Andrew Blauvelt, MD, discusses switching therapies for atopic dermatitis (AD) treatment. 

Switching Therapies in AD

Andrew Blauvelt, MD 

On February 10, 2022, the US Centers for Disease Control and Prevention (CDC) 

 of their revised guideline for prescribing opioids for chronic pain. While the 

 is more than 200 pages, the most important part is the actual guideline itself, which is 12 statements that take the place of the 12 statements that comprised the 2016 version that this draft is intended to replace.

Because it is likely that the primary intended audience of clinicians will not read the full document but will focus on the 12 statements, it’s key to examine what has changed, what has not, and the potential impact of this new guideline on the lives of millions of patients with chronic pain whose lives have been 

The biggest change is the removal of specific dosage cautions and limits in statement 4 and 5 and specific days duration of opioid therapy for acute pain in statement 6.These dosage and duration limits were arbitrary and unsupported by clinical evidence yet widely implemented across the country and even codified in law in at least 33 states. Prescribers, insurers, and even pharmacies, implemented them as strict limits. They have caused the most egregious harms over the past six years including forced tapering, hundreds of documented suicides, sudden loss of access to medication triggering withdrawal, dismissal from physician practices, inability to find medical care, and loss of function and quality of life.

In an acknowledgement of these harms to patients with chronic pain from abrupt discontinuation of opioid therapy, statement 5 now includes repeated cautions to “exercise care”, “gradually taper” and “not discontinue abruptly or rapidly” when reducing dosage.

The other less significant changes in the guideline itself are slightly easing the directives on patient surveillance and softening the absolute restriction on concurrent prescribing of benzodiazepines. Statement 9 changed checking the prescription drug monitoring program (PDMP) “ranging from every prescription to every 3 months” to when starting opioid therapy and periodically thereafter.Statement 10 changed the recommendation to use urine drug testing when starting opioid therapy and annually to “consider toxicology testing”.Statement 11 changed “avoid” concurrent prescribing of benzodiazepines and opioids to “use extreme caution” if doing so.

What has not changed in the revised guideline is the lack of balance in the discussion of whether to initiate, continue or discontinue opioid therapy.As in the 2016 version there is a focus on the risks and harms of opioids without any mention of the benefits of opioids for pain control when medically supervised or the risks and harms of inadequately managed pain, especially when other therapies have proven inadequate or contraindicated.

With their focus on patient surveillance through regularly checking the PDMP and using toxicology, the risk the guideline is most concerned about is the risk of addiction.Yet, repeated research has shown the risk of addiction in medically supervised pain patients on opioid therapy to be very small – between less than 1% to 8%. Stated another way, between 99% and 92% of chronic pain patients on opioid therapy do not become addicted to their medication.

However, millions of patients on stable doses of their medication have been forced to taper off their medication since 2016 due in large part to the widespread adoption of the CDC Guideline and the consequent fear of scrutiny and loss of licensure they have created in the minds of U.S. physicians. In 2015, the National Institutes of Health (NIH) reported that there were between 5 and 8 million Americans on opioid therapy for chronic pain.

Further, what has also not changed is the weak body of evidence most of the 12 statements are based on, as in the 2016 version.Using the Group Reading Assessment and Diagnostic Evaluation (GRADE) system which rates the strength of the evidence underlying each guideline statement, 7 out of 12 statements have a rating of 4 on a 1 – 4 scale, where 4 is the weakest level of evidence considered “very weak”. Three additional statements have an evidence rating of 3 or “weak”. Yet, 4 out of the 7 statements with very weak evidence were given the strongest “A” level recommendation rating by the CDC Guideline authors. That is, simply put, intellectual dishonesty.

This revised guideline again excludes certain pain conditions (cancer, sickle cell disease, palliative care, and end-of-life care) as more worthy of pain control where the stated risks and harms don’t apply. Pain is pain, and chronic pain is fundamentally a disease of the nervous system and brain regardless of the etiology. Due to great variation in individual differences regarding disease progression, severity of condition, sensitivity to pain, metabolic variables and more, benefits and risks must be considered on an individual basis. A person with any given pain condition could be in much worse pain for longer duration than a person with one of the excluded conditions.

Will the Revised Guideline Change Practice?

I think it’s unlikely that there will be a renewed willingness on the part of physicians to prescribe opioids again to chronic pain patients who were removed from opioid treatment against their will. According to a report from the US Department of Health and Human Services (HSS) to Congress in April 2020, at least 33 states have adopted statutory limits on opioid analgesic prescriptions. It’s doubtful that any of these codified restrictions will be repealed anytime soon. Once laws are on the books it’s very hard to change them. And, as long as the intense scrutiny of opioid prescribing continues as a result of these laws, regulations and US Drug Enforcement Administration (DEA) investigations of prescribers, I don’t anticipate that access will improve for chronic pain sufferers.

Of course, nothing will bring back all the pain sufferers who committed suicide as a result of being forced off their medication. And nothing can give back all the years lost to relentless pain and suffering of the innocent people living with debilitating chronic pain who were forced off their medication since 2016.

What is more likely to improve in the short term is payer coverage of non-opioid restorative, behavioral and complementary treatments, and medical devices for those with chronic pain, and perhaps with increased recognition of the harms caused by the guideline, a lessening of the punishing stigma associated with being a person in pain in the US. In the long term, I remain hopeful that the current trend of significant increases in public and private investments in neuroscience pain research will lead to novel therapeutics to more effectively treat chronic pain.

Listen to Cindy Steinberg discuss the implications of these changes in an 

interview featured on our DocTalk podcast.

Cindy Steinberg is the Director of Policy and Advocacy for the 

and Policy Council Chair for the Massachusetts Pain Initiative. She is a nationally prominent and articulate spokesperson for the needs of people living with pain and has won numerous awards for her pain policy accomplishments. In 2018, she was appointed by HHS Secretary Alex Azar to serve on the 

HHS Pain Management Best Practices Task Force 

and in 2019 she was invited to testify before the US Senate HELP Committee.

The Director of Policy and Advocacy for the US Pain Foundation addresses the important changes made to the updated draft of the CDC Clinical Practical Guideline for Prescribing Opioids 2022.

