Updated GOLD Guidelines and Novel Therapeutic Approaches in the Management of Chronic Obstructive Pulmonary Disease

Introduction

Chronic obstructive pulmonary disease (COPD) remains a substantial contributor to morbidity and mortality in the United States with an estimated 3.8% age-adjusted prevalence and 141,733 COPD deaths among US adults in 2023.¹ Additionally, COPD causes considerable economic burden. Medical costs attributed to this disease in 2020 were projected to be $33.5 billion (2019 US$) and they are projected to increase 80% by the end of the decade.²

Consistent with its chronic, progressive nature, severe COPD tends to result in more use of health care resources and, subsequently, higher total medical costs and COPD-related expenditures.³ Despite the considerable burden of COPD in the US, problems persist in terms of accurate diagnosis,⁴ guideline-adherent treatment,^5,6 access to effective medical therapies,⁷ and coordinated management of comorbid conditions,⁸ all of which may contribute to suboptimal care for patients with COPD.

To facilitate more effective care, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) publishes an annual report each November for use by health care professionals worldwide as a guide to manage the care of patients with COPD.⁹ Indeed, compliance with GOLD guidelines is associated with less health care resource use, lower annual medical costs per patient, and fewer disease exacerbations.¹⁰ Despite this annual report, prescription rates for GOLD-compliant treatment regimens consistently account for only about one-third of interventions.¹⁰

To support the care of patients with COPD, this article summarizes updates in the 2025 GOLD guidelines (GOLD 2025), reviews recent data surrounding treatment options, and explores managed care considerations regarding these recent developments in COPD management.

Evolving Guidelines in the Management of COPD

GOLD 2025—the second edition of a major revision introduced in 2023— incorporates 15 “novel and important” updates.⁹ Among those considered most important by independent reviewers are an updated diagnostic approach, new methods for periodic assessment of patients with COPD, and callouts for novel pharmacologic therapies that include a first-in-class biologic medication and a nebulized PDE3/4 inhibitor, the first new class of medication for COPD in 30 years.¹¹

Revised Diagnostic and Assessment Approaches

The goal of an updated diagnostic approach for COPD is to facilitate disease diagnosis during earlier stages when treatment interventions may result in better clinical outcomes.⁹ In line with this guidance, GOLD 2025 emphasizes the importance of pre-bronchodilator spirometry, noting that a ratio of forced expiratory volume in 1 second to forced vital capacity that is less than 0.7 (FEV₁/FVC < 0.7) is highly indicative of COPD; a ratio of 0.7 or greater (FEV₁/FVC ≥ 0.7) is likely to rule out COPD.¹¹ The guidelines still require that a post-bronchodilator FEV₁/FVC < 0.7 be established to confirm a COPD diagnosis,⁹ but they emphasize the role of pre-bronchodilator spirometry as a less complicated and time-consuming diagnostic approach.¹¹ This simplification may benefit patients in the primary care setting, where primary care physicians and family medicine practitioners are disproportionally responsible for COPD diagnosis and treatment.¹² In this setting, some 40% of pulmonary function spirometry test results may be unacceptable.¹³ By emphasizing the importance of pre-bronchodilator spirometry, GOLD 2025 removes a complex, time-consuming testing requirement for practitioners most likely to initiate COPD care, enabling earlier diagnosis with fewer testing requirements. As an exception, pre- and post-bronchodilator spirometry are still recommended for the relatively few patients who may be at high-risk (eg, the few individuals who are volume responders [ie, have an increase in FVC after bronchodilation]). Post-bronchodilator increases to FVC may reverse FEV₁/FVC from ≥ 0.7 to <0.7 due to a higher value denominator in the ratio fraction.¹¹

While the FEV₁/FVC < 0.7 remains a mandatory diagnostic criterion for COPD,⁹ GOLD 2025 considers the utility of normalized z-score values of FEV₁/FVC as an individualized approach to assess each patient.¹¹ Such a shift would allow physicians and health care providers to consider whether patients’ respiratory testing falls below the lower limit of normal for their demographic characteristics and to individualize diagnostic assessments.⁹ This change could allow earlier diagnosis and more intense treatment of COPD in its early stages by reclassifying younger patients with more severe airway obstruction; reclassification of older patients into milder disease categories could also occur and have unknown clinical implications.¹¹

