Nancy Reau, MD, is Professor of Internal Medicine, Richard B. Capps Chair of Hepatology, Associate Director of Solid Organ Transplantation, and Section Chief of Hepatology at Rush University Medical Center.

Liver Lineup: Managing MASLD and MASH Amid Limited Awareness, Overlapping Risk Factors

Liver Lineup: Updates and Unfiltered Insights

, Nancy Reau, MD, and Kimberly Brown, MD, turn their attention to 

metabolic dysfunction–associated steatotic liver disease (MASLD) and metabolic dysfunction–associated steatohepatitis (MASH)

, conditions that now dominate hepatology clinics but continue to pose major diagnostic and therapeutic challenges. As new drugs enter the clinic and others advance through the pipeline, the hosts explore what meaningful progress looks like in a disease space defined by heterogeneity, comorbidities, and ongoing uncertainty around long-term outcomes.

The conversation opens with reflections on the transition from NAFLD/NASH to MASLD/MASH. Reau and Brown discuss how the updated terminology better captures the metabolic underpinnings of the disease and may help reduce stigma, while acknowledging that changing nomenclature alone does not solve longstanding issues around diagnosis, risk stratification, or patient engagement. They emphasize that many patients with advanced disease are still being identified late in their clinical course.

A central theme of the episode is how clinicians should think about treatment in MASH today. The hosts discuss the significance of having a therapy available for this patient population and what that means for hepatology practice. They underscore the importance of appropriate patient selection, fibrosis assessment, and setting realistic expectations around treatment goals, particularly given the complexity and heterogeneity of the disease.

Reau and Brown also address the role of weight loss and metabolic management in MASLD and MASH. They discuss how improvements in metabolic parameters can translate into liver-related benefits, while noting that sustained lifestyle change remains difficult to achieve and maintain. Pharmacologic approaches that support weight loss are discussed in the context of their broader metabolic effects, rather than as liver-specific therapies.

The episode concludes with a discussion of system-level challenges, including underdiagnosis, inconsistent use of noninvasive testing, and limited awareness outside of hepatology. As MASLD becomes an increasingly common cause of advanced liver disease, the hosts stress the need for better collaboration across specialties and clearer pathways for identifying patients who would benefit from referral and treatment.

Editors’ note: Relevant Disclosures for Reau include AbbVie, Gilead, Salix, Arbutus, and VIR. Relevant disclosures for Brown include Mallinckrodt Pharmaceuticals, Gilead, Salix, Intercept, Ipsen, and Madrigal.

Podcasts

Reau and Brown discuss new data on MASH/MASLD, including awareness, referral patterns, discussions around alcohol, and emerging pharmacotherapies.

News

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Hepatology

MASH / MASLD

The HCPLive MASH & MASLD page is a comprehensive resource for clinical news and insights on metabolic dysfunction-associated steatotic liver disease and steatohepatitis. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for fatty liver disease, steatohepatitis, and more.

Liver Lineup: Updates & Unfiltered Insights

Introducing Liver Lineup: Updates & Unfiltered Insights — an exciting new podcast delivering timely, candid perspectives on the most pressing topics in the fast-moving world of hepatology. Created by Nancy Reau, MD, and Kimberly Brown, MD, and hosted by HCPLive, this series dives into the cutting edge of liver disease research, clinical care, and real-world practice.

Ryan Livingston joined the MJH Life Sciences team in March of 2025, shortly after graduating from TCNJ with a bachelor’s degree in English. He enjoys creative writing, reading, and scuba diving. He can be reached at rlivingston@mjhlifesciences.com.

Image Credit: US Food and Drug Administration

 has approved a labeling supplement permitting repeat administration of iDose TR (travoprost intracameral implant) for the reduction of intraocular pressure (IOP) in patients with 

Drug: iDose TR (travoprost intracameral implant)

Class: Prostaglandin analog, sustained-release intracameral therapy

Indication: Reduction of intraocular pressure in open-angle glaucoma or ocular hypertension

Regulatory Action: FDA approval of labeling supplement allowing repeat administration

Key Evidence: Phase 3 and phase 2b trials showing favorable corneal endothelial safety through 3 years; 12-month safety data from an implant exchange study

Key Safety Signals: Iritis, ocular hyperemia, increased IOP, iris pigmentation; contraindicated in patients with corneal endothelial disease or prior corneal transplantation

Regulatory Status: FDA-approved in the United States

Announced on January 28, 2026, this update modifies prior labeling that limited use to a single administration and is based on accumulated clinical safety data, including corneal endothelial outcomes, submitted by the manufacturer.