Assessing the Draft Revised CDC Clinical Practice Guideline for Prescribing Opioids 2022

Cindy Steinberg

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC

Hello, and thank you for joining this MEDcast series titled “

Concurrent Management of Inflammatory Bowel Disease and Psoriatic Arthritis

.” I am Dr David Hudesman, co-director at the Inflammatory Bowel Disease Center at NYU Langone Health in New York.

I’m Dr Jordan Axelrad, director of Clinical and Translational Research at the Inflammatory Bowel Disease Center at NYU Langone Health in New York.

In this program we’ll discuss strategies for managing coexisting inflammatory bowel disease [IBD] and psoriatic arthritis, and the importance of a multidisciplinary approach to providing comprehensive care. To discuss more of this, we are joined by Dr Jose Scher, Steere-Abramson Associate Professor of medicine and rheumatology at the NYU Grossman School of Medicine, New York. Thank you so much for joining us. Let’s begin.

Jordan, just to kick off this discussion, talk about extraintestinal manifestations [EIMs] in inflammatory bowel disease? How often are we seeing this? What are the most common types?

Sure. Extraintestinal manifestations are disease findings that are external to the GI [gastrointestinal] tract in patients with inflammatory bowel disease. In some studies, these are incredibly common. Up to 40% or 50% of patients may have an extraintestinal manifestation of their IBD, inflammatory bowel disease. These commonly involve skin, joints, liver, kidney, eyes, really any organ outside of the GI tract. Skin and joints tend to be the most common, which hopefully we’re going to get into today, but these can be incredibly difficult to manage and may require expert consultation with colleagues in rheumatology or dermatology.

We’re happy to have our expert here, Jose. Jose, on the flip side, in your rheumatology clinic, how often are you seeing GI symptoms or something that concerns you that there might be something underlying, some type of subclinical bowel inflammation or IBD in your rheumatology patients, specifically psoriasis and psoriatic arthritis?

Thank you both for the invitation. It’s a pleasure to be here. I’d say it’s fairly common if you take the entire spectrum of manifestation. By that I mean, in general, we would see somewhere in the order of 5% of our patients with psoriatic disease and/or axial spondyloarthritis having clinically overt IBD or concomitant IBD. The intriguing part of it is that depending on the studies up to half of our patients have a form of subclinical, meaning not clinically evident gut inflammation, which may or may not manifest itself over time.

I think such high rates on both ends of the spectrum that the collaboration is extremely important. For us, we see some of that data as well, as Jordan was alluding to, especially when we’re looking at arthralgias and spondyloarthropathies, rates as low as 10% to upwards of 50%. So when you’re seeing a patient like that in your office, what’s the usual workflow when you’re concerned about any subclinical GI inflammation? Are you sending anything into your office? Are you referring to us right away?

I call you guys up quickly. We do a physical exam. We take the history that we know how to take. We’re not super comprehensive as you all are. You guys have scores that you go through and screening methodology more specifically. We do a little bit of protecting, an ASCA [anti-Saccharomyces cerevisiae antibodies] type approach or looking at biomarkers to discern whether or not there’s something that merits a quicker referral. We certainly ask about the usual questions of bowel movement frequency, hematochezia, abdominal pain, etc. And so, obviously, we have this ongoing and smooth collaboration between our centers that is very helpful to us as clinicians, but most importantly to our patients because we have this ongoing dialogue that’s helpful for clinical care.

Jordan, how do you ask about extraintestinal manifestations when you’re seeing somebody in the office? Because I think we all, including myself, don’t do as good of a job as we should.

I think that it’s probably underappreciated in the GI office. The actual magnitude of extraintestinal manifestations, in particular, the joint and skin manifestations of IBD are really underappreciated and I think we’re learning the right way to ask that. I learned from Jose that I should be asking about back pain, which I now ask specifically about in addition to just joint pain because you want to know about spondyloarthropathy and axial involvement and whatnot. That also influences how we think about the right medications and also the right types of doctors that they also need to see to be on the same treatment team as far as dermatology or rheumatology. Back pain has come into joint pain, and then, of course, I go into things like vision, skin, rash. Those are really the big ones.

I think that’s a great point. When we ask, when I first started, I would just say, do you have joint pains? Yes or no? Then they say, “No,” and then they’ll just bring it up later. I think we need to do a better job of asking these questions in the office because, as you just alluded to, it’s really going to affect our treatment decisions now that we have more therapeutic options, some that are more targeted, which might be good for 1 reason but maybe not as good for patients with extraintestinal manifestations.

Jose, let’s say I have a patient I asked about joint pains that said their knee hurts or their back hurts. What other questions should we be asking as gastroenterologists that could help us determine if this is something to call our rheumatologist about? Should we send other tests, or is it somebody that’s just ran a few miles or they’re getting older and it’s just a little wear and tear?

Really good question, Dave. Patients with diabetes, and similarly to those with spondyloarthritis or psoriatic arthritis, tend to be on the young side. Obviously, young is a relative term, at least for me it is. But we’re talking about patients in their 20s, 30s, and 40s and therefore you eliminate right away the wear and tear type of joint pain, osteoarthritis, and the like. You really want to focus on whether or not this pain is secondary to trauma or exercising. A lot of people, particularly in New York where we practice, are runners or do high-impact sports. You really want to know whether that’s a meniscal tear or if they’ve been having some other trauma or microtrauma that would explain that particular joint pain.

What we’re interested in are symptoms of pain in a specific joint that associate with swelling, for example. Swelling is a huge one. If you have swelling and pain, that’s more likely to be inflammatory in nature unless there was trauma to begin with. Redness and warmth are other signs leading towards a differential diagnosis of inflammatory disease. The third one could be a history of infection. Again, the Northeast and Lyme disease go together. So that’s a good question to ask. Have you been bitten by one of these bugs at all? Or any other infections, Caribbean-related trips where you have the viral syndromes like chikungunya, Zika virus, etc.? Beyond that, I think we want to make sure that there’s a screening process where not every joint pain equals inflammatory arthritis.

