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

Patient Case No. 2

Patient No. 2 has stage 3 CKD and uncontrolled hypertension. They have a moderate reduction in their estimated glomerular filtration rate, confirming stage 3 CKD. Their hypertension is likely contributing to CKD progression.

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 chronic kidney disease (CKD) and uncontrolled hypertension create a damaging cycle, in which hypertension accelerates kidney damage while declining kidney function makes blood pressure harder to control.

John M. Flack, MD, MPH, FASH

Focusing in on Novel Oral Systemic Therapies for Moderate Plaque Psoriasis: Medcast Video

03:15 The role of APP’s in getting patients access to dermatological care.

06:06 Managing patients with suboptimal controlled plaque psoriasis

13:05 Breaking down barriers to access new treatments for plaque psoriasis.

20:23 Deciding between oral and injectable systemic therapies.

24:25 The mechanism of action of TYK-2 inhibitors

28:24 The safety profile of deucravacitinib

33:14 Monitoring your patients with plaque psoriasis

Lauren Miller, MPAS, PA-C, leads an expert discussion surrounding exciting developments in the treatment landscape of plaque psoriasis.

Kristine Kucera, PA-C, MPAS, DHS

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

Payal Kohli, MD, FACC

Another case, case number 2. We’ll have Sheetal run this one. A 26-year-old female coming in with a near history of pain in multiple joints. Pain started in the knees with some mild intermittent swelling, a fairly insidious onset of pain, and then over the next 2, 3 months, it migrated to involve the symmetric ankles, elbows, feet, and shoulders. She complained of some persistent inflammatory low back pain—so they actually call out inflammatory low back pain—associated with morning stiffness going on for about 2 hours. Then for the past month before coming, she has developed these lesions that seem to spare the face, the palms, and the soles. She complained of some fever and fatigue. On exam, she had some mild knee tenderness with some mild swelling, MCP [metacarpophalangeal joints], PIP [proximal interphalangeal joint], pretty diffuse involvement. They don’t talk much about the skin exam, but we’ll assume that the lesions are where they said they were. Routine blood testing, the CBC [complete blood count], comprehensive metabolic panel were normal. CRP [c-reactive protein], SED [erythrocyte sedimentation] rate was elevated, RF [rheumatoid factor] was negative. The only imaging result we have thus far is a hand radiograph that showed right second PIP erosion, and then right fifth PIP fixed flexion deformity. We have intermittent history of exam here, but that being said, initial impressions, testing, then of course looking at the fatigue part of this as well. Give me some thoughts on how you would start approaching this patient.

: If I’m pretending a fellow is presenting this patient and coming out of the room, I would say, it’s a young female, 26-year-old, around the age that we would see psoriatic arthritis about, close to 30 years old, 30 to 50, 1 to 1. Even though the last case was female and she’s female, we see it with equivalent levels in both men and females. The arthritis has been going on for some time. We have a chronic arthritis that has an inflammatory component, symmetric polyarticular arthritis, like the old Moll and Wright criteria would be RA [rheumatoid arthritis] -like in this situation. She also has inflammatory back pain with prolonged morning stiffness. This patient has psoriasis only over the last month, but I guess she’s had a year history of inflammatory arthritis. I would focus on how psoriasis does precede the majority of patients who get psoriatic arthritis approximately 70% of the time, but in a minority of patients, 15% of them, the psoriasis and the arthritis can present simultaneously, and then in another 15%, you can get the psoriasis after they have the inflammatory arthritis.

She has significant fatigue. She is CR negative, rheumatoid factor, has elevation in her inflammatory markers, and after 1 year of disease, she has an erosion seen on radiograph, and has ankylosis. It’s concerning to me that this is somewhat of a rapid progressor with significant polyarticular symmetric psoriatic arthritis with a good amount of progression. I would feel comfortable with the diagnosis of psoriatic arthritis here. For further testing, I’d recommend some imaging of her sacroiliacs, of her spine if she complains of any other areas like cervical disease just to get an idea if we can find inflammation and finding sacroiliitis.

When it comes to the treatment regimen we would recommend, it would be reviewing the domains involved. Her domains involved are her peripheral arthritis, she has axial involvement, she has skin involvement. She has no mention, at least in this stem that I’m reading right here, of dactylitis or enthesitis, although I find that unless you go looking, you won’t find it. I find the more I look for enthesitis, the more I find enthesitis. But currently, the domains based on the stem we have are peripheral joint, axial inflammation, and skin. There’s no mention made of nail changes. It would be going along the lines of agents that would work in these areas. Because we have axial involvement, we would be straying away from the conventional synthetic DMARDS [disease modifying anti-rheumatic drugs]. In this patient we would be looking at a combination of, for her arthritis, possibly NSAIDs [nonsteroidal anti-inflammatory drugs] plus a biologic, but for her skin disease, it would be the biologic. The biologics that I would consider here, I’m not reading any concerning features of demyelination as a comorbidity or inflammatory bowel disease symptoms, but we do need to ask them if they have any diarrhea, mucus, or blood in their stools on a frequent basis. If she doesn’t, then I would be open to anything along the lines from a TNF [tumor necrosis factor] or an IL-12/23, an IL-23, IL-17. There’s nothing that’s stopping me from consideration. One would argue that given her axial involvement, though, maybe we would put the TNF and possibly even the IL-23 family a bit higher than the other families.

: They call out the fatigue as well. There’s some consideration, but they all do a good job. It’s interesting that they call that out.

: Right, this is how I think through it. It’s nice that we have some data on the IL-23 MOA [mechanism of action] with the guselkumab [Tremfya] with fatigue. My hope, as Len said, that we’ll start to look at some of these more patient important metrics in the future clinical trials in PsA [psoriatic arthritis].

: This case is nice because it asks the question of how would you differentiate her pain and fatigue from fibromyalgia? This is important. This patient, this woman clearly has inflammatory disease. She has clinically inflamed joints, she has elevated inflammatory markers, I would say that even if she has overlapping fibromyalgia, this is not so relevant because it’s not going to influence my choice of therapy. It can complicate measuring improvement down the road, but I don’t think that this would be particularly relevant at the first visit because she would also be in pain and fatigued due to her active disease.

: Thank you for highlighting that, Ana-Maria. I agree with you. In this situation, differentiating the pain and fatigue from her inflammatory conditions vs fibromyalgia is clearer because she has a clear inflammation that becomes much grayer when they don’t have much inflammation on exam and then they have these metrics and you’re trying to figure out what it is. Len, were you saying something?

: Yes. I would only add, in fact I agree with everything, it’s a first visit and you know how you’re going to start this therapy. She probably has fibromyalgia and that may become more important down the line as Ana-Maria said. I would get more aggressive earlier in sorting out this inflammatory back pain and whether this is like the pseudo fibromyalgia of spondyloarthritis that we’re trying to understand in young women. Maybe she has a mixed picture of this. Obviously, we’d start with a pelvis film and maybe somewhere down the line, if it was negative, get MR [magnetic resonance] imaging of this. But I agree with everything otherwise. Right now, she has clearly inflammatory disease and needs to be treated.

: First off, sometimes when you see this much of inflammation in a particularly young patient, female or male for that matter, and they do describe IBP, inflammatory back pain, that well, I start believing it more, which is not necessarily fair. You almost start reading into the most subtle changes on the radiograph that you might not otherwise. But, with what’s going on peripherally, we need to be thinking fast that she’s going to be needing something beyond just most likely a conventional DMARD. But I agree, there’s a lot on the checklist to do that first visit, but, at a minimum, getting a radiograph of the sites.

Sheetal Desai, MD, leads the discussion on a real-world case scenario of a 26-year-old woman with polyarticular symmetric psoriatic arthritis and shares her approach to treatment.

Case 2: 26-Year-Old Woman With PsA

Sheetal Desai, MD

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 HCPLive's advisory board and co-host of Don't Miss a Beat, a podcast presented by Inside Cardiology.

