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One-Dose Malaria Tx; New Option in MS: It’s PodMed Double T! (with audio)

PodMed Double T is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week. A transcript of the podcast is below the summary.

This week’s topics include treatment of multiple sclerosis, malaria treatment, overprescription of antibiotics, and fecal transplant for ulcerative colitis.

Program notes:

0:43 Overprescribing of antibiotics

1:45 13% appropriately prescribed

2:45 Antibiotic stewardship

3:32 Malaria treatment

4:30 Tafenoquine about 67% effective

5:30 Fecal transplant for ulcerative colitis

6:30 Primary outcome achieved in about a third

7:33 Better identify patients who would benefit

8:26 Treatments for multiple sclerosis

9:26 Stem cell therapy

10:30 From experienced centers

11:31 End


Elizabeth Tracey: There’s no question we’re prescribing too many antibiotics.

Rick Lange, MD: A new, exciting treatment for multiple sclerosis.

Elizabeth: Can fecal transplant help people with irritable bowel syndrome and ulcerative colitis?

Rick: And a more convenient therapy for malaria.

Elizabeth: That’s what we’re talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a medical journalist at Johns Hopkins, and this will be posted on January 18th, 2019.

Rick: And I’m Rick Lange, President of the Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, I’d like to start with the antibiotics one, if you’re okay with that. This is in the British Medical Journal. We talk a lot about, gosh, when we frame up the study, should we use questions or should we use statements? In this case, I used a statement. We are no question prescribing way too many antibiotics. In this really powerful study, because the N is just so huge, 19 million enrollees. They had 15+ million outpatient antibiotic prescriptions filled by this cohort, and they basically identified four categories of antibiotic prescription. Was it appropriate based on ICD-9 codes, potentially appropriate, inappropriate, or [was it] not associated with a recent diagnosis code?

When they took a look at that, as I said, 15+ million outpatient antibiotic prescriptions, the most common were azithromycin, amoxicillin, amoxicillin clavulanate. It turned out that a lot of them, in fact, the majority of them were either inappropriate or not associated with a recent diagnosis. And in point of fact, just under 13% were appropriate, 35.5% were potentially appropriate, and the remainder were inappropriate or not associated with a recent diagnosis. So this is pretty sad. It suggests, of course, that there’s way too many antibiotics being prescribed out there.

Rick: As you mentioned, it’s a large cohort, Elizabeth. This represents about an eighth of those who have insurance, private insurance, throughout the U.S. They looked at children, that is between the ages of 0-17, and adults between the ages 18 and 64.

And as you mentioned, a fourth of the time antibiotics were prescribed for inappropriate conditions. These were diagnoses that almost never justify antibiotic use such as acute respiratory tract infections and acute bronchitis. And another quarter didn’t have any recent diagnosis code, so it tells me that we have a lot of work to do making sure that antibiotics are prescribed appropriately, and the major reason for this is to prevent antibiotic resistance, which is a major issue worldwide.

Elizabeth: It seems hard to say anything else about this other than, “Hey, we’re prescribing too many antibiotics.” Here, of course, at Johns Hopkins, we have this antibiotic stewardship group, and I guess those are probably around all over the place, aren’t they?

Rick: They are and many times they’re situated in the hospital, but this particular study dealt with the outpatient basis. And the interesting thing about this study was the inappropriate antibiotic use was more likely or more prevalent among adults than it was children, about 25.2% of the fills in adults and about 17% of the prescriptions filled in children.

Elizabeth: And I guess we would say to patients and parents, “Hey, don’t ask for one unless you really need one.”

Rick: As you mentioned, Elizabeth, a lot of this is driven by patients that tell the doctor, “I want an antibiotic. It will help me feel better.” If it’s a viral condition, it gets better on its own. The antibiotics have nothing to do with it.

Elizabeth: Let’s turn now to the New England Journal of Medicine, a couple of studies we’re going to treat together, taking a look at malaria.

Rick: There are different types of malaria. The one that we’re going to talk about today, Plasmodium vivax, causes almost half of the cases of malaria outside Africa. There are about 2.5 billion people in areas where they could potentially contract this. Now the interesting thing about this particular type of malaria is, once the people develop an infection — and it’s a mosquito-borne infection — it affects the red blood cells, but it also lives in the liver in a latent phase, so treatment requires not only treating what’s in the blood, but what’s in the liver.

So now we have a newer, longer-acting medication with a half-life of 15 days that can actually treat the malaria in its liver form. So these studies compared the old treatment, primaquine, for 14 days versus a newer one, tafenoquine, which is a single dose. What they discovered was that current therapy, the 14 days, is a little bit better, but not that much better.

Those that received primaquine, about 73% of them remained malaria-free — no recurrence after 6 months — whereas with the newer drug, it was about 67%. That 4% or 5% absolute difference clinically is not really very important, and I would suggest that even though it wasn’t quite as good as the current therapy, because of the fact it’s a single dose, compliance will be better. In real-world experience, it’s probably just as effective. We should embrace it. Safety-wise, no increased adverse effects. It’s a single dose. Just barely less effective, but I think worldwide this has profound implications.