Other than changes to respiratory testing protocols, GOLD 2025 recommends taking advantage of incidental findings from respiratory imaging tests like low-dose chest CT (LDCT).⁹ Absent behavioral risk factors for COPD (eg, smoking), LDCT coupled with an accurate patient history of environmental, genetic, and developmental risk factors can enable earlier disease diagnosis.⁹ Moreover, such tests may reveal imaging evidence of emphysema, complex airways, or comorbidities helping providers identify patients at particularly high risk from COPD exacerbations.⁹

The major refinement to assessing and monitoring patients with COPD emphasizes an approach that began with the 2023 major revision. That report introduced a condensed symptom assessment tool leveraging 2 factors: patient exacerbation history and patient scores on symptom assessment tools like the modified Medical Research Council (mMRC) dyspnea scale and the COPD Assessment Test (CAT).The mMRC and CAT assessments are short, questionnaire-based tests that are clinically useful and well correlated with future mortality, alluding to their utility in primary care settings. Care providers should document the frequency, severity, type, and likely causes of exacerbations experienced by their patients with COPD, including unplanned/unscheduled health care visits or services (ie, critical care services, ventilation support).The resulting assessment tool is a simple, tripartite schema that groups patients into A, B, or E categories to guide initial pharmacologic intervention. Information on prior treatment responses may help to inform treatment approaches among patients with exacerbating COPD. Additionally, the questionnaire-based assessments may be used to monitor disease progression over time, since changes across testing sessions indicate progressively worsening respiratory health.⁹

Spirometry respiratory function tests are not required within the modified monitoring and assessment schema, but they are still recommended at least annually to identify patients with rapidly declining disease. The use of electronic telehealth services may help monitor the health of some patients with COPD. However, because data describing the patients most likely to benefit are insufficient and not studied long enough to allow endorsements backed by robust information, GOLD 2025 stops short of outright recommending such services.⁹

Personalized Treatment Selection in COPD

To prevent or reduce COPD symptoms, clinicians commonly prescribe bronchodilators for regular use; these include short-acting or long-acting muscarinic antagonists and β₂-agonists (SAMA/SABA or LAMA/LABA, respectively).Since short-acting bronchodilators are not recommended as maintenance therapy in patients with COPD, they will not be discussed further in this article. In contrast, long-acting bronchodilators are recommended for initial pharmacologic treatment and follow-up maintenance therapy.⁹

LAMAs block muscarinic acetylcholine receptors (mAchR), primarily of the M₃ subtype; expressed on airway smooth muscle cells, these receptors cause bronchoconstriction. Therefore, blocking M₃ mAchR causes bronchodilation. LABAs relax airway smooth muscle cells by activating β₂-adrenergic receptors and increasing cyclic adenosine monophosphate (cAMP). The functional effect of increased cAMP in airway smooth muscle is bronchodilation.⁹

Inhaled corticosteroids (ICSs) are a third class of medication commonly used in patients with COPD. ICS therapy targets COPD-mediated inflammation, but the precise mechanism is still debated. Regardless, ICSs benefit patients with COPD by improving lung function and reducing COPD exacerbation rates. Triple therapy involves use of a LAMA, a LABA, and an ICS.⁹

GOLD 2025 recommendations update the COPD treatment selection algorithm to collectively consider patients’ symptom burden, exacerbation history, blood eosinophil count (BEC), and possible comorbid conditions. Specifically, the algorithm calls for providers to initiate pharmacologic intervention according to the ABE assessment schema and to escalate treatment following an algorithm that accounts for dyspnea symptoms and exacerbations. Patients in group A, who have the lowest symptom burden and a limited history of COPD exacerbations, may begin treatment with any single bronchodilator (LAMA or LABA). Patients in group Bhave a limited exacerbation history and an increased symptom burden, which calls for starting dual therapy with a LAMA and a LABA, preferably in a single inhaler. Group E patients may or may not have a high symptom burden, but they have an extensive history of past-year exacerbations and exacerbations leading to hospitalizations that calls for initiation of more intensive dual treatment (a LAMA and a LABA); triple therapy is indicated if the BEC is at least 300 cells/μL.⁹

