced the anti-leukemic effects of TKI treatment” in mouse models of CML and “strongly diminished LSC leukemia-initiating capacity.”

“This could be a major breakthrough for people who are in remission for CML because there is always a concern that the disease will come back if TKI treatment is stopped,” said study author Bin Zhang, PhD, of City of Hope Medical Center in Duarte, California.

“Miristen could be the drug that sends the disease into permanent remission.”

For this study, Dr Zhang and her colleagues tested miristen alone and in combination with the TKI nilotinib in mouse models of CML.

The best results were seen in mice treated with miristen and nilotinib. Transplantation of bone marrow cells collected from mice treated with miristen and nilotinib resulted in no sign of leukemia in the healthy recipient mice, meaning all LSCs were eliminated.

The researchers believe miristen simply makes TKIs more effective in killing LSCs. The team also thinks they have discovered the key to the treatment’s success.

The researchers found that endothelial cells in the blood vessels of the bone marrow contain high levels of miR-126. These endothelial cells transfer miR-126 to LSCs, essentially feeding the leukemia what it needs to survive and grow.

The team hypothesized that to eliminate CML, miristen had to lower miR-126 in both the LSCs and the endothelial cells. Testing proved this theory correct.

“What we have discovered is how the microenvironment surrounding the leukemia stem cells supports them and how you need to target miR-126 in the leukemia stem cells and the microenvironment to completely eradicate the disease,” said study author Guido Marcucci, MD, of City of Hope.

“Our current study showed these findings may also apply to other types of leukemia.”

2018 BMT Tandem Meetings

SALT LAKE CITY—An expanded umbilical cord blood (UCB) product can produce favorable outcomes as a stand-alone graft, according to a presentation at the 2018 BMT Tandem Meetings.

The product, MGTA-456, provided “rapid and durable” engraftment in patients with hematologic malignancies, according to John E. Wagner, MD, of the University of Minnesota in Minneapolis.

He also said MGTA-456 “preserved the clinical benefits” of UCB transplant, including low rates of graft-vs-host disease (GVHD) and high overall survival (OS).

Dr Wagner presented these results as one of the “Best Abstracts” at this year’s BMT Tandem Meetings (abstract 4). The research was supported by Novartis and Magenta Therapeutics.

MGTA-456 is developed by dividing a UCB unit into a CD34- portion and a CD34+ portion, then expanding the CD34+ portion for 15 days via culture with an aryl hydrocarbon receptor antagonist (SR-1), stem cell factor, FLT3 ligand, interleukin-6, and thrombopoietin.

In a previous study,* MGTA-456 enhanced hematopoietic recovery when given as half of a double UCB transplant.

With the current research, Dr Wagner and his colleagues evaluated MGTA-456 as a stand-alone graft. The team conducted two phase 2 trials of MGTA-456, one in which patients received myeloablative conditioning (MAC) and one in which patients received non-myeloablative conditioning (NMAC).

Treatment

Each trial included 10 patients with a high-risk hematologic malignancy and a partially HLA-matched UCB unit. In each trial, 1 patient could not receive MGTA-456 due to low expansion.

So 9 patients received MAC—cyclophosphamide (CY) at 60 mg/kg/day on days -6 and -5, fludarabine (FLU) at 25 mg/m²/day on days -7 to -5,  and total body irradiation (TBI) at 1320 cGy on days -4 to -1.

And 9 patients received NMAC—CY at 50 mg/kg on day -6, FLU at 40 mg/m²/day on days -6 to -2, and TBI at 200 cGy on day -1. Some patients who had not received recent chemotherapy also received antithymocyte globulin as part of their conditioning regimen.

For MAC recipients, the median expansion of CD34+ cells was 406-fold (range, 162-1643). The median CD34 cell dose they received was 16.2 x 10⁶/kg.

For NMAC recipients, the median expansion of CD34+ cells was 274-fold (range, 42-527). The median CD34 cell dose they received was 13.4 x 10⁶/kg.

All patients received cyclosporine and mycophenolate mofetil as GVHD prophylaxis.

Dr Wagner and his colleagues compared outcomes in these MGTA-456 recipients to outcomes in historical control subjects—151 patients who received MAC and 132 who received NMAC.

MAC recipients

The 9 MAC/MGTA-456 recipients had a median age of 25 (range, 15-53). Seven of the patients had acute leukemia, 1 had myelodysplastic syndrome (MDS), and 1 had lymphoma.

Eleven percent of patients had high-risk disease, 89% were cytomegalovirus seropositive, and 89% had a Karnofsky performance score of 90 to 100.

The only significant difference between the MGTA-456 recipients and historical controls was weight. The median weight was 93.8 kg (range, 41-107) for MGTA-456 recipients and 66.7 kg (range, 11-136) for controls (P=0.04).

The MGTA-456 recipients had superior hematopoietic recovery compared to historical controls.

The rate of neutrophil engraftment was 100% for MGTA-456 recipients and 89% for controls. The median time to neutrophil engraftment was 14 days and 23 days, respectively (P<0.01).

The rate of platelet engraftment was 89% for MGTA-456 recipients and 71% for controls. The median time to platelet engraftment was 46 days and 64 days, respectively (P=0.01).

There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.

The incidence of grade 3-4 acute GVHD at 100 days was 22% for MGTA-456 recipients and 24% for controls (P=0.78). The incidence of chronic GVHD at 1 year was 11% and 21%, respectively (P=0.48).

The 2-year OS rate was 67% in MGTA-456 recipients and 55% in controls (P=0.59).

NMAC recipients

There were significant differences between the 9 NMAC/MGTA-456 recipients and the 132 NMAC historical controls when it came to age (P=0.03), disease type (P<0.01), and disease status (P=0.03).

The median age was 65 (range, 29-70) for MGTA-456 recipients and 53 (range, 6-72) for historical controls. The median weights were 93.4 kg (range, 55-111) and 81.4 kg (range, 22-145), respectively.

Diagnoses among MGTA-456 recipients included acute leukemia (n=1), MDS (n=4), chronic leukemia (n=1), lymphoma (n=1), and “other” (n=2). Diagnoses among historical controls included acute leukemia (n=61), MDS (n=25), chronic leukemia (n=9), lymphoma (n=35), and “other” (n=2).

Eighty-nine percent of MGTA-456 recipients and 49% of historical controls had high-risk disease. Sixty-seven percent and 64%, respectively, were cytomegalovirus seropositive. Sixty-seven percent and 85%, respectively, had a Karnofsky performance score of 90 to 100.

NMAC recipients who received MGTA-456 had superior neutrophil recovery but platelet recovery that was comparable to that of historical controls.

The rate of neutrophil engraftment was 100% in MGTA-456 recipients and 95% in historical controls. The median time to neutrophil engraftment was 7 days and 15 days, respectively (P<0.01).

