MedPod Today: Thumbs Down for MDMA; NEJM Embargo Policy Reversed; ‘Margarita Burn’

The following is a transcript of the podcast episode:

Rachael Robertson: Hey everybody, welcome to MedPod Today, the podcast series where MedPage Today reporters share deeper insight into the week’s biggest healthcare stories. I’m your host, Rachael Robertson.

Today, we’re talking with Michael DePeau-Wilson about what happened earlier this week at the FDA advisory committee meeting on MDMA for PTSD treatment. Then, Kristina Fiore will tell us about how MedPage Today‘s own reporting helped to reverse NEJM‘s embargo policy that limited access for physician-focused publications. Then I’m going to share some of my reporting on the unexpected skin risk of margaritas by the pool this summer.

On to the show.

This week, an FDA advisory committee voted against MDMA as an adjunct to psychotherapy in PTSD. They declined to recommend that the agency approve the controversial first-in-class treatment. At the request of the FDA staff, the committee held two votes. In the first, the committee largely agreed that the available data failed to show that MDMA was effective in treating patients with PTSD. In the second vote, the committee overwhelmingly decided that the risks of MDMA outweighed its benefits, even with the FDA’s proposed risk evaluation and mitigation strategy. Michael DePeau-Wilson listened in on the whole thing, and he’s here to tell us about it now.

Michael, why did the committee vote this way? Tell us more about the conversations they were having.

Michael DePeau-Wilson: Of course. In both votes, the FDA committee members were largely in agreement that the company, Lykos Therapeutics, had failed to adequately prove that MDMA warranted approval for treating PTSD. In fact, the members voted 9-to-2 that the data failed to show MDMA was effective in treating PTSD, and 10 of the 11 voted “no” on whether the risk outweighed the benefits, even with additional FDA oversight. But even those “yes” votes came with strong caveats that the data was lacking. In both cases, those members expressed more concern about the lack of available treatment options for PTSD on the market today, rather than a ringing endorsement for the company’s drug. For example, the lone member who voted yes on both questions, Walter Dunn, MD, PhD, of the West Los Angeles Veterans Affairs (VA) Medical Center, said that his confidence was “low” regarding the risk-benefits, but that “We are in dire need of new treatments for PTSD.”

Robertson: Not exactly a ringing endorsement. What were the concerns that led so many of the other members to vote no?

DePeau-Wilson: Well, the most important concerns seem to center around the poor quality of the efficacy data, according to the members. The company presented data from two phase III clinical trials that showed MDMA plus psychotherapy led to significantly greater improvement in PTSD symptoms compared to placebo plus psychotherapy, but neither study was able to effectively blind the patients in the process, mostly because MDMA causes very obvious and profound changes in mood, sensation, and cognition in people who take it. For example, roughly 90% of patients in both studies guessed correctly that they had received MDMA.

Robertson: Yeah, that’s not surprising.

DePeau-Wilson: Exactly! So the FDA referred to this as “functional unblinding,” and the committee members felt that it could have had a major impact on the study results. Similarly, the members were concerned that the study population was poorly selected. One reason for this was that many of the patients had already taken MDMA and presumably had positive experiences with the drug. The committee felt this could have similarly biased the overall results of the trial.

Robertson: Okay, so study design was a meaningful issue for all of the committee members. Did they have any other concerns about the drug?

DePeau-Wilson: There were plenty of other concerns that came up. They discussed some of the issues around the lack of clear safety data, especially around potential cardiac harms that might be caused by taking MDMA. They also felt that there could be issues with patients abusing the drug, although there really wasn’t any data presented about that specific concern.

The other major concern the committee had was the potential for patient abuse during therapy sessions. Because patients who take MDMA are typically in a significantly altered state, the committee noted there was notable risk that they could be taken advantage of. And this was not a hypothetical concern. There were actually several public comments from people sharing stories about real abuse in these trials. In fact, there was an investigation into one incident that involved a therapist having sex with the patient from the study while the study was ongoing. One of the committee members, Elizabeth Joniak-Grant, PhD, of the University of North Carolina at Chapel Hill, said, “I have real concerns about the validity of the data and the allegations of misconduct” and that she couldn’t “in good conscience support something where these many harms are being reported.”

Robertson: Thanks for filling us in on hours and hours of conversation on this, Michael.

DePeau-Wilson: Anytime, Rachael.

Robertson: Last month, Kristina Fiore reported that the New England Journal of Medicine was going to cut off embargoed access for publications that focused on physicians, including us at MedPage Today. But now, about a month after that story was published, NEJM has rescinded that policy. Kristina is here again to update us on the situation.