Jose, what do you think about the patients that come in and say, they wake up in terrible back pain or terrible joint pain and then throughout the day it starts to get better? Is that good enough to help differentiate between inflammatory and noninflammatory?

I would say yes, for the most part. Just for the record, what I was referring to before was peripheral arthritis … etc. Embedded in your question is, is this a lower back pain that’s inflammatory in nature? We indeed classify those as back pain that starts in the morning, typically in someone who is 40 years of age or younger that associates with morning stiffness of an hour or more. As you pointed out, typically it gets better or improves with mobility or exercise. Unlike, and the huge differentiating factor, is if you had a slipped disc or you had some sort of radiculopathy, where that pain is there constantly. No matter what you do, if you have a herniated disc you will not get any improvement with mobility. Actually, you may worsen that pain because the slipped disc will be in contact with the nerves that are being impacted by the slipped disc. So yes, those questions are very important.

The fifth point on discerning inflammatory back pain from noninflammatory back pain has come up recently, and that is the use of NSAIDs [non-steroidal anti-inflammatory drugs]. If a patient says that with NSAIDs they get better, then that’s more likely to be related to an inflammatory process. The challenge there is that the new data doesn’t necessarily show that. That improvement with NSAIDs is true for both inflammatory and noninflammatory pain. I don’t think we’re going to hold you guys accountable to that. And I will add that you don’t use that many NSAIDs in your patients anyway.

I think those are all great points and we need to do a better job taking that history. That’s just a couple of extra questions separating joint and back pains, asking is it better or worse with rest, and looking at their age. Then on physical exams, actually looking at the joint. Is it swollen and so forth? Let’s say we’re doing this in our office, the patient gets a little worse at rest and is better with exercise. Is this the right time to send them over to you? Should we be doing any other tests in the first place before sending them over to you? Is there a specific time that you think is best?

We’ve collaborated in some studies to try to understand how to screen inflammatory back pain in those kind of patients. I think that for the general practitioner this is a very straightforward and linear imaging test. I’m referring to sacroiliac [SI] joint x-rays, plain x-rays. The reason for that is that that’s very helpful. We’re going to do that no matter what in general. So if you have that patient whom you suspect inflammatory type back pain, you could help us and help the patient accelerate or expedite the workup by doing the x-ray. The reason for that is if we find any images that are representative of sacroiliitis, then we’re done. We say that patient has radiographic axial spondyloarthritis. So we’re done with the assessment.

I understand that it’s hard and you may not want to order the wrong x-ray, but this one in particular is very straightforward. It’s a dedicated sacroiliac joint x-ray. You can’t go wrong with that. Any radiologist would understand that order. Other than that, I think we can do a quick visit and then think about whether or not the next level of imaging studies are necessary, referring to the MRI.

Jose raises a good point about the MRI because our patients with Crohn’s disease in particular get these very often. Many of our radiologists may even comment on the SI joints and we may not be looking. As a gastroenterologist, we don’t really focus on the GI components, but that’s important.

 Jose, maybe you want to comment on this? We had a collaborative publication looking at exactly what Jordan’s saying. Looking at our MR [magnetic resonance] enterographies [MREs] that we have already for Crohn’s disease and actually going back and having our radiologists take a little closer look at the SI joints.

It was a fascinating study. That’s one of those where we made really good use of our collaborations. You guys do MREs. You look at the inflammatory component in the intestinal lumen, but as an add-on, you could look at the sacroiliac joints. It’s in the same area and it’s using MR technology. So we went back and found that somewhere in the order of 20% of the patients you see with Crohn’s disease will have MRIs consistent with sacroiliitis. It is a magnificent way of screening those patients for not necessarily clinically active or symptomatic but yet concomitant axial spondyloarthritis. That’s important because treatment is not necessarily the same, as you were alluding to, Dave. If you have a patient with Crohn’s disease with axial spondyloarthropathy, we have all these new biologic treatments that may or may not affect the spine, for example, or the peripheral joint.

It’s a great point. Now, from this study, our radiologist specifically comments on the SI joints in the report. It was sort of a request we had. Again, there are other tests you can do, but that’s something easy since you already have that information. You’re not spending more time in your office to get that.

Why don’t we pivot to that, Jose, looking at approaches to therapy. Start with psoriatic arthritis. When you’re thinking about treatment options for your patients, what would you go to regularly? Let’s take out IBD for a second and then we could bring that back in. Then, Jordan, let’s hear your thoughts on how we approach it with the concomitant diagnosis.

Great question. Similarly, to the IBD field, psoriatic arthritis patients present in a heterogeneous fashion. It’s not a linear one-size-fits-all therapeutic algorithm. To us it’s very important to understand the intensity or activity of the different domains. It’s not the same to treat someone who has a lot of psoriasis in their skin or someone with a lot of joints with little psoriasis.

I’ll take you through 2 or 3 scenarios. If you have a patient that presents to you with severe active psoriasis and peripheral arthritis, we tend to use a medication or a set of medications that can help both domains. By that, I mean an IL [interleukin]-23 blocker or an IL-17 blocker, because those are superior in some ways to the TNF [tumor necrosis factor] blockers when it comes to psoriasis of the skin. If you have a patient with mostly arthritis and little psoriasis, a TNF is the go-to mechanism for a variety of reasons. It has been for the last decade or decade and a half and would seem to me that it will continue to be the go-to MOA, or mechanism of action, because of the advent of biosimilars. Then we have patients that present, as we were discussing, with axial or spine arthritis. That complicates matters because there are not that many drugs or options. We’re limited to a TNF or an IL-17 blocker. After that we have the JAK [Janus kinase] inhibitors that are being approved for the use in axial or spondyloarthritis. So those are the 3 main scenarios. Purposefully, I didn’t comment on the presence or absence of IBD, but I’m hearing that you have some thoughts on that.

So, Jordan, let’s throw in IBD there with an extraintestinal manifestation, so skin or joint. How are you approaching those patients?

Sure. There’s a couple of really important considerations. What I’ll say is that in IBD we don’t have IL-17 inhibitors. Those have actually been associated with some flares of IBD, so we don’t have them as treatment options. But they are sort of academically interesting for patients who develop GI symptoms on these drugs. That’s almost a separate chat in and of itself.

Similar to what Jose said, a lot of times if there’s axial involvement with inflammatory bowel disease, anti-TNFs tend to be the therapy of choice that seem to benefit both. I think when there’s psoriasis present in psoriatic arthritis, in particular with peripheral arthritis, I think that’s a good indication for the IL-23, IL-12/23 inhibitors. That seems to have pretty good coverage. Now, if a patient has disease severity of their IBD that makes me want to use an anti-TNF or infliximab then I’m still going to use that in that patient, but I think we have some data that suggests IL-12/23 and IL-23s work really well for that patient. Then of course the JAK inhibitors, which are not yet approved in Crohn’s disease but are approved in moderate-to-severe ulcerative colitis, are another option for many of these folks.

The other really important scenario, and Jose it’d be great to get your feedback on this, are for the patients who develop psoriasis while they’re on IBD therapies. This is a different patient in and of itself. So not the patients who come to you treatment naïve with joint pains, new diagnosis of ulcerative colitis, or Crohn’s disease, but the patients who we already have on therapy who now develop a skin manifestation. What are you thinking about?

That’s a great question. It depends on what the background regimen is. We do this all the time at both of our centers. It really is dependent on what the patient has been treated with. In general, that may occur for 2 reasons. One, the medication that’s being used stopped working. Two, something to consider is the paradoxical effects of TNF blockers, for example. We have those patients commonly. It’s not hyper frequent but it’s there. So you have to consider the possibility that some of these patients develop psoriasis secondary to using a TNF blocker. In those scenarios, whether there’s a secondary inadequate response or there’s a paradoxical emergence of psoriasis, we do switch medications or try and think first of using an IL-23 or an IL-12/23 in the absence of axial arthritis. So with peripheral arthritis, for example, or no arthritis at all, but when a patient with IBD on a TNF blocker develops psoriasis we tend to switch to IL-12/23 for obvious reasons. IL-12/23 or IL-23 blockers are exceedingly efficacious in psoriasis. We all know that. And so because they work as well in IBD, then that’s the immediate answer. Could you switch from 1 TNF blocker to the next? Yes, you could. We typically avoid that though. We switch drug classes.

I think it is interesting. Earlier literature for IBD, before we had ustekinumab and risankizumab or IL-12/23, and IL-12 and IL-23, we would switch. Maybe certain TNFs had lower rates of reaction to having another psoriasiform reaction, but it’s still a chance. Jose, briefly comment on how does that psoriasis usually present? Is it differently than a regular psoriasis if it’s from a TNF blocker?

Paradoxical psoriasis more frequently presents as either palmoplantar psoriasis. It’s not infrequent. It could present as plaque or guttate psoriasis, but its the minority of cases. When we get a hint that someone who either never had psoriasis to begin with or had a different type of psoriasis now presenting with palmoplantar lesions, we tend to suspect that that’s paradoxical in nature.

That’s a great point. We are discussing the difference between IL-23 and an IL-12/23. We don’t have great data yet to say that one is necessarily better than the other. They’re equivalent. In rheumatology, do you lean towards one over the other? So would you lean towards an IL-23 inhibitor over ustekinumab, and why?

Unlike the IBD field, we moved away from the IL-12/23. Rheumatologists and the dermatologists as well. It is simply a P19 blocker. A pure IL-23 is simply superior for skin and joints. There’s data for both, more for skin than there is for joints. We actually never used that drug. There’s only one in the market. I don’t think we’ve ever actually used that drug the way you or the dermatologists have. If you ask the company they will tell you that the rheumatologist never went there. And it’s true that the joint response for IL-12/23 is not robust. There are patients that are on it and respond well, but majority won’t. So that’s why we like the P19s now.

Up until recently we only had ustekinumab in our field and now we have risankizumab that obviously brings something different to the table. I guess one of the more challenging things for us, Dave, and it’d be good to get your perspective, is when we have a patient who’s had very severe disease of their IBD and are finally well controlled on maybe a dose-escalated anti-TNF therapy, who now develops a psoriasiform reaction. Is that someone that you think about switching therapies, adding therapies, or what do we do here?

Great point. I would say most of the time the IBD disease burden is more of a significant inflammatory burden than the joint or the skin. If we’re saying that this is a sick patient that failed multiple therapies, maybe had past surgery, or whatever that is, it’s all about efficacy and keeping them in remission. So if I found a therapy that’s working for them and they’re doing well from their IBD perspective, my goal is to keep them on it.

Now, what is the severity of that psoriasiform reaction? Usually if they’re doing well on something, if they could be treated with topical medications or where you could have these mild reactions, I’m keeping them on their TNF. I need to be pushed, and this is my view on a lot of our patients with IBD, especially our more complex patients. If I have them well on something, I really need to be pushed to stop. I’ve had these patients with that exact scenario where they have significant scalp psoriasis and I have to get them off of it, then we’ll talk about it. But in those scenarios, I do whatever I can to stay on the TNFs and then depending on the severity, those are the patients where I think JAK inhibitors are going to play a nice role. We do need some more data on that, but that’s where I think we might lean towards to cover both.

If I may interject, I think it is exactly what you’re saying for the burden of inflammation. We do the same in arthritis. When a patient failed so many other drugs in the past and we finally got them under control, we typically don’t switch that medication at all. The dermatologists, our friends and colleagues, have multiple tricks that they can use. There are topical medications, UV [ultraviolet] light, a little bit of cyclosporine. There’s plenty of things that they can do.

I’m not going to talk about clinical management, but there are clinical trials ongoing where the question is, in patients particularly early in the game, is there a role for combining with the second targeted agent? And again, for the sake of this discussion, this is not clinically available. But a study such as VEGA, which you guys know very well, combining a TNF with an IL-23, or in our case, we have a similar design in the trial that is called AFFINITY. This study is on someone who fails a TNF with the additional IL-23 in psoriatic arthritis. Will it be better than an IL-23 alone to switch to an IL-23? So intriguing times. Those secret patients are important for that particular reason. It may very well be that we get to a combination on those that need it the most.