The rate of platelet engraftment was 56% for MGTA-456 recipients and 77% for historical controls. The median time to platelet engraftment was 107 days and 47 days, respectively (P=0.19).

There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.

The incidence of grade 3-4 acute GVHD at 100 days was 43% for MGTA-456 recipients and 15% for controls (P=0.11). The incidence of chronic GVHD at 1 year was 0% and 19%, respectively (P=0.17).

The 2-year OS rate was 44% in MGTA-456 recipients and 49% in controls (P=0.80).

*Wagner JE Jr et al; Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft. Cell Stem Cell 2016; 18(1):144-155.

2018 BMT Tandem Meetings

SALT LAKE CITY—An expanded umbilical cord blood (UCB) product can produce favorable outcomes as a stand-alone graft, according to a presentation at the 2018 BMT Tandem Meetings.

The product, MGTA-456, provided “rapid and durable” engraftment in patients with hematologic malignancies, according to John E. Wagner, MD, of the University of Minnesota in Minneapolis.

He also said MGTA-456 “preserved the clinical benefits” of UCB transplant, including low rates of graft-vs-host disease (GVHD) and high overall survival (OS).

Dr Wagner presented these results as one of the “Best Abstracts” at this year’s BMT Tandem Meetings (abstract 4). The research was supported by Novartis and Magenta Therapeutics.

MGTA-456 is developed by dividing a UCB unit into a CD34- portion and a CD34+ portion, then expanding the CD34+ portion for 15 days via culture with an aryl hydrocarbon receptor antagonist (SR-1), stem cell factor, FLT3 ligand, interleukin-6, and thrombopoietin.

In a previous study,* MGTA-456 enhanced hematopoietic recovery when given as half of a double UCB transplant.

With the current research, Dr Wagner and his colleagues evaluated MGTA-456 as a stand-alone graft. The team conducted two phase 2 trials of MGTA-456, one in which patients received myeloablative conditioning (MAC) and one in which patients received non-myeloablative conditioning (NMAC).

Treatment

Each trial included 10 patients with a high-risk hematologic malignancy and a partially HLA-matched UCB unit. In each trial, 1 patient could not receive MGTA-456 due to low expansion.

So 9 patients received MAC—cyclophosphamide (CY) at 60 mg/kg/day on days -6 and -5, fludarabine (FLU) at 25 mg/m²/day on days -7 to -5,  and total body irradiation (TBI) at 1320 cGy on days -4 to -1.

And 9 patients received NMAC—CY at 50 mg/kg on day -6, FLU at 40 mg/m²/day on days -6 to -2, and TBI at 200 cGy on day -1. Some patients who had not received recent chemotherapy also received antithymocyte globulin as part of their conditioning regimen.

For MAC recipients, the median expansion of CD34+ cells was 406-fold (range, 162-1643). The median CD34 cell dose they received was 16.2 x 10⁶/kg.

For NMAC recipients, the median expansion of CD34+ cells was 274-fold (range, 42-527). The median CD34 cell dose they received was 13.4 x 10⁶/kg.

All patients received cyclosporine and mycophenolate mofetil as GVHD prophylaxis.

Dr Wagner and his colleagues compared outcomes in these MGTA-456 recipients to outcomes in historical control subjects—151 patients who received MAC and 132 who received NMAC.

MAC recipients

The 9 MAC/MGTA-456 recipients had a median age of 25 (range, 15-53). Seven of the patients had acute leukemia, 1 had myelodysplastic syndrome (MDS), and 1 had lymphoma.

Eleven percent of patients had high-risk disease, 89% were cytomegalovirus seropositive, and 89% had a Karnofsky performance score of 90 to 100.

The only significant difference between the MGTA-456 recipients and historical controls was weight. The median weight was 93.8 kg (range, 41-107) for MGTA-456 recipients and 66.7 kg (range, 11-136) for controls (P=0.04).

The MGTA-456 recipients had superior hematopoietic recovery compared to historical controls.

The rate of neutrophil engraftment was 100% for MGTA-456 recipients and 89% for controls. The median time to neutrophil engraftment was 14 days and 23 days, respectively (P<0.01).

The rate of platelet engraftment was 89% for MGTA-456 recipients and 71% for controls. The median time to platelet engraftment was 46 days and 64 days, respectively (P=0.01).

There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.

The incidence of grade 3-4 acute GVHD at 100 days was 22% for MGTA-456 recipients and 24% for controls (P=0.78). The incidence of chronic GVHD at 1 year was 11% and 21%, respectively (P=0.48).

The 2-year OS rate was 67% in MGTA-456 recipients and 55% in controls (P=0.59).

NMAC recipients

There were significant differences between the 9 NMAC/MGTA-456 recipients and the 132 NMAC historical controls when it came to age (P=0.03), disease type (P<0.01), and disease status (P=0.03).

The median age was 65 (range, 29-70) for MGTA-456 recipients and 53 (range, 6-72) for historical controls. The median weights were 93.4 kg (range, 55-111) and 81.4 kg (range, 22-145), respectively.

Diagnoses among MGTA-456 recipients included acute leukemia (n=1), MDS (n=4), chronic leukemia (n=1), lymphoma (n=1), and “other” (n=2). Diagnoses among historical controls included acute leukemia (n=61), MDS (n=25), chronic leukemia (n=9), lymphoma (n=35), and “other” (n=2).

Eighty-nine percent of MGTA-456 recipients and 49% of historical controls had high-risk disease. Sixty-seven percent and 64%, respectively, were cytomegalovirus seropositive. Sixty-seven percent and 85%, respectively, had a Karnofsky performance score of 90 to 100.

NMAC recipients who received MGTA-456 had superior neutrophil recovery but platelet recovery that was comparable to that of historical controls.

The rate of neutrophil engraftment was 100% in MGTA-456 recipients and 95% in historical controls. The median time to neutrophil engraftment was 7 days and 15 days, respectively (P<0.01).

The rate of platelet engraftment was 56% for MGTA-456 recipients and 77% for historical controls. The median time to platelet engraftment was 107 days and 47 days, respectively (P=0.19).

There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.

The incidence of grade 3-4 acute GVHD at 100 days was 43% for MGTA-456 recipients and 15% for controls (P=0.11). The incidence of chronic GVHD at 1 year was 0% and 19%, respectively (P=0.17).

The 2-year OS rate was 44% in MGTA-456 recipients and 49% in controls (P=0.80).

*Wagner JE Jr et al; Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft. Cell Stem Cell 2016; 18(1):144-155.

2018 BMT Tandem Meetings

SALT LAKE CITY—An expanded umbilical cord blood (UCB) product can produce favorable outcomes as a stand-alone graft, according to a presentation at the 2018 BMT Tandem Meetings.

The product, MGTA-456, provided “rapid and durable” engraftment in patients with hematologic malignancies, according to John E. Wagner, MD, of the University of Minnesota in Minneapolis.

He also said MGTA-456 “preserved the clinical benefits” of UCB transplant, including low rates of graft-vs-host disease (GVHD) and high overall survival (OS).