Despite treatment with the maximum dose of recommended triple therapy, some 14.8% of patients continue to experience exacerbations.¹⁴ Likewise, persistent dyspnea has been reported in 23% to 57% of patients on single or dual bronchodilators or triple therapy.¹⁵ For these patients, GOLD 2025 highlights ensifentrine and dupilumab as medications that may be added to current pharmacologic regimens for patients with persistent dyspnea or exacerbations, respectively. ⁹ Ensifentrine is a PDE3/4i indicated for the maintenance treatment of adult patients with COPD.¹⁶ Dupilumab is an antagonist of the interleukin-4 (IL-4) receptor α subunit that isindicated for add-on maintenance treatment of adults with inadequately controlled COPD and an eosinophilic phenotype.¹⁷ After the publication of GOLD 2025, mepolizumab—an IL-5 antagonist monoclonal antibody—also gained an indication as add-on maintenance therapy to treat adults with inadequately controlled COPD and an eosinophilic phenotype.¹⁸

The inhibition of PDE3/4 by ensifentrine allows for intracellular accumulation of cAMP and cyclic guanosine monophosphate,¹⁶ resulting in bronchodilation from the relaxation of airway smooth muscle in addition to anti-inflammatory activity.⁹ Investigators studied ensifentrine’s safety and efficacy in two 24-week, phase 3, multicenter clinical trials (ENHANCE-1 [NCT04535986] and ENHANCE-2[NCT04542057]).¹⁹ Participants included patients aged 40 to 80 years with physician-diagnosed COPD; whose post-bronchodilator FEV₁ was between 30% and 70% of predicted normal, FEV₁/FVC was less than 0.7, mMRC dyspnea scale scores were 2 or greater; and who had an extensive smoking history.¹⁹ Patients could be maintained on a LABA or LAMA with or without ICS, but exclusion criteria disqualified patients on LAMA/LABA combinations or triple therapy; starting or stopping new COPD maintenance therapies was not permitted unless medically necessary, and patients with asthma were also excluded.¹⁹ The primary efficacy end point was the mean FEV₁ area under the curve from time 0 to 12 hours (AUC_{0-12 h}) to assess bronchodilation in the 12 hours after treatment.¹⁹

In both trials, ensifentrine was associated with improvements in the mean FEV₁ AUC_{0-12 h} from baseline to week 12; compared with those given placebo, patients treated with ensifentrine exhibited mean improvements of 87 mL (95% CI, 55-119 mL) and 94 mL (95% CI, 65-124 mL) in ENHANCE-1 and -2, respectively (P < .001).¹⁹ Secondary efficacy outcomes that were significant across both trials included improvement to week 12 peak FEV₁ for ensifentrine versus placebo (ENHANCE-1,147mL [95% CI,111-183 mL]; ENHANCE-2, 146 mL [95% CI, 113-179 mL]; P < .001), an effect that was sustained through week 24.¹⁹ In addition, dyspnea symptoms as measured by the transition dyspnea index at week 24 also were improved for ensifentrine as compared with placebo (ENHANCE-1, 1.0 [95% CI, 0.6-1.5]; ENHANCE-2, 0.9 [95% CI, 0.4-1.4]; P < .001).¹⁹ As measured at 24 weeks, the annualized rate of moderate or severe COPD exacerbations among patients given ensifentrine was reduced by 36% and 44% in ENHANCE-1 and -2, respectively (24-week rate ratio [RR]: ENHANCE-1, 0.64 [95% CI, 0.40-1.00, P = .050];ENHANCE-2: 0.57 [95% CI, 0.38-0.87; P = .009)¹⁹, although the trial population was not enriched to examine exacerbation risk.⁹ In a post hoc subgroup analysis of patients who were on a LABA or a LAMA plus an ICS during the ENHANCE trials, patients exhibited improvements in lung function that were similar to those of the full trial population when they used ensifentrine as an addition to background maintenance therapy.²⁰ Likewise, ensifentrine use over a background of LABA plus ICS resulted in improved lung function relative to placebo over the same background.²¹ Per safety assessments, adverse events (AEs) that occurred in the ENHANCE-1 and -2 trials in more than 1% of patients and that were more common among patients in the ensifentrine arm than the placebo arm included back pain (1.8% vs 1.0%), hypertension (1.7% vs 0.9%), urinary tract infections (UTIs) (1.3% vs 1.0%), and diarrhea (1.0% vs 0.7%).¹⁶ Based on these efficacy and safety assessments, the GOLD guidelines position ensifentrine as a potential addition for patients who exhibit persistent dyspnea despite dual long-acting bronchodilator therapy.⁹

