Blockmans discussed data supporting upadacitinib’s new indication and why the approval is important for patients with giant cell arteritis.

Adding Upadacitinib to the Treatment Landscape of GCA, with Daniel Blockmans, MD, PhD

The FDA last month approved Upadacitinib 15 mg once daily for the treatment of adults with giant cell arteritis (GCA), under the name Rinvoq, making the therapy the second disease modifying therapy approved for GCA after tocilizumab’s approval in 2017.

Upadacitinib’s approval was based off of data from the phase 3 SELECT-GCA clinical trial in which 46.4% (95% CI, 39.6-53.2) of patients receiving upadacitinib 15 mg in combination with a 26-week steroid taper regimen achieving sustained remission from week 12 to week 52, compared with 29.0% (95% CI, 20.6-37.5) of patients receiving placebo in combination with a 52-week steroid taper regimen (

spoke with Daniel Blockmans, MD, PhD, Department of General Internal Medicine, University Hospitals Leuven, Belgium, who served as a primary investigator on the SELECT-GCA trial, to learn more about the data supporting upadacitinib’s approval and how the new approval is important for adding to the treatment landscape. He discussed the unmet need for new treatments that exists within the population of patients with GCA and the importance of being able to successfully taper steroids in patients who might be sensitive to them or typically relapse without them.

“Steroids are great. I'm very grateful that we have them. But of course, they come with side effects, and some people are much more vulnerable to these than others, and for these vulnerable patients, we need something else than steroids,” Blockmans told 

Blockmans reported no relevant disclosures.

RINVOQ® (upadacitinib) Receives U.S. FDA Approval for Giant Cell Arteritis (GCA). News release. AbbVie. April 29, 2025. 

https://news.abbvie.com/2025-04-29-RINVOQ-R-upadacitinib-Receives-U-S-FDA-Approval-for-Giant-Cell-Arteritis-GCA

FDA approves first drug to specifically treat giant cell arteritis. News release. FDA. May 22, 2017. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-specifically-treat-giant-cell-arteritis

Blockmans D, Penn SK, Setty AR, et al. A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis. 

 Published online April 2, 2025. DOI: 10.1056/NEJMoa2413449

Daniel Blockmans, MD, PhD

David T. Ahn, MD

 pandemic has shown us how quickly science can move when we collectively dedicate time and resources towards addressing an issue, it reminds me as an OBGYN with a true focus on women’s health that there is a lot of opportunity for us to adapt to the evolving healthcare needs of women today, especially in a post-pandemic environment.

On the subject of unplanned pregnancy, as healthcare professionals, as partners, as potential future moms or dads, we have to come together as a worldwide community to help reduce the rates. This begins with a conversation.

But let’s first start with the facts. Unplanned pregnancy remains a significant public health issue, with nearly half of pregnancies being unplanned in the U.S. alone, according to data from 

. Globally, more than 1 billion women have a need for family planning, but for 270 million of them, that need for modern methods is 

. In my view, we have to do something to ensure she has the resources she needs to help make informed decisions with her HCP.

The average U.S. woman spends about 30 years avoiding pregnancy, which is three-fourths of her 

 An unplanned pregnancy can translate into a multitude of health factors and risks for both the mother and the baby, regardless of her socioeconomic background. For example, prenatal care may be delayed, and one study estimated that direct medical cost of unplanned pregnancy in the U.S. was more than 

. This does not account for the personal financial costs associated with 

, which may be even more challenging during the current pandemic, when many women may have lost jobs or faced new financial pressures.

Help Fuel the Conversation and Meet Her Where She Is

While these numbers surprise me even as an OBGYN, we are in a unique position to help change those numbers. This starts by having an open, honest conversation with our patients. We can be that objective source; we can ask the questions: “what are your family planning goals?,” “what is your plan?” We can listen to her needs and customize a plan that’s right for her. It’s important that healthcare providers and women work together to discuss what options are best for her.

I’ve appreciated my time at Organon, as we hope to provide education and access to information for patients, all while helping to listen to the needs of women. By increasing these pivotal conversations, increasing access to family planning options, and educating women about their choices, we can help them make informed choices about their sexual and reproductive health to help reduce the rates of unplanned pregnancy. Educating male partners about pregnancy planning can also help limit unplanned pregnancies, reduce the stigma associated with it, and encourage more open conversations.

As physicians on the front lines of women’s health, and as an industry committed to doing better for every woman everywhere, let's come together to spark a dialogue that fuels much-needed attention to this global public health issue. Let’s talk about unplanned pregnancy and change the conversation from one of stigma to one of impact. I invite you to join healthcare providers and women from across the globe to share your perspective on how to help reduce unplanned pregnancies at 

Dr. Edio Zampaglione is the Head of Global Medical Affairs and Outcomes Research at Organon, a global healthcare company formed in 2021 through a spinoff from Merck, known as MSD outside of the United States and Canada, to focus on improving the health of women throughout their lives. He served as a pharmacist and a practicing OBGYN before starting a career in the pharmaceutical industry in 2001. Throughout his career in the pharmaceutical industry, Dr. Zampaglione has always focused on helping improve access and a broader understanding of women’s health.

An unplanned pregnancy can translate into a multitude of health factors and risks for both the mother and the baby.

Reducing the Stigma of Unplanned Pregnancy Starts with a Conversation

Edio Zampaglione, MD

Jack Arnold, MBBS, is a clinical research fellow working within Dr. Edward Vital's lupus team at the Leeds Centre of Rheumatic and Musculoskeletal Medicine. He graduated Distinction in Clinical Sciences from University College London in 2015 and has previously worked as a clinical tutor for Harris Manchester College Oxford. His work primarily focuses on systemic lupus erythematosus (SLE), antineutrophil cytoplasm antibodies (ANCA)-associated vasculitis and new approaches to the classification of autoimmune connective tissue diseases.

Anxiety and depression are 2 of the most common conditions encountered by budding physicians irrespective of their primary specialty. Within rheumatology, these conditions can negatively impact the patient experience at several junctures. They can limit engagement with healthcare or treatment leading to later diagnosis, poor treatment adherence, and resultant poor disease control with associated negative sequelae. The clinical presentation of anxiety and depression can also overlap with features of active rheumatic disease, exacerbating the symptom burden experienced by patients.

 Within the paradigm of systemic lupus erythematosus (SLE), fatigue symptoms can be more prominent and can worsen with a coexistent diagnosis of depression.

 Furthermore, poorly treated depression and anxiety features can become a significant confounder when assessing outcome measures such as the Visual Analogue Scales (VAS), Short Form 36, FACIT-Fatigue, and other patient reported outcome scores.

A recent Chinese observational single center cross-sectional study assessed the impact of SLE disease activity on the prevalence of anxiety or depressive features.

 This study enrolled 325 patients over the age of 18 with SLE as defined by the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Key exclusion criteria were a previous diagnosis of anxiety/depression or other psychiatric illness, major organ pathology, and those with a history of substance abuse. Depressive features were assessed using the Patient Health Questionnaire 9 (PHQ-9) and anxiety features were assessed using the 7 item General Anxiety Disorders Scale (GAD-7). SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI).

Within the 325 patients enrolled to the study, 61.5% had a PHQ-9 score compatible with significant depression and 54.4% had a GAD-7 score compatible with significant anxiety. Patients with significant depressive/anxiety features had significantly higher SLEDAI scores than their counterparts (p=0.001) and had significantly higher rates of musculoskeletal and neuropsychiatric involvement. This is concordant with previous work which has shown musculoskeletal features to be key drivers of the patient experience in SLE.

Key confounders were mostly similar between the anxiety/depression and non-anxiety/depression groups except for household income. Those with a low household income defined as >50,000 Renminbi (RMB) had higher rates of depression than those with a higher income (p=0.005).

The authors used receiver operating characteristic (ROC) curve analysis to assess the utility of SLEDAI as a predictor of depression or anxiety in SLE patients. The optimal cut-off of SLEDAI >8.5 demonstrated a sensitivity of 50.5% and specificity of 78.4% in predicting depression (AUC 0.660, p <0.001). This cut-off had a sensitivity of 54.2% and specificity of 78.4% in predicting significant anxiety (AUC 0.684, p <0.001).

There are several limitations to this study; the authors identify the lack of longitudinal data as a key factor. The lack of ethnic diversity within the cohort is another important consideration. As with most SLE research, the chosen disease activity score has several additional limitations. SLEDAI scores features such as arthritis, rash, and oral ulceration based on the presence or absence of these features. Therefore, a patient with a severe rash encompassing >50% of their body surface area scores the same as one with a mild malar rash. Additionally, a patient with 2 synovitic joints scores the same as one with 12 synovitic joints, despite their very different clinical presentation. Therefore, the use of an alternative measurement such as the British Isles Lupus Assessment Group (BILAG-2004) score might allow for greater fidelity when describing a patient’s individual symptom burden.

 Exclusion of those with a pre-existing diagnosis of anxiety/depression in this study is understandable but given the widespread prevalence of these diagnoses, it may limit the generalizability of these findings in the rheumatology clinic.

This study does provide welcome data on an underappreciated and often poorly addressed feature of long term SLE management. The association between high disease activity and worsening depressive/anxiety features would seem obvious; however, this paper provides welcome quantitative evidence to the fact. Holistic care in SLE is critical and the mental health sequelae of high disease activity require addressing in a similar manner to the musculoskeletal or mucocutaneous features.