Dr Wagner presented these results as one of the “Best Abstracts” at this year’s BMT Tandem Meetings (abstract 4). The research was supported by Novartis and Magenta Therapeutics.

MGTA-456 is developed by dividing a UCB unit into a CD34- portion and a CD34+ portion, then expanding the CD34+ portion for 15 days via culture with an aryl hydrocarbon receptor antagonist (SR-1), stem cell factor, FLT3 ligand, interleukin-6, and thrombopoietin.

In a previous study,* MGTA-456 enhanced hematopoietic recovery when given as half of a double UCB transplant.

With the current research, Dr Wagner and his colleagues evaluated MGTA-456 as a stand-alone graft. The team conducted two phase 2 trials of MGTA-456, one in which patients received myeloablative conditioning (MAC) and one in which patients received non-myeloablative conditioning (NMAC).

Treatment

Each trial included 10 patients with a high-risk hematologic malignancy and a partially HLA-matched UCB unit. In each trial, 1 patient could not receive MGTA-456 due to low expansion.

So 9 patients received MAC—cyclophosphamide (CY) at 60 mg/kg/day on days -6 and -5, fludarabine (FLU) at 25 mg/m²/day on days -7 to -5,  and total body irradiation (TBI) at 1320 cGy on days -4 to -1.

And 9 patients received NMAC—CY at 50 mg/kg on day -6, FLU at 40 mg/m²/day on days -6 to -2, and TBI at 200 cGy on day -1. Some patients who had not received recent chemotherapy also received antithymocyte globulin as part of their conditioning regimen.

For MAC recipients, the median expansion of CD34+ cells was 406-fold (range, 162-1643). The median CD34 cell dose they received was 16.2 x 10⁶/kg.

For NMAC recipients, the median expansion of CD34+ cells was 274-fold (range, 42-527). The median CD34 cell dose they received was 13.4 x 10⁶/kg.

All patients received cyclosporine and mycophenolate mofetil as GVHD prophylaxis.

Dr Wagner and his colleagues compared outcomes in these MGTA-456 recipients to outcomes in historical control subjects—151 patients who received MAC and 132 who received NMAC.

MAC recipients

The 9 MAC/MGTA-456 recipients had a median age of 25 (range, 15-53). Seven of the patients had acute leukemia, 1 had myelodysplastic syndrome (MDS), and 1 had lymphoma.

Eleven percent of patients had high-risk disease, 89% were cytomegalovirus seropositive, and 89% had a Karnofsky performance score of 90 to 100.

The only significant difference between the MGTA-456 recipients and historical controls was weight. The median weight was 93.8 kg (range, 41-107) for MGTA-456 recipients and 66.7 kg (range, 11-136) for controls (P=0.04).

The MGTA-456 recipients had superior hematopoietic recovery compared to historical controls.

The rate of neutrophil engraftment was 100% for MGTA-456 recipients and 89% for controls. The median time to neutrophil engraftment was 14 days and 23 days, respectively (P<0.01).

The rate of platelet engraftment was 89% for MGTA-456 recipients and 71% for controls. The median time to platelet engraftment was 46 days and 64 days, respectively (P=0.01).

There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.

The incidence of grade 3-4 acute GVHD at 100 days was 22% for MGTA-456 recipients and 24% for controls (P=0.78). The incidence of chronic GVHD at 1 year was 11% and 21%, respectively (P=0.48).

The 2-year OS rate was 67% in MGTA-456 recipients and 55% in controls (P=0.59).

NMAC recipients

There were significant differences between the 9 NMAC/MGTA-456 recipients and the 132 NMAC historical controls when it came to age (P=0.03), disease type (P<0.01), and disease status (P=0.03).

The median age was 65 (range, 29-70) for MGTA-456 recipients and 53 (range, 6-72) for historical controls. The median weights were 93.4 kg (range, 55-111) and 81.4 kg (range, 22-145), respectively.

Diagnoses among MGTA-456 recipients included acute leukemia (n=1), MDS (n=4), chronic leukemia (n=1), lymphoma (n=1), and “other” (n=2). Diagnoses among historical controls included acute leukemia (n=61), MDS (n=25), chronic leukemia (n=9), lymphoma (n=35), and “other” (n=2).

Eighty-nine percent of MGTA-456 recipients and 49% of historical controls had high-risk disease. Sixty-seven percent and 64%, respectively, were cytomegalovirus seropositive. Sixty-seven percent and 85%, respectively, had a Karnofsky performance score of 90 to 100.

NMAC recipients who received MGTA-456 had superior neutrophil recovery but platelet recovery that was comparable to that of historical controls.

The rate of neutrophil engraftment was 100% in MGTA-456 recipients and 95% in historical controls. The median time to neutrophil engraftment was 7 days and 15 days, respectively (P<0.01).

The rate of platelet engraftment was 56% for MGTA-456 recipients and 77% for historical controls. The median time to platelet engraftment was 107 days and 47 days, respectively (P=0.19).

There was no significant difference between MGTA-456 recipients and historical controls when it came to GVHD or OS.

The incidence of grade 3-4 acute GVHD at 100 days was 43% for MGTA-456 recipients and 15% for controls (P=0.11). The incidence of chronic GVHD at 1 year was 0% and 19%, respectively (P=0.17).

The 2-year OS rate was 44% in MGTA-456 recipients and 49% in controls (P=0.80).

*Wagner JE Jr et al; Phase I/II Trial of StemRegenin-1 Expanded Umbilical Cord Blood Hematopoietic Stem Cells Supports Testing as a Stand-Alone Graft. Cell Stem Cell 2016; 18(1):144-155.

Seema Verma

The US Centers for Medicare & Medicaid Services (CMS) has announced new initiatives designed to give patients control of their healthcare data.

One initiative, MyHealthEData, is intended to “break down the barriers” that prevent patients from having electronic access to, and control of, their own health records, according to CMS Administrator Seema Verma.

The other initiative, Medicare’s Blue Button 2.0, is a new way for Medicare beneficiaries to access and share their personal health data in a universal digital format.

Verma discussed these programs and other changes CMS is making in a speech at the HIMSS18 Conference in Las Vegas.

MyHealthEData

The Trump Administration is launching MyHealthEData, a government-wide initiative intended to give patients electronic access to their healthcare data and allow patients to take that data with them from healthcare provider to healthcare provider.

The idea is that patients will be able to choose the provider that best meets their needs and give that provider secure access to their data.

“MyHealthEData makes it clear that patients should have access and control to share their data with whomever they want, making the patient the center of our healthcare system,” Verma said.

“Patients need to be able to control their information and know that it’s secure and private. Having access to their medical information will help them make decisions about their care and have a better understanding of their health.”

The MyHealthEData initiative is led by the White House Office of American Innovation, with participation from the Department of Health and Human Services and its CMS, Office of the National Coordinator for Health Information Technology, and National Institutes of Health, as well as the Department of Veterans Affairs.