Glaucoma remains a leading cause of irreversible blindness worldwide, with IOP reduction as the only proven modifiable risk factor.

 Prostaglandin analog eye drops are widely recommended as first-line therapy due to their efficacy and once-daily dosing.

 However, real-world adherence to topical therapy is suboptimal, with studies estimating that 30% to 50% of patients do not use drops as prescribed. Factors include ocular surface disease, difficulty with instillation, cost, and treatment fatigue.

Procedural drug delivery approaches, including intracameral implants, aim to bypass adherence barriers while providing sustained IOP control. Until recently, these strategies were constrained by questions surrounding repeatability, reversibility, and long-term corneal safety—particularly endothelial cell loss, a known risk with intraocular devices and procedures.

For clinicians managing chronic glaucoma, the labeling change addresses a practical limitation of long duration intracameral therapy: how to maintain sustained prostaglandin exposure beyond the life of an initial implant while preserving corneal safety. Repeat dosing may expand the role of procedural pharmacotherapy for patients who struggle with adherence or tolerability of topical medications, although long-term comparative effectiveness data remain limited.

iDose TR is a titanium-based intracameral implant that continuously elutes a proprietary, preservative-free formulation of travoprost into the anterior chamber via membrane-controlled diffusion. The device contains 75 µg of travoprost and is implanted through the trabecular meshwork into the scleral tissue. The FDA originally approved iDose TR in 2023 for a single administration to reduce IOP in adults with OAG or OHT.

Travoprost is a prostaglandin F2α analog that lowers IOP by increasing uveoscleral outflow. Its efficacy and safety as a topical agent are well established. iDose TR represents an extension of this mechanism via continuous intraocular delivery rather than episodic topical dosing.

The newly approved labeling supplement allows re-administration in patients who maintain a “healthy cornea,” defined by corneal endothelial cell density parameters outlined in the updated prescribing information. According to the new label, repeat administration requires removal of the original implant and intracameral placement of a new device under standard aseptic conditions.

The approval was supported by pooled corneal safety data from phase 3 pivotal trials and a phase 2b study, which followed patients for up to 3 years after implantation. In these studies, no clinically significant corneal endothelial cell loss was observed over time. The manufacturer also cited results from an “exchange” study evaluating removal of the original implant and placement of a second iDose TR, with 12 months of follow-up demonstrating acceptable safety and tolerability. As of this writing, peer-reviewed publication of the exchange trial data is limited, and detailed efficacy outcomes following re-administration have not been widely reported.

Across controlled studies of single administration, commonly reported ocular adverse reactions (2%–6%) included increased IOP, iritis, dry eye, ocular hyperemia, eye pain, visual field defects, and reduced visual acuity. Consistent with other prostaglandin analogs, increased iris pigmentation has been reported and may be permanent.

In the phase 3 GC-010 and GC-012 trials, iDose TR demonstrated sustained IOP reduction comparable to topical timolol through 12 months, with durability extending beyond 24 months in extension analyses. These trials primarily evaluated a single implant, and while efficacy waned over time in some patients, corneal safety outcomes were favorable, supporting further investigation of repeat use.

However, the labeling update does not establish superiority over topical therapy or other sustained-release options, nor does it define optimal timing for re-administration. Head-to-head comparisons with other long-acting approaches, such as bimatoprost intracameral implants, are lacking.

Evidence supporting repeat administration is primarily safety-focused, with limited published data on long-term efficacy after reimplantation. Real-world outcomes, cost-effectiveness, and patient-reported measures will be critical to defining the role of repeat intracameral therapy in routine practice. Ongoing postmarketing surveillance and future comparative studies will be needed to clarify these questions.

