How well do patients with rheumatoid arthritis adhere to treatment with a TNF inhibitor and how likely and long lasting is remission? Test your knowledge with this quiz. 

Rheumatoid Arthritis Quiz: TNF Inhibitors

Ingrid Torjesen

Multidisciplinary Teams in CKD Management

How can multidisciplinary teams contribute to holistic patient care in managing CKD and associated risks? Why is ongoing education and collaboration across disciplines crucial in enhancing CKD care?

What protocols for screening and testing have you established for your health system to improve the outcomes of patients with type 2 diabetes at risk for or currently diagnosed with CKD? What are some challenges with implementing your protocol?

Chronic kidney disease (CKD) in Type 2 Diabetes patients necessitates early detection to prevent progression and associated complications. Identifying at-risk patients involves considering factors such as hypertension, family history of kidney disease, and elevated blood glucose levels. Screening tests include estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Early detection is crucial as it allows timely intervention, potentially slowing disease progression and reducing cardiovascular risks. CKD is a significant risk factor for heart failure, making early detection vital for comprehensive cardiovascular risk management.

Panelists discuss how multidisciplinary teams can enhance holistic patient care in managing chronic kidney disease (CKD) and its associated risks, emphasizing the importance of ongoing education and collaboration across disciplines, along with established protocols for screening and testing in health systems and the challenges faced in their implementation for patients with type 2 diabetes at risk for or currently diagnosed with CKD.

Mark A. Meeker, DO, FACP, CPE 

Retina specialists review the current challenges with biosimilars in ophthalmology, commenting on insurance coverage and patient assistance programs

Biosimilars in Ophthalmology: Challenges, Access, and Patient Assistance Programs

 What are the challenges you think are facing ophthalmologists and retina specialist in regard to adopting biosimilars as it stands right now?

 Very good question. I think biosimilars are still pretty new. We’ve heard about them in the meetings maybe for the past 2 to 3 years, but they are here now and out for almost a whole year. I think in retina, especially with vision, we treat a lot of vision-threatening complications, vascular disease; we always have some pause injecting something new into the eye. So I think that first injection is really the biggest barrier for an established retina specialist, especially because we have such products that that are great and work well, and we want to do what’s best for that individual patient in our chair. However, I would say education on biosimilars, as we’re doing here, [and] looking at the data, this is not a study that involved 100 patients, there are 500 patients in the study. They’re looking at drug immunogenicity to show that it actually shows the same response to the reference product. They also look at drug antibodies. All these are very similar and really, at the heart of it, it’s the same amino acid sequence. And ranibizumab is actually like a pretty simple amino acid sequence from the basic scientists I’ve talked to, so it’s probably favorable that we started with something that’s relatively on the easier side to manufacture. But I think once you have that first patient and a good outcome, then you start having confidence in using it more in the future. But that first injection I think is a little bit tough for some established retina specialists.

Yeah, I think you’re right, I think that there’s this wariness. With all the information that’s been out there in the past couple years on various drugs, they’re just a little bit wary about adopting a new drug, and I agree with you. I think these drugs have been shown thus far. There have been some nice studies already done and presented at some of our major meetings, which have shown that thousands of injections of these have been done in practice without any significant intraocular inflammation events or anything else that’s a really major concern. So I’m glad to see that that has come to fruition for those drugs so far. [Let’s talk] a little bit about the insurance coverage. Are you running into any insurance issues? I can tell you a little bit about our practice in Ohio. Our practice in Ohio has recently faced some challenges in regard to using a biosimilar as an option following…ranibizumab and then going through a branded drug. So we had to adopt a biosimilar as a result of that. Are you facing similar challenges in regard to insurance in your area?

 Yes, I think that it’s quite variable with the insurers. Obviously in the neovascular AMD [age-related macular degeneration] population, like a regular Medicare patient, you really have choice to use typically whatever you want, whether that’s off-label bevacizumab, a ranibizumab biosimilar, or another branded medication. For other insurers, yes, one issue we’ve encountered is [that] someone may have been on reference ranibizumab since, say, 2016 for maintenance of age-related macular degeneration…. Now we have a biosimilar, and we’re more than willing to be cost-conscious and switch to that medication. But a lot of insurers have step therapy now, which didn’t exist in 2016, and so they’ll look historically and say, “Well, this patient never received off-label bevacizumab. We’d like you to restart step therapy,” which kind of creates an interesting situation for a patient and physician; should you go back to step therapy and try to get a biosimilar, or should you just continue with the reference product? But I think insurers are not only focused on ophthalmology; they have oncology and rheumatology. So we are a major cost center, but all those details haven’t been figured out. So I see evolving policies over time. And we’ve gone to some insurers and said, “Look, this is an interchangeable product. Can we please use this?” And they said, “Oh, interchangeability, great. Now we understand what the FDA means, and we do approve this.” So some with education [they] will be willing to allow a switch.

