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Medscape
4 days ago
- Business
- Medscape
Tezepelumab Curbs Oral Corticosteroid Use in Severe Asthma
The addition of tezepelumab to standard treatment allowed half the adults with severe asthma to discontinue their use of oral corticosteroids (OCS) after 1 year, according to new data from nearly 300 individuals. Tezepelumab, a human monoclonal antibody, has been associated with reduction in the use of OCS in patients with OCS-dependent asthma, David J. Jackson, MD, professor and clinical director, Guy's Severe Asthma Centre at Guy's Hospital King's College London, London, England, and colleagues wrote in an abstract presented at American Thoracic Society (ATS) 2025 International Conference. Many patients with severe asthma take OCS, but previous research has shown associations between extended OCS use and increased risk for a range of side effects including osteoporosis and fractures, hypertension, and infections, and more strategies are needed to help these patients reduce OCS use, the researchers noted. 'We know prolonged oral corticosteroid use leads to adverse effects, including bone, cardiovascular, metabolic, gastrointestinal and psychiatric disorders, and adrenal insufficiency,' Jackson said in an interview. 'The WAYFINDER trial is a multicenter, open-label, single-arm trial evaluating the efficacy and safety of tezepelumab compared to placebo in severe asthma patients who require maintenance use of OCS alongside their standard treatment,' he said. A previous phase 3 OCS-sparing study known as SOURCE did not meet its primary endpoint, but patients with baseline blood eosinophil counts ≥ 150 cels/μL who received tezepelumab achieved a reduction in daily maintenance OCS (mOCS) dose compared with placebo patients, the researchers wrote in their abstract. 'The WAYFINDER trial was designed to accelerate data collection and specifically address the complexities in the SOURCE trial design that may have contributed to the result of the primary endpoint,' Jackson told Medscape Medical News . The WAYFINDER trial enrolled 298 adults with severe asthma who had received OCS for at least 3 months before starting the study. All participants received 210 mg of subcutaneous tezepelumab every 4 weeks for up to 52 weeks after a 4-week induction period. The co-primary endpoints were the proportion of patients who reduced their daily mOCS to 5 mg/d or less or discontinued OCS without loss of asthma control. A total of 273 patients completed the study; the mean baseline mOCS was 10.8 mg/d, and patients were assessed at 28 weeks and 52 weeks. Overall, 88.9% and 89.9% of patients reduced their mOCS to 5 mg/d or less by week 28 and week 52, respectively, while 32.2% and 50.3% discontinued OCS at these time periods, respectively. In a post hoc analysis, 82.2% of patients whose reason for systemic corticosteroids was related to adrenal insufficiency achieved an mOCS dose of 5 mg/d or less without loss of asthma control at week 52. The study was limited by the open-label design, but the safety profile was consistent with previous studies of tezepelumab, researchers said. A 2023 meta-analysis of safety data on tezepelumab for uncontrolled asthma showed that the most common adverse events were nasopharyngitis, headache, and bronchitis, and most AEs occurred within a month of starting tezepelumab. Rates of serious adverse events were lower in patients receiving tezepelumab than those receiving placebo in a pooled analysis. The standout findings from the study are the clinically meaningful reductions in maintenance OCS use or complete discontinuation achieved with tezepelumab among a broad severe asthma patient population, Jackson told Medscape Medical News . In addition, two thirds of participants remained exacerbation-free despite OCS dose reductions, and the OCS-sparing effect of tezepelumab was observed across pre-specified patient subgroups, including those defined by baseline blood eosinophil counts (BEC), fractional exhaled nitric oxide (FeNO) level and allergy status, Jackson said. 'These findings reinforce tezepelumab's efficacy in severe asthma as the first and only biologic targeting thymic stromal lymphopoietin (TSLP) with demonstrated efficacy for severe asthma patients across phenotypes and irrespective of biomarker levels including BEC, allergic status, and FeNO,' he said. Improving Short-Term Health and Long-Term Wellness 'For people living with severe asthma, achieving stable control and reducing or eliminating reliance on oral corticosteroids is a critical goal, not only for respiratory health but also for long-term well-being,' Jackson told Medscape Medical News . 