We’ve had a lot of discussion on combination therapy just in our practices and how we use them, and EIMs I think is a perfect scenario where we are starting to do that by necessity. But I think we need to be more thoughtful in how we use combination therapies. Then something you had just brought up about how we haven’t really seen that benefit in the IL-12/23s for joints. What’s your experience with the selective IL-23 inhibitors with joint symptoms, joint swelling, and so forth?

 It’s a step up compared to an IL-12/23. It really is, the clinical trials show that. Early use compared to a second-line use doesn’t really make a difference. That’s also an advantage. You can use it a second-line and it’s still efficacious. The downside is the spine, as discussed, it doesn’t seem to work on the spine, and therefore we avoid the use of pure IL-23s in those scenarios.

Great. I just want to get your final thoughts on if we’re seeing a patient, when we should refer? If you are seeing a patient, when do you reach out to us? It really sounds like from everything we’re discussing, from IL-17s possibly leading to flares of Crohn’s disease, to side effects of certain medications of our therapies, to the selectivity of our therapies, we should do this before we start. But how does this workflow usually work in your practice?

In general, to me the key here is to have a fluent, fluid, smooth relationship and communication channel open with you guys and the dermatologists. Where you could truly either pick up a phone or send a MyChart note and say, “Here’s a scenario. Can I take 3 minutes of your time? I’ve done fecal calprotectin and it’s borderline. Do you think you want to see this patient, or do you want to wait?” I think that communication is missing in some geographic regions. The more we can do to incorporate those channels of communications to other practices the better for our patients.

Secondly, I think educating on the role of combined care will be very important. Embedded into that is the question of screening. What can we do to help screen for IBD? What can you do in the IBD world to screen for joints? What will we discuss? A third component here is forensic dermatologist, because we have these other EIMs that are so relevant to our patients. By the way, the patients are an N-of-1. They’re their own statistics. So if you only treat the gut, or the joints, or the skin, then we’re losing time, we’re not communicating, and we’re not making anybody any favor.

I think the collaboration is really key and working with the team of course. I think as gastroenterologists it’s important that we recognize our limitations. We’re not dermatologists. We’re not rheumatologists, and so it’s not good enough if patients are really struggling despite being on a therapy that we think is directed for their IBD. If they’re still experiencing active psoriasis or active joint symptoms, then they really need to have expert referral and collaboration to improve care.

I think those are all great points. Early collaboration is key. Finding those people in your area that you could reach out to that you could text or email on thoughts. I think what we could do better as gastroenterologists is just a couple of simple things. Asking those questions about skin, about timing of when these skin or joint symptoms started around medication. Asking that separate question between joint and back pains. Asking about whether that pain is better or worse with rest and exercise. Asking our radiologists to sort of take another look at the MRE at these SI joints. These are very simple things we could do as gastroenterologists that could really help hopefully diagnose or at least take these patients and get them over to rheumatologists so Jose and this team could help out. But I want to thank you, Jose, for joining us. This is a great discussion and we’ll see you soon.

Dr David Hudesman, Dr Jordan Axelrad, and Dr Jose Scher discuss strategies for managing coexisting inflammatory bowel disease and psoriatic arthritis and highlight the importance of a multidisciplinary approach to providing comprehensive care.

Concurrent Management of Inflammatory Bowel Disease and Psoriatic  Arthritis

Jose Scher, MD

, associate professor of medicine (infectious diseases), was inspired to work in HIV research because of what he was seeing across his community.

“I was bothered by seeing so many new infections and wanted to find solutions that were effective and that the community felt they had ownership of as well—that they had a stake in, that they had a role in designing and choosing,” said Wickersham.

So when he was offered the serendipitous opportunity to work as a postdoctoral fellow in the Yale School of Medicine (YSM) lab of 

, he took it. Wickersham arrived at YSM in 2009 and began to work with Malaysia’s incarcerated population and HIV prevention.

“The first case of HIV in Malaysia was detected in 1986, five or so years after the first cases emerged in the United States. It was almost entirely an injection drug use-driven epidemic for the first 10-15 years. When methadone became more accessible in Malaysia, those cases started to account for a smaller share of new diagnoses. And sexually-driven transmission of HIV exploded. Now nine out of 10 new cases are sexually transmitted, and just over half of those cases are occurring among gay and bisexual men or other men who have sex with men,” explained Wickersham.

He started making connections with the Universiti Malaya and the LGBTQ NGOs in the country. He saw a need for public health prevention research. He started his work to lower HIV transmission among gay and bisexual men in Southeast Asia. This focused on sexualized drug use, known as chemsex.

Previous research demonstrates that the use of drugs like methamphetamine, ecstasy, and GHB can lead to risk-taking behavior like multiple sexual partners, reduced condom use, and poor adherence to pre-exposure prophylaxis (PrEP) or medications that can prevent HIV infection.

Wickersham and his co-principal investigator 

, assistant professor at the University of Connecticut, designed a micro-randomized trial using a just-in-time adaptive intervention to determine whether using an app could reduce HIV-uninfected gay or bisexual men from engaging in high-risk behavior that would put them at risk for HIV transmission. They recently received an R01 grant from the National Institute of Drug Abuse for this work.

The app, called JomCare, will ask study participants twice a day about their substance cravings and their intention to engage in drug use. The researchers will randomize the participants to receive one of three types of interventions. Within 12 hours, the men will be assessed to see if they engaged in any kind of sexualized drug use activity and will undergo urine testing for stimulant drugs as an objective measure. Participants are followed for 90 days.

“Sexualized drug use is hard to intervene on. Unfortunately, there are no medication-based therapies like those that are available for opioid dependence, such as buprenorphine or naltrexone. There are no approved therapies for people experiencing dependence on these drugs,” explained Wickersham.

Through this study, the research team is trying to refine which prompts at which time and under which conditions are the most impactful in reducing risk-taking behaviors. The team will use that data with machine learning to predict under which conditions, which answers at which times of day, and which intervention prompts yield the greatest reduction in those risk behaviors.

, associate professor in the Department of Electrical Engineering at UT Tyler, will lead the machine learning component of the study.