I’ll add to that. I think that our biggest challenge in our patient population is retention of them on therapy, right? If we had to look at it, I mean, even if we gave a drug frequently every other month as we were doing kind of in practice right now, the average is around 8 to 9 weeks per retina specialist. As long as it was a low-cost option for our patients, we might actually be able to retain them, albeit that would still give the same durability from the injection profile. And that [would] certainly be a way to improve outcomes overall for our populations. What about patient assistance and reimbursement support programs available for biosimilars? Are you aware of any that are helpful to you or are there things you’re using in your practice right now for others to know about?

 I think the easiest one to tackle is the patient assistance programs. They are essentially equivalent to what you’ve been used to with other manufacturers. Many of these manufacturers contribute to different funds that allow patients who meet financial need to have assistance if needed or if they’re uninsured. These programs are very similar in some cases, [offering] even less of a co-pay for patients. So I’ve seen very strong support there, and it’s great to have those for our patients to have options. With regard to reimbursement, one interesting thing I’ve seen is, even when the biosimilars first come to market with biologics for intravitreal injection, typically they have a J code. Well, biosimilars have a Q code, and from a billing standpoint, I would say we’ve had some of the highest confidence.

And the Q codes I think are helpful to us as practices to improve the billing efficiency which we’re used to in the J code model. And I think that will obviously increase the adoption. As you said, like the hesitancy, the adoption had been around that sometimes for that. And we know that the reimbursement models are out there now so they can help with that as well. And certainly co-pay assistance and patient assistance, hub services programs that you mentioned before, incredibly valuable chronic disease funds that we tap into sometimes free drugs for those who are in the injured in populations of people adding around the poverty rates can be very helpful too. And they have all those available for all the biosimilars which are out there right now.

Transcript is AI-generated and edited for clarity and readability.

Retina specialists review the current challenges with biosimilars in ophthalmology, commenting on insurance coverage and patient assistance programs.

Michael A. Klufas, MD

Scientific Affairs, Innovation, and New Technology

Parvez Mantry, MD, discusses the burden of HCV and challenges to diagnosis and therapy. He also explores general awareness regarding HCV and opportunities for screening.

HCV: A Population Health Perspective

Parvez Mantry, MD

Current Therapeutic Guidelines for Managing Resistant Hypertension

Video content above is prompted by the following:

Briefly, what are the current therapeutic guidelines for managing resistant hypertension?

Difficult-to-treat hypertension is a condition where blood pressure remains uncontrolled despite the use of three or more antihypertensive medications, including a diuretic. This condition is distinct from resistant hypertension, which is more common and involves blood pressure that is not controlled with three medications but may not include a diuretic. Difficult-to-treat hypertension is less frequent, affecting a smaller subset of patients with high blood pressure. It often requires a more comprehensive approach, including lifestyle modifications and potential secondary causes evaluation, to achieve optimal management.

Panelists discuss how resistant hypertension management requires a structured approach combining lifestyle modifications, optimal doses of multiple drug classes, and the identification of underlying causes such as sleep apnea.

Payal Kohli, MD, FACC

One of the issues has been that there does appear to be a therapeutic ceiling with all our agents. We’re seeing about 40% to 60% clinical remissions along those lines, depending on where these drugs are positioned. Both of us have been very aggressive about trying to get these drugs earlier in the course to prevent complications. If you look in the clinical trials with ustekinumab or vedolizumab, the average duration of Crohn disease is 10 years. Patients with 10 years of disease are already developing the problems that we’re trying to prevent. One of the things that I would like to focus on in the future is earlier intervention with these highly effective therapies that we’ve been discussing. What other unmet needs do you see in the pediatric and adult populations for IBD [inflammatory bowel disease]?