'By showing the benefit of targeting TSLP at the top of the inflammatory cascade and controlling asthma effectively with tezepelumab, we may be able to reduce these risks from OCS and significantly improve control for patients living with severe asthma,' Jackson said. 'We look forward to sharing a manuscript in the future for the phase 3b WAYFINDER study,' he added. Support for Steroid-Sparing The current study highlights an important population: Patients with asthma who are dependent on OCS, said Sucharita Kher, MD, pulmonologist and vice chair of clinical operations and quality for the Department of Medicine at Tufts Medical Center, in an interview. The endpoint tapering OCS without loss of asthma control is clinically meaningful because of the known side effects of OCS, said Kher, who was not involved in the study. The results were not unexpected, but more details on whether patients with eosinophils below 150 cells/µL also benefitted from tezepelumab would be helpful, Kher noted. The data are exciting because they suggest another option for patients with OCS dependent asthma, said Kher. 'The data also guide clinicians to adopt a strategy to wean patients off OCS when on tezepelumab with the goal of reducing OCS exposure and hence, side effects of prolonged OCS use,' she said. 'We know that OCS have side effects and negative consequences on factors including bone health, blood pressure, and blood sugar control and infection risk,' she added. Potential barriers to expanding the use of tezepelumab for reducing OCS in asthma patients exist at the patient and healthcare systems levels, Kher told Medscape Medical News . Patient-level barriers include cost sharing, worry/hesitancy about injections, lack of specialty access, and patient health literacy, she said. In addition, healthcare system barriers include a lack of knowledge on the part of primary care providers, and even some specialty physicians, of the benefits of biologics for severe asthma, said Kher. Other potential challenges include limited infrastructure in clinician offices, such as trained personnel and staff to navigate prior auth/insurance mandates, pre-authorization barriers, and denials based on tiers by insurance companies, she noted. 'Overcoming the barriers requires a multipronged approach, improving awareness and education for healthcare professionals, improve access to specialty care for patients, and advocacy to reduce the processes for insurance approvals,' Kher said.
Medscape
28-05-2025
- Business
- Medscape
Deupirfenidone Shows Promise Against IPF-Linked Lung Decline
SAN FRANCISCO — A molecular variant of an older, hard-to-tolerate antifibrotic agent showed promise for reducing decline in forced vital capacity (FVC) over 26 weeks among patients with idiopathic pulmonary fibrosis (IPF). These findings come from the phase 2B ELEVATE IPF trial, results of which were reported at the American Thoracic Society (ATS) 2025 International Conference here. The trial compared the investigational agent deupirfenidone to placebo for protection against FVC decline in 257 patients with IPF. The deupirfenidone molecule is nearly identical in conformation to pirfenidone, except for the substitution of hydrogen in pirfenidone for deuterium, or 'heavy hydrogen,' in deupirfenidone at the site of metabolism. This process, known as 'deuteration,' is designed to make the modified compound less toxic than pirfenidone, said lead investigator Toby Maher, MD, PhD, from the Keck School of Medicine at the University of Southern California, Los Angeles. Although the primary endpoint of the study was decline in FVC over 26 weeks, 'when we've looked at the open-label extension of patients continuing on the high dose, we've seen a sustained stabilization in FVC over 52 weeks, again suggesting a durable effect of treatment,' he said in an oral abstract session. Multinational Trial In the ELEVATE IPF trial, 257 patients with IPF from 87 sites in 14 countries were enrolled and randomly assigned to one of four treatment arms: 550 mg deupirfenidone thrice per day, 825 mg deupirfenidone thrice per day, 801 mg pirfenidone thrice per day, or placebo thrice per day. The primary Bayesian analysis showed that the mean adjusted change in FVC from baseline to 26 weeks was −48.4 ml for all patients randomized to deupirfenidone compared with −110.7 ml for patients assigned to placebo (posterior probability vs placebo, 98.5%). The respective adjusted mean changes from baseline in FVC% predicted were −48.4% and −1.1% (posterior probability, 99.6%). In a Frequentist inference analysis, compared with placebo the higher dose of deupirfenidone but not the lower dose was associated with significantly less decline in FVC and FVC% predicted. The adjusted mean changes over baseline were −21.5 ml for the 825 mg deupirfenidone group vs −112.5 ml for the placebo group ( P = .02), and the respective changes in FVC% predicted were −21.5% and −3.43% ( P = .01). Both pirfenidone and deupirfenidone 825 mg (but not 550 mg) significantly delayed time to progression compared with placebo. The respective hazard ratios were 0.50 ( P = .0076) and 0.439 ( P = .0033). In the placebo, pirfenidone, deupirfenidone 550 mg and 825 mg arms, respectively, treatment-emergent adverse events commonly associated with antifibrotics were nausea (7.7%, 27.0%, 16.9%, 20.3%), dyspepsia (3.1%, 22.2%, 12.3%, 14.1%), diarrhea (9.2%, 11.1%, 10.8%, 7.8%), abdominal pain (4.6%, 7.9%, 6.2%, 14.1%), photosensitivity reaction (0%, 7.9%, 6.2%, 7.8%), decreased appetite (7.7%, 14.3%, 18.5%, 20.3%), fatigue (1.5%, 11.1%, 7.7%, 9.4%), dizziness (3.1%, 7.9%, 9.2%, 12.5%), and headache (4.6%, 12.7%, 7.7%, 3.1%). GI Signal In the question and answer, session co-moderator Rachel Knipe, MD, from Massachusetts General Hospital in Boston, commented that there appeared to be a small signal for increased abdominal pain with deupirfenidone but less so for diarrhea and other gastrointestinal symptoms. She asked Maher whether investigators had also looked at liver function tests. 'The liver function tests didn't flag up as an adverse event that differed across groups or reached the threshold for inclusion in the table,' Maher said. Maher acknowledged that there are gastrointestinal events associated with the drug, but added that it's difficult to distinguish specific events from one another. 'The challenge with clinical trials in interpreting adverse events is that we are beholden on the individual investigators to label the side effects,' he said, noting that one center's dyspepsia, may be another center's loss of appetite or abdominal pain. In an interview, Medscape Medical News asked Knipe, whose laboratory at Mass General has a special focus on PF, for her impression of deupirfenidone. 'I think the data looks pretty good; it's exciting, and it looks like it has good effect on lung function,' she said, adding that the adverse event profile appears to be more favorable than that of pirfenidone. The study was funded by PureTech Health. Maher reported receiving grants and funding and serving as a consultant for the company and others. Knipe had no disclosures relevant to the study.
Medscape
22-05-2025
- Health
- Medscape
BLVR Requires Revision in 20% of Patients
Approximately 20% of patients who undergo bronchoscopic lung volume reduction (BLVR) lose the effects of the treatment within 2 years, according to data presented at the American Thoracic Society (ATS) 2025 International Conference in San Francisco. Although BLVR has become common, data on the need and reasons for revision are limited, wrote Jiji Thomas, MBBS, Manager of Special Procedures at the Temple Lung Center, Philadelphia, and colleagues in their abstract. The current study was designed to identify some factors behind the need for revision procedures, Thomas said in an interview. In the study, Thomas and colleagues reviewed data from all patients that were treated with endobronchial valves in their center's BLVR program since the therapy was approved by the US Food and Drug Administration in 2018. The study population included 251 adults, 49 of whom (20%) required adjustments to maintain lobar volume reduction. The mean age of the patients was 67 years; approximately 43% were men. The time from the initial procedure to a loss of treatment effect was 7.3 months. The most common area for the loss of treatment effect was the left upper lobe (16 patients), followed by the left lower lobe (14 patients), right lower lobe (10 patients), right upper lobe (8 patients), and right upper plus right middle lobe (5 patients). Most of the initial procedures involved Zephyr valves (78%); the remainder used Spiration valves. Granulation of tissue was the most common cause of treatment loss (53%), followed by valve migration (34%), pneumothorax (7%), and excessive coughing (6%). BLVR revisions were effective and well accepted by patients, the researchers wrote. Among the patients who needed