Dupilumab inhibits inflammation driven by IL-4 and IL-13;¹⁷ it was the subject of the BOREAS (NCT03930732) and NOTUS (NCT04456673) clinical trials that investigated dupilumab as an addition to standard inhaled triple therapy.^22,23 General eligibility criteria were almost identical to those of the ENHANCE-1 and -2 trials.^22,23 Additionally, maintenance treatment with standard inhaled triple therapy was required, participants had to have a BEC of at least 300 cells/μL, and patients’ medical history had to include exacerbations in the year before trial enrollment; patients with asthma or an asthmatic history were excluded. ^22,23 The primary efficacy end point was the annualized rate of moderate or severe COPD exacerbations.^22,23

In both the BOREAS and NOTUS trials, participants who took dupilumab (300 mg subcutaneously [SC] once every 2 weeks) had a significantly lower annualized rate of moderate or severe exacerbations compared with participants who took placebo (RR: BOREAS, 0.70 [95% CI, 0.58-0.86]; NOTUS, 0.66 [95% CI, 0.54-0.82]; P < .001 for both).^22,23 Additionally, dupilumab use was associated with sustained improvements in mean FEV₁ measures of lung function and patient-reported outcomes.^22,23 In terms of safety, participants generally tolerated dupilumab well with similar rates of AEs reported in both the dupilumab and placebo groups.^22,23 More common AEs among patients treated with dupilumab compared to those given placebo included viral infections (14.2% vs 12.3%, respectively), headache (7.8% vs 6.6%), nasopharyngitis (7.8% vs 7.4%), back pain (4.5% vs 3.1%), diarrhea (3.7% vs 3.2%), arthralgia/joint pain (3.1% vs 2.7%), UTIs (3.0% vs 1.9%), administration reactions (2.8% vs 0.6%) including injection-site reactions (1.2% vs 0.2%), rhinitis (2.6% vs 1.8%), eosinophilia (defined as BEC > 3000 cells/μL; 2.3% vs 0.7%), toothache (2.1% vs 1.2%), and gastritis (2% vs 0.7%).¹⁷

Because the timing of the BOREAS and NOTUS trials coincided with the COVID-19 pandemic,^22,23 up-front results failed to compare mortality and disease progression rates between the dupilumab and placebo groups.²⁴ Results of a subsequent long-term effectiveness study indicated that dupilumab was associated with a lower risk of all-cause mortality (HR, 0.53; 95% CI, 0.43-0.65), emergency department visits (HR, 0.78; 95% CI, 0.69-0.89), AEs (HR, 0.59; 95% CI, 0.53-0.65), new-onset pneumonia (HR, 0.65; 95% CI, 0.50-0.86), and new-onset acute respiratory failure (HR, 0.57; 95% CI, 0.44-0.73); dupilumab also significantly reduced development of new-onset acute respiratory distress syndrome (HR, 0.36; 95% CI, 0.22-0.58).²⁵ Moreover, patients who initiated dupilumab reported fewer respiratory conditions and required fewer uses of rescue inhalers including SABA (HR, 0.48; 95% CI, 0.43-0.52), SAMA (HR, 0.43; 95% CI, 0.37-0.49), and mucolytic agents (HR, 0.63; 95% CI, 0.43-0.92).²⁵Comorbidities like new-onset heart failure (HR, 0.69; 95% CI, 0.53-0.90) or anxiety (HR, 0.70; 95% CI, 0.53-0.93) were reduced among patients who started using dupilumab.²⁴ Finally, patients who began using dupilumab exhibited a lower subsequent incidence of BEC of at least 100 cells/μL (HR, 0.67; 95% CI, 0.50-0.89).²⁴ Altogether, initial safety and efficacy assessments plus long-term follow-up data resulted in the GOLD 2025 recommendation that dupilumab may be added to standard-of-care triple therapy in patients with refractory COPD exacerbations whose BEC is equal to or exceeds 300 cells/μL.⁹