 I also have a very keen interest in preconception and fertility in the management of women’s reproductive health, which does tie in to everything we’re talking about. The message to all our female patients is that it’s all about safety and being able to have your disease under control. It is paramount that having anti-inflammatories onboard is what is most important. We know the risk benefit profiles associated with therapies and how to use these therapies in pregnancy, particularly the biologics. We need to be focused on teaching the right thing to our physician partners and patients, that it’s all about controlled inflammation. 

Chronic pelvic inflammation can never end well. That is something I’m vocal about within my preconception clinic, and I counsel women appropriately. But it does have to do with some of these small molecules. We’ll add a layer of complexity when we are looking at bringing these therapies to the clinic. With some therapies, such as the small molecules, we don’t have a lot of real-world experience on the impact in the first trimester because they cross the placenta. That is the question that we need to get more data on. For example, with ozanimod, it will be in the label to stop 3 months before conception. With JAKs you need to stop it. It does add a layer of complexity—we’ve become ob-gyns in terms of figuring out how to use these therapies. An unmet need is also understanding the safety of these therapies in women of reproductive age.

 Did that also apply to pediatric patients? Are there other unmet needs besides improving the efficacy and maintaining a good safety profile in kids?

Marla Dubinsky, MD: It’s a similar concept once you get beyond the VEO [very early onset] IBD. We have the same principles. Similar to what you talked about, whether those extraintestinal manifestations were activity linked or not, the same applies to growth. For all our therapies, just because you heal the intestine, does not equate to growth improvement. We don’t know. We need more data. Does gut-specific therapy have the same impact as systemic therapies? These are things that we need to see from our clinical trials.

There are a couple of unmet needs that you made me think about. I do believe, as I noted before, the future is combination therapy. It could be diet plus biologic. It could be small molecule plus biologic. It could be fecal restorative therapy. It doesn’t matter. The concept of combination means that 1 therapy alone is not going to be the answer. I was addressing your plateau. This is the way I’m thinking about it. Also, sequence will be a hugely important topic to address, meaning understanding the sequence over the long lifetime of a patient who has an evolving immune system based on the therapies we’re using.

I have to plug something that both you and I believe strongly. The plateau may also be the fact that we are not addressing the emotional or behavioral well-being of our patients in clinical trials or the real world, so we can understand how social determinants of behavior, mental health, and comorbidities impact outcomes. We may see a different percentage of remission at week 52. That is an important unmet need that we need to focus on.

I want to amplify your recognition of the social determinants. Certainly in 2021, we’ve seen social determinants of COVID-19 infections and increasingly recognize the disparities of health care in treating chronic illnesses such as ulcerative colitis, Crohn disease, inflammatory bowel disease. We really need to address these disparities and try to improve, whether it’s with psychology, social workers, diet, and education. All these combinations—as your group and our group have shown—really impact patients. They keep them out of the emergency department. Keep them out of the hospital. We need our systems to help us address these disparities. As practitioners, it’s challenging for us and our staff to address this full spectrum of the patients’ needs, from diet to psychological or behavioral support. Economically, 1 of the biggest issues we all have is access to these highly effective therapies. We’re dealing with different insurance programs that may not allow us to use these drugs in the most effective manner that we think we could.

Thank you for watching this HCPLive® Peers & Perspectives®. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peers & Perspectives® and other great content right in your in-box. Thank you.

Current treatment limitations in inflammatory bowel disease and the rationale for earlier initiation and use of newer therapies to manage pediatric and adult patients.

Addressing Current Treatment Gaps in Pediatric and Adult IBD 

Stephen B. Hanauer, MD, Northwestern University Feinberg School of Medicine

Stephen Greene, MD, is an associate professor of medicine at Duke University School of Medicine and cardiologist at the Duke Clinical Research Institute in Durham, NC. Greene is a member of Practical Cardiology's advisory board and co-host of Don't Miss a Beat, a podcast presented by Inside Cardiology.

Don't Miss a Beat: Putting Evidence-Based Cardiometabolic Therapies into Practice, with Taher Modarressi, MD

In this episode of Don't Miss a Beat, hosts Muthiah Vaduganathan, MD, MPH, a cardiologist and codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, and Steve Greene, MD, an advanced heart failure specialist at Duke University School of Medicine, sit down with Taher Modarressi, MD, a cardiometabolic health specialist, to discuss the practical challenges of integrating cardiometabolic therapies into clinical practice.
Modarressi, who launched and owns a standalone practice in the Princeton, NJ area, shares his perspective on his career, what led to establishing the clinic, and the steps he takes to ensure the successful implementation of new therapies, such as GLP-1 receptor agonists and SGLT2 inhibitors, for complex, chronic conditions, including diabetes, obesity, and cardiovascular disease. During the conversation, Modarressi highlights the critical role of insurance coverage, patient assistance programs, and prior authorizations in ensuring patients can access these life-changing therapies.
Modarressi also provides practical tips and nuggets of wisdom on how clinicians can work to streamline the process of helping patients obtain guideline-recommended therapies by working with them to understand insurance formularies, using copay cards, and leveraging tools, like CoverMyMeds, for prior authorizations.