, professor of emergency medicine, of biostatistics, and of medicine (endocrinology) and 

, professor of emergency medicine at The Ohio State University, and 

, associate professor of medicine at the Universiti Malaya in Kuala Lumpur, Malaysia, are also part of the research team.

Wickersham and team plan to continue these efforts in the future to focus specifically on HIV prevention.

Yale School of Medicine’s Department of Internal Medicine Section of Infectious Diseases engages in comprehensive and innovative patient care, research, and educational activities for a broad range of infectious diseases. Learn more at

A new app being developed, JomCare, will ask study participants twice a day about their substance cravings and their intention to engage in drug use.

Reducing High-risk Behaviors for HIV Prevention

Julie Parry

Kimberly A. Davidow, MD, pediatric hematology/oncology, Nemours Children’s Health

Davidow discussed how a new cohort study has helped support findings of an older European study and the need for a prospective trial to confirm the increased risk.

Kimberly A. Davidow, MD: Elucidating Risk of Autoimmune Disease in Childhood Cancer Survivors

A new, real-world cohort study has further identified an increased risk of autoimmune disease in childhood cancer survivors after an initial Scandinavian cohort study suggested this increased risk.

Findings from the study were presented at the

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California, by Kimberly A. Davidow, MD, pediatric hematology/oncology, Nemours Children’s Health.

“With the increased availability of these different kinds of large data platforms, Jefferson [Health] had access to Trinetics, which pulls in a large amount of healthcare data, and [they] wanted to use that to try to look at autoimmune diseases and try to cancer survivors,” Davidow told 

Although limited by constraints inherent to many electronic healthcare records, Davidow and colleagues found that childhood cancer survivors had an increased risk of rheumatoid arthritis, Sjogren disease, ulcerative colitis, and Crohn disease. Davidow shared that these associations should be looked further into in prospective trials, and primary care providers should keep in mind these increased risks when treating adult childhood cancer survivors.

“If you are a primary care provider who's taking care of someone who's a childhood cancer survivor, there's a lot of things you need to know, but this is also important to know. If they're starting to have complaints about joint pains or unusual rashes that, in another patient who didn't have this history, you might not think much of it yet, you need to think more about it for them, because there is this increased risk, and so you should screen sooner than you might for someone else,” Davidow stressed.A new, real-world cohort study has further identified an increased risk of autoimmune disease in childhood cancer survivors after an initial Scandinavian cohort study suggested this increased risk.

“If you are a primary care provider who's taking care of someone who's a childhood cancer survivor, there's a lot of things you need to know, but this is also important to know. If they're starting to have complaints about joint pains or unusual rashes that, in another patient who didn't have this history, you might not think much of it yet, you need to think more about it for them, because there is this increased risk, and so you should screen sooner than you might for someone else,” Davidow stressed.

Davidow KA, Rohan TZ, Roslund CR, et al. Real-World Data Shows Increased Incidence of Autoimmune Disease in Survivors of Childhood Lymphoid Malignancies. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 5094

Kimberly A. Davidow, MD

Margaret Bobonich, DNP, FNP-C, DCNP, FAANP: 

What do we do? How can we assist our colleagues in helping them look at one, how do we choose therapies, and when do we collaborate and refer these patients, and what kind of patient education can we provide for these patients?

Well, I think just to kind of bring this all the way back around, first off an accurate diagnosis always leads to successful treatments. So, make the diagnosis. Familiarize yourself with the different presentations of atopic dermatitis and the neonate versus the toddler versus the teen versus the elderly. And I think have a high clinical index of suspicion. If it is coming back, if it is very pruritic, if it’s life-altering, even if it doesn’t look like classic atopic dermatitis, it likely is a phenotypic presentation of that even if it’s not what’s inside your dermatology textbook. So, get the right diagnosis because the right diagnosis will then lead you to begin to move into the more, what I call the empathic side of treating this How is this impacting your life? How would your life change, how are the treatments that you’ve been using working? And so, begin that dialogue with patients and just kind of let them open up a little bit. It doesn’t have to be two-hour long visits for them to really feel like why this is different than other people have seen. Just asking a few questions lets them know that you're into the diagnosis, that you're not just going to run for a cream and send them out the door, and that you can make a difference. And if you don’t have that time to really tell them everything; you're not going to unload everything on the first visit. Tell them about comorbidities, tell them about every single systemic option, you're going to get their acute flare under control with topicals. And then you're going to bring them back in, you're going to earn their trust, you're going to continue to talk to them about it, and then you're going to begin – I’m always introducing non-steroidal options to patients right up front. If I feel like I have to use a topical steroid to calm it down – I may not need to once we get this new topical JAK out but I’m always introducing the idea of us moving off the topical steroids. I don’t use them much but systemics onto these new treatments. So it’s kind of a progressive revelation of talking to them about the disease, what you believe it is, how you want to open up the box and let them know that you know how this impacts you and the family, that we’ve got good treatments out there, we’re going to start off with this, but it’s important for me to see you back because we want to look into other treatments that are on the horizon that can control this for long periods of time without having to lead the anxiety about when am I going to break out next time. 

You know I think you summarized it very well Doug. I think it’s exciting where we’ve been and where we’re going. We don’t have to use systemic agents with these high toxicities that are really rescue agents, like the cyclosporine. We have choices now. And letting the patients know that and one of the interesting things is I’ve heard people say well that’s an injection. But guess what, let’s let our patients make that choice. Let’s give a fair representation of all the treatment options that we have and the ones that are coming because the truth is that an injection may be nothing compared to the quality of life that atopic dermatitis is having on these patients. A lot more to come for us especially our adult, some of the newer agents will be anticipated FDA-approved for adults. Some of the resources you like to give your patients Doug, what are they? 

Well certainly the National Eczema Association, the NEA, I think is an excellent resource with information about clinical trials that we may have mentioned in this presentation, great patient support, practical data that’s there, practical recommendations on bathing and moisturizing. I really, really like the NEA as a great resource. Do you have others? 

