Kevin Kunzmann

It’s so hard to avoid spoilers online. Take, for example, right now.

, our annual end-of-year recap series that highlights the greatest stories, challenges, moments and innovations in health care. On every Monday, Wednesday and Friday this December, our team will be publishing feature articles and video content reviewing every major development in our specialties of focus.

Same as every year, the series will feature contributions from every team in the 

Readers can follow the recap series on Facebook, Twitter and LinkedIn through the hashtag #ThisYearInMedicine, and each new entry will also be shared on 

Now, for those spoilers: to kick off this year’s series, we asked 

’s inaugural Editorial Advisory Board—a collection of caregivers from various specialties and backgrounds—to answer the question, “In 10 years, what will we remember as the biggest story in medicine from 2023?” The board provided answers that highlighted 7 unique storylines from the last 12 months—6 stories that we’ve already planned to cover in our series in the coming weeks.

Enjoy our board’s thoughts on the half-dozen storylines that made 2023 and stay tuned for more at-length reflections—and spoiler-free features—in our latest This Year in Medicine.

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

I think the biggest story of 2023 are the SELECT results with semaglutide and cardiovascular benefits in people with overweight and obesity, with established cardiovascular disease. While we have had the cardiovascular data in people with diabetes for several years (LEADER, SUSTAIN, HARMONY, AWARD, etc), this is the first time we have a large randomized controlled trial showing the cardiovascular benefits of a GLP-1 agonist in people with overweight and obesity without diabetes.

I think this is especially significant because it will hopefully change the coverage/payor landscape of these agents and make them more accessible for weight management.

In the upcoming years, we are likely to see more incretins become available and cardiovascular outcome data published for tirzepatide and others for weight management. We hope that data will look favorable as well, but this will always be remembered as the first, landmark trial to show benefits of an incretin therapy for treatment of overweight and obesity to improve cardiovascular outcomes. This also takes weight management beyond what many unfortunately think of as a cosmetic condition and showcase how this is a chronic disease that should be treated to improve health outcomes.

We will remember 2023 as the year of the GLP-1 receptor agonist, and specifically semaglutide. This year we saw evidence that obesity can be a pharmacologically modifiable risk factor to improve hard clinical outcomes. However, in 2023, the story also started that the cardiovascular benefits of GLP-1 receptor agonist therapy likely extend to mechanisms beyond weight loss, and that these drugs may be best viewed as cardiovascular drugs that happen to cause weight loss, rather than as solely a weight loss therapy.

While not directly related to dermatology, I believe the biggest story of 2023 relates to the recognition of GLP-1 agonists as ‘paradigm changers’ in response to obesity. In the lay press, and our medical articles, this year has pushed us to see the weight loss associated with use of these agents with more and more evidence focusing in on positive impacts on type 2 diabetes, pre-diabetes, and heart disease. I expect that many of our dermatologic conditions that may be influence by overweight and obesity, including acanthosis nigricans, metabolic risks associated with psoriasis and perhaps hidradenitis suppurativa may be positively impacted by use of these agents.

As will the general health of the individuals, if they use the peptide as a ‘kick-start’ for life changes, that may reduce the chance for gaining weight back and losing some of the positive health benefits. A second part of the story is disparities in access to these medications—it seems like much of affluent Los Angeles is on the drug, while there is little use of it in our teenagers and pre-teens with severe obesity, already having secondary health complications. I hope we can get these drugs where they can give us the greatest yield in health impact over time!”

Therapy Breakthroughs for Geographic Atrophy

A decade from now, we will reflect on 2023 as the foundational year when we initiated the effective management of geographic atrophy. Although the progress may seem incremental, the advancements achieved this year are set to catalyze a significant transformation in our perception and treatment of this condition, ultimately enhancing the quality of life for our patients.

I suspect we'll remember the biggest story of medicine from 2023 as being a landmark year for the treatment of geographic atrophy with FDA-approval of 2 therapies. We now, for the first time, have therapy to slow progression of disease!

