00:55 Educating your patients with actinic keratosis on progression to squamous cell carcinoma and field cancerization.

06:15 The different treatments options available for actinic keratosis.

07:42 Evidence based treatment selection in actinic keratosis; sequencing and combining therapies

10:48 Photodynamictherapy for treatment of actinic keratosis

20:30 Comparison studies on photodynamic therapy used with various used in combination with formulations of photosensitizing agent

24:10 Optimizing the use of photodynamic therapy for extremities in patients with actinic keratosis

27:50 The efficacy, safety and adherence of the different treatment modalities based in actinic keratosis

In this episode of MEDcast, expert dermatologists discuss actinic keratosis, a premalignant skin condition. They are sharing their thoughts on the importance of early diagnosis and treatment and are delving into treatment options, in particular photodynamic treatments.

 Empowering Patients: Navigating the Progression Risks of Actinic Keratosis and Optimizing Treatment Selection

Anthony Rossi, MD

Iron deficiency is currently screened at a ferritin threshold of 15 ug/mL, well below an accepted 25 ug/mL threshold.

Daniel Wang: A More Appropriate Ferritin Threshold is Cost-Effective for Iron Deficiency Screening

Screening for iron deficiency (ID) at a ferritin threshold of under 25µg/L is a cost-effective and more accurate identification and treatment strategy for women with ID.

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

, held December 7-10, 2024, in San Diego, California, by Daniel Wang, Yale School of Medicine.

“The current world health organization guidelines have the lower limit of normal for serum ferritin at 15 micrograms per liter, whereas we know from physiological studies… that a more appropriate threshold is probably 25-to-30, maybe even as high as 50 micrograms per liter, so a huge swath of women of reproductive age who are just going undiagnosed and untreated in a lot of cases,” Wang told 

Wang and colleagues found that screening for ID with a ferritin threshold under 25µg/L is the cost-effective strategy in 100% of 10,000 Monte Carlo iterations, accruing $212,000 in costs and generating 24.3 Quality-Adjusted Life Years (QALYs), compared with $211,000 and 23.3 QALYs with a screening threshold of 15 µg/L, or $210,000 and 22.3 QALYs with no screening. Overall, the data show that the incremental cost-effectiveness ratio of 25 µg/L compared to no screening is $940/QALY which is accepted under willingness-to-pay thresholds in the United State.

The investigators also found that treatment with iron dextran (ICER = $1,700/QALY) is also cost-effective in patients with ID. These findings were supported with sensitivity analyses.

“…Cost should not be a barrier for the screening and treatment of these women and at a population level. If we can raise the bar, I really think so, so many people would benefit,” Wang said.

Wang D, Glaeser-Khan S, Wang DY, et al. Sex, Lies, and Iron Deficiency in 2024: Cost-Effectiveness of Screening Ferritin Thresholds for the Treatment of Iron Deficiency in Women of Reproductive Age. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 277

Daniel Wang

 What’s really important—and we’re not here to give advice to the manufacturer of inclisiran—is the reputation a drug develops when it’s brought to the marketplace. It sticks. To Dean’s point, if you look at data published by Seth Baum and others, they found that the utilization of PCSK9 was somewhere about 0.3% of those who were eligible.

What happened was you had the insurance payers creating these incredible speed bumps. It didn’t really matter. The manufacturers of PCSK9 inhibitors cut their price in half. As Dean, Manesh, and Linda have said, the access to the PCSK9 inhibitors has certainly become easier. But the doctors just aren’t interested in prescribing. As far as they’re concerned, it’s a drug that’s very difficult for patients to access. It’s an “expensive” drug. I urge the manufacturer of inclisiran to think the process through, so that when this drug finally comes to market, it is accessible. 

Otherwise, you’re going to have the same issues that we face with PCSK9 inhibitors. Perhaps we need to inject some artificial intelligence into value-based care instead of what seems to be artificial insanity. We need to be able to count on really good algorithms to determine appropriate use for these compounds.