Blue Button 2.0

Verma said Medicare’s Blue Button 2.0 will enable patients who participate in the traditional Medicare program to connect their claims data to the secure applications, providers, services, and research programs they trust.

“Beneficiaries will maintain complete control in how and when their data is used . . .,” Verma said.

In addition, Medicare’s Blue Button 2.0 is expected to foster increased competition among technology innovators to serve Medicare patients and their caregivers. More than 100 organizations have signed on to use Medicare’s Blue Button 2.0 to develop applications that will provide new tools to help patients manage their health.

“CMS serves more than 130 million beneficiaries through our programs, which means we are uniquely positioned to transform how important healthcare data is shared between patients and their doctors,” Verma said.

“Today, we are calling on private health plans to join us in sharing their data with patients because enabling patients to control their Medicare data so that they can quickly obtain and share it is critical to creating more patient empowerment.”

Additional changes

Verma announced that CMS intends to overhaul its Electronic Health Record (EHR) Incentive Programs to refocus them on interoperability and reduce the time and cost required of providers to comply with the programs’ requirements.

Verma also noted that CMS has implemented laws regarding information blocking, a practice in which providers prevent patients from accessing their data. Under some CMS programs, hospitals and clinicians must show they have not engaged in information-blocking activities.

Other ways in which CMS plans to empower patients with data include:

• Requiring providers to update their systems to ensure data sharing
• Requiring that patients’ data follow them after they are discharged from the hospital
• Working to streamline documentation and billing requirements for providers to allow doctors to spend more time with their patients
• Working to reduce the incidence of unnecessary and duplicative testing, which occurs as a result of providers not sharing data.

Seema Verma

The US Centers for Medicare & Medicaid Services (CMS) has announced new initiatives designed to give patients control of their healthcare data.

One initiative, MyHealthEData, is intended to “break down the barriers” that prevent patients from having electronic access to, and control of, their own health records, according to CMS Administrator Seema Verma.

The other initiative, Medicare’s Blue Button 2.0, is a new way for Medicare beneficiaries to access and share their personal health data in a universal digital format.

Verma discussed these programs and other changes CMS is making in a speech at the HIMSS18 Conference in Las Vegas.

MyHealthEData

The Trump Administration is launching MyHealthEData, a government-wide initiative intended to give patients electronic access to their healthcare data and allow patients to take that data with them from healthcare provider to healthcare provider.

The idea is that patients will be able to choose the provider that best meets their needs and give that provider secure access to their data.

“MyHealthEData makes it clear that patients should have access and control to share their data with whomever they want, making the patient the center of our healthcare system,” Verma said.

“Patients need to be able to control their information and know that it’s secure and private. Having access to their medical information will help them make decisions about their care and have a better understanding of their health.”

The MyHealthEData initiative is led by the White House Office of American Innovation, with participation from the Department of Health and Human Services and its CMS, Office of the National Coordinator for Health Information Technology, and National Institutes of Health, as well as the Department of Veterans Affairs.

Blue Button 2.0

Verma said Medicare’s Blue Button 2.0 will enable patients who participate in the traditional Medicare program to connect their claims data to the secure applications, providers, services, and research programs they trust.

“Beneficiaries will maintain complete control in how and when their data is used . . .,” Verma said.

In addition, Medicare’s Blue Button 2.0 is expected to foster increased competition among technology innovators to serve Medicare patients and their caregivers. More than 100 organizations have signed on to use Medicare’s Blue Button 2.0 to develop applications that will provide new tools to help patients manage their health.

“CMS serves more than 130 million beneficiaries through our programs, which means we are uniquely positioned to transform how important healthcare data is shared between patients and their doctors,” Verma said.

“Today, we are calling on private health plans to join us in sharing their data with patients because enabling patients to control their Medicare data so that they can quickly obtain and share it is critical to creating more patient empowerment.”

Additional changes

Verma announced that CMS intends to overhaul its Electronic Health Record (EHR) Incentive Programs to refocus them on interoperability and reduce the time and cost required of providers to comply with the programs’ requirements.

Verma also noted that CMS has implemented laws regarding information blocking, a practice in which providers prevent patients from accessing their data. Under some CMS programs, hospitals and clinicians must show they have not engaged in information-blocking activities.

Other ways in which CMS plans to empower patients with data include:

• Requiring providers to update their systems to ensure data sharing
• Requiring that patients’ data follow them after they are discharged from the hospital
• Working to streamline documentation and billing requirements for providers to allow doctors to spend more time with their patients
• Working to reduce the incidence of unnecessary and duplicative testing, which occurs as a result of providers not sharing data.

Seema Verma

The US Centers for Medicare & Medicaid Services (CMS) has announced new initiatives designed to give patients control of their healthcare data.

One initiative, MyHealthEData, is intended to “break down the barriers” that prevent patients from having electronic access to, and control of, their own health records, according to CMS Administrator Seema Verma.

The other initiative, Medicare’s Blue Button 2.0, is a new way for Medicare beneficiaries to access and share their personal health data in a universal digital format.

Verma discussed these programs and other changes CMS is making in a speech at the HIMSS18 Conference in Las Vegas.

MyHealthEData

The Trump Administration is launching MyHealthEData, a government-wide initiative intended to give patients electronic access to their healthcare data and allow patients to take that data with them from healthcare provider to healthcare provider.

The idea is that patients will be able to choose the provider that best meets their needs and give that provider secure access to their data.

“MyHealthEData makes it clear that patients should have access and control to share their data with whomever they want, making the patient the center of our healthcare system,” Verma said.

“Patients need to be able to control their information and know that it’s secure and private. Having access to their medical information will help them make decisions about their care and have a better understanding of their health.”

The MyHealthEData initiative is led by the White House Office of American Innovation, with participation from the Department of Health and Human Services and its CMS, Office of the National Coordinator for Health Information Technology, and National Institutes of Health, as well as the Department of Veterans Affairs.

Blue Button 2.0

Verma said Medicare’s Blue Button 2.0 will enable patients who participate in the traditional Medicare program to connect their claims data to the secure applications, providers, services, and research programs they trust.

“Beneficiaries will maintain complete control in how and when their data is used . . .,” Verma said.

In addition, Medicare’s Blue Button 2.0 is expected to foster increased competition among technology innovators to serve Medicare patients and their caregivers. More than 100 organizations have signed on to use Medicare’s Blue Button 2.0 to develop applications that will provide new tools to help patients manage their health.

“CMS serves more than 130 million beneficiaries through our programs, which means we are uniquely positioned to transform how important healthcare data is shared between patients and their doctors,” Verma said.

“Today, we are calling on private health plans to join us in sharing their data with patients because enabling patients to control their Medicare data so that they can quickly obtain and share it is critical to creating more patient empowerment.”