1. Arnaud L, Mertz P, Amoura Z, Voll RE, Schwarting A, Maurier F, et al. Patterns of fatigue and association with disease activity and clinical manifestations in systemic lupus erythematosus. Rheumatology [Internet]. 2021 Jun 18 [cited 2021 Jul 7];60(6):2672–7. Available from: https://pubmed.ncbi.nlm.nih.gov/33175957/

2. Figueiredo-Braga M, Cornaby C, Cortez A, Bernardes M, Terroso G, Figueiredo M, et al. Depression and anxiety in systemic lupus erythematosus: The crosstalk between immunological, clinical, and psychosocial factors. Medicine (Baltimore) [Internet]. 2018 Jul 1 [cited 2023 Jan 17];97(28). Available from: /pmc/articles/PMC6076116/

3. Meacock R, Dale N, Harrison MJ. The humanistic and economic burden of systemic lupus erythematosus: A systematic review [Internet]. Vol. 31, PharmacoEconomics. Springer; 2013 [cited 2021 Jul 2]. p. 49–61. Available from: https://link.springer.com/article/10.1007/s40273-012-0007-4

4. Liao J, Kang J, Li F, Li Q, Wang J, Tang Q, et al. A cross-sectional study on the association of anxiety and depression with the disease activity of systemic lupus erythematosus. BMC Psychiatry [Internet]. 2022 Dec 1 [cited 2022 Oct 6];22(1):591. Available from: https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-022-04236-z

5. Chaigne B, Chizzolini C, Perneger T, Trendelenburg M, Huynh-Do U, Dayer E, et al. Impact of disease activity on health-related quality of life in systemic lupus erythematosus - a cross-sectional analysis of the Swiss Systemic Lupus Erythematosus Cohort Study (SSCS). BMC Immunol [Internet]. 2017 Mar 28 [cited 2022 Mar 18];18(1). Available from: https://pubmed.ncbi.nlm.nih.gov/28351341/

6. Carter LM, Gordon C, Yee CS, Bruce I, Isenberg D, Skeoch S, et al. Easy-BILAG: a new tool for simplified recording of SLE disease activity using BILAG-2004 index. Rheumatology (Oxford) [Internet]. 2022 Oct 6 [cited 2023 Jan 17];61(10):4006. Available from: /pmc/articles/PMC9536795/

Anxiety and depression can limit engagement with healthcare or treatment leading to later diagnosis, poor treatment adherence, and poor disease control with associated negative sequelae. 

Quantifying the Association Between Anxiety and Depressive Features and High Disease Activity Scores in SLE 

Jack Arnold, MBBS, MRCP

Jeff McIntyre is the vice president of Liver Health Programs at the Global Liver Institute.

Reflecting on Resmetirom’s Historic FDA Approval for MASH

On March 14, 2024, the US Food and Drug Administration (FDA) made history when it granted accelerated approval to Madrigal Pharmaceuticals’ resmetirom (Rezdiffra), making it the first and only treatment for noncirrhotic nonalcoholic steatohepatitis (NASH), now known as 

metabolic dysfunction-associated steatohepatitis (MASH)

One year later, resmetirom’s impact on clinical practice and patient care continues to evolve. In recognition of the anniversary of the landmark decision, the latest 

 spotlights a conversation between a trio of subject matter experts reflecting on the past year of having resmetirom as a treatment option for patients, remaining unmet needs in MASH management, and the evolving therapeutic pipeline poised to further transform care.

Estimated to affect more than 30% of the global population, MASLD is the most common chronic liver disease around the world. MASH represents an advanced stage of MASLD and has historically lacked treatment options beyond lifestyle changes with diet and exercise. In the absence of pharmacologic therapies, weight loss served as the cornerstone of disease management.

This changed in March 2024, when resmetirom became the first and only FDA-approved MASH therapeutic, earning accelerated approval for the treatment of noncirrhotic MASH with moderate to advanced fibrosis. Although lifestyle interventions continue to play a pivotal role in MASH care, as the thyroid hormone receptor-beta selective agonist is indicated in conjunction with diet and exercise, they are no longer the only tools available for disease management.

 on the 1-year anniversary of resmetirom’s FDA approval and the evolving landscape of MASH management, moderator Jeff McIntyre asks Mazen Noureddin, MD, MHSc, and Juan Pablo Arab, MD, about the clinical impact resmetirom has had since being approved and whether it lived up to the expectations set for it as the first-ever MASH therapeutic.