I still have heterozygotes being turned down for PCSK9 inhibitors. It’s insanity out there. What we really need is really good artificial intelligence, not artificial insanity, in terms of making sure these drugs are being used in the appropriate patient at the appropriate time.

 Norman, that was a wonderful take-home message. In fact, I’m going to start with Dean, Manesh, and Linda; you’ll be last. Give me a similar take-home message, something you think our audience needs to hear from you. Dean?

 In secondary prevention, the LDL [low-density lipoprotein] goal is less than 70 mg/dL and probably lower for all our patients. That’s going to require combination therapy, the best statin dose you can get them on, and then other drugs.

If the cost of the medicine is too expensive, then use ezetimibe. For primary prevention, family history, pay attention to risk-enhancing factors in the guidelines and calcium scoring. That’s how we can get these patients treated earlier, so we’re not in the situation where they’ve already had events and you’ve got to be that much more intensive with regard to their treatment.

 We’re at the age where we have an explosion of possible therapies for our patients, which is great. The take-home message for me is this isn’t about cardiology or specialty care; it’s about primary care. This is about getting the message and the care pattern and the access to the primary care. That’s how we’re going to affect the population health, by getting these therapies—statin, inclisiran if it comes on the market, PCSK9 as we’ve just heard—into the hands of our primary care doctors and getting them comfortable with having the conversation with patients to get the therapies to them.

 That’s a great comment. Linda, you have the last take-home.

I just want to reemphasize lifestyle. Diet is absolutely critical. You can have somebody who is not at goal and they’re eating a terrible diet, and they can have really good results from changing that diet. Using our licensed nutrition folks and getting these people to improve their diet is very much a part of the picture.

 Thank you very much. I’m Dr Keith Ferdinand for HCPLive®. We’ve had a rich and informative discussion. Linda, Dean, Norm, and Manesh have given us a wealth of ideas and information, reviewed data, and given some opinions on where we are now with the intent of lowering risk in patients who are high risk, including the FH [familial hypercholesterolemia] patients, patients with ASCVD [atherosclerotic cardiovascular disease].

If you enjoyed watching this HCPLive® Peer Exchange, if you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box. Thank you very much for listening to this program.

Final thoughts from expert KOLs regarding treatment decisions and how they relate to patient accessibility when manage dyslipidemia. 

Treatment Decisions and its Relation to Patient Accessibility  

Dean Karalis, MD

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

One of the things I think we should revisit in this discussion is the staging of diabetes. 10 or 20 years ago, there wasn't really staging at all. Either you didn't have type 1 or you did have type 1 diabetes. We asked Dr Sims to revisit that when she discussed it too. Type 1 staging is where you're antibody positive, but there are no symptoms, but there's also no change in blood sugar fluctuation. If you give someone a glucose tolerance test, they produce plenty of insulin still, but the antibodies are doing their magic and working against those beta cells. And then we have stage 2 where the antibodies are positive and yet during a glucose tolerance test that those blood sugars start to rise. And that was that first phase insulin response that she was discussing. That's the hardest time that you need the most insulin is when you eat carbohydrates. If you think about that as a clinician, that makes the most sense is that that would fail first and not the fasting blood sugar. When you think about fasting, the patient has had all night to make enough insulin to get that blood sugar down when you check it.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: 

Can you tell us, I know when someone has 2 or more auto antibodies, what's the chance that they're going to develop type 1 diabetes?

Almost 100% in their lifetimes. And in the beginning, we thought about diabetes as something that came on as a child. It was juvenile onset for so many years. We have lots of patients who get it as a child, but we also have lots of people who get it as an adult. And you and I both have had patients in their 60s, 70s, 80s develop type 1 diabetes. How do we know how long they were antibody positive? We don't. But you have a 100% chance or close to it if you have two or more antibodies positive.