Based on the years that went into its development and the ultimate impact on children and adults alike, I believe the RSV vaccines and monoclonal antibody approvals will have the greatest impact on reducing morbidity and mortality from this viral disease. The biggest challenge now is for it to be accepted by the population most at risk.

The Mainstream Introduction of Artificial Intelligence

I had to think about the question for a bit, but I think the biggest research that will define this year and era in gastroenterology will likely be the advent and propagation of AI in GI/Endoscopy. Whether it comes to detecting polyps or lesions or its use in research, I think this era will be defined by the reliance of AI not only for patient care, but also improvements in the practice of medicine.

Breaking Ground on Lesser-Known Skin Diseases

From a dermatology perspective, 2023 was the tipping point for clinical investigation into the other diseases’: chronic immune-mediated conditions that we both poorly understood and had few or no unique, pathogenesis-driven treatment options. Seborrheic dermatitis resides at the top of this list, followed closely by hidradenitis suppurativa and alopecia areata. In addition, diseases that are better understood and have multiple targeted therapies also had a stellar year as well, with major advancement seen in efficacy for psoriasis therapy.

Gene and Cell Therapy Nears the Market for Chronic Disease

It is always difficult to not approach a question like this without the bias of contemporary context and perhaps a little bit of hubris that what we consider a ‘big story’ real-time in 2023 will stand the test of a decade. While seemingly ‘lower key’ than the news of yet another GLP-1 receptor agonist success—this time semaglutide in patients without diabetes but known coronary disease and BMI >27—CRISPR-Cas9, I suspect, via the VERVE-101 and NTLA-2001 trials, will be looked back upon as the biggest story to come out of 2023. The medical community has been discussing its potential impact on disease and in-animal studies before 2023; however, this is the year in which we learned of in-human results for efficacy and safety. Durability, efficacy, long-term safety, and adherence will be the markers that will determine just how ‘big’ on reflection of the in-human application of CRISPR-Cas9, 10 years forward from now.

I think within rheumatology you would have to talk about CAR-T cell therapy in SLE. Whilst I don't consider it to be the panacea that many think it is, it's definitely an interesting development and long-term follow up in those cases will be very interesting.

The CAR T cell data was presented, initially last year, so it's just been over 12 months. But I think the excitement that's been driven from that—the expanded patient numbers, the development of trials and looking at a number of other indications for cell-based therapies in rheumatology—it's incredibly exciting. It certainly seems to be the thing that's caused the biggest buzz in the community in terms of clinicians, patients, and industry all moving toward this. And it's going to be the thing that potentially revolutionizes how we treat our patients in the future if these results are borne out. I think those results are incredibly fascinating and gives us a good hint towards why we may change or shift the paradigm in the future.

So, although those results initially came out more than 12 months ago, I think the enthusiasm that's followed, that's continued to grow over this year, has been one of the highlights for me. And having recently returned from ACR Convergence 2023 in San Diego—that was the thing that most people were talking about and I spoke to most people about. Whether we look back at this in in 2033 and say we got it wrong, and that wasn't the right thing at that time, it's interesting to know. But it does seem that we have an exciting new therapy to potentially work with, and we will only learn more about the disease with this therapy.

Articles

We kick off our annual recap series with some reflections from our expert advisory board, on topics ranging from AI and cell therapies, to semaglutide and RSV vaccines.

The 6 Biggest Stories in Medicine in 2023

The US Food and Drug Administration (FDA) has approved nirogacestat tablets (Ogsiveo) for the treatment of progressing 

 in adult patients. The indication granted to SpringWorks Therapeutics marks nirogacestat as the first therapy approved to treat adults with the rare, non-cancerous, painful tumors.