Noureddin begins by highlighting resmetirom’s “game-changing” impact, citing strong clinical results, guideline updates, and the shift toward noninvasive testing. He notes that patients are seeing benefits and that long-term data continues to support the drug’s efficacy.

Arab expresses agreement, emphasizing that resmetirom has not only improved patient outcomes but also changed how clinicians approach MASH. Previously, primary care providers and endocrinologists were reluctant to screen for at-risk MASH due to a lack of treatment options. Now, with an FDA-approved therapy, he says there is greater urgency in identifying and managing these patients.

Discussing challenges, Arab points to the need for broader screening, improved access to noninvasive tests, and overcoming reimbursement hurdles, additionally stressing that implementing a new treatment requires systemic change across healthcare.

Noureddin adds that while hepatology clinics were well-prepared for resmetirom’s arrival, uptake in gastroenterology practices has been mixed. He sees a need for more education on noninvasive tests and fibrosis staging but says that overall, awareness and access are improving. He remains optimistic about the drug’s future and the potential for combination therapies to further transform MASH treatment.



Mazen Noureddin, MD, MHSc, is a professor of medicine and a transplant hepatologist at Houston Methodist and director of the Houston Research Institute.

Juan Pablo Arab, MD, is an associate professor of medicine in the division of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University School of Medicine.

Noureddin has relevant disclosures with Altimmune, Madrigal Pharmaceuticals, Merck, Takeda, Terns, and others. Arab and McIntyre have no relevant disclosures.

US Food and Drug Administration. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. March 14, 2024. Accessed March 13, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease

Brooks, A. Stephen Harrison, MD: Promising Phase 3 Data for Resmetirom in NASH, Fibrosis. HCPLive. February 7, 2024. Accessed March 13, 2025. 

https://www.hcplive.com/view/stephen-harrison-md-promising-phase-3-data-resmetirom-nash-fibrosis

In the opening segment of this 6-part HCPLive RX Review, experts reflect on resmetirom’s FDA approval for MASH and clinical challenges to implementing it.

Jeff McIntyre

University of Rhode Island College of Pharmacy

 In the little time that we have left, I want to go around and get some final thoughts from each one of you. I would like you to address the whole issue of using naloxone. How do you address this with patients? How do you address this with clinicians, and what is your view about going forward? How is this going to change the landscape of opioid use in the United States? Why don’t we start with Jeremy, and we will keep going from there? Take 30 seconds, and we will just keep going.

 I think we have covered a lot of ground today. We know, and have known for a long time, that opioids have certain risks. They pose risks to patients, and they pose risks in the community when they are taken unsupervised or misused. From a safety measure perspective, there are things we can do. We can do a better job identifying the patients at risk or when identifying those patients who should or should not receive opioids. At the same time, I think we need more community awareness, and we can do this by using the naloxone program or some of the other programs discussed today. Rhode Island sounds amazing, and I am interested to learn more about what is happening out there. The tools we have today can enhance the safety of what we are doing on the medical side and help out there in the community with the substance misuse and illicit side. That is outside of the reach for some of us who do not work in settings where one can reach out to the community, but I think that these types of tools are underutilized. If these tools are utilized on a more frequent basis, and in a more normalized way, we have the potential to reverse what we have seen here with opioids and the subsequent harm caused by them.

 While acknowledging that opioids are still commonly used as part of a multidisciplinary approach to pain management and that opiates are still being misused illicitly, we need to have strategies that emphasize the availability of naloxone so that people can be as safe as possible. As Dr Adler said, this must be normalized, and we need to realize, when we think about this, it is going to take more years than we would like before it will become normalized, but we need to step it up and work toward that.

 I cannot agree more with my colleagues. I think that, when it comes to normalizing naloxone, we need to take the lessons we have learned from what successfully normalizes this method of treatment. Whether it is enacting policy interventions, having naloxone everywhere, putting up billboards, or getting that access. What we are doing is studying people, saying what makes you dispense naloxone, to pharmacists? Saying what makes you dispense it, to primary care physicians? What makes you want to give it, to a caregiver? What are those barriers? How do we break them down? I look forward to the day of over-the-counter naloxone that is still covered by insurance so we do not have financial barriers. There is a lot that we know, areas where we have been successful, and I think that yes, it is going to be around a long time. We have seen how COVID-19 has created these divisions. I think, by solving those divisions during COVID-19, we will solve some of the divisions in access to care for people with opioid use disorder or people who use opioids.

I see naloxone as one part of the puzzle here, one part of the comprehensive approach that we try to take in the emergency department [ED], and that is decreasing the barriers that patients need to overcome to get naloxone. This is improving their access to naloxone not only in the ED but also in other areas of life where they have access to health care, and in their daily lives. Having it available works, whether it is having a naloxone box sitting next to an AED [automated external defibrillator] box somewhere or offering it to patients proactively and not requiring them to have to ask for it.