Counting down the biggest news from major medical meetings, it's the HCPLive Five!

HCPLive Five at Heart in Diabetes 2025

 is a medical conference bringing together world-renowned clinical leaders in 

. Designed to evaluate state-of-the-art clinical data and research while focusing on the management of the heart and 

 in diabetes, the meeting’s goal is to align cardiologists, endocrinologists, diabetologists, 

, nephrologists, and all other interested clinicians in their understanding and development of appropriate comprehensive clinical management plans for high-risk patients.

’s on-site coverage, the editorial team conducted expert interviews and reported on timely topics across implementation science, cardiometabolic health, combination therapy, and more. In this edition of the HCPLive Five, the team highlights key conversations on barriers to evidence-based cardiometabolic care, recognizing 

 as a chronic disease, data on cardiovascular disease trends, the CONFIDENCE trial of combined finerenone plus empagliflozin in patients with both 

 and type 2 diabetes, and data accessibility issues in an era of unprecedented technological innovation.

Improving Evidence-Based Cardiometabolic Care, with Neha Pagidipati, MD, MPH

While innovation in cardiovascular, kidney, and metabolic care often centers around emerging therapies, the underuse of established, evidence-based treatments in clinical practice remains a major and under-discussed challenge. In this interview with 

 at HiD, Neha Pagidipati, MD, MPH, an assistant professor of medicine and cardiovascular disease prevention specialist at Duke University School of Medicine, reviews different barriers to implementing guideline-directed medical therapy as well as facilitators and potential avenues for improvement moving forward.

Classifying Obesity as a Chronic Disease with W. Timothy Garvey, MD

Given the limitations surrounding BMI measurement of obesity, a recent Lancet Commission aimed to better define obesity as a condition of illness that comes as a direct result of excess adiposity and its effect on the function of tissues and organs. In this interview with 

 at HiD, Timothy Garvey, MD, breaks down some of the key points from the paper and how they will influence the treatment of obesity and its complications moving forward.

Moving the Needle on Cardiovascular Disease, with Seth Martin, MD, MHS

Despite decades of progress and innovation in cardiovascular care, recent data from the American Heart Association (AHA) suggest that the momentum has stalled—and in some cases, reversed. At HiD, Seth Martin, MD, MHS, a professor of medicine in the division of cardiology at Johns Hopkins Hospital and co-founder at Corrie Health, offered a data-driven overview of the current state of cardiovascular disease (CVD) in the United States and globally, based on the AHA’s 2024 statistical update. In this interview with 

, he reviews key trends and calls for urgent action to improve implementation of prevention and treatment strategies at scale.

Don’t Miss a Beat: CONFIDENCE Trial and Combination T2D, CKD Therapy at Heart in Diabetes 2025

, 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, review key findings and clinical implications of the CONFIDENCE trial. The data, which were also presented at the 

62nd European Renal Association (ERA 2025) Congress

 in Vienna, Austria, suggest the potential benefits of combination initial therapy with finerenone plus empagliflozin in patients with both CKD and type 2 diabetes.

Confronting Cardiology's Data Accessibility Problem, with Robert Califf, MD

, Robert Califf, MD, an instructor of medicine at Duke University School of Medicine and former commissioner of the US Food and Drug Administration, provided his perspective on the ongoing difficulties in implementation of digital technologies and preventative measures for cardiovascular diseases and diabetes. He points to shortcomings of the cardiology field and the medical industry at large in adapting technological advances to practical, clinical usability, citing the high number of new programs and mechanisms for tracking individual risk factors and their failure to collate this data meaningfully for patients.

These 5 represent only some of the data the 

 team covered at this year's meeting! Check out more KOL insight and our full conference coverage on our 

From barriers to implementing evidence-based care to innovations in combination therapy, here are 5 key updates from the annual meeting.

Stephen Greene, MD

Professor Stephen Nicholls is a world-renowned cardiologist, and leads the Victorian Heart Hospital (VHH) at Monash University.