Desmoid tumors are a rare subtype of soft tissue sarcomas commonly characterized by impact on structures and organs that which may cause pain, restricted movement, and poorer quality of life. Prior to the FDA approval for nirogacestat, surgical removal has been the primary treatment option—however, the risk of returning tumors or other health challenges are frequent following procedures. It’s for this reason that such systemic therapies have been increasingly assessed for affected patients, according to the FDA.

"The FDA continues to address unmet medical need and advance the development of safe and effective therapies for the millions of Americans whose lives are affected by rare tumors," Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research, said in a statement. "Desmoid tumors are rare tumors that can lead to severe pain and disability. Today's approval will offer the first approved treatment option for patients beyond surgery and radiation."

Nirogacestat tablet’s benefit for treating desmoid tumors was evidenced by findings from the phase 3, pivotal, randomized, double-blind, placebo-controlled DeFi trial across multiple international centers including 142 adult patients with progressing tumors not amenable to surgery. Patients were randomized 1:1 to either 150 mg nirogacestat or oral placebo, twice daily, and received treatment until observed disease progression or unacceptable toxicity.

Investigators sought a primary efficacy endpoint of progression-free survival (PFS), defined as length of time after treatment initiation in which a person is alive and their tumors do not grow nor spread. Secondary efficacy endpoints including objective response rate, per measured tumor shrinkage.

The team reported a statistically significant improvement in PFS with nirogacestat—a 71% reduced risk of disease progression versus placebo (hazard ratio [HR], 0.29; 95% CI, 0.15 – 0.55; 

 <.001). Median PFS was 15.1 months in the placebo arm, versus not being reached among treated patients. They additionally observed a significant improvement in objective response rate among patients receiving nirogacestat, in which 41% of treated patients achieved the marker for tumor shrinkage versus just 8% of the placebo arm (

Median time to first response was halved among treated patients versus the placebo arm (5.6 months vs 11.1 months); investigators additionally observed early and sustained improvements in patient-reported outcomes including pain, desmoid tumor-specific symptoms, and physical functioning (

The most common adverse events to occur in ≥15% of patients in either arm of the trial included diarrhea; ovarian toxicity; rash; nausea; fatigue; stomatitis; headache; abdominal pain; cough; alopecia; upper respiratory tract infection; and dyspnea.

In a statement accompanying the approval, DeFi trial investigator Mrinal M. Gounder, MD, sarcoma medical oncologist at Memorial Sloan Kettering Cancer, praised the clinical breakthrough for patients with the difficult, invasive, and recurring tumor condition.


“OGSIVEO is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms,” Gounder said. “As a treating physician, it was encouraging to see in the DeFi trial that OGSIVEO achieved statistically significant and clinically meaningful improvements across the primary and all key secondary endpoints, while also having a manageable safety profile. This approval represents an important therapeutic advance for patients.”

US Food & Drug Administration. FDA Approves First Therapy for Rare Type of Non-Cancerous Tumors. Press release. Published November 27, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-rare-type-non-cancerous-tumors

Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors. N Engl J Med. 2023;388(10):898-912. doi:10.1056/NEJMoa2210140

SpringWorks Thereapeutics. SpringWorks Therapeutics Announces FDA Approval of OGSIVEO™ (nirogacestat) as the First and Only Treatment for Adults with Desmoid Tumors. Press release. Published November 27, 2023. https://ir.springworkstx.com/news-releases/news-release-details/springworks-therapeutics-announces-fda-approval-ogsiveotm

The approval is the first for a systemic therapy to treat desmoid tumors, offering patients an alternative to surgery.

FDA Approves Nirogacestat Tablets for Rare Desmoid Tumors

Safer discusses how symptoms and quality of life often go unaddressed in the few clinician-patient interactions about primary sclerosing cholangitis.

Ricky Safer: What Clinicians Need to Know About PSC

The physician-patient relationship at it pertains to managing a chronic disease is pivotal—both sides need to communicate and also be heard, at risk of worsening condition or missed opportunities to better the patient’s livelihood. When the condition at hand is also rare to the physician, the dynamic can become even more precarious.

In the second segment of an interview at 

The Liver Meeting 2023 from the American Association for the Study of Liver Diseases (AASLD)

patient and chief executive officer and founder of the PSC Partners Seeking a Cure, shared her advice for clinicians looking to improve their communication with patients about PSC. One thing she has learned from fellow patient feedback over 2 decades is their need for less discussion around disease levels including LFTs, and more about their quality of life.

“We want to talk about our symptoms, but obviously don't have time,” Safer said. “We were thinking if we could somehow set up sort of a set of questions, very short, that physicians would be willing to ask the PSC patients when they come in—for example, 'Are you dealing with sleep problems, are you feeling really anxious? Are you feeling really depressed?' Symptoms like this that obviously feed into our quality of life and make it all a vicious cycle...some of the mental parts of it that most patients would never speak to the doctor about.”

Safer referenced her own experience in dealing with pruritus when she was first diagnosed—a common symptom of the disease, but an effect she said is “almost indescribable” for patients.

“You can't sleep—it just takes over your life,” Safer said. “And I think if doctors were more aware of some of the symptoms and how strongly they affect their lives...if somehow we could set something up so they could just quickly ask patients and know how our quality of life is affecting us.”

Lastly, Safer discussed the mission of PSC Partners Seeking a Cure—including millions of dollars in research grants, a massive patient network, an annual conference, and a name that which still defines the non-profit organization’s aspirations.

“Those are some of the things that are really leading us where we want to go to find that ultimate cure—which I will say we have had some of our providers say to me, 'I wish you would change your name because when you say finding a cure...that's way, way off,' and we're like, 'That's still our goal’,” Safer said.

Videos

Guillaume Lassailly discusses the role of bariatric surgery versus weight-loss treatments like semaglutide for patients with MASH.

How Do We Value Bariatric Surgery in 2023?

The role and understood value of bariatric surgery may be evolving in the treatment of fatty liver disease, though it may take some time for clinicians to appreciate that new value.

In the second segment of an interview with 

 in Boston this month, study author Guillaume Lassailly, from the Centre Hospitalier Universitaire de Lille in France, discussed the implications of his team’s real-world analysis of 15-year survival rates among patients who resolved 

metabolic dysfunction-associated steatohepatitis (MASH)

 without worsening fibrosis after bariatric surgery.

Though his team’s research showed such patients had markedly improved survival rates when achieving these markers after the surgery, Lassailly believes there remains a “mental bias” among clinicians who may have a patient eligible for bariatric surgery.

“Bariatric surgery is something that when you perform it, you can't go backwards,” Lassailly said. “When you have a drug effect, you can still stop the drug, which you can't do with bariatric surgery. So there's something in this treatment that is quite radical.”

Lassailly noted that the introduction of GLP-1 agonists to clinical obesity management strategies has added to the “opposition” against bariatric surgery. He argues the invasive procedure should be looked at as an “additive therapeutic,” not an opposing idea.

“And the way we can see it is you will have patients that will be more suitable for surgery because they're severe, they have a lot of metabolic comorbidities, and you really think that they will also benefit outside the liver with bariatric surgery,” Lasailly said. “And if this patient did not have sufficient weight loss, we can also think of adding drugs afterwards. And on the other hand, you can also proceed with drugs as a first strategy and then get to bariatric surgery.”

For now, clinicians are not operating with an understanding of which treatment should come first for which patient—caregivers must consider the full patient profile before choosing.

In discussing next steps for his team research, Lasailly said the field remains limited by the reliance of a liver biopsy to initiate care.

“I think the next step is to link biopsy with non-invasive markers, because at a patient point of view, liver biopsy is invasive, painful, and also has a cost,” he said. “And so, if you can reduce pain and reduce cost, well, you will win in all the fields.”

Lassailly discusses the role of bariatric surgery versus weight-loss treatments like semaglutide for patients with MASH.