Additional changes

Verma announced that CMS intends to overhaul its Electronic Health Record (EHR) Incentive Programs to refocus them on interoperability and reduce the time and cost required of providers to comply with the programs’ requirements.

Verma also noted that CMS has implemented laws regarding information blocking, a practice in which providers prevent patients from accessing their data. Under some CMS programs, hospitals and clinicians must show they have not engaged in information-blocking activities.

Other ways in which CMS plans to empower patients with data include:

• Requiring providers to update their systems to ensure data sharing
• Requiring that patients’ data follow them after they are discharged from the hospital
• Working to streamline documentation and billing requirements for providers to allow doctors to spend more time with their patients
• Working to reduce the incidence of unnecessary and duplicative testing, which occurs as a result of providers not sharing data.

ANSWER

The correct interpretation includes sinus bradycardia, marked sinus arrhythmia, junctional escape beats with sinus arrest or a transient atrioventricular (AV) block, and an intraventricular conduction defect.

Sinus bradycardia is diagnosed based on narrow QRS intervals < 60 beats/min. Marked sinus arrhythmia is indicated by the narrow QRS intervals of similar size but with an irregular rhythm.

When the rate is slow and irregular, rather than use the 300/150/100 method, it is more accurate to count the number of QRS complexes in the rhythm strip and multiply by six (an ECG at standard paper speed takes 10 s; 6 × 10 s = 60 s). If the patient does not have a pacemaker, a range within two to three beats of the computer measurement is acceptable. In this case, 9 × 6 = 54 beats/min—very close to the interval measured by the computer.

The first three beats on the rhythm strip are sinus with a normal PQRST complex. After that, there is a pause (either sinus arrest or a transient AV block—we can’t tell which) that is interrupted by a junctional escape beat (no P wave, but the QRS is similar to the prior, normal complexes). The fifth, sixth, and seventh beats are normal sinus, followed by another pause with an ensuing junctional escape. The last QRS complex is another sinus beat.

Finally, although the QRS duration (122 ms) is greater than normal, the complexes in leads V₁ and V₆ do not constitute a right or left bundle branch block.

ANSWER

The correct interpretation includes sinus bradycardia, marked sinus arrhythmia, junctional escape beats with sinus arrest or a transient atrioventricular (AV) block, and an intraventricular conduction defect.

Sinus bradycardia is diagnosed based on narrow QRS intervals < 60 beats/min. Marked sinus arrhythmia is indicated by the narrow QRS intervals of similar size but with an irregular rhythm.

When the rate is slow and irregular, rather than use the 300/150/100 method, it is more accurate to count the number of QRS complexes in the rhythm strip and multiply by six (an ECG at standard paper speed takes 10 s; 6 × 10 s = 60 s). If the patient does not have a pacemaker, a range within two to three beats of the computer measurement is acceptable. In this case, 9 × 6 = 54 beats/min—very close to the interval measured by the computer.

The first three beats on the rhythm strip are sinus with a normal PQRST complex. After that, there is a pause (either sinus arrest or a transient AV block—we can’t tell which) that is interrupted by a junctional escape beat (no P wave, but the QRS is similar to the prior, normal complexes). The fifth, sixth, and seventh beats are normal sinus, followed by another pause with an ensuing junctional escape. The last QRS complex is another sinus beat.

Finally, although the QRS duration (122 ms) is greater than normal, the complexes in leads V₁ and V₆ do not constitute a right or left bundle branch block.

ANSWER

The correct interpretation includes sinus bradycardia, marked sinus arrhythmia, junctional escape beats with sinus arrest or a transient atrioventricular (AV) block, and an intraventricular conduction defect.

Sinus bradycardia is diagnosed based on narrow QRS intervals < 60 beats/min. Marked sinus arrhythmia is indicated by the narrow QRS intervals of similar size but with an irregular rhythm.

When the rate is slow and irregular, rather than use the 300/150/100 method, it is more accurate to count the number of QRS complexes in the rhythm strip and multiply by six (an ECG at standard paper speed takes 10 s; 6 × 10 s = 60 s). If the patient does not have a pacemaker, a range within two to three beats of the computer measurement is acceptable. In this case, 9 × 6 = 54 beats/min—very close to the interval measured by the computer.

The first three beats on the rhythm strip are sinus with a normal PQRST complex. After that, there is a pause (either sinus arrest or a transient AV block—we can’t tell which) that is interrupted by a junctional escape beat (no P wave, but the QRS is similar to the prior, normal complexes). The fifth, sixth, and seventh beats are normal sinus, followed by another pause with an ensuing junctional escape. The last QRS complex is another sinus beat.

Finally, although the QRS duration (122 ms) is greater than normal, the complexes in leads V₁ and V₆ do not constitute a right or left bundle branch block.

A reasonable number of patients with treatment-resistant epilepsy experienced a decrease in the frequency of seizures when treated with pharmaceutical-grade cannabidiol, according to findings from a systematic review.

The review, published online March 6 in the Journal of Neurology, Neurosurgery and Psychiatry, centers on 36 studies testing the use of cannabinoids as adjunctive treatments for treatment-resistant epilepsy, including six randomized controlled trials involving a total of 555 patients and 30 observational studies involving 2,865 patients.

IvelinRadkov/Thinkstock

Two randomized, controlled trials representing a total of 291 patients (one with 120 patients with Dravet syndrome and another with 171 patients with Lennox-Gastaut syndrome) found cannabidiol (CBD) treatment was 74% more likely than placebo to achieve a greater than 50% reduction in seizures. In the observational studies, nearly half (48.5%) of the 970 patients across a range of epilepsy subtypes achieved a 50% or greater reduction in seizures.

Emily Stockings, PhD, of the National Drug and Alcohol Research Centre at the University of New South Wales, Sydney, and her coauthors estimated that eight patients would need to receive CBD treatment to achieve a 50% reduction in seizures in one person. However, they also pointed out that the quality of the evidence was mixed.

“There is insufficient evidence from moderate-quality or high-quality studies to assess whether there is a treatment effect of Cannabis sativa, CBD:THC combinations, or oral cannabis extracts,” they wrote.

There were three randomized, controlled trials that also looked at complete seizure freedom, finding a sixfold higher likelihood of total seizure freedom with CBD, compared with placebo. However, the number needed to treat to achieve this was 171, and again, the quality of evidence was described as “mixed.”

Just over half of patients treated with CBD reported improved quality of life, and significantly more parents and caregivers of those treated with CBD said the patient’s overall condition had improved. The pooled estimates from observational studies suggested that 55.8% of patients experienced improvements in their quality of life when using cannabinoids.

Studies involving patients with Dravet syndrome reported the greatest improvements in quality of life, compared with studies involving a mix of epilepsy syndromes. However, the authors noted that the studies that involved Dravet syndrome patients were all case series in which every patient responded and suggested they should be interpreted with caution.