revision, the residual volume/total lung capacity ratio was 63% at baseline and after initial valve placement and 58% after adjustment. Forced expiratory volume in 1 second was 0.78 at baseline, 0.84 after initial valve placement, and 0.89 after adjustment. The researchers were not surprised by the improvement patients had following their revision procedure. However, 'it was a little surprising that, in some cases, loss of benefit happened almost 18-24 months after the initial procedure; this emphasizes the need for long-term follow-up,' Thomas told Medscape Medical News . The results confirmed that loss of treatment benefits of BLVR can be easily corrected with a revision procedure, said Thomas. 'Patients need to be educated about revision, and treatment centers should give importance to long-term follow-ups on this group of patients,' he said. No particular strategies can prevent the need for a BLVR revision, said Thomas. 'The loss of treatment benefits in a certain percentage of patients who undergo BLVR cannot be avoided, but it can be easily corrected with a revision procedure,' he said. However, 'Future research may look into physiological and radiological factors that can predict which patients have higher chances of getting a revision procedure,' he added. Support Despite Shortcomings 'Bronchoscopic lung volume reduction with valves is an option for some patients with severe emphysema,' said David Mannino, MD, a part-time professor at the University of Kentucky, Lexington, Kentucky, in an interview. 'Some patients have a good initial response that does not persist over time, and this study looks at options for additional valves in those patients,' said Mannino, who was not involved in the study. 'I thought that the improvement in those patients who required additional valves was surprising; that is a good sign for those patients who have initial improvement that fails to persist,' Mannino told Medscape Medical News . To reduce the need for revisions, BLVR is best done at highly experienced centers that are prepared to manage any complications, Mannino said. Looking ahead, more research to help identify which patients can expect the most improvement from BLVR would be helpful, he added.
Medscape
22-05-2025
- Health
- Medscape
Quick Turn to Mechanical Thrombectomy Improves PE Outcomes
Patients with pulmonary embolism (PE) who were treated with mechanical thrombectomy (MT) within 12 hours of hospital admission had significantly better pulmonary outcomes than patients treated with mechanical thrombectomy more than 12 hours after admission, based on new data from the FLASH registry. The benefits of prompt treatment with MT for patients with high-risk PE are evident, but data on the impact of MT timing on outcomes in patients with intermediate-risk PE are limited, wrote Krunal Patel, MD, and Parth M. Rali, MD, of the Lewis Katz School of Medicine, Temple University Hospital, Philadelphia, in a study presented at the American Thoracic Society (ATS) 2025 International Conference in San Francisco. The FLASH registry is a prospective, multicenter registry of patients with acute intermediate-risk and high-risk PE who were followed for 6 months after treatment with a large-bore aspiration MT system, the authors wrote. 'The safety of mechanical thrombectomy has been established through the FLASH study, but as more centers adopt advanced interventions such as MT and catheter-directed thrombectomy, it is critical to determine the optimal timing for these procedures,' Patel said in an interview. 'Understanding when to intervene could significantly impact outcomes for patients with pulmonary embolism,' he said. The researchers classified 726 patients with intermediate-risk PE into two groups: Short time to MT (short TtMT, defined as 12 hours or less) and long time to MT (long TtMT, defined as more than 12 hours). The short TtMT group included 215 patients with a median time of 6.12 hours to treatment, and the long TtMT group included 511 patients with a median of 24.78 hours to treatment. Patients were assessed for outcomes including mean pulmonary artery pressure (mPAP) and systolic pulmonary artery pressure (sPAP), as well as right ventricle to left ventricle (RV/LV) ratio, distance on the 6-minute walk test, and Pulmonary Embolism Quality of Life score. At baseline, patients in the short TtMT group had a higher lactate and higher RV/LV ratio than those in the long TtMT group. Both mPAP and sPAP reductions were significantly greater in the short TtMT group vs the long TtMT group (9.0 mm Hg vs 7.0 mm Hg and 14.0 mm Hg vs 12.0 mm Hg, respectively; P < .0001 for both). Patients in the short TtMT group also had greater reductions in RV/LV ratios from baseline to follow-ups of 48 hours, 30 days, and 6 months than those in the long TtMT group. The short TtMT group also had a significantly longer median distance on the 6-minute walk test at the 6-month follow-up visit than the long TtMT group (450.5 m vs 390.0 m; P = .0260). No differences in safety events including major bleeding through 48 hours and mortality at 30 days were observed between the groups. Revised Guidance Needed 'We suspected, much like with [ST-elevation myocardial infarction] STEMI and stroke, that the principle of 'time is tissue' would apply, meaning that earlier intervention would lead to better outcomes,' Patel told Medscape Medical News . 'We focused solely on intermediate-risk PE patients to limit confounding from illness severity, and we observed meaningful clinical improvements in the early group,' he said. One major barrier to the rapid initiation of MT following hospital admission is that current guidelines haven't kept pace with emerging interventional strategies, Patel told Medscape Medical News . 'Broad adoption requires consensus and updated protocols,' he said. 'Implementing a Pulmonary Embolism Response Team (PERT) can also be pivotal in streamlining patient evaluation and ensuring timely access to advanced therapies,' he noted. 'A prospective trial would provide the strongest evidence but may be challenging in high-risk patients, where most clinicians already agree on the need for rapid intervention, and in the meantime, we rely on retrospective data,' said Patel. 'More importantly, we need to revise how we classify PE patients,' he said. A modern classification system should integrate multiple therapies including MT into the risk stratification framework, Patel said. 'Globally, a patient dies of a PE every minute, and with advanced interventions this will hopefully become a thing of the past, but more focus needs to be taken on timing and developing a new way of classifying patients so interventions can take an algorithmic approach incorporating these new treatment modalities,' he said. Data May Drive Increased Use of Technology 'The treatment of intermediate-risk pulmonary embolism is one of the clinical areas where there is wide variability because the data we have leaves room for interpretation,' said Anthony Faugno, MD, a pulmonologist at Tufts Medicine, Boston, in an interview. Not every center has advanced invasive capabilities for MT, he noted. 'More clarity on the benefits of these invasive therapies will help individual centers identify the need to adopt these technologies and build systems for their best use,' Faugno said. Regarding the current study, 'Being that this was a registry and not a randomized controlled trial, it is likely that the patients in the early intervention group were recognized as being clinically sicker, resulting in faster treatment,' Faugno told Medscape Medical News . The baseline differences in RV/LV ratio and lactate support that a sicker group received earlier intervention, and one would expect their hemodynamics to benefit more, he said. 'It is surprising that the sicker initial group had enhanced quality of life at follow-up, but it is hard to draw conclusions about this without an understanding of the different comorbidities in each group,' he noted. Because the current study did not adjust for factors such as chronic medical illness that might affect patient function at 6 months, the results should be interpreted with some caution, Faugno noted. However, more data such as these may prompt more centers to rapidly mobilize the resources needed for invasive procedures in cases of intermediate-risk PE, he said. As for additional research, 'I think the most important clinical question in the intermediate-risk pulmonary embolism group is deciding who can be treated with systemic anticoagulation alone and who benefits from the invasive, and sometimes costly, procedures,' Faugno told Medscape Medical News . 'There are some centers, specifically small and rural hospitals, that will be unable to provide advanced invasive treatments at all hours,' he noted. 'I think there is still a benefit to noninvasive treatment of intermediate-risk pulmonary embolism in the properly selected patient; research to understand who these patients are will help us develop future clinical trials on treatments,' he said. The study received no outside funding.