Although not approved in time for a callout in the GOLD 2025 update, mepolizumab has an indication identical to that of dupilumab as add-on maintenance treatment for adult patients with inadequately controlled COPD and an eosinophilic phenotype.¹⁸ An antibody antagonist of IL-5, mepolizumab reduces production and survival of eosinophils presumably controlling IL-5 mediated cellular inflammation.¹⁸ The METREX (NCT02105948) and METREO (NCT02105961) clinical trials were the initial studies investigating mepolizumab for COPD, but a statistical analysis of the primary efficacy outcome yielded mixed results. In METREX, which included patients with or without an eosinophilic phenotype,²⁶ mepolizumab (100 mg SC once every 2 weeks) was associated with a reduced mean annualized rate of moderate or severe exacerbations (RR, 0.82; 95% CI, 0.68-0.98, P = .04) but only among patients with an eosinophilic phenotype. METREO included only patients with an eosinophilic phenotype and featured a dose comparison of 100 mg or 300 mg, but rate reductions along the primary efficacy end point did not reach statistical significance compared to findings in patients treated with placebo (100 mg: RR, 0.80 [95% CI, 0.65-0.98], P = .07; 300 mg: RR, 0.86 [95% CI, 0.70-1.05], P = .14).²⁶

More recently, the MATINEE clinical trial (NCT04133909) investigated mepolizumab (100 mg SC once every 4 weeks) among patients with COPD who had an eosinophilic phenotype (BEC ≥ 300 cells/μL) and who were receiving triple therapy at the time of enrollment.²⁷ As in the BOREAS and NOTUS trials of dupilumab, mepolizumab treatment resulted in a reduced mean annualized rate of moderate or severe exacerbations compared to placebo (RR, 0.79, 95% CI, 0.66-0.94; P = .01).²⁷ Across all 3 mepolizumab trials, AEs that occurred more commonly in the mepolizumab treatment group than in the placebo group included back pain (7% vs 6%, respectively), diarrhea (5% vs 4%), cough (5% vs 4%), oropharyngeal pain (4% vs 2%), UTIs (4% vs 3%), and pain in the extremities (4% vs 3%).¹⁸ Otherwise, patients generally tolerated mepolizumab well, and reports of other AEs or death during and after the trial period were similar between the mepolizumab and placebo groups.²⁷ The main differences ineligibility criteria between the MATINEE trial and studies of dupilumab were a slightly broader range in the post-bronchodilator FEV₁ relative to the predicted normal values and no upper age limit in the MANITEE trial.^22,23,27 Systematic comparisons of the clinical trial populations enrolled to investigate mepolizumab or dupilumab are not otherwise available. Therefore, since the drugs exhibited similar efficacy in reducing rates of moderate or severe COPD exacerbations, the positioning of mepolizumab within the recommended COPD treatment algorithm in future updates to the GOLD Report may offer another viable treatment option.

Beyond pharmacologic management of COPD and the new medication callouts, GOLD 2025 updated several nonpharmacologic approaches to manage the disease. Specifically, it aligns the recommended vaccine schedule with guidance from the Centers for Disease Control and Prevention. This schedule includes vaccines against infections caused by influenza, SARS-CoV-2, Streptococcus pneumoniae, and respiratory syncytial virus; a vaccine against tetanus, diphtheria, and pertussis for patients not vaccinated as adolescents; and a herpes zoster vaccine to protect against shingles. Lifestyle changes like smoking cessation continue to be recommended for all patients with COPD who continue to smoke.⁹

Aligning Payer and Provider Efforts for Optimal Access

With novel medication options available to care for patients with COPD come new considerations of cost and access to ensure that the maximal proportion of patients who could benefit from these new medications receive them. For instance, ensifentrine requires a nebulizer for medication delivery.¹⁶ Nebulizers are typically covered by US payers under durable medical equipment benefits, but nebulizer cleaning kits and maintenance equipment generally are not covered,²⁸ potentially adding an out-of-pocket financial barrier.