Additionally, I think that, as science for medication-assisted treatment continues to be redefined every day—how effective that is for treatment—it is our responsibility to not only make sure that our patients are safe as they go out and use this, or that their community is safer because naloxone is out there. But we also need to provide multiple opportunities for patients to get linked to treatment, to be linked to peers, and to have access to medication-assisted treatment. I think this is equally important and should be offered as routinely as possible.

Theresa, some people hate to be the last one to speak when all the good stuff is taken.

Theresa Mallick-Searle, MS, RN-BC, ANP-BC:

heresa Mallick-Searle, MS, RN-BC, ANP-BC: 

As the token nurse on the platform here, I am really big into listening to my patients. It is not that my colleagues are not, but I want to hear what is important to the patient. I want to be able to have them partner with me in their health care. I want to be able to encourage my peers to look at the bigger community and be in it for the long term, to decrease the amount of fear out there. As a health care provider, for anything that we do, we are trying to do the best we can to take care of our patients.

Thank you all very much. I want to thank you at home as well for watching this HCPLive® Peer Exchange. If you enjoyed this content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

I am Dr Peter Salgo, and I will see you again next time.

The multidisciplinary panel of experts share final thoughts on strategies to normalize naloxone and decrease barriers to its obtainment and utilization. 

Final Thoughts on the Opioid Crisis and Normalizing Naloxone

Jeffrey Bratberg, PharmD, FAPhA, University of Rhode Island College of Pharmacy 

Natalie Staplin, PhD, a senior statistician within the Renal Studies Group at the Clinical Trials Service Unit & Epidemiological Studies Unit at the University of Oxford.

A new pooled analysis of four major randomized trials confirms that empagliflozin (Jardiance) significantly reduces the risk of 

 (AKI), regardless of the predicted size of acute eGFR dip at treatment initiation or baseline markers of disease severity.

62nd European Renal Association (ERA 2025) Congress

, the study leveraged individual participant-level data from EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved, and EMPA-KIDNEY trials spanning patients with type 2 diabetes, heart failure, and chronic kidney disease. Across the combined cohort of 23,340 participants, the mean eGFR was 59 mL/min/1.73 m² and the median urinary albumin-to-creatinine ratio was 34 mg/g.

Investigators stratified participants by predicted risk of an acute eGFR dip using multivariable modeling. Two outcomes were assessed: (1) a ≥50% increase in serum creatinine compared with recent baseline and (2) investigator-reported AKI using MedDRA criteria. Empagliflozin reduced the risk of a ≥50% increase in serum creatinine by 19% (HR, 0.81; 95% CI, 0.74 to 0.90) and the risk of AKI adverse events by 27% (HR, 0.73; 95% CI, 0.63 to 0.85). These effects were consistent across subgroups, including those stratified by predicted eGFR dip size (

 for trend = .41 and .65, respectively) as well as baseline characteristics such as eGFR, NT-proBNP, and primary kidney disease.

Independent predictors of a larger eGFR dip included older age, higher baseline eGFR and albuminuria, use of renin–angiotensin system inhibitors or diuretics, elevated systolic blood pressure, and lower hematocrit or body mass index. Despite initial dips, only a proportion of patients discontinued therapy during follow-up, with similar rates across risk strata, according to the ERA 2025 data.

In an interview, primary investigator Natalie Staplin, PhD, a senior statistician within the Renal Studies Group at the Clinical Trials Service Unit and Epidemiological Studies Unit at the Nuffield Department of Health at University of Oxford, emphasized that these findings reinforce the safety of empagliflozin in at-risk populations. To explore more on how these findings inform real-world treatment decisions, check out our full interview with Staplin from ERA 2025 below.

Q&A with Natalie Staplin, PhD, on eGFR Dip Data from ERA 2025

 Can you offer some historic context on the subject and explain why you wanted to examine this so closely?

 I've worked directly on some of the large trials of SGLT2 inhibitors, particularly the EMPEROR-Kidney trial. My specialty is kidney diseases, as you might guess from attending ERA, and the acute eGFR dip is a question that comes up a lot when we're discussing these studies.

People are often concerned, especially when there's a large dip in eGFR, about whether that might reduce the beneficial effect on outcomes, or even potentially cause harm. So, based on those questions, we gathered as much individual participant data as we could to try to answer it.

It’s not an easy question to address because you need to ensure the analyses are properly randomized. Much of the existing literature has looked at patients who experienced a certain dip in eGFR and then examined outcomes, but without comparing that within a randomized treatment framework. That’s why we set out to do this study.