All episodes of Don’t Miss a Beat are available in an audio-only format on 

 include Amgen, Novo Nordisk, Abbott Laboratories, and Boston Scientific. Relevant disclosures for 

 include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for 

 include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others.

Taher Modarressi, MD, sits down with hosts to share tips and practical nuggets for cardiometabolic health specialists to optimize prescription and adherence to newer therapies. 

Stephen Greene, MD

Takeda Pharmaceuticals

 You mentioned clinical data. Reggie, are you familiar with the published data, especially from the ICONIC trial, which allowed the FDA approval of these drugs for children with Alagille syndrome?

 I have some knowledge. I love the name of the trial. ICONIC sounds iconic. Interestingly, it’s one of what I call backward placebo-controlled trials. It’s a medication withdrawal trial—that’s the fancy name—where everybody up front received the drug openly, indifferent to the usual trial where half the patients get the drug up front and half don’t. In this one, everybody got it up front. Supposedly, this improves or diminishes the subjective bias of itching.

Patients received maralixibat 380 µg/kg once a day for 18 weeks. Half the patients were continued on therapy, and in the other half, the medicine was removed. No one knew who was in which group. That was done for 4 weeks. Then everybody got back on open label for an extended period of time, up to 48 weeks. That’s where the ICONIC trial stopped. There’s an ongoing long-term arm of this trial, but ICONIC stopped at 48 weeks.

The take-home message was that in the first 18 weeks of open label, their ItchRO [Itch Reported Outcome] score dropped by almost 2 points. One point is considered clinically important in validation of the ItchRO, so a drop in 2 points is quite significant. As you might have imagined, during the 2 to 4 weeks where the drug was withdrawn, the effect remained in those who continued on drug. But in those where the drug was withdrawn, their itch scores rose back to baseline, clearly suggesting that this medicine was helping the itch.

Furthermore, after everybody gets on open label again, even the patients on placebo get back on the drug, and their ItchRO scores improve. The differences in improvement during the open labels and placebo are pretty dramatic. If you look at these patients at a year out, about 80% of the patients experienced a greater than or equal to 20% reduction in serum bile acids. Serum bile acid reduction was correlated to improved pruritus.

The medicine showed not only improvement in itch but also improvement in the serum bile acids, which may be getting a little off topic or to the next topic. There’s a conversation about serum bile acids being a biomarker of liver outcome. If you lower your serum bile acids, you might get more bang for your buck. You might get rid of the pruritus, but you might also be able to improve or prevent progression of the liver disease, although that might be a question for another one of these conversations. That’s a summary of the efficacy data of ICONIC.

Of course, you have to talk about adverse events, which did happen. As you might imagine, the most common were GI [gastrointestinal] related. Vomiting, abdominal pain, and diarrhea occurred in 50%-plus of the patients on treatment. Fortunately, these adverse events rarely led to drug discontinuation. They were quite tolerable, so the vast majority of patients were able to complete the trial. In the ongoing long-term arm, that seems to be the norm.

 Reggie, thank you for very nicely summarizing it. The drug, of course, was maralixibat.

Regino Gonzalez-Peralta, MD, reviews clinical implications from the phase 2 ICONIC trial evaluating the use of maralixibat for the management of Alagille syndrome in pediatric patients.

Using Maralixibat for the Management of Pediatric ALGS

William F. Balistreri, MD

 Does anything else catch your eyes, Ed or Jessica?

 I’m most excited for, at the current moment, the selective JAKs to be coming down the line, especially for Crohn disease. That’s really what I have my eye on, in addition to, as Bill just mentioned, the IL-23 inhibitors. Those are the things that are coming the soonest, and I’m excited to have more hopefully safe and efficacious options when treating Crohn disease. Those are what I have my eye on, in addition to, of course, my personal biases: the microbiome therapeutics, of which there are several under investigation. We did see some intriguing initial data from Seres Therapeutics in 1 of their agents in the treatment of ulcerative colitis, although these are still very early days. We also know there are several companies working on FMT [fecal microbiota transplantation]–like products, but really more selective microbiome therapeutics. I’m very excited for those. The positioning of microbiome therapeutics earlier or in combination with other advanced therapies is really exciting.