Glaukos Corporation. Glaukos Announces US FDA Approval of NDA Supplement Allowing for Re-Administration of iDose TR. 

. January 28, 2026. Accessed January 28, 2026. 

https://www.businesswire.com/news/home/20260128062505/en/Glaukos-Announces-US-FDA-Approval-of-NDA-Supplement-Allowing-for-Re-Administration-of-iDose-TR

Glaukos Corporation. Glaukos Announces FDA Approval of iDose TR (travoprost intracameral implant). December 14, 2023. Accessed January 28, 2026. 

https://investors.glaukos.com/news/news-details/2023/Glaukos-Announces-FDA-Approval-of-iDoseTR-travoprost-intracameral-implant/default.aspx

Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040. 

Singh IP, Berdahl JP, Sarkisian SR, et al. Long-term safety and efficacy evaluation of Travoprost intracameral implant based on pooled analyses from two phase III trials. Drugs. 2024;84(10):1299-1311. 

Prum BE Jr, Rosenberg LF, Gedde SJ, et al. Primary open-angle glaucoma preferred practice pattern. 

https://www.aaojournal.org/article/S0161-6420(15)01276-2/pdf

Newman-Casey PA, Robin AL, Blachley T, et al. The most common barriers to glaucoma medication adherence. Ophthalmology. 2015;122(7):1308-1316. 

Lass JH, Benetz BA, Gal RL, et al. Donor age and corneal endothelial cell loss 5 years after successful corneal transplantation. Ophthalmology. 2013;120(10):1949-1956. 

Netland PA, Gross RL, Peace JH, et al. Long-term efficacy and safety of travoprost compared with timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001;132(4):472-484. 

Lewis RA, Christie WC, Day DG, et al. Bimatoprost sustained-release implants for glaucoma therapy: 24-month results from a phase 1/2 clinical trial. Ophthalmology. 2017;124(12):1687-1694. 

Articles

The FDA has approved repeat administration of iDose TR, a travoprost intracameral implant, for patients with open-angle glaucoma or ocular hypertension. This update, based on clinical safety data, addresses adherence issues associated with topical therapies. iDose TR offers sustained intraocular pressure reduction through continuous drug delivery, bypassing barriers of topical administration. The approval is supported by safety data from clinical trials, although long-term efficacy and comparative effectiveness remain under investigation. Repeat administration requires removal and replacement of the implant, with ongoing studies needed to assess real-world outcomes.

The new approval allows for repeat administration of iDose TR, modifying the existing single-administration label.

Ophthalmology

Ophthalmology page, resources on the topics of medical news and expert insight into ophthalmic disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on eye disease research, treatment, and drug development.

Cardiology

Cardiology condition center page is a comprehensive resource for clinical news and insights on cardiovascular and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for heart disease and cardiovascular events, as well as associated diabetes, renal failure, and more...

Hypertension

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FDA News

FDA Approves Labeling Update for iDose TR for Open-Angle Glaucoma and Ocular Hypertension

Alex Hillenbrand is an assistant editor for 

. She earned her BA in English from Lafayette College in 2023 and went on to write for pop culture, entertainment, and sports media outlets before joining MJH Life Sciences in 2025. In her free time, Alex enjoys cooking, going on walks, and meeting new people. Contact her at mjhlifesciences.com.

Credit: International Society of Glomerular Diseases

In a 12-week, 31-center phase 2 clinical trial in 10 countries, apecotrep (BI 764198) reduced proteinuria by 40% in individuals with primary

 focal segmental glomerulosclerosis (FSGS)

Boehringer Ingelheim announced the findings, which were published in the 

 on January 27, 2026, highlighting apecotrep’s potential as a new disease-modifying treatment option for primary FSGS.

“The results underscore Boehringer’s scientific leadership in kidney health and deep commitment to people living with cardiovascular, renal, and metabolic diseases, including rare kidney conditions like FSGS,” said Paola Casarosa, head of innovation unit from the board of managing directors at Boehringer Ingelheim, in a company statement. “With the Phase III trial now underway, we are advancing apecotrep driven by the potential to deliver the first disease-modifying treatment for primary FSGS and redefine the standard of care for patients.”

Mechanistically, in FSGS, the transient receptor potential channel 6 (TRPC6) is thought to be overactivated on podocytes, allowing for excessive calcium to enter the cells. This progression causes podocyte injury and loss, ultimately leading to proteinuria and kidney disease progression.

Apecotrep, a potential first-in-class, oral, selective TRPC6 inhibitor, is being investigated as a novel, targeted, nonimmunosuppressive therapy in FSGS. The therapy is designed to protect podocytes and decrease the rate of disease progression by reducing proteinuria.

“Primary FSGS is a serious glomerular disease and an important cause of kidney failure in both children and adults. By targeting the underlying mechanism of primary FSGS, apecotrep reduced proteinuria by 40% compared to placebo, with a favorable tolerability profile in adults,” said lead study investigator Howard Trachtman, MD, from the NYU Langone Medical Center. “These clinically relevant findings reinforce the importance of further investigation of its potential as a first-in-class targeted treatment for primary FSGS, where the unmet need remains high.”

Tratchman and colleagues conducted a 12-week phase 2 multicenter, double-blind, placebo-controlled, randomized controlled trial to assess 20 mg (n = 18), 40 mg (n = 14), or 80 mg (n = 14) once daily apecotrep compared to placebo (n = 14). They randomized patients in a 1:1:1:1 ratio, stratifying them according to use of corticosteroids. Participants were receiving stable conservative and immunosuppressive therapy, with screening urine protein–creatinine ratio (UPCR) ≥ 1·0 g/g and estimated glomerular filtration rate (eGFR) ≥ 30 mL/min per 1·73 m2.

The primary endpoint was the proportion of participants with proteinuria response, defined as ≥25% UPCR reduction from baseline, at week 12. The other key outcomes were safety and tolerability.

There were 67 participants, 18 to 75 years of age, with biopsy confirmed primary FSGS or with a disease-causing TRPC6 variant. Overall, 37 participants (60%) were male, and 25 participants (40%) were female. The mean age was 40·7 years (Standard Deviation [SD] 12·6) and 63% of the trial cohort were White (39/62).

Investigators observed proteinuria response in 44% (Odds Ratio [OR], 10·0; 95% Confidence Interval [CI], 1·6–118·1), 14% (OR, 1·5; 95% CI, 0·2–19·5), and 43% (OR, 6·0; 95% CI, 0·9–73·6) of patients receiving apecotrep in patients receiving 20 mg, 40 mg, or 80 mg apecotrep compared to 1 receiving placebo.

Overall, investigators noted there were treatment-emergent adverse events reported by 71% of participants (44/62), with similar frequencies of adverse events observed in the placebo group (10/14). Overall, apecotrep was well tolerated with no meaningful differences in adverse event frequencies across treatment arms.

Boehringer Ingelheim’s investigational asset apecotrep delivers proteinuria reduction in Phase II kidney trial. Boehringer-ingelheim.com. Published January 27, 2026. Accessed January 28, 2026. https://www.boehringer-ingelheim.com/human-health/chronic-kidney-disease/boehringer-announces-phase-2-results-fsgs-rare-kidney-disease

Trachtman H, Kretzler M, Gesualdo L, et al. TRPC6 inhibition for the treatment of focal segmental glomerulosclerosis: a randomised, placebo-controlled, phase 2 trial of BI 764198. 

. Published online January 2026. doi:https://doi.org/10.1016/s0140-6736(25)02255-x

A 12-week phase 2 trial across 31 centers in 10 countries demonstrated that apecotrep (BI 764198) reduced proteinuria by 40% in patients with primary focal segmental glomerulosclerosis (FSGS). Apecotrep, a selective TRPC6 inhibitor, offers a novel, nonimmunosuppressive approach to treating FSGS by targeting podocyte protection. The trial involved 67 participants, with a primary endpoint of achieving a ≥25% reduction in proteinuria. Apecotrep was well tolerated, with adverse events comparable to placebo. These findings support further investigation of apecotrep as a potential first-in-class treatment for FSGS.