 What were the primary findings, and how does this add to our understanding of the effects of SGLT2 inhibitor use?

 Our main findings came from a meta-analysis where we looked at two key kidney-related outcomes. The first was a 50% or greater increase in serum creatinine across consecutive samples. The second was AKI adverse events, as defined by the MedDRA (Medical Dictionary for Regulatory Activities) preferred terms.

We found that empagliflozin reduced the risk of those large serum creatinine increases by 20%, and reduced AKI adverse events by 27%. These findings held across a broad patient population, including people with chronic kidney disease, diabetes, and heart failure.

A unique part of our study was how we handled the eGFR dip. We developed a prediction model for the size of the acute eGFR dip using data from the empagliflozin arms of four trials. Because the model was based only on baseline characteristics, we could apply it to all participants in both the placebo and treatment arms.

When we stratified participants by the predicted magnitude of eGFR dip and looked at treatment effects across those groups, we saw no evidence of effect modification. The benefits of empagliflozin were consistent across all levels of predicted dip.

To address concerns about AKI occurring around the time of the eGFR dip, we also looked at the timing of those events. There was no indication of increased early AKI risk.

 Are you comfortable now concluding on whether these dips are benign? Has your interpretation changed over time?

 That’s a good question, and it actually ties into one of the conclusions I’ll be highlighting in my talk next week. Based on the data so far, including our study, we feel reassured that the acute eGFR dip is a benign event.

We’ve also seen in the data—which will be published soon—that these dips tend to rebound after treatment is stopped. Along with the additional analyses we did on the risks associated with the dip, all of this supports the view that it’s a benign phenomenon.

 Was there anything else you wanted to add about the study?

 Yes, one other aspect we looked at was whether the size of the acute dip predicted treatment adherence. We had expected that people with large dips might be more likely to discontinue treatment, but in fact, those with the largest dips were only slightly more likely to stop therapy.

Overall, the discontinuation rate at the visit just after the acute dip was very low. That was reassuring and suggests most patients were kept on the drug.

Our interpretation is that routinely rechecking eGFR shortly after starting an SGLT2 inhibitor might not be necessary for every patient. If someone is starting multiple foundational therapies at once, you might expect a significant dip and want to monitor. But if you're starting just one of these agents, in most cases, the dip probably isn’t something to worry about.

How much more confident do you think this data should make clinicians regarding the potential of an eGFR dip?

 I think this data could really help. Right now, some of the product labels list acute eGFR dips and AKI as concerns, which could worry prescribers, especially those less familiar with SGLT2 inhibitors—though that group is likely shrinking.

Our findings suggest these concerns might be overstated. Based on this evidence, some of those warnings might not need to be on the label at all. That could help ease some of the hesitation around prescribing these drugs.

Empagliflozin significantly reduces the risk of acute kidney injury (AKI) and large serum creatinine increases, regardless of the predicted size of the acute eGFR dip or baseline disease severity. This pooled analysis of four major trials, presented at the ERA 2025 Congress, involved 23,340 participants with type 2 diabetes, heart failure, and chronic kidney disease. The study found consistent benefits across subgroups and no increased early AKI risk. The findings suggest that acute eGFR dips are benign, and routine eGFR monitoring may not be necessary for all patients.

An ERA 2025 analysis confirms empagliflozin significantly lowers acute kidney injury risk, reassuring clinicians about its safety in at-risk patients.

Pooled SGLT2i Data Reaffirm Empagliflozin Safety, Even With Acute eGFR Dips

Natalie Staplin, PhD

Vitiligo is a chronic autoimmune condition resulting in depigmented lesions of skin that can appear on any part of the body. The condition, which has been diagnosed in approximately 1.5 million people in the United States

, occurs with similar frequency in all ethnic groups and can occur at any age, although initial symptoms often appear before the age of 30

Given the visual nature of the disease, vitiligo is sometimes viewed as a cosmetic issue rather than as an autoimmune condition

. Because of this misconception, the severity and impact of vitiligo – both physical and emotional – can often be downplayed or overlooked. In addition, the limited treatment options currently available for vitiligo can lead people living with this condition to believe they have little to no choices

More than cosmetic: The role of the immune system in vitiligo

Research suggests vitiligo develops in genetically-susceptible individuals when environmental triggers – e.g., sun exposure, chemical exposure, physical skin trauma or psychological strain – induce stress responses in the skin

.This causes a localized autoimmune response in which melanocytes are targeted and destroyed by CD8+ T-cells

An environmental trigger combined with genetic factors leads to melanocyte stress, causing an inflammatory response

Innate immune cells activate CD8+ T-cells that target melanocytes and release IFN-γ

JAK-STAT activation and inflammatory cycle triggering: 

IFN-γ activates the JAK-STAT pathway (by binding to JAK 1 and 2) to induce production of immune mediators (CXCL9/10) by keratinocytes. More autoreactive T-cells are attracted to the site, where they continue the inflammatory cycle by producing more IFN-γ in a positive feedback loop

The T-cell attack creates a hostile environment resulting in melanocyte death, which leads to depigmentation

People living with vitiligo would benefit from additional options to consider with their health care team.