Yes. The staging system is interesting. There's not a ton of awareness about it. It's in the ADA standards of care, but I don't think a lot of people are aware of it. And especially in adults where type 1 diabetes tends to be more slow progressing, The staging is very helpful. For example, a common, I guess it's not so common, but I've experienced it in a number of my patients where a woman is diagnosed with gestational diabetes, right? And then come to find out, she actually has the auto antibodies. And I've seen several cases where the endocrinologist, someone thought hey, let's, you didn't seem like a person, you didn't have the characteristics that might put you at higher risk of developing gestational diabetes. Let's go ahead and check those auto antibodies. And sure enough, they've had them. But the neat thing about it is we've been able to catch it so early that in terms of the treatment, often we don't have to go straight to needing basal bolus insulin or using an insulin pump. When you catch it early, especially in adults where it's slower progressing, we can start off sometimes with even other therapies like with using metformin, but often maybe just with a long-acting insulin and not requiring mealtime insulin. It's interesting. There's a lot of benefits to this staging and to early detection.

Yes, and think about, when you think about diabetes, type 1 diabetes and the burden that comes with the management, the day-to-day management, every time you look at food, every time you think about how far is the gate that I walk to at the airport? Is that going to drop my blood sugar? What's going to happen next? There is a real burden that comes with this disease. Knowing ahead of time and using therapies as quickly as possible and addressing them as opposed to waiting will be a real option for patients.

I'm curious your thoughts on this. Of course there is a burden, but now we do have so many better tools, so many better technologies. We've got all these automated insulin delivery systems. I mean, I've got several patients that are easily able to get that 70-80% time in range. What do you think with all the new technologies, is it still as much of a burden? Do we still, should prevention or should cure? Is it still important?

I think it is. And some of the reasons are that we don't know. It's very hard sometimes. We can all talk about the patient, the person with diabetes who's had an A1C of 12 and they end up with eye disease, right? And those people that suffer and that they're trying to just get food on the table and trying to get their heat turned on a regular basis, their blood sugar sometimes can reflect those challenges in their lives. The social determinants of health when you, with type one diabetes are very similar to the social determinants of health with type 2 diabetes and the management of it all and the overwhelming feeling. So AID, automated insulin delivery, is still not for everyone. And I certainly, I have amazing patients who do very, very well. But I also have a lot of patients who really struggle, even with amazing technology that wasn't here 20 years ago, to get to goal and not feel like that's all they do every day. There is a place for delaying the onset. You could choose not to use the medication. We always want to provide a fair and balanced discussion. And this is a harder one because if you don't use the drug, there isn't another drug option. But you could just wait for the diabetes to come. And I don't know that we can always pick the patient that will suffer or have higher burden from the disease than other people. Because you and I both have those, we have both patients who seem to suffer a lot and who just struggle with the management, the daily management, and others who don't have that same challenge with it. They don't like it. They never wake up and say, there's a great diabetes day. But they also don't have the depression and some of the other things that kind of come with that wear and tear of diabetes daily.

Yes, I'm with you. I mean, I'm thrilled with all the different tools and the technologies we have. And I do tell my patients, I'm like, this is, if you must develop diabetes, this is the best time in history to have it because we have all these tools. But the reality is for automated insulin delivery currently, it does require wearing 2 sites. Your pump, you have your CGM, maybe at some point it'll be consolidated into one, but it's still wearing something all the time. And when you wear something, it's you have something on your body. If it falls off, that's a problem, right? You're not getting what you need. I agree with you. I think the cure, the prevention should still be a major focus. And I'm very excited to see that we are finally moving the needle on this. I mean, how many times have you heard a cure is five years away?

50 years now. Right? We've been hearing it for our whole careers. Right.

Right, and I don't know if the cure is 5 years away, but I know that we have gotten a lot closer. The fact that we can delay diabetes by a few years. And even the thing is, it's not just the delay. Because it's also the preservation of those beta cells. Even if you say, ok, well, the person got 2 or 3 extra years of not having type 1 diabetes, well, when they did get it, what were those first few years like? Maybe they were a lot easier. Maybe they were able to be managed on initially a long, or just a little bit, a tiny bit of insulin. They weren't having these wide fluctuations in glucose levels. If we've improved their quality of life for several years, that is something.