The authors said they were more confident of the benefits of CBD in children than in adults, because the more recent, larger, and better-conducted randomized, controlled trials focused on children and adolescents.

“In RCTs, and most of the non-RCTs, cannabinoids were used as an adjunctive therapy rather than as a standalone intervention, so at present, there is little evidence to support any recommendation that cannabinoids can be recommended as a replacement for current standard [antiepileptic drugs].”

The review also looked at the number of withdrawals, which they said could serve as an indicator of the tolerability and effectiveness of a treatment. The randomized, controlled trials showed no difference in withdrawal rates between patients on CBD and those on placebo, although CBD patients were more likely to withdraw because of adverse events.

There was a small but significant increase in the risk of adverse events with CBD, compared with placebo: particularly drowsiness, diarrhea, fatigue, and changes in appetite. There also was a higher incidence of serious adverse events (AEs), including status epilepticus and elevated aminotransferase levels.

“The fact that more patients withdrew or experienced AEs when receiving CBD than placebo indicates the need for clinicians and patients to weigh the risks and benefits of adding CBD to other AED [antiepileptic drug] treatment,” the authors wrote.

The study was supported by the Commonwealth Department of Health, the New South Wales Government Centre for Medicinal Cannabis Research and Innovation, the Victorian Department of Health and Human Services, and the Queensland Department of Health. Four authors were also supported by National Health and Medical Research Council grants. Three authors declared grants from the pharmaceutical industry, and one author has provided evidence to parliamentary committees on medical uses of cannabis in Australia and the United Kingdom, and is on the Australian Advisory Council on the Medicinal Use of Cannabis. No other conflicts of interest were declared.

SOURCE: Stockings E et al. J Neurol Neurosurg Psychiatry. 2018 Mar 6. doi: 10.1136/jnnp-2017-317168

A reasonable number of patients with treatment-resistant epilepsy experienced a decrease in the frequency of seizures when treated with pharmaceutical-grade cannabidiol, according to findings from a systematic review.

The review, published online March 6 in the Journal of Neurology, Neurosurgery and Psychiatry, centers on 36 studies testing the use of cannabinoids as adjunctive treatments for treatment-resistant epilepsy, including six randomized controlled trials involving a total of 555 patients and 30 observational studies involving 2,865 patients.

IvelinRadkov/Thinkstock

Two randomized, controlled trials representing a total of 291 patients (one with 120 patients with Dravet syndrome and another with 171 patients with Lennox-Gastaut syndrome) found cannabidiol (CBD) treatment was 74% more likely than placebo to achieve a greater than 50% reduction in seizures. In the observational studies, nearly half (48.5%) of the 970 patients across a range of epilepsy subtypes achieved a 50% or greater reduction in seizures.

Emily Stockings, PhD, of the National Drug and Alcohol Research Centre at the University of New South Wales, Sydney, and her coauthors estimated that eight patients would need to receive CBD treatment to achieve a 50% reduction in seizures in one person. However, they also pointed out that the quality of the evidence was mixed.

“There is insufficient evidence from moderate-quality or high-quality studies to assess whether there is a treatment effect of Cannabis sativa, CBD:THC combinations, or oral cannabis extracts,” they wrote.

There were three randomized, controlled trials that also looked at complete seizure freedom, finding a sixfold higher likelihood of total seizure freedom with CBD, compared with placebo. However, the number needed to treat to achieve this was 171, and again, the quality of evidence was described as “mixed.”

Just over half of patients treated with CBD reported improved quality of life, and significantly more parents and caregivers of those treated with CBD said the patient’s overall condition had improved. The pooled estimates from observational studies suggested that 55.8% of patients experienced improvements in their quality of life when using cannabinoids.

Studies involving patients with Dravet syndrome reported the greatest improvements in quality of life, compared with studies involving a mix of epilepsy syndromes. However, the authors noted that the studies that involved Dravet syndrome patients were all case series in which every patient responded and suggested they should be interpreted with caution.

The authors said they were more confident of the benefits of CBD in children than in adults, because the more recent, larger, and better-conducted randomized, controlled trials focused on children and adolescents.

“In RCTs, and most of the non-RCTs, cannabinoids were used as an adjunctive therapy rather than as a standalone intervention, so at present, there is little evidence to support any recommendation that cannabinoids can be recommended as a replacement for current standard [antiepileptic drugs].”

The review also looked at the number of withdrawals, which they said could serve as an indicator of the tolerability and effectiveness of a treatment. The randomized, controlled trials showed no difference in withdrawal rates between patients on CBD and those on placebo, although CBD patients were more likely to withdraw because of adverse events.

There was a small but significant increase in the risk of adverse events with CBD, compared with placebo: particularly drowsiness, diarrhea, fatigue, and changes in appetite. There also was a higher incidence of serious adverse events (AEs), including status epilepticus and elevated aminotransferase levels.

“The fact that more patients withdrew or experienced AEs when receiving CBD than placebo indicates the need for clinicians and patients to weigh the risks and benefits of adding CBD to other AED [antiepileptic drug] treatment,” the authors wrote.

The study was supported by the Commonwealth Department of Health, the New South Wales Government Centre for Medicinal Cannabis Research and Innovation, the Victorian Department of Health and Human Services, and the Queensland Department of Health. Four authors were also supported by National Health and Medical Research Council grants. Three authors declared grants from the pharmaceutical industry, and one author has provided evidence to parliamentary committees on medical uses of cannabis in Australia and the United Kingdom, and is on the Australian Advisory Council on the Medicinal Use of Cannabis. No other conflicts of interest were declared.

SOURCE: Stockings E et al. J Neurol Neurosurg Psychiatry. 2018 Mar 6. doi: 10.1136/jnnp-2017-317168

A reasonable number of patients with treatment-resistant epilepsy experienced a decrease in the frequency of seizures when treated with pharmaceutical-grade cannabidiol, according to findings from a systematic review.

The review, published online March 6 in the Journal of Neurology, Neurosurgery and Psychiatry, centers on 36 studies testing the use of cannabinoids as adjunctive treatments for treatment-resistant epilepsy, including six randomized controlled trials involving a total of 555 patients and 30 observational studies involving 2,865 patients.

IvelinRadkov/Thinkstock

Two randomized, controlled trials representing a total of 291 patients (one with 120 patients with Dravet syndrome and another with 171 patients with Lennox-Gastaut syndrome) found cannabidiol (CBD) treatment was 74% more likely than placebo to achieve a greater than 50% reduction in seizures. In the observational studies, nearly half (48.5%) of the 970 patients across a range of epilepsy subtypes achieved a 50% or greater reduction in seizures.

Emily Stockings, PhD, of the National Drug and Alcohol Research Centre at the University of New South Wales, Sydney, and her coauthors estimated that eight patients would need to receive CBD treatment to achieve a 50% reduction in seizures in one person. However, they also pointed out that the quality of the evidence was mixed.