Elizabeth: It’s really good news, and especially I’m going to suggest in our era of climate change, we’re going to be seeing a lot more widely distributed malaria, I’m predicting, because I think the mosquitoes are moving north. I think getting our arms around this is important. The next one, let’s turn to the Journal of the American Medical Association, a look at fecal transplant for ulcerative colitis. We’ve been talking a lot about fecal transplant for it seems like, [LAUGHTER] I don’t know how many years. What would you guess?

Rick: Well, for a long time because primarily to treat C. diff. infections.

Elizabeth: Yes, exactly, and so in this case, they decided, “We’re going to take a look at this with regard to treating active ulcerative colitis,” a really important and very impactful disease for people in terms of quality of life. This admittedly small study from Australia took a look at a total of 73 adults with mild to moderately active ulcerative colitis in three Australian tertiary referral centers. So it’s interesting it took a while to accrue them, this particular patient population. Patients either received anaerobically prepared, pooled donor fecal microbiota transplant or autologous transplant, followed by two enemas over 7 days.

Open-label therapy was then offered to the autologous recipients at 8 weeks, and then everyone was followed up for a year. In this case, they were able to see, “Are we able to prevent relapse?” And the primary outcome was achieved in 12 of the 38 participants who received the pooled donor fecal microbiota transplant or FMT compared with just 3 of the 35 who received the autologous transplant. So this is looking like a pretty good strategy for trying to help people overcome this very debilitating disease.

Rick: FMT has been used to treat C. diff. infections. Inflammatory bowel disease or ulcerative colitis is a multifactorial disease. It’s interaction between genetics, the environment, the immune system, and the microorganisms in the gut. Previously, we’ve addressed the immune system in these patients and used anti-inflammatory medications. This is an attempt to actually replace the microbiome to see what part that plays.

And as you alluded to, Elizabeth, a third of patients actually received benefit from using FMT. What that tells us is it plays a role, but there are other factors as well, because two-thirds of patients actually didn’t respond. Now we need to more mechanistically look at how does this actually improve people with ulcerative colitis and how can we better identify patients that would benefit?

Elizabeth: Well, a couple things I think are also worth noting. One is that the downside of employing fecal transplant in these folks, I think, is substantially less problematic than keeping them on long-term steroids, which are used very frequently in this condition and we know are associated with a host of really negative, long-term consequences. The other thing is I’m wondering, if we initiated this earlier in the course of a disease — let’s say at first presentation or even second presentation rather than in mild to moderate — maybe it would be better.

Rick: It may be. The other thing you didn’t mention, Elizabeth, is how long-standing does this work? This is a fairly short-duration study that looked at response at 8 weeks, but if you look and carry it out to 12 months, only about 40% of people that had a response at 8 weeks with the FMT actually remained in remission 12 months later.

Elizabeth: Very good. Let’s turn to yours, then, also in the Journal of the American Medical Association, a look at treatments for multiple sclerosis.

Rick: This is another autoimmune disease and it really results from break down of immune tolerance towards our own nervous system. So people’s immune system attacks the nervous system. It often results in repeated, acute episodes of focal inflammation in the nervous system. It causes neurologic events and relapses. Ultimately, people end up with profound neurologic disabilities.

Our current therapies are designed to affect the immune system. They’re called disease-modifying therapies. And we know that compared to placebo they can reduce the incidence of relapse. Two studies in the New England Journal — one of them confirms that. Disease-modifying therapy is effective in reducing the MRI lesions and slows the appearance of persistent disabilities. That was shown in an over 1,500-patient study that looked at different immune-regulating agents. However, they don’t halt the disease. They just slow it down.

So the second study addresses what are called stem-cell therapies. You give agents that reduce the intolerant immune system what the patient has. It’s called cytoreduction. You reduce the white blood cells that are causing the immune dysfunction, and then you re-establish it by giving stem cells that are free of the immune issues with the ones the patient previously had.

In 110 patients, they compared stem-cell therapy to disease-modifying therapy, and the results were dramatic. Disease progression was reduced by 93% with the stem-cell therapy versus disease-modifying therapy. That was over about a 12-month period. When they extended it out even for a longer period of time, the results were pretty dramatic. At 5 years, only about 10% in the stem-cell treated group had disease progression versus 75% in those that received one of common disease-modifying therapies.

Elizabeth: Yeah, especially because, gosh, this ultimately progresses from the relapsing/remitting into a relentlessly progressive disease and truncates lifespan.

Rick: Yeah, I want to stress one thing. This was delivered at centers that were very experienced in the clinical care of a patient with multiple sclerosis and in stem-cell therapy. There’s stem-cell therapy tourism now. People are traveling around the world to get stem-cell therapies for various things, and we’ve talked before about both the dangers of that, the harms associated with it, and the fact that it may not be proven. This is a particular protocol delivered at particular centers. I don’t want individuals to think that stem-cell therapy is the same across the world or across the nation.

Elizabeth: And that’s a really excellent point, because, gosh, we’ve seen some dangers resulting from stem-cell transplantation.

Rick: Yeah. But again, to have a 93% reduction in disease progression in this terrible disease, this is terrific news.

Elizabeth: On terrific news, then, we’ll end for this week. So that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: I’m Rick Lange. Y’all listen up and make healthy choices.