Vitiligo has a significant burden of disease

The social stigma around vitiligo, and the idea that it is a cosmetic issue rather than an autoimmune condition, can significantly impact people with vitiligo. Findings from the global 

ernational Communities (VALIANT) study underscore the profound impact vitiligo has on people’s lives. This was an observational, cross-sectional evaluation of the burden of vitiligo from the perspective of patients aged 18 years and older with vitiligo and health care professionals who treat patients with vitiligo

Of the more than 3,500 adults with vitiligo surveyed, nearly 60% said they had been diagnosed with mental health conditions, including anxiety (28.8%) and depression (24.5% )

49% said having vitiligo made them feel less confident and more self-conscious

Some of those surveyed also said they experience sleep disturbance and approximately half said the progression of their disease worries them

Additionally, a patient-focused meeting held by the U.S. Food and Drug Administration (FDA) in March 2021 explored the health effects and daily impact of vitiligo as well as management goals

. Among the key findings was that vitiligo can lead to feelings of loss of identity, particularly among African Americans

. Some participants expressed that others are unable to see past their condition, making it hard to establish successful friendships or secure employment

As such, it is critical for health care providers to approach discussions about vitiligo with their patients as an autoimmune condition and to consider the full impact that vitiligo can have on a person’s daily life. By educating people with vitiligo about the science behind their condition and forming a doctor-patient relationship based on trust, an individualized management plan tailored to a patient’s specific needs and goals can be established.

Supporting patients and managing vitiligo

As a result of their disease, people with vitiligo may feel frustrated, misunderstood and unheard, and their health care teams may have a challenging time supporting their needs. It is essential that dermatologists and other health care providers who diagnose and manage vitiligo discuss the science behind the condition and the impact it may have with their patients. Approaches to engage in these conversations can include:

Explain the autoimmune nature of vitiligo

Establish a regular cadence of appointments to ensure appropriate follow up

It is important that dermatologists take the time to understand how the condition impacts their patients’ quality of life and emotional well-being. Management of vitiligo is a process, and expectations need to be set based on each patients’ individualized management plan. We need to form open lines of communication with patients early on and provide easily understood information about the science behind the condition. We can thereby help people living with vitiligo see it as an autoimmune rather than cosmetic issue and support informed decisions about their health and the overall management of their disease.

Note: Dr. Batra has been compensated for her time.

Bowcock AM, Fernandez-Vina M. Targeting skin: vitiligo and autoimmunity. 

. https://www.sciencedirect.com/science/article/pii/S0022202X1535452X. Accessed June 23, 2022.

National Library of Medicine. Medline Plus. Vitiligo. 

https://medlineplus.gov/genetics/condition/vitiligo/

Frisoli M, Essien K, Harris JE, et al. Vitiligo: mechanisms of pathogenesis and treatment. 

U.S. Food and Drug Administration. The voice of the patient: A series of reports from the U.S. Food and Drug Administration’s (FDA’s) patient-focused drug development initiative. https://www.fda.gov/media/155068/download. Accessed May 4, 2022.

Manga P, Elbuluk N, Orlow SJ. Recent advances in understanding vitiligo. 

Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE; Vitiligo Working Group. New discoveries in the pathogenesis and classification of vitiligo. 

Strassner JP, Harris JE. Understanding mechanisms of autoimmunity through translational research in vitiligo. 

Damsky W, King BA. JAK inhibitors in dermatology: the promise of a new drug class. 

Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. 

Bibeau K, Hamzavi IH, Ezzedine K, et al. Mental health and psychosocial burden among patients living with vitiligo: findings from the global VALIANT survey. Presented at Maui Derm for Dermatologists, January 2022.


More Than a Cosmetic Concern – Increasing Understanding of and Addressing Challenges and Care in Vitiligo, an Autoimmune Condition

R. Sonia Batra, MD, MSc, MPH, Board-Certified Dermatologist at Batra Dermatology

metabolic dysfunction-associated steatotic liver disease (MASLD)

 and bariatric surgery are becoming increasingly common in light of the rising obesity epidemic. Bariatric surgery offers well-established benefits on MASLD outcomes, including reduced adverse liver and cardiovascular events, improvement in steatohepatitis, and potential histologic regression of fibrosis.