: I agree with you wholeheartedly. I also loved her discussion around adding other drugs. This is not going to be the 1 and only drug that is ever going to be used to delay the onset of all kinds of autoimmune diseases. They're looking at Crohn disease, they're looking at, other groups are looking, other companies are looking, right? And that's important too. Is there going to be where we say, you have these 3 antibodies, but you don't have this one. Can we make that person a cocktail in the future to delay the onset longer, to prevent, what if you could get to 10 years? Would you do that? Those are the discussions in the future that we can have.

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES

: Yes, it's definitely very exciting. Well, thank you for this very rich and informative discussion, and thanks to our audience for tuning in. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming MedCast® episodes and other great content in your inbox.

Drs Diana Isaacs and Natalie Bellini discuss the everyday challenges of managing type 1 diabetes and underscore the need for new treatments to improve the quality of life for people living with type 1 diabetes

Challenges in Managing Type 1 Diabetes and Pressing Need for New Therapies

Emily Sims, MD

Fast, accurate diagnosis of multiple sclerosis (MS) can be life-changing for patients, and new updates to the existing criteria are aiming to make that possible, ensuring that those living with the condition get the treatment they need when it matters most. Building on decades of research and clinical experience, the McDonald diagnostic criteria have served as a cornerstone in diagnosing MS, evolving over the years to keep up with the advancements occurring in the field. First established in 2001

, the criteria aim to balance sensitivity and specificity in identifying MS.

Since 2021, a panel of experts has been refining the guidelines to integrate cutting-edge insights into the disease’s biological mechanisms. This latest update prioritizes earlier and more accurate diagnoses by incorporating advanced imaging and biomarker tools alongside clinical evaluations, enabling timely treatment and improved outcomes for patients. Earlier this year, at the 

2024 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 18-20 in Copenhagen, Denmark

, unveiled these newly updated criteria during a scientific session cochaired by 

Overall, these revisions included the adoption of advanced diagnostic methods and the development of age-specific criteria to more accurately diagnose MS in both younger and older populations. The aim of these changes is to enhance diagnostic precision by examining biomarkers of MS-related damage that go beyond observable symptoms. The finalized guidelines are expected to be published in a peer-reviewed journal by early 2025, although delays in the review process are possible. Once released, organizations like the 

 and ECTRIMS plan to educate providers and patients, ensuring that clinicians effectively implement the updates into their practice.

Voices of clinicians featured in recent conversations with 

 offer a collective and valuable perspective on how the updated McDonald criteria will influence MS diagnosis in clinical practice. Each of the insights from the experts bridge the gap between the progress made in cutting-edge research and the experiences of day-to-day patient care. As part of 

 series, these clinical views expand the conversation surrounding the new criteria beyond the guidelines themselves, highlighting their practical implications for improving outcomes in MS management overall.

Proposed New Guidelines for Diagnosing MS

"During my presentation, I realized that while they may look quite complex, they are not so. Again, I want to highlight that the criteria are very much evidence based. I think this is the first time the entire set of criteria is truly evidence-based—they are sensible, logical, and the diagnostic algorithm is very easy to follow,” Montalban, chair of neurology at Hospital Universitari Vall d’Hebron, told 

 in a recent interview. As highlighted by Montalban, the proposed new revisions to the MS diagnostic criteria aim to improve accuracy and consistency in diagnosis.

Key changes in the new criteria presented at ECTRIMS 2024 included recognizing radiologically isolated syndrome (RIS) as MS in specific cases, adding the optic nerve as a fifth anatomical location, and removing the requirement for dissemination in time (DIT). Updates to dissemination in space criteria were introduced alongside the inclusion of kappa free light chains as a diagnostic tool. Montalban also highlighted in the presentation that the same criteria can be applied to both primary progressive MS and relapsing-remitting MS, with stricter standards for diagnosing older patients or those with comorbidities like migraine or vascular disorders.

“I view this as a significant shift in how we diagnose MS, primarily because we no longer require a clinical syndrome, such as a relapse or progression. So, we’ll be diagnosing MS in patients with atypical symptoms or even no symptoms,” said 

, consultant neurologist at Queen's Square MS Center in London, told 

. “It's going to be an interesting time ahead.”

Additional key changes featured in the presented criteria included the recommendation of optional tools, such as the central vein sign (CVS) and paramagnetic rim lesions (PRLs), for specific cases, and myelin oligodendrocyte glycoprotein antibody tests suggested for diagnosing children and adolescents. During the presentation, Montalban emphasized using paraclinical evidence for the confirmation of MS diagnoses across different patient populations. According to the clinicians 

 spoke with, these revisions may reflect a more nuanced approach to MS diagnosis, accommodating a broader range of clinical presentations.

Calabresi, codirector of the Precision Medicine MS Center at Johns Hopkins University, shared with 

that incorporating the optic nerve as a "fifth topology" or classic location represents a significant change in the diagnostic criteria for MS. While optic neuropathy or optic neuritis has long been recognized as a common MS manifestation, it was not previously included in the criteria.

"I think adding that will be useful," he said. He also highlighted the integration of newer imaging technologies, such as optical coherence tomography (OCT), which can now assess inter-eye differences. Specifically, an inter-eye difference of more than 6 microns in the retinal nerve fiber layer or 4 microns in the ganglion cell inner plexiform complex could help confirm a diagnosis of optic neuropathy.

Joseph Kuchling, MD, a postdoctoral research assistant at Charité University Berlin, also highlighted an important update to the diagnostic criteria: the inclusion of specific markers like the CVS and PRLs. "These additions could help improve the specificity of diagnoses," Kuchling told 

, noting that although the 2017 McDonald criteria were highly sensitive, they lacked specificity in real-world practice.

With the new criteria, there is hope for greater confidence in diagnosing MS and initiating treatment earlier in patients presenting with strong indicators such as CVS, without needing to consider other differential diagnoses like sarcoidosis or neuromyelitis optica spectrum disorder. However, Kuchling emphasized the importance of observing how the new criteria perform in clinical practice.

Marcello Moccia, MD, PhD, assistant professor at the University of Naples, explained to 

that a major advancement in the updated criteria is the transition from viewing MS as a purely clinical diagnosis to recognizing it as a biological disease. "This shift is evident in two key aspects of the criteria," he said. The first involves RIS, which was previously described as a set of MRI findings but can now be diagnosed as MS in specific cases where biological evidence of the disease is present. Additionally, the criteria for relapsing and progressive forms of MS have been unified.

"In the past, we used two separate criteria for different clinical presentations, but biologically, the disease is the same," Moccia explained. He added that although this change may have a minimal impact on clinical practice, it significantly advances the understanding and interpretation of MS.

As the revised MS diagnostic criteria continue to evolve, several open questions remain for clinicians to take into future consideration. According to Montalban’s presentation, one area that may require further investigation could be the demonstration of DIT using advanced techniques such as visual evoked potentials (VEP) and OCT, which could offer more precise diagnostic insights. Additionally, the refinement of using PRLs and CVS as diagnostic tools in specific contexts may need further exploration according to Montalban and colleagues.

The criteria’s application to cases of solitary sclerosis and other atypical MS presentations also could warrant further study to ensure broader applicability. Another key question presented at ECTRIMS 2024 on future revision is how the criteria perform across diverse populations, particularly in regions like Asia and Latin America, where MS presentations and risk factors may differ. Finally, Montalban highlighted the integration of other emerging biomarkers for MS diagnosis, beyond the currently accepted standards, that could be an essential consideration in the future revisions.

"A lot of the discussion hinged on what we should do for the next round of criteria. Another point is that we change the criteria every few years, right? That's the model we've been using. But is there a different model that might work better, where we adjust the criteria more frequently as data is produced? We heard some of that,” said 

, associate professor of neurology at the Cleveland Clinic Lerner College of Medicine, told 

. “So, definitely, I think just because we have a new set of diagnostic criteria doesn't mean we've solved all the problems. We need to continue working on things and evolving how we make a diagnosis of MS."