 Ed, do you have any final words on therapies?

 Some of the etrolizumab UC [ulcerative colitis] results were clearly mixed and somewhat disappointing, but don’t forget, we still have a Crohn [disease] trial out there. At some point, we’re going to have some anti-integrin data, and more on Crohn, so there may be something. There are a few other molecules in that realm, so who knows what will happen?

 In that same vein, there’s an orally systemically bioavailable alpha(4) beta(7) [LPAM] inhibitor that’s a small molecule. Think of it as oral vatelizumab. That’s in phase 1 testing. Then there’s another that’s a short peptide that gets down into the more distal gut, and you can think of it as inside out instead of outside in. We always knew that vatelizumab didn’t work solely the way it was proposed because, at doses and drug concentrations that are one-tenth of what’s required for clinical efficacy, you can completely saturate the alpha(4) beta(7) receptors on the appropriate lymphocytes in the periphery. If the entire mechanism of action of vatelizumab is blocking lymphocyte trafficking from the periphery to the gut, then that should be sufficient for efficacy, and it’s not. It makes you think that there’s some other mechanism beyond that, possibly with an antibody in the tissue affecting cell-cell interactions of cells that have already trafficked. With this inside-out peptide, you can see efficacy, and they saw it in a pilot study in the clinic, as well as in animal models, at concentrations where you got some into the blood but only to the point that it was 60% saturating the receptor in the periphery. You wouldn’t expect that to work, yet it did. Anyway, I’m with that. We’re going to see an evolution in anti-integrins and maybe oral therapies. Wouldn’t that be cool?

 That’s a lot to unpack and look forward to. With that, I want to thank everyone for the rich and informative discussion. Before we conclude, I’d like to get some final thoughts from each of you about what you’d like to say to our clinical colleagues. What should they be striving for in treatment and looking for the future? Jessica, why don’t we start with you?

 As we’re evolving in this space, it can potentially feel a bit overwhelming. There are almost too many potential choices coming down the line, so what I would tell my colleagues is to assess your patients. Look for prognostic factors to help you make those treatment decisions, pick targets that you’re going to follow, and do that systematically with your patients every time. It’s going to be different for every patient, but really that’s a way to keep things straight and organized. Stay attuned to the data and all these exciting developments coming down the pipeline. Remember, you can always lean on some of your colleagues at IBD [irritable bowel disease] centers if you’re unsure about therapies or want assistance. For example, I’m always happy to have discussions with my colleagues about which agent we should be choosing, why, or if they’re uncomfortable with potential therapeutic options, because until you have a lot of hands-on experience with some of these drugs, it takes a bit to get comfortable with them. That would be some of my advice to anybody out there treating IBD, but it’s starting to feel a bit overwhelming by all these new advances coming down.

 I’m going to a total side thing. We’re seeing patients with complicated diseases. One of our jobs is to stay rational but also project confidence and hope. Sometimes, we see these patients who have lost hope. Usually, for almost every patient, there’s something you can do to improve their quality of life. Just keep that in mind.

 We’re at the end of the beginning of the revolution of IBD therapy. Buckle up—a lot of new stuff will come, but we have an amazing repertoire of therapies that we can use today. Be students of the field and the craft, and learn to use those therapies and, as Ed said, improve the lives of your patients.

 I always say to the fellows here [Cumming School of Medicine at the University of Calgary], “We need to demand more.” We need to demand more of ourselves to help the patients, demand more of science to push things forward to improve the lives of the patients and to pay attention to those little things that we’ve all talked about tonight. Ed summed it up nicely, that even if you’re on your fourth biologic or advanced therapy, there’s something you can do for that patient that will make tomorrow better for them. Always look at what you can do for that individual patient. With that, to all of you, this was just fantastic stuff. I hope the audience enjoyed it.

 If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming 

 and other great content right in your in-box. I’m sure you’ll see the folks in front of you on future programs. Thank you very much.

Jessica Allegretti, MD, MPH, and Edward Loftus Jr., MD, review emerging agents in the later phases for the management of IBD.

Authors