In a 31-center phase 2 trial in 10 countries, apecotrep BI 764198 reduced proteinuria in patients with primary focal segmental glomerulosclerosis.  


Nephrology

The HCPLive nephrology page is a resource for medical news and expert insights on kidney disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in nephrology, and more.

Focal Segmental Glomerulosclerosis

The HCPLive focal segmental glomerulosclerosis page is a resource for medical news and expert insights on FSGS. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments in FSGS, and more. 

Apecotrep Delivers 40% Proteinuria Reduction in Phase 2 FSGS Trial

Ruth Frikke-Schmidt, MD, PhD, is a professor and chief physician at Copenhagen University Hospital.

Connecting Vascular Dementia to Obesity and High Blood Pressure, With Ruth Frikke-Schmidt, MD, PhD

Patients with a higher body mass index (BMI) may have a higher risk of vascular-related 

 later in life; this association is mediated in part through genetic predisposition to 

A recent Mendelian randomization study has revealed the correlation between vascular dementia and 

, a connection difficult to investigate directly due to the advanced age of most patients with dementia. The Mendelian format instead mimics a randomized controlled trial by using common genetic variants causing high BMI as proxies for BMI-altering medications.

“What we were interested in was to create causal evidence for modifiable risk factors for dementia, because then they are actionable,” Ruth Frikke-Schmidt, MD, PhD, professor and chief physician at Copenhagen University Hospital, told 

 in an exclusive interview. “The association has been out there in literature as observational, but if it’s causal, that’s something we should deal with and prevent.”

Frikke-Schmidt and colleagues collected data from the UK Biobank and the Copenhagen General Population Study, among other databases. The study’s primary endpoint was the diagnosis of Alzheimer’s or dementia, the latter of which included vascular dementia and unspecified dementia due to sharing similar cardiovascular risk factors. Additionally, due to associations between BMI and 

, investigators included IHD as a positive control.

The team performed Cox regression restricted cubic splines with 3 knots placed to give the best model fit in both the Copenhagen and UK Biobank groups. A multivariable model was fitted, adjusted for sex, age, smoking status, physical activity, alcohol consumption, and level of education. Observational associations between mediators and vascular-related dementia were also analyzed with the same methods.

A total of 504,410 patients were included in the study, with 126,655 coming from the Copenhagen studies and 377,755 from the UK Biobank. Among the Copenhagen arm, 2260 participants developed vascular-related dementia, including 413 with vascular dementia and 1847 with unspecified dementia. 2111 developed Alzheimer’s disease, and 14,188 developed IHD. Of the 377,755 participants sourced from the UK Biobank, 3317 developed vascular-related dementia, including 1145 with vascular dementia and 2172 with unspecified dementia. Additionally, 2215 UK Biobank patients developed Alzheimer’s disease, and 45,539 developed IHD.

Among the Copenhagen group, the observational association between BMI and vascular-related dementia risk was U-shaped after adjusting for age, sex, cohort, et cetera. Higher BMI was associated with a higher risk of IHD, while lower BMI was associated with a higher risk of Alzheimer’s disease. These results were similar in the UK Biobank cohort. However, following 1-sample Mendelian randomization, the odds ratio (OR) of risk of vascular-related dementia per 1-SD higher BMI in analyses using well-established genetic variants was 1.63 (95% CI, 1.13-2.35) in a meta-analysis of all involved studies. Corresponding estimates were 1.04 (0.92-1.16) for Alzheimer’s disease and 1.24 (1.1-1.39) for IHD.

2-sample mendelian randomization analysis found an OR per 1-SD higher BMI for vascular-related dementia were 1.54 (95% CI, 1.1-2.16) using the inverse-variance weighted, 1.87 (1.22-2.85) using weighted median, and 1.98 (1.21-3.22) using weighted mode methods. Corresponding estimates were 1.08 (0.72-1.64) for Alzheimer’s disease and 1.23 (1.08-1.4) for IHD. Additionally, systolic blood pressure mediated 18% (95% CI, 10%-61%) and diastolic blood pressure mediated 25% (13%-75%) of the genetic effect of BMI on vascular-related dementia.