“There is insufficient evidence from moderate-quality or high-quality studies to assess whether there is a treatment effect of Cannabis sativa, CBD:THC combinations, or oral cannabis extracts,” they wrote.

There were three randomized, controlled trials that also looked at complete seizure freedom, finding a sixfold higher likelihood of total seizure freedom with CBD, compared with placebo. However, the number needed to treat to achieve this was 171, and again, the quality of evidence was described as “mixed.”

Just over half of patients treated with CBD reported improved quality of life, and significantly more parents and caregivers of those treated with CBD said the patient’s overall condition had improved. The pooled estimates from observational studies suggested that 55.8% of patients experienced improvements in their quality of life when using cannabinoids.

Studies involving patients with Dravet syndrome reported the greatest improvements in quality of life, compared with studies involving a mix of epilepsy syndromes. However, the authors noted that the studies that involved Dravet syndrome patients were all case series in which every patient responded and suggested they should be interpreted with caution.

The authors said they were more confident of the benefits of CBD in children than in adults, because the more recent, larger, and better-conducted randomized, controlled trials focused on children and adolescents.

“In RCTs, and most of the non-RCTs, cannabinoids were used as an adjunctive therapy rather than as a standalone intervention, so at present, there is little evidence to support any recommendation that cannabinoids can be recommended as a replacement for current standard [antiepileptic drugs].”

The review also looked at the number of withdrawals, which they said could serve as an indicator of the tolerability and effectiveness of a treatment. The randomized, controlled trials showed no difference in withdrawal rates between patients on CBD and those on placebo, although CBD patients were more likely to withdraw because of adverse events.

There was a small but significant increase in the risk of adverse events with CBD, compared with placebo: particularly drowsiness, diarrhea, fatigue, and changes in appetite. There also was a higher incidence of serious adverse events (AEs), including status epilepticus and elevated aminotransferase levels.

“The fact that more patients withdrew or experienced AEs when receiving CBD than placebo indicates the need for clinicians and patients to weigh the risks and benefits of adding CBD to other AED [antiepileptic drug] treatment,” the authors wrote.

The study was supported by the Commonwealth Department of Health, the New South Wales Government Centre for Medicinal Cannabis Research and Innovation, the Victorian Department of Health and Human Services, and the Queensland Department of Health. Four authors were also supported by National Health and Medical Research Council grants. Three authors declared grants from the pharmaceutical industry, and one author has provided evidence to parliamentary committees on medical uses of cannabis in Australia and the United Kingdom, and is on the Australian Advisory Council on the Medicinal Use of Cannabis. No other conflicts of interest were declared.

SOURCE: Stockings E et al. J Neurol Neurosurg Psychiatry. 2018 Mar 6. doi: 10.1136/jnnp-2017-317168

In the September 2017 issue of JAMA Neurology, Louis R. Caplan, MD, wrote an excellent editorial, “Patient care is all about stories.” He notes that we all hear from patients about a recurrence of their previous stroke deficits, typically caused by infections, medications, or metabolic changes.

His point is that, telling the difference between true vascular events and recrudescence of old deficits can be difficult, but generally can be gleaned by taking a thorough history. He also notes, quite correctly, that the generic, automated features of modern charting systems often make it harder to get the details you need from previous visits.

Obviously, being able to accurately tell the difference between them can save health care costs, too. In a study in the same issue, Mehmet Topcuoglo, MD, and his colleagues discuss methodologies to differentiate between the causes of recrudescence of stroke-related deficits. Currently, the main approach is to admit patients to the hospital, do a knee-jerk repeat work-up with MRI, magnetic resonance angiogram, and echocardiogram (typically ordered before the neurologist has even been told of the consult) and then conclude that nothing has changed neurologically and that it was all caused by a bladder infection.

Surely, if we had an accurate way of telling the difference between them with a careful history, we’d save a lot of time and money on unnecessary hospital admissions. Right?

It sounds good in principle, but, sadly, the answer is “probably not.”

This is where the idealism of medicine meets the reality of its practice.

In the world of the emergency department, time and resources are limited. Emergency medicine physicians don’t have the luxury of taking a detailed neurologic history, nor are they trained (or expected) to be able to do so. Their job is to decide what is (and isn’t) life-threatening and who does (or doesn’t) need to be admitted.

But probably the main reason why Dr. Topcuoglo and his colleagues’ methodologies will never be implemented is defensive medicine. It’s a heck of lot easier and safer for any doctor – emergency medicine, hospitalist, and neurologist – to admit the patient and order more studies than it is to get served for malpractice and have to defend why you didn’t do that.

People can bemoan defensive medicine and its costs all they want. But, if you’ve been sued, you won’t care. You’ll order any test to protect yourself. Claiming that you followed a guideline from a journal, no matter how well researched it was, will likely be worthless the one time a stroke was missed. It’s easy for a plaintiff’s attorney to find someone to say you fell below the standard of care for doing so.

For an example of where this stands, here’s something from personal experience: One of my patients went to the emergency department for recrudescence of an old left hemiparesis, likely caused by a urinary tract infection. This wasn’t the first time it had happened. A head CT was stable while a urine analysis was abnormal. Because of my schedule, I wasn’t in a position to go see him in the ED in an expedient fashion. The ED physician was planning on admitting him and called to notify me. Knowing the history, I suggested sending him home with treatment for the UTI and to follow up with me the next day.

I thought that seemed reasonable, but the ED doctor didn’t. He said, “If you want to do that, then I am going to document that it’s on your instructions, that you are assuming all responsibility for care and outcome if a stroke is missed, and that I entirely disagree with your decision.”

I’m sure another neurologist might have said, “Okay, tell him to come in here tomorrow,” and hung up, but I really don’t have that kind of fortitude or desire for conflict with another physician. So I backed down and let the person on the scene make the decision. I saw the patient later that day as a consult, all his tests (except the urine analysis in the ED) were fine, and he went home the next day. I’m sure the bill was at least $50,000 (what really got paid is another matter), and defensive medicine had, for better or worse, won out over probability and reason.

Dr. Caplan, quite correctly, emphasizes the importance of taking a careful history, and I absolutely agree with him. Unfortunately, the lack of time in the ED setting, and fears driven by legal consequences, often make a good history irrelevant. Even when it’s done, there are other forces that push it to the background in making medical decisions.
I’m not saying that’s a good thing – it isn’t. But that’s the way it is right now in American medicine, and this aspect of the system shows no sign of changing.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the September 2017 issue of JAMA Neurology, Louis R. Caplan, MD, wrote an excellent editorial, “Patient care is all about stories.” He notes that we all hear from patients about a recurrence of their previous stroke deficits, typically caused by infections, medications, or metabolic changes.

His point is that, telling the difference between true vascular events and recrudescence of old deficits can be difficult, but generally can be gleaned by taking a thorough history. He also notes, quite correctly, that the generic, automated features of modern charting systems often make it harder to get the details you need from previous visits.