Medscape
20-05-2025
- Health
- Medscape
COPD Diagnosis Reboot Identifies More At-Risk Individuals
SAN FRANCISCO — A new diagnostic schema incorporating chest CT and respiratory symptoms into the diagnosis of chronic obstructive pulmonary disease (COPD) can help to better identify patients at risk for poor respiratory outcomes and rule out those with airflow obstruction who have neither respiratory symptoms nor evidence of structural lung disease. The recommendation for a new diagnostic paradigm, based on a cohort study incorporating data from two large longitudinal studies, was presented at the American Thoracic Society (ATS) 2025 International Conference and published online simultaneously in JAMA. 'We have developed a new, multidimensional diagnostic schema for COPD that incorporates spirometry, symptoms, and imaging and goes beyond how we diagnose COPD now. It results in an additional number of individuals with high risk for all-cause mortality, respiratory-caused mortality, exacerbation, and lung function decline but also, importantly, excludes some people with airflow obstruction who do not have poor outcomes,' said lead author Surya P. Bhatt, MD, MSPH, from the University of Alabama at Birmingham, in an oral abstract session at ATS 2025. 'Using the new COPD diagnostic schema, compared with individuals classified as not having COPD, those with a new diagnosis of COPD had greater all-cause and respiratory-specific mortality, more frequent exacerbations, and faster FEV1 [forced expiratory volume in 1 second] decline,' wrote Bhatt and colleagues in the Genetic Epidemiology of COPD (COPDGene) 2025 Diagnosis Working Group and Canadian Cohort Obstructive Lung Disease (CanCOLD) investigators. 'This study marks a pivotal point in the understanding and management of COPD. By introducing a broader, multicriteria framework, it moves the field beyond traditional diagnostic limitations and sets the stage for more individualized and inclusive COPD patient care,' wrote Francesca Polverino, MD, PhD, from Baylor College of Medicine in Houston, in an editorial accompanying the study in JAMA. Rewriting the Diagnostic Script Current recommendations for diagnosis of COPD in patients with respiratory symptoms require detection of airflow obstruction on spirometry following a bronchodilator and an FEV1/forced vital capacity (FVC) ratio < 0.70 or below the lower limit of normal. Yet as the study authors pointed out, 'spirometry does not capture all aspects of this complex heterogeneous disease, and there is growing consensus in the respiratory community that a COPD diagnosis should not be based on spirometry alone.' To see whether adding CT imaging abnormalities and respiratory symptoms to the COPD diagnostic toolbox could improve the identification of patients at risk for poor outcomes, the investigators conducted a cohort study combining data from 9416 adults in the COPDGene cohort and 1341 participants in the CanCold cohort to derive and evaluate the new schema and test associations with clinical outcomes. The proposed system includes the major criterion of the presence of airflow obstruction based on a postbronchodilator FEV1/FVC ratio < 0.70, plus either 1 of 5 minor diagnostic criteria (emphysema or bronchial wall thickening on CT, dyspnea, poor respiratory quality of life, and chronic bronchitis) or, for patients who have respiratory symptoms that could potentially be due to other causes, at least 3 of 5 minor criteria, with the obligatory inclusion of emphysema or bronchial wall thickening. Among 5250 patients without airflow obstruction in the COPDGene cohort, 811 were reclassified according to the new system as having COPD by minor diagnostic category. Conversely, of 4166 with airflow obstruction, the new system determined that 282 patients did not have COPD. Compared with patients classified under the new system as not having COPD, those patients who were reclassified with a new COPD diagnosis had significantly higher risks for all-cause mortality (adjusted hazard ratio [aHR], 1.98; P < .001), respiratory-specific mortality (aHR, 3.58; P = .003), more exacerbations (adjusted incidence rate ratio, 2.09; P < .001), and more rapid decline in FEV1 (adjusted β = −7.7 mL; P = .006). Among patients who were deemed to have airflow obstruction on spirometry, those who were reclassified under the new system as not having COPD had clinical outcomes similar to those of patients without airflow obstruction. When the new criteria were applied to 1341 adults in the CanCOLD cohort, the investigators found that those patients who were newly classified as having COPD had a twofold risk for more frequent exacerbations (adjusted incidence rate ratio, 2.09; P < .001). 'Groundbreaking' 'What truly sets this reclassification apart is its groundbreaking assertion that airflow obstruction is no longer a requirement for a COPD diagnosis,' Polverino wrote in her editorial. 'Likewise, its presence alone does not automatically confirm the diagnosis. This shift acknowledges that many individuals have classic COPD-related pathology and symptoms without meeting the old spirometry thresholds. In cases in which patients present with comorbidities that could plausibly explain symptoms better than COPD itself, the model suggests that at least 2 of the 3 minor criteria should be imaging-based to support a COPD diagnosis,' she added. The study was funded by the National Institutes of Health (NIH). Bhatt reported receiving grants from NIH during the conduct of the study and consulting fees from multiple entities, including Medscape Medical News. Polverino disclosed serving on multiple advisory boards, as a spokesperson for the American Lung Association, grants from Sanofi and Regeneron, and serving as a section editor for the European Respiratory Journal .