Ultimately, investigators concluded that, observationally (U-shaped) and genetically (linear), high BMI is associated with an increased risk of vascular-related dementia, which is partly mediated through high blood pressure.

“We should, of course, advocate as professionals for a heart-healthy diet in the general population,” Frikke-Schmidt said. “What is good for the heart is good for the brain – and we can start with the guidelines for heart-healthy diets and the guidelines for treating and preventing high blood pressure.”

Editor’s Note: Frikke-Schmidt reports a disclosure with Novo Nordisk.

The Endocrine Society. People with obesity may have a higher risk of dementia. 

. January 22, 2026. Accessed January 28, 2026. 

https://www.eurekalert.org/news-releases/1112842

Nordestgaard LT, Luo J, Emanuelsson F, et al. High body mass index as a causal risk factor for vascular-related dementia: A Mendelian randomization study. The Journal of Clinical Endocrinology &amp; Metabolism. Published online January 22, 2026. 

Videos

Frikke-Schmidt discusses the newfound genetic correlation between vascular-related dementia and an increased BMI, partially mediated by high blood pressure.

Endocrinology

The HCPLive endocrinology page is a comprehensive resource for clinical news and insights on endocrine system conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for diabetes, hormonal disease, and more.

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Alexander Mathioudakis, MD, PhD, from the biology department at The University of Manchester.

chronic obstructive pulmonary disease (COPD)

, with real-world adherence to inhaled maintenance therapies estimated at just 20–30%. With COPD affecting an estimated 480 million adults globally in 2020 and projected to reach 600 million by 2050, the clinical consequences of treatment discontinuation warrant careful evaluation.

A post-hoc analysis of the 52-week FLAME trial, which included 3362 patients with moderate-to-severe COPD and a history of exacerbations, suggests discontinuation is not clinically neutral.

The analysis showed that stopping long-acting muscarinic antagonists (LAMA) was associated with a transient increase in moderate-to-severe exacerbations during the first quarter after withdrawal, with rate ratios as high as 2.2 in certain subgroups. Inhaled corticosteroid (ICS) discontinuation was linked to an earlier rise in severe exacerbations, with effects observed regardless of baseline blood eosinophil counts.

These withdrawal-related peaks were most pronounced within the first 3 months and appeared to attenuate over time, supporting a time-limited vulnerability window. The study also identified potential LAMA withdrawal effects with rate ratios approaching 3.7 in patients least influenced by concomitant therapy.

In this Q&A, Alexander Mathioudakis, MD, PhD, from the biology department at The University of Manchester, discusses the clinical interpretation of these findings and how they should inform adherence counseling, deprescribing decisions, and post-withdrawal monitoring in routine COPD care.

What prompted your team to investigate the effects of discontinuing ICS and (AMA in COPD patients?

 Treatment withdrawal effects are more common than we often acknowledge and have been described across many drug classes, including corticosteroids, beta-blockers, statins, anti-depressants, and anti-epileptics. In COPD, where adherence to inhaled therapy is frequently poor, periods of unintentional discontinuation are common in real-world practice.

While ICS withdrawal effects have been suggested previously, data on LAMA withdrawal were lacking. This prompted us to systematically explore whether discontinuing these treatments is associated with short-term increases in exacerbation risk. The findings from FLAME were revealing and clinically relevant.

 Your post-hoc analysis of the FLAME trial identified early increases in exacerbation risk after discontinuing ICS or LAMA. How should clinicians interpret these transient withdrawal effects in the context of routine COPD care?

 The first implication is the importance of supporting and reinforcing treatment adherence. Patients should understand that intermittent use or unplanned gaps in maintenance therapy may carry a short-term risk of exacerbations.

Second, when treatments are intentionally discontinued or switched, clinicians should anticipate a possible transient increase in risk. This is particularly relevant for ICS, where inappropriate initiation can make later withdrawal challenging. Aligning initiation and discontinuation decisions with GOLD recommendations remains essential to minimize avoidable harm.

 The study shows differences between moderate-to-severe and severe exacerbations. Could you clarify how these risks vary depending on prior therapy and baseline eosinophil counts?

 FLAME included relatively few severe exacerbations, meaning these analyses were underpowered to detect clear differences by severity. We do not believe this reflects a true biological difference in withdrawal effects between moderate and severe events.

Importantly, our findings suggest that ICS withdrawal effects may not be confined to patients with elevated blood eosinophil counts. Even patients who may derive limited benefit from ICS could still experience withdrawal-related risk. For LAMA, there is no biological rationale for an eosinophil-dependent effect. Apparent differences reflect trial design, as ICS initiation likely masked withdrawal effects in patients with higher eosinophil counts.

 In practice, many patients discontinue inhaled therapy intermittently. How might real-world patterns of non-adherence affect the risk of early exacerbations compared with what you observed in the trial?

 In real-world practice, many patients are non-adherent and intermittently stop and restart inhaled therapies. It is likely that such patterns of non-adherence could trigger withdrawal effects similar to those observed in FLAME.

Further evaluation using real-world data or studies with detailed adherence monitoring is needed to quantify the frequency and magnitude of these effects. Our analysis underscores the importance of treating treatment discontinuation as an active exposure state, rather than assuming non-adherence is clinically neutral.

 For patients being considered for ICS or LAMA withdrawal, what clinical factors or baseline characteristics should guide decision-making to minimize exacerbation risk?

 Current GOLD and international guidelines provide clear indications for ICS withdrawal, and LAMA discontinuation is generally rare, usually limited to intolerance or adverse effects. These recommendations remain appropriate.

Our findings reinforce the importance of avoiding unnecessary initiation of ICS, as inappropriate use increases the likelihood of difficult or risky withdrawal later. Decisions to discontinue therapy should be deliberate, guideline-aligned, and accompanied by appropriate clinical follow-up.

 Did your analysis suggest an optimal monitoring strategy after discontinuation to detect and manage early exacerbations effectively?

Our data suggest that the first 3 months after discontinuing ICS or LAMA represent a period of increased vulnerability to exacerbations. Heightened clinical awareness during this window is therefore reasonable. Exacerbations should, as always, be recognized and treated promptly.

 How might these findings inform step-down or de-escalation strategies, particularly for patients with moderate-to-severe COPD who are stable on combination therapy?

 Guidelines recommend considering ICS step-down in patients who are stable, have low exacerbation risk and low blood eosinophil counts, or in those experiencing recurrent pneumonia or infective exacerbations. Our findings do not challenge this approach.

However, they suggest that early exacerbations after ICS withdrawal may reflect a transient withdrawal effect rather than immediate treatment failure. Clinicians may therefore wish to assess exacerbation characteristics and eosinophil levels before rapidly re-escalating therapy during the first three months, where clinically appropriate.

Derman C. Stopping Inhaled Corticosteroids or LAMA in COPD Linked to Early Exacerbations. HCPLive. Published on January 15, 2026. Accessed on January 27, 2026. 

https://www.hcplive.com/view/stopping-inhaled-corticosteroids-lama--copd-linked-early-exacerbations

Mathioudakis AG, Bate S, Chatzimavridou-Grigoriadou V, et al. Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial. Thorax. Published online December 15, 2025. 

Chronic obstructive pulmonary disease (COPD) treatment discontinuation is prevalent, with adherence to inhaled therapies at 20-30%. A post-hoc analysis of the FLAME trial revealed that stopping long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS) leads to a transient increase in exacerbations, particularly within the first three months. These findings emphasize the importance of adherence, careful deprescribing, and monitoring post-withdrawal. The study suggests that withdrawal effects are not limited to patients with high eosinophil counts, highlighting the need for guideline-aligned decision-making in COPD management.

In this Q&A, Mathioudaki discusses the post-hoc FLAME trial, which links ICS and LAMA discontinuation to transient exacerbation risk in COPD.

Pulmonology

Infectious Disease condition center page is a comprehensive resource for clinical news and insights on respiratory health. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for asthma, COPD, interstitial lung disease, COVID-19, and more.

COPD

COPD condition center page, resources on the topics of medical news and expert insight into chronic obstructive pulmonary disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on COPD research, treatment, and drug development.

COPD Drug Withdrawal Tied to Early Exacerbation, With Alexander Mathioudakis, MD, PhD

Tim Smith joined the MJH Life Sciences team in 2022 and is currently an associate editor for HCPLive. He is also the executive producer of two podcasts: Skin of Color Savvy and The Medical Sisterhood. Previously, he was the producer of the Lungcast podcast. He graduated from UC Berkeley and worked in multimedia journalism as a staff writer prior to joining MJH. You can contact him at tsmith@mjhlifesciences.com.

At the 2026 Maui Derm Hawaii meeting, recent data on icotrokinra’s use in patients with psoriasis were highlighted.

Plaque Psoriasis

The HCPLive plaque psoriasis page is a resource for medical news and expert insights on psoriasis. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for psoriatic disease, and more.

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 conference coverage page features articles, videos, and expert-led live coverage from major medical meetings throughout the year.

Icotrokinra Data at Maui Derm 2026 Reaffirm Efficacy in Psoriasis

Neal Bhatia, MD, speaks in this interview regarding his discussion at Maui Derm Hawaii of new and emerging therapies in dermatology.

Discussing GLP-1s, New Dermatology Therapies in 2026, With Neal Bhatia, MD

Robert Negrin, MD, is president of the American Society of Hematology and a professor of medicine at Stanford University. 

ASH’s new president, Robert Negrin, explains key takeaways from the 67th meeting and sets the scene for ASH 2026. 


Hematology

Looking Ahead to ASH’s 68th Meeting, With President Robert Negrin, MD

This interview from the Maui Derm 2026 conference features Lawrence Eichenfield, MD, discussing takeaways from his talk ‘Acne and Rosacea: Update 2026.’

Acne

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Rosacea

On the HCPLive rosacea page, resources on the topics of medical news and expert insight into acne rosacea can be found. Content includes articles, interviews, videos, podcasts, and breaking news on the skin condition, and more.

Acne and Rosacea Treatment Updates for 2026, With Lawrence Eichenfield, MD

David Golden, MD, clinical associate professor of medicine at Johns Hopkins University School of Medicine.

As the January 31 PDUFA date approaches, Golden discusses that epinephrine sublingual film may deliver symptom relief as rapidly as autoinjectors, with added portability.

Allergy

Allergy condition center page is a comprehensive resource for clinical news and insights on allergic and inflammatory diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for food and seasonal allergies, as well as allergic asthma and related conditions.

Anaphylaxis

The HCPLive anaphylaxis page is a comprehensive resource for clinical news and insights on acute allergic reactions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for preventing anaphylaxis, and more.

Anticipating The FDA Decision of Anaphylm for Anaphylaxis, With David Golden, MD

Andrew Kau, MD, PhD, is an associate professor in the John T. Milliken Department of Medicine at WashU Medicine.

Andrew Kau, MD, PhD, and Audrey John, MD, PhD, discuss their recent research exploring exhaled breath analysis as a noninvasive way to probe the gut microbiome.

Gastroenterology

Gastroenterology condition center page is a comprehensive resource for clinical news and insights on digestive and GI conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for 

, IBS and IBD, Crohn's disease, and more.

Exploring Exhaled Breath as a New Platform for Gut Microbiome-Based Diagnostics

The investigational dual GLP-1/GIP receptor agonist resulted in substantial weight loss without plateau after 48 weeks in patients with obesity.

Latest News

Liver Lineup: Managing MASLD and MASH Amid Limited Awareness, Overlapping Risk Factors

FDA Approves Labeling Update for iDose TR for Open-Angle Glaucoma and Ocular Hypertension

Apecotrep Delivers 40% Proteinuria Reduction in Phase 2 FSGS Trial

Connecting Vascular Dementia to Obesity and High Blood Pressure, With Ruth Frikke-Schmidt, MD, PhD

COPD Drug Withdrawal Tied to Early Exacerbation, With Alexander Mathioudakis, MD, PhD