Margaret Bobonich, DNP, FNP-C, DCNP, FAANP:

 The National Eczema Foundation is my choice. But I think as far as resources for you as clinicians, I think one of the best ammunitions I would have for you is if you're in primary care or if you're in derm and you're not comfortable with prescribing some of these agents that are here now or the newer ones that we anticipate that will be FDA-approved in the near future, if you're not comfortable, reach out to a local dermatologist or dermatology NPPA and let us help you. One, we’ll help you with that patient and supporting them and getting them the best treatment and optimal outcomes, but also to help you learn about it. We really, really want to support you as colleagues and that’s my suggestion. Any last words Doug? 

 I just want to echo that. You know the study is a few years old, but it showed that only 19 percent of patients with severe atopic dermatitis got referred from primary care to dermatology. I think that’s improved, especially with some of the commercials that have been out about eczema and dupilumab’s campaigns. But we just want to say that this is – our medicine is a collaborative effort. We’re not living in silos here. We want to – we in dermatology want to partner with our primary care providers, we want to partner with our allergy specialists, we want to partner with the folks that are going to help us out too. I want to tell Margaret, you're helping your patients and you're helping yourself because these folks are living with infections, they’re living with scratching, they’re living with anxiety and depression. And we now have treatments out there that can radically change and improve that. So that’s the biggest message of today’s time together is that there is help out there, that we can get these medicines covered by most insurances, and that they can really change patients’ lives. 

 Thank you so much Professor Doug. This is why we call him Professor Doug. And thank you so much. Thank you for watching 

. If you’ve enjoyed this content, please subscribe to our newsletters to receive the upcoming programs and great content right in your inbox. So thank you everyone. Be safe and live well.

Experts in dermatology discuss patient education and clinical pearls to assist colleagues in the management of atopic dermatitis.  

Care Collaboration in Atopic Dermatitis 

Margaret Bobonich, DNP, FNP-C, DCNP, FAANP

 I want to give us all an opportunity to give some advice or practice pearls to all of our viewers including other hematologists, maybe focusing a bit on red blood cell health or other areas that you think are important including decreasing long term organ damage. I’ll start with you Elna. What advice or practice pearls do you have for our audience?

 I think it is the shifting paradigm that yes sickle cell is an anemia and it causes pain, but the thing that reduces survival and still has maintained the early mortality in sickle cell disease patients compared to the general population is not necessarily the pain or the pain episodes. It is the progressive organ dysfunction and so we should slowly move away from the deception of sickle cell being a mild disease. We should consider it like diabetes or hypertension and that the organ damage is also a silent killer. If we shift that paradigm the way we approach them and how we approach our practice even towards them, we will shift an emphasis in embracing and offering disease-modifying agents to almost all of our patients and having the discussion of the impact of end organ dysfunction and damage in overall longevity and mortality.

 Thank you so much, Elna. Nirmish, you’re next.

 I would just extend the conversation in the sense that educate and be real, continue to educate. I love the descriptions that came up in our conversation today. As I told Matt, I’m going to use some of those. I’m very graphic about drawing pictures and being in the room and getting them to really understand and see what’s happening inside of them because that gives them a little bit of control of knowing what’s happening to themselves. Otherwise, it’s a chronic disease that they have no control of. What control can you give them? It’s educating them about the disease and being able to tell others about what’s happening to them. I think the pearl for me is to educate them and that includes education about these new therapies, and the new drugs that are available now. I even actually started to talk to them about the new drugs that potentially could come.

When we talk about gene therapy, I still kind of give a teaser about it. We’re not there yet. It’s all about being real with them. We don’t have the data. I’m trying to get them to understand that’s why research studies are occurring; this is what we hope that patients can be involved enough with. The patients, I can’t say this enough, they’re really smart. They’re really savvy about connecting to others and they want the information. They just take it up and soak up this information and I think it’s good for the community. Those are some of the pearls. And I mentioned it before, talk about these new medicines when they don’t need it. Talk about everything but pain until you have to talk about pain. Elna brought this up, that there might be the pediatrician inside of us trying to think about the whole world and not the adult side, but I think that our adult colleagues, and I know Biree you do this as well, I think we’re understanding that the quality of life is a big deal. Thus, I think those are some things to consider as we have our colleagues continue to see patients with these new drugs.

 I’ll leave you with 2 more images or analogies that I use because I think that there’s nothing sexy about having a chronic disease and a lot of it is just persistence of the patients, families, and providers in meeting the treatment goals and treatment plan. As I tell families when they’re going for their annual ophthalmology visit or their annual TCD [Trans Cranial Doppler], there’s nothing sexy about this. It’s like changing the oil in your car. It’s a pain. It’s annoying. It costs a little money. But if you don’t do it, what happens to the car? All the kids know the answer to that. It breaks down. Thus, that’s why [there is] this constant persistent pressure to keep on the plan is really very important.

The other one that I find useful to try and sometimes improve adherence to the treatment plan is the idea that organs are like a rock on the beach and the waves every day hit the beach, and they hit that rock and every day you don’t see anything. It’s just like the damage which is done every day with sickling even though you have no symptoms. There’s some clinical inexorable accrual of organ damage is what my mentor used to call it. There’s a little bit of damage every day that’s imperceptible. When you come back to that beach at the end of high school and you see the rock there, it’s still getting pounded by the wave and then you go away to college and then you have kids and you come back and all of a sudden there’s no rock on the beach. It’s just sand. It’s that daily pounding of that rock by a wave that you don’t notice the rock changes, but it’s becoming sand slowly and that’s what we’re trying to prevent with the daily damage of sickle cell disease on your organs.

Hydroxyurea and other disease-modifying agents are trying to prevent that from the daily point of view so that, as Nirmish pointed out or Elna pointed out, we’re trying to improve the overall health and organs of our patients who we present to our adult colleagues so that they can ultimately hopefully have a prolonged life and that sickle will no longer be an either immediately life-threatening or life-limiting disease, but hopefully have normal lifespan and quality of life. That’s really the goal. It’s hard. It’s hard to do that as a child, as a teen, and as an adult with so many other pressures on us but to encourage them to continue to follow the treatment plan with what we have while also being cognizant of what’s coming and what might be until something better comes along, as I say. Let’s follow this plan now. My promise is to keep them informed of what’s potentially available, both experimental and approved, and then they can choose collaboratively with us to potentially take on some of those new therapies.