New findings from the KRAKEN trial highlight the potential of muvalaplin, an oral treatment, for lowering lipoprotein (a) [Lp(a)] levels in adults with elevated Lp(a) and high cardiovascular risk.

American Heart Association (AHA) Annual Scientific Sessions 2024

, the trial represents the first evidence of an oral agent for lowering Lp(a), according to trial sponsor Eli Lilly and Company.

“High levels of Lp(a) have been shown to be a significant risk factor for atherosclerotic cardiovascular disease, affecting over one billion adults globally," said principal investigator Stephen J. Nicholls, MBBS, PhD, director of the Victorian Heart Hospital and Institute, and professor of cardiology at Monash University, Australia. "Current cholesterol-lowering therapies are not approved to lower Lp(a) levels, highlighting an unmet need for people living with cardiovascular disease. These data represent a needed scientific advancement with the potential to reduce the risk of cardiovascular events such as heart attacks or strokes with a once-daily pill."

A 12-week, double-blind, placebo-controlled, phase 2, 233-patient trial conducted in 43 sites across 5 countries, KRAKEN was designed to assess the efficacy and safety of muvalaplin at doses of 10 mg/d, 60 mg/d, or 240 mg/d. The trial’s primary endpoint, placebo-adjusted percentage change in Lp(a) levels, was assessed using intact Lp(a) and apolipoprotein(a)-based assays.

For inclusion in the trial, patients were required to have Lp(a) levels of at least 175 nmol/L and a history of atherosclerotic cardiovascular disease, diabetes, or familial hypercholesterolemia.

At 12 weeks, placebo-adjusted reductions in Lp(a) using the intact assay were 47.6% (95% CI, 35.1% to 57.7%), 81.7% (95% CI, 78.1% to 84.6%), and 85.8% (95% CI, 83.1% to 88.0%) with muvalaplin 10 mg, 60 mg, and 240 mg doses, respectively. Using the apo(a)-based assay, the corresponding reductions were 40.4% (95% CI, 28.3% to 50.5%), 70.0% (95% CI, 65.0% to 74.2%), and 68.9% (95% CI, 63.8% to 73.3%). Secondary endpoints showed reductions in apolipoprotein B levels, while high-sensitivity C-reactive protein remained unchanged.

For more on the trial and the potential of muvalaplin, check out our interview with Nicholls from the floor of AHA 2024.

 HCPLive Nicholls KRAKEN AHA 24

Relevant disclsoures for Nicholls include Amgen, Eli Lilly, Novartis, Sanofi-Regeneron, Silence Therapeutics, and others.

Nicholls SJ, Ni W, Rhodes GM, et al. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. 

 Published online November 18, 2024. doi:10.1001/jama.2024.24017

Eli Lilly and Company. Lilly’s muvalaplin lowered lipoprotein(a) levels in adults with high risk for cardiovascular events by up to 85% at highest tested dose. Eli Lilly and Company. November 18, 2024. Accessed November 18, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-muvalaplin-lowered-lipoproteina-levels-adults-high-risk.

Muvalaplin, an oral treatment, shows promise in reducing lipoprotein (a) [Lp(a)] levels in high cardiovascular risk patients, as demonstrated in the KRAKEN trial. This phase 2 trial, presented at the AHA Annual Scientific Sessions 2024, is the first to provide evidence of an oral agent effectively lowering Lp(a). Conducted across 43 sites, the trial involved 233 patients and revealed significant placebo-adjusted reductions in Lp(a) levels with muvalaplin doses of 10 mg, 60 mg, and 240 mg. Secondary endpoints indicated reductions in apolipoprotein B levels, with no change in high-sensitivity C-reactive protein.

Stephen Nicholls, MBBS, PhD, provides additional insight into KRAKEN trial data and the potential of muvalaplin.

Phase 2 Data Support Muvalaplin for Lowering Lp(a), with Stephen Nicholls, MBBS, PhD

Stephen J. Nicholls, MD, PhD

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.

Authors