So Kristina, what prompted NEJM to reverse course on this?

Kristina Fiore: Well, Rachael, I’d like to think it was all our reporting, but we have to give a lot of credit to the Association of Healthcare Journalists, who played a key role in getting the policy reversed. In mid-May, AHCJ sent a letter to New England Journal editor-in-chief Dr. Eric Rubin saying that the policy was unfair and that it would impede the free flow of information. AHCJ President Felice Freyer said that Rubin responded to her immediately, and he told her that it’s “important for us to help journalists tell their stories, and this [policy] doesn’t do it.”

I also spoke with Dawn Peters, who’s the director of strategic communications and media relations at NEJM Group, and she confirmed that the policy was indeed rescinded. So the journal also scrapped language on its Media Center homepage that said embargoed access was for media producing content for the public and for freelancers writing for non-clinical audiences.

Robertson: Okay, so what happens now?

Fiore: Rubin told Freyer that the New England Journal will continue to require certain credentials before granting access to embargoed papers, but the rules will be applied equally to all journalists and that no publications will be discriminated against. Peters noted that reporters who recently applied for credentials and were only given access to published content, can now re-apply for full access to embargoed and published content.

Robertson: That’s really great that a MedPage Today story had so much impact!

Fiore: I just want to say in reporting the story, I confirmed that a lot of other medical journalists had lost embargoed access to New England Journal, but they hadn’t said anything about it yet. So our story was really the first to bring it to a wider audience, and then AHCJ’s Right-to-Know Committee just ran with it. And I think Felice Freyer was absolutely right when she said this was a “great example of collective action and why having an association like ours can be so helpful. We can speak for the group and it carries so much more weight.”

Robertson: Thanks, Kristina for both stories.

Fiore: Thanks, Rachael.

Robertson: Kristina will now take the host seat for me for this last segment.

Fiore: Think twice about having a margarita by the pool this summer. Or if you do, wash your hands really well and be careful not to spill. The combination of a citrusy cocktail and even five minutes of sun exposure can lead to phytophotodermatitis, which is commonly referred to as margarita burn, or margarita dermatitis. Rachael Robertson will tell us more about it.

So Rachael, what is margarita burn?

Robertson: Margarita burn is a phototoxic skin reaction that occurs when someone touches certain plants and then is in the sun. Raman Madan, MD, who is a dermatologist with Northwell Health, he put it this way to me: “Phytophotodermatitis happens not just because of margaritas, but mainly because of margaritas.”

While it’s colloquially referred to as a burn, it’s actually more of an allergic reaction, he said. Citrus plants are the main culprit here, hence the nickname margarita burn, but other plants, like fennel, celery, and figs also produce that class of chemical compounds. Exposure to them can cause the rash, too. These plants make the skin more sensitive to the sun, and then the ultraviolet rays from the sun weaken the skin, which increases sensitivity. I read some case reports of people who developed phytophotodermatitis after hiking through cow parsnip, pruning a fig tree, and, of course, after spilling their margarita.

Fiore: So how is margarita burn treated then?

Robertson: Madan told me that in the summer months, he sees several cases a week, and most of those cases are mild. He treats those similarly to poison ivy, with topical corticosteroids and ant-inflammatories. But severe cases warrant antibiotics or oral steroids. For prevention, he recommends washing the skin really thoroughly and wearing sunscreen. After the rash heals, a lot of patients are left with discoloration, which gradually fades. The wild thing is, the rash doesn’t appear right away! Most of the time it takes 24 to 72 hours to present. Madan said that that’s because the immune system hasn’t yet mounted a response.

I actually got this very condition a few years ago, and it was so confusing. The rash randomly appeared all over my hand, and I had no idea what caused it. But after going to the dermatologist and getting treatment, it slowly healed, and my skin was left purple for several months. It’s totally normal now, though.

Fiore: Oh, wow. Okay, so Rachael, you can tell us … was it from margaritas?

Robertson: Ah, you know, Kristina, I’ll leave that for you to fill in.

Fiore: Well, like any good journalist, I have my suspicions. Thanks so much, Rachael.

Robertson: Thanks, Kristina.

That’s it for today. If you like what you heard, please leave us a review wherever you listen to podcasts and hit subscribe if you haven’t already, we’ll see you again in two weeks.

This episode was hosted and produced by me, Rachael Robertson. Sound engineering by Greg Laub. Our guests were MedPage Today reporters Michael DePeau-Wilson, Kristina Fiore, and Rachael Robertson. Links to the stories are in the show notes.

MedPod Today is a production of MedPage Today. For more information about this show, check out medpagetoday.com/podcasts.

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