The development of the revised McDonald diagnostic criteria represents a significant milestone in the field of MS for both clinicians and patients receiving care, supported by a forthcoming publication of a paper and diagnostic algorithm. As highlighted in the ECTRIMS 2024 presentation by experts, these updates are the result of extensive consultation with the wider MS community and are designed to address both current challenges and emerging insights.

Based on Montalban’s presentation, clinicians can expect additional papers planned to expand on specific aspects such as imaging advancements, visual system assessments, and the role of biomarkers. Overall, experts recognize that the implementation of these changes globally will possibly require careful consideration of resources, education for providers, and patient accessibility. Thus, a global education campaign may be essential to ensure that MS clinicians worldwide can adopt these criteria effectively into their practice, improving diagnostic accuracy and patient outcomes as well as addressing the unique challenges and perspectives of patients living with MS.

“In essence, the disease hasn’t changed but every few years, new criteria are introduced. The question is, what are these criteria really for? I think they serve several purposes. One is for non-specialists who need help in defining what the disease might be. I believe some of the additions to the new criteria—partly based on new technologies—have genuinely improved the criteria,” said 

, the William S. and Lois Stiles Edgerly Professor of Neurology at Yale School of Medicine, 

. “But ultimately, I should point out that the diagnosis of MS is a pathological diagnosis, and what we do clinically is add various measurements that increase the probability of making an accurate diagnosis.”

McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-127. doi:10.1002/ana.1032

Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173. doi:10.1016/S1474-4422(17)30470-2

Montalban X. 2024 Revisions of the McDonald Criteria. Presented at ECTRIMS Congress; September 18-20, 2024; Copenhagen, Denmark. Scientific Session 1: New diagnostic criteria.

European Committee for Treatment and Research in MS. McDonald Diagnostic Criteria. Accessed November 12, 2024. https://ectrims.eu/mcdonald-diagnostic-criteria#

Recent updates to the McDonald diagnostic criteria for multiple sclerosis (MS) aim to enhance diagnostic accuracy and timeliness, incorporating advanced imaging and biomarkers. These revisions, presented at the 2024 ECTRIMS Congress, include recognizing radiologically isolated syndrome as MS in specific cases, adding the optic nerve as a diagnostic location, and removing the requirement for dissemination in time. The criteria now apply uniformly to both primary progressive and relapsing-remitting MS. Future revisions may explore further integration of emerging biomarkers and diagnostic tools.

With new revisions of the MS diagnostic criteria being made, clinicians highlighted key updates and the broader implications it has for diagnosis, treatment, and healthcare practices worldwide.

Advancing the Diagnostic Criteria for Multiple Sclerosis: A New Era of Early Detection and Precision 

Isabella Ciccone, MPH

Targeting Disease Modification for Psoriasis and Psoriatic Arthritis

17:30 - Defining Minimal Disease Activity

35:35 - Preventing Progression from PSO to PSA

Medical experts engage in a discussion surrounding the treatment and management of patients diagnosed with psoriasis and psoriatic arthritis.

Jennifer Soung, MD

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

This article was originally published in 

The US Food and Drug Administration (FDA) has approved Abrysvo, a 

The approval will allow Pfizer to move forward with the vaccine for individuals aged 60 years and older to prevent lower respiratory tract disease caused by RSV.

) vaccine, is composed of 2 preF proteins specifically chosen to optimize protection against RSV A and B strains.

“A vaccine to help prevent RSV had been an elusive public health goal for more than half a century," said Annaliesa Anderson, PhD, senior vice president and chief scientific officer of vaccine research and development at Pfizer, in a statement. “Abrysvo will address a need to help protect older adults against the potentially serious consequences of RSV disease. We are extremely grateful to the clinical trial participants, study investigator teams and our dedicated Pfizer colleagues for their roles in making this vaccine available.”