Despite this, patients may still develop cirrhosis following bariatric surgery, either through progressive steatosis or other mechanisms. While many have sought to validate the efficacy and safety of performing bariatric surgery on patients with compensated cirrhosis, there is a paucity of literature describing the effect of bariatric surgery on outcomes of cirrhosis decompensation events.

We performed a retrospective, population-based analysis using the National Inpatient Sample database from October 2015 - December 2020 to identify all adults with obesity hospitalized with decompensated cirrhosis, including ascites, variceal hemorrhage, hepatic encephalopathy, or portal hypertension. These patients were then stratified into those with (n = 14,500) or without (n = 1,010,955) a history of bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy).

On outcomes analysis, inpatient mortality rates were lower in the bariatric surgery cohort (2.9% vs 4.1%; 

= .002), as were rates of acute kidney injury (24% vs 27%; 

<.001), respiratory failure requiring mechanical ventilation (0.7% vs 1.5%; 

<.001), and upper GI bleed (6.7% vs 9.6%; 

<.001). On univariate logistic regression analysis, bariatric surgery was protective against inpatient mortality (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.58-0.89; 

= .002). However, after adjusting for age, race, Baveno stage, and Charlson Comorbidity Index, protective significance was lost (OR, 0.82; 95% CI, 0.66-1.03; 

Weight loss is the primary treatment for MASLD, and despite a growing armamentarium of non-surgical weight loss strategies, bariatric surgery remains the most effective and enduring treatment for obesity. A recent systematic review reported an overall lower risk of adverse liver outcomes among patients with obesity who underwent bariatric surgery compared to those who did not (Hazard ratio, 0.33; 95% CI, 0.31-0.34), including significantly reduced risk of developing cirrhosis.

 However, despite surgery, fibrosis may still progress and patients remain susceptible to other causes of cirrhosis, such as viral hepatitis or alcohol-associated liver disease. In fact, bariatric surgery is known to increase the risk of alcohol use disorder post-operatively, facilitating more rapid and higher peak alcohol delivery to the systemic circulation.

Regardless of etiology, our study illustrates improved outcomes among patients with obesity and a history of bariatric surgery hospitalized with decompensated cirrhosis compared to nonsurgical patients. This likely relates to overall improved metabolic and comorbid health conferred by bariatric surgery. Though an important finding, future analyses are needed to further understand this relationship, including identifying temporal relationships between surgery and the onset of cirrhosis and decompensation, as well as subanalysis based on cirrhosis etiology and ongoing risk factors.

Aminian A, Al-Kurd A, Wilson R, et al. Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis. 

. Nov 23 2021;326(20):2031-2042. doi:10.1001/jama.2021.19569

Lassailly G, Caiazzo R, Ntandja-Wandji LC, et al. Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis. 

. Oct 2020;159(4):1290-1301.e5. doi:10.1053/j.gastro.2020.06.006

Verrastro O, Panunzi S, Castagneto-Gissey L, et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial. 

. May 27 2023;401(10390):1786-1797. doi:10.1016/S0140-6736(23)00634-7

Are VS, Knapp SM, Banerjee A, et al. Improving Outcomes of Bariatric Surgery in Patients With Cirrhosis in the United States: A Nationwide Assessment. 

. Nov 2020;115(11):1849-1856. doi:10.14309/ajg.0000000000000911

Bai J, Jia Z, Chen Y, Li Y, Zheng S, Duan Z. Bariatric Surgery is Effective and Safe for Obese Patients with Compensated Cirrhosis: A Systematic Review and Meta-Analysis. 

. May 2022;46(5):1122-1133. doi:10.1007/s00268-021-06382-z

Wang G, Huang Y, Yang H, Lin H, Zhou S, Qian J. Impacts of bariatric surgery on adverse liver outcomes: a systematic review and meta-analysis. 

. Jul 2023;19(7):717-726. doi:10.1016/j.soard.2022.12.025

Pepino MY, Okunade AL, Eagon JC, Bartholow BD, Bucholz K, Klein S. Effect of Roux-en-Y Gastric Bypass Surgery: Converting 2 Alcoholic Drinks to 4. 

. Nov 2015;150(11):1096-8. doi:10.1001/jamasurg.2015.1884

King WC, Chen JY, Mitchell JE, et al. Prevalence of alcohol use disorders before and after bariatric surgery. 

. Jun 20 2012;307(23):2516-25. doi:10.1001/jama.2012.6147

The retrospective analysis highlights improved outcomes among patients with obesity and a history of bariatric surgery hospitalized with decompensated cirrhosis.

Bariatric Surgery in Patients Hospitalized with Decompensated Cirrhosis: A Nationwide Analysis

Stephen Firkins, MD

Chief Pharmacist, Express Scripts® Pharmacy

Authors