Obviously, being able to accurately tell the difference between them can save health care costs, too. In a study in the same issue, Mehmet Topcuoglo, MD, and his colleagues discuss methodologies to differentiate between the causes of recrudescence of stroke-related deficits. Currently, the main approach is to admit patients to the hospital, do a knee-jerk repeat work-up with MRI, magnetic resonance angiogram, and echocardiogram (typically ordered before the neurologist has even been told of the consult) and then conclude that nothing has changed neurologically and that it was all caused by a bladder infection.

Surely, if we had an accurate way of telling the difference between them with a careful history, we’d save a lot of time and money on unnecessary hospital admissions. Right?

It sounds good in principle, but, sadly, the answer is “probably not.”

This is where the idealism of medicine meets the reality of its practice.

In the world of the emergency department, time and resources are limited. Emergency medicine physicians don’t have the luxury of taking a detailed neurologic history, nor are they trained (or expected) to be able to do so. Their job is to decide what is (and isn’t) life-threatening and who does (or doesn’t) need to be admitted.

But probably the main reason why Dr. Topcuoglo and his colleagues’ methodologies will never be implemented is defensive medicine. It’s a heck of lot easier and safer for any doctor – emergency medicine, hospitalist, and neurologist – to admit the patient and order more studies than it is to get served for malpractice and have to defend why you didn’t do that.

People can bemoan defensive medicine and its costs all they want. But, if you’ve been sued, you won’t care. You’ll order any test to protect yourself. Claiming that you followed a guideline from a journal, no matter how well researched it was, will likely be worthless the one time a stroke was missed. It’s easy for a plaintiff’s attorney to find someone to say you fell below the standard of care for doing so.

For an example of where this stands, here’s something from personal experience: One of my patients went to the emergency department for recrudescence of an old left hemiparesis, likely caused by a urinary tract infection. This wasn’t the first time it had happened. A head CT was stable while a urine analysis was abnormal. Because of my schedule, I wasn’t in a position to go see him in the ED in an expedient fashion. The ED physician was planning on admitting him and called to notify me. Knowing the history, I suggested sending him home with treatment for the UTI and to follow up with me the next day.

I thought that seemed reasonable, but the ED doctor didn’t. He said, “If you want to do that, then I am going to document that it’s on your instructions, that you are assuming all responsibility for care and outcome if a stroke is missed, and that I entirely disagree with your decision.”

I’m sure another neurologist might have said, “Okay, tell him to come in here tomorrow,” and hung up, but I really don’t have that kind of fortitude or desire for conflict with another physician. So I backed down and let the person on the scene make the decision. I saw the patient later that day as a consult, all his tests (except the urine analysis in the ED) were fine, and he went home the next day. I’m sure the bill was at least $50,000 (what really got paid is another matter), and defensive medicine had, for better or worse, won out over probability and reason.

Dr. Caplan, quite correctly, emphasizes the importance of taking a careful history, and I absolutely agree with him. Unfortunately, the lack of time in the ED setting, and fears driven by legal consequences, often make a good history irrelevant. Even when it’s done, there are other forces that push it to the background in making medical decisions.
I’m not saying that’s a good thing – it isn’t. But that’s the way it is right now in American medicine, and this aspect of the system shows no sign of changing.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In the September 2017 issue of JAMA Neurology, Louis R. Caplan, MD, wrote an excellent editorial, “Patient care is all about stories.” He notes that we all hear from patients about a recurrence of their previous stroke deficits, typically caused by infections, medications, or metabolic changes.

His point is that, telling the difference between true vascular events and recrudescence of old deficits can be difficult, but generally can be gleaned by taking a thorough history. He also notes, quite correctly, that the generic, automated features of modern charting systems often make it harder to get the details you need from previous visits.

Obviously, being able to accurately tell the difference between them can save health care costs, too. In a study in the same issue, Mehmet Topcuoglo, MD, and his colleagues discuss methodologies to differentiate between the causes of recrudescence of stroke-related deficits. Currently, the main approach is to admit patients to the hospital, do a knee-jerk repeat work-up with MRI, magnetic resonance angiogram, and echocardiogram (typically ordered before the neurologist has even been told of the consult) and then conclude that nothing has changed neurologically and that it was all caused by a bladder infection.

Surely, if we had an accurate way of telling the difference between them with a careful history, we’d save a lot of time and money on unnecessary hospital admissions. Right?

It sounds good in principle, but, sadly, the answer is “probably not.”

This is where the idealism of medicine meets the reality of its practice.

In the world of the emergency department, time and resources are limited. Emergency medicine physicians don’t have the luxury of taking a detailed neurologic history, nor are they trained (or expected) to be able to do so. Their job is to decide what is (and isn’t) life-threatening and who does (or doesn’t) need to be admitted.

But probably the main reason why Dr. Topcuoglo and his colleagues’ methodologies will never be implemented is defensive medicine. It’s a heck of lot easier and safer for any doctor – emergency medicine, hospitalist, and neurologist – to admit the patient and order more studies than it is to get served for malpractice and have to defend why you didn’t do that.

People can bemoan defensive medicine and its costs all they want. But, if you’ve been sued, you won’t care. You’ll order any test to protect yourself. Claiming that you followed a guideline from a journal, no matter how well researched it was, will likely be worthless the one time a stroke was missed. It’s easy for a plaintiff’s attorney to find someone to say you fell below the standard of care for doing so.

For an example of where this stands, here’s something from personal experience: One of my patients went to the emergency department for recrudescence of an old left hemiparesis, likely caused by a urinary tract infection. This wasn’t the first time it had happened. A head CT was stable while a urine analysis was abnormal. Because of my schedule, I wasn’t in a position to go see him in the ED in an expedient fashion. The ED physician was planning on admitting him and called to notify me. Knowing the history, I suggested sending him home with treatment for the UTI and to follow up with me the next day.

I thought that seemed reasonable, but the ED doctor didn’t. He said, “If you want to do that, then I am going to document that it’s on your instructions, that you are assuming all responsibility for care and outcome if a stroke is missed, and that I entirely disagree with your decision.”

I’m sure another neurologist might have said, “Okay, tell him to come in here tomorrow,” and hung up, but I really don’t have that kind of fortitude or desire for conflict with another physician. So I backed down and let the person on the scene make the decision. I saw the patient later that day as a consult, all his tests (except the urine analysis in the ED) were fine, and he went home the next day. I’m sure the bill was at least $50,000 (what really got paid is another matter), and defensive medicine had, for better or worse, won out over probability and reason.

Dr. Caplan, quite correctly, emphasizes the importance of taking a careful history, and I absolutely agree with him. Unfortunately, the lack of time in the ED setting, and fears driven by legal consequences, often make a good history irrelevant. Even when it’s done, there are other forces that push it to the background in making medical decisions.
I’m not saying that’s a good thing – it isn’t. But that’s the way it is right now in American medicine, and this aspect of the system shows no sign of changing.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.