Thank you, Matt. I really love the imagery in those analogies. I think we’ll all start to use them. I just wanted to add that I think when I speak to colleagues, clinicians of any specialty, patients, the community, family members who help to support their loves ones living with sickle cell disease; I really tell them that the tide is changing in sickle cell disease and it’s changing pretty quickly. Not only do we have more therapies available now, but our understanding of new potential targets is also growing exponentially and we’re seeing that playing out in the clinical trials that are available and that will be emerging in the near future. I think that sickle cell disease as we know it is changing. It is changing. Our patients may not feel that way today, but I do talk to my pediatric colleagues including some of you on the webinar today and I’m always heart-warmed when I hear the hydroxyurea story, for example. My colleagues say that ever since we’ve been giving it to babies starting at 9 months of age, we have such a healthier kindergarten class when we see those 5-year-old’s go off. That just warms my heart.

I think as an adult practitioner I’ve not yet begun fully to that extent to see the effects of novel agents or disease-modifying therapies or even transplant for that matter because we don’t do enough of it in the adult world. But I think that that tide is really changing. Just like hemophilia, for example, where we’ve come a long way, the expectation in hemophilia management is no leads. When we think about HIV care and we were making people toxic, sick with therapy as we knew it a few decades ago, and now people can be on 1 pill once a day. I think that there’s the potential in the very near future, hopefully in all of our lifetimes, to see that amazing impact on those affected by sickle cell disease. I’d say the future is definitely bright. I want to thank Elna, Nirmish, and Matt. And I want to thank you all for watching this 

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A panel of experts in hematology discuss the future directions for sickle cell disease and share practice pearls for disease management. 

Practice Pearls for the Management of SCD

Matthew M. Heeney, MD

Medical Sisterhood: Polished and Powerful—Women Leading the Charge in Advocacy

, host Mona Shahriari, MD, an assistant clinical professor of dermatology at the Yale University School of Medicine and the associate director of clinical trials at Central Connecticut Dermatology Research, is joined by Shadi Kourosh, MD, MPH, an associate professor at Harvard Medical School and founder of the Pigmentary Disorder and Multiethnic Skin Clinic at Massachusetts General Hospital, to discuss advocacy, mentorship, and the empowerment of women in medicine. 

After introducing herself, Kourosh reflects on her path to legislative advocacy, which began with patient-centered initiatives through organizations like the National Psoriasis Foundation. She emphasizes physician-patient teams' power in conveying healthcare policies' real-world impact to lawmakers. From addressing insurance step therapies to advocating for sustainable physician reimbursement, her efforts highlight the critical role of education in influencing health policy. She notes how many lawmakers lack a nuanced understanding of medical issues, making physician input essential.

Use this link to view US News and World Report article, titled "

Medicare is Breaking. Senior Citizens are Paying the Price.

", authored by Kourosh referenced in this recording.

The conversation shifts to empowering women to engage in advocacy despite time constraints. Kourosh encourages leveraging local opportunities, such as district meetings with legislators, joining committees remotely, or supporting initiatives via social media. She underscores how impactful contributions can start with small actions, like responding to pre-drafted advocacy emails from professional organizations.

The episode closes with a heartfelt reminder about the value of friendships and collegial support in navigating challenges, preventing burnout, and fostering career growth. Kourosh advises physicians to invest in building and maintaining strong professional relationships, as collaboration and community are key to resilience and success in medicine.

Want to join The Medical Sisterhood community? Click here to join our LinkedIn Group!

Shadi Kourosh, MD, MPH, joins The Medical Sisterhood to discuss advocacy, mentorship, and the empowerment of women in medicine. 

The Medical Sisterhood: Polished and Powerful—Women Leading the Charge in Advocacy

Shadi Kourosh, MD, MPH

Welcome to Kidney Compass: Navigating Clinical Trials!

Kidney Compass: Hierarchical Composite Endpoints in Nephrology, with Dustin Little, MD, and Niels Jongs, PhD

Welcome to the first installment of a 4-part series on 

 exploring the use of hierarchical composite endpoints (HCEs) in kidney disease clinical trials.

In this installment, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, begin by introducing their guests Dustin Little, MD, Global Clinical Lead at AstraZeneca, and Niels Jongs, PhD, a statistician at the University of Groningen.

The discussion starts with an overview of traditional composite endpoints commonly used in nephrology trials, such as cardiovascular death, kidney failure, and sustained eGFR decline. Little explains key limitations of these traditional endpoints, including their reliance on first-event analysis and the disproportionate influence of rapid progressors on overall trial results. He emphasizes the need for more efficient trial designs that account for the entire study population rather than just those who reach predefined endpoints.

Jongs and Little both go on to explain how HCEs aim to address these shortcomings by structuring outcomes in a prioritized hierarchy, ensuring every patient contributes meaningfully to efficacy assessments. They discuss the addition of eGFR slope as a component of HCEs, allowing for a more comprehensive evaluation of treatment effects, especially in trials where only a small subset of participants progress to major clinical events.

Jongs expands on these concerns by highlighting statistical limitations, including how composite endpoints weigh events equally despite differences in clinical significance. The conversation then shifts toward the structure of HCEs, which build upon traditional endpoints by incorporating eGFR slope to ensure that all patients contribute to efficacy assessments. By structuring events hierarchically, HCEs aim to better reflect disease progression and provide a more comprehensive assessment of treatment effects.

For ease of viewing, we've divided this episode into 4 sections and highlighted them below.

Kidney Compass: Hierarchical Composite Endpoints in Nephrology

Part 1: Introductions, HCEs in Nephrology

Part 2: HCEs in Nephrology Clinical Trials

Part 3: Addressing HCE Skepticism, Potential Limitations

Part 4: Applying HCEs in Kidney Disease Trials

 include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for 

 include the National Institute of Diabetes and Digestive and Kidney Diseases, GSK, Calliditas, and Travere Therapeutics. Relevant disclosures for 

In part 1 of 4 from this episode, the discussion focuses on traditional composite endpoints in nephrology trials and the use of HCEs.

Authors