Experts discuss the recent use of biosimilars like inolimomab as treatment for ulcerative colitis (UC).

Biosimilar Treatment Options for Patients With UC

David P. Hudesman, MD

Geoffrey Grammer, MD closes this series highlighting the administration options of esketamine, its safety profile, and the importance of monitoring patients using this treatment.

Esketamine Safety Mechanisms and Bioavailability

Geoffrey Grammer, MD

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

Payal Kohli, MD, FACC

Furie shared how Obinutuzumab could enrich the treatment landscape of LN.

Anticipating Obinutuzumab’s Approval for Lupus Nephritis, with Richard Furie, MD

Patients with active lupus nephritis treated with obinutuzumab (Gazya/Gazyvaro) achieved achieving more complete renal responses than those receiving standard therapy alone.

These findings are from the phase 3 REGENCY trial, which has met its primary end point, with 46.4% of patients treated with obinutuzmab achieving complete renal response at 76 weeks compared to 33.1% of people treated with standard therapy alone (adjusted difference, 13.4%; 95% CI, 2.0 to 24.8; 

The data primary investigator Richard Furie, MD, the Marilyn and Barry Rubenstein Chair in Rheumatology and Chief of the Division of Rheumatology at Northwell Health, and colleagues found no unexpected safety signals identified in the trial, but the obinutuzumab group did have a higher incidence of serious adverse events of mainly infections and events related to coronavirus disease 2019, emphasizing the importance of up-to-date vaccinations for this population.

 spoke Furie to learn more about the REGENCY trial and new questions that the findings may have prompted. He stressed that while the benefits of obinutuzumab may not be dramatic, they are clinically meaningful, and compared it to other milestone approvals of belimumab and voclosporin.

“I do think it will get an approval, and I do think people will be using it. We have been using it off label, because it's been approved since 2013 so for a patient with refractory disease, that's our go-to medicine. But we'll use it more extensively than just for that sub population,” Furie said.

Furie's relevant disclosures include Alexion Pharmaceuticals, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Eli Lilly, EMD Serono, galapagos, Genentech, GlaxoSmithKline, Janssen, Kezar Life Sciences. Kyowa Kirin, Kyverna Therapeutics, Merck, Novartis, Remegen, Sanofi, Takeda, and UCB.

Furie RA, Rovin BH, Garg JP. Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis. 

 Published online February 7, 2025. doi:10.1056/NEJMoa2410965

FDA accepts supplemental Biologics License Application for Roche’s Gazyva/Gazyvaro for the treatment of lupus nephritis. News release. Roche. March 5, 2025. Accessed March 17, 2025.

Richard Furie, MD

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

Sorana Segal-Maurer, MD, offers clinical insights on treating patients with HIV who have viral mutations, including M184V, highlighting guideline recommendations.

HIV: Treating Patients with Viral Mutations

Video content above is prompted by the following questions:

Patients with viral mutations, including 

, require a different and more tailored therapeutic approach to manage their disease.

Can you share your treatment approach for a patient with a viral mutation, such as 

What are the current treatment guideline recommendation on this?

Sorana Segal-Maurer, 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

 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