In the more than 50 years of working to develop an RSV vaccine, Abrysvo is the world’s second-ever to be granted approval. Last month, 

GSK’s Arexvy (RSVPreF3 +AS01E) was approved

 to prevent lower respiratory tract disease (LRTD) caused by RSV in adults 60 years and older.

The FDA's decision to approve Abrysvo as well was based on data obtained from the pivotal Phase 3 clinical trial (NCT05035212) known as RENOIR (RSV vaccine Efficacy study iNOlder adults Immunized against RSV disease). RENOIR is a global, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, immunogenicity, and safety of a single dose of the vaccine in adults aged 60 and older.

Approximately 37,000 participants were enrolled in RENOIR, with half receiving RSVpreF 120 μg and the other half receiving placebo in a 1:1 ratio. RENOIR is an ongoing study, with efficacy data being collected during the second RSV season.

Edward E. Walsh, MD, Professor of Medicine at the University of Rochester Medical Center and principal investigator of the RENOIR trial, commented, "This 

 demonstrated the serious consequences and potential health risks this virus poses for older adults. Today’s FDA approval of Abrysvo recognizes significant scientific progress, and importantly helps provide older adults potential protection against RSV and an opportunity to improve community health by helping prevent the disease.”

RSV is a contagious virus that commonly causes respiratory illnesses worldwide. It primarily affects the lungs and breathing passages, often leading to severe illness or even death. In the US, RSV poses a considerable burden on older adults, with disease severity increasing with age and comorbidities such as chronic obstructive pulmonary disease, asthma, and congestive heart failure.

In most healthy individuals, RSV manifests with mild, cold-like symptoms. Most people recover within 2 weeks, often without knowing they had contracted RSV. Infants and young children, however, are also susceptible to the worst of RSV infection. Thus, Pfizer is also seeking approval to administer 

 to pregnant persons, with the goal of preventing medically attended lower respiratory tract disease (MA-LRTD) and severe MA-LRTD caused by RSV in infants from birth to 6 months of age.

 by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), and a decision is expected by August 21, 2023.

Regarding the use of RSV vaccines in older adults, the US Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) is scheduled to meet on June 21, 2023, to discuss recommendations. Pending the outcome of this meeting, Pfizer expects Abrysvo to be available in the third quarter of 2023, just ahead of the anticipated RSV season this fall.

In addition to this recent approval, Pfizer reported positive top-line results earlier this month from a Phase 3 study that evaluated the safety and immunogenicity of Abrysvo coadministered with seasonal inactivated influenza vaccine (SIIV) in adults aged 65 and older.

Furthermore, Pfizer announced its plans to conduct multiple clinical trials evaluating RSVpreF in healthy children aged 2-5 years, children aged 5-18 years with comorbidities, adults aged 18-60 years with comorbidities, and adults aged 18 years and older who are immunocompromised and at high risk for adverse RSV outcomes.

The approval for Abrysvo represents the second RSV vaccine approved for adults aged 60 years and older in the last month.

FDA Approves RSV Vaccine for Older Adults

Nina Cosdon

Biomarkers and Improving IgAN Diagnostic Accuracy

What other biomarkers can be integrated with proteinuria measurements to improve diagnostic accuracy for IgA nephropathy?

Biomarkers and clinical indicators play a crucial role in predicting disease outcomes, offering insights into disease progression, treatment response, and patient prognosis. These indicators can be genetic, molecular, or cellular, and are often identified through advanced diagnostic techniques. For instance, specific gene mutations or protein expressions can indicate the likelihood of disease recurrence or metastasis. Additionally, clinical indicators such as tumor size, stage, and patient health status are integral in assessing outcomes. Personalized medicine leverages these biomarkers to tailor treatment plans, enhancing therapeutic efficacy and patient survival rates.

Panelists discuss how integrating additional biomarkers with proteinuria measurements can enhance the diagnostic accuracy for IgA nephropathy.

Authors