Ensifentrine is an expensive medication with an anticipated annual price of $35,400 ($2950/month).²⁹ Independent analysis by the Institute for Clinical and Economic Review placed the incremental cost effectiveness ratio (ICER) of ensifentrine at $492,000 per quality adjusted life year (QALY) gained and $426,000 per equal-value life year gained,²⁹ far exceeding typical ICER thresholds of $50,000 to $200,000 per QALY.³⁰ This high cost could limit uptake of ensifentrine to as few as 0.5% of US patients with COPD in a 5-year period.²⁹ Of note,23% to 57% of patients with COPD experience persistent dyspnea despite single or dual bronchodilator therapy or triple therapy.³¹ Since GOLD 2025 guidance positions ensifentrine as a potential added treatment option for patients experiencing persistent dyspnea despite bronchodilator therapy,⁹ a high cost barrier along with considerations regarding route of administration may hinder uptake of the medication as recommended. Indeed, ICER’s analysis of ensifentrine resulted in an affordability and access alert.²⁹

Cost and access considerations for dupilumab and mepolizumab are slightly more complex, since independent agencies and researchers have not analyzed the costs of these medications for their COPD indications. As an alternative, a direct cost comparison of these medications to treat patients with severe asthma is available. (NOTE: Dupilumab and mepolizumab have identical indications for asthma and separate but identical indications for COPD. The asthma and COPD indications specify an eosinophilic phenotype, yet asthma and COPD are not equivalent disease states.^17,18) Overall, the cost comparison found that medication costs for dupilumab and mepolizumab per patient over a 2-year period amounted to $78,908 and $81,021, respectively, and over a 4-year period amounted to $156,222 and $162,041, respectively.³² Accounting for cost offsets due to reduced use of nonbiologic medications, estimated total health care costs for patients treated with dupilumab were $50,197 in a 2-year period and $97,223 in a 4-year period. Applying the same accounting offsets to patients treated with mepolizumab, 2- and 4-year estimated total health care costs amounted to $53,408 and $105,599, respectively.³² The dosing strategy for mepolizumab is the same for both its asthma and COPD indications¹⁸;dupilumab, however, has a more variable dosing strategy for asthma than for COPD.¹⁷ Therefore, while this cost comparison relative to severe asthma may be informative in an anticipatory sense, full independent cost-effectiveness analyses of dupilumab and mepolizumab relative to their COPD indications remain necessary.

Cost-analyses notwithstanding, payer policies and restrictions (eg, prior authorizations, formulary changes, and step therapy) may also impose barriers for patients with COPD seeking access to new medications, even if their disease phenotype aligns well with GOLD guideline recommendations. For example, the results of 1 study found that Medicare Part D prescription drug plans were more likely than standalone prescription drug plans to impose prior authorization requirements to cover guideline-directed COPD medications,³³ potentially slowing access to needed therapies. Regarding formulary changes, a different study examined clinical outcomes among veterans forced to switch from a budesonide-formoterol metered dose inhaler to a fluticasone-salmeterol dry-powder inhaler following a change to the national formulary for the Veterans Health Administration; results of the primary analysis indicated increased rates of emergency care and hospitalizations after patients switched medications. Subgroup analyses similarly revealed adverse outcomes associated with the inhaler switch in the subsample (69%) of veterans in this study who had been diagnosed with COPD.³⁴ Step therapy seems an uncommon payer restriction affecting less than 4% of inhalers across all guideline-directed therapeutic categories³³ despite GOLD 2025 issuing a strategic treatment algorithm that guides escalations while accounting for patient symptoms and exacerbation history.⁹

Such restrictions may influence access and continuity of care, thus strategies that promote collaborative, shared decision-making among key stakeholders and that may support optimal patient outcomes are essential. Of that ilk, value-based contracting is an approach that reimburses health care providers and health systems based on patient outcomes, which may reduce the impact of chronic conditions like COPD.³⁵ Another strategy is managing health care with coordinated care teams and patient education, which are central for ensuring medication adherence, appropriate use, and effective disease management. Regularly assessing patients’ conditions, including checks on inhaler technique and reinforcing adherence to prescribed medications, is emphasized by GOLD 2025 as a practical step that supports treatment effectiveness and helps optimize outcomes in routine practice.⁹

Conclusions

GOLD 2025 introduced several important updates regarding the diagnosis, treatment, and monitoring of patients with COPD. These include an updated diagnostic approach,¹¹ new pharmacologic recommendations, and refinements for monitoring protocols that optimize ongoing management.⁹ Notably, GOLD 2025 recognizes ensifentrine and dupilumab as therapies that may be added to standard interventions to address persistent dyspnea symptoms and reduce the frequency of exacerbations, respectively;⁹ mepolizumab is also indicated for patients with COPD and an eosinophilic phenotype.¹⁸

These additions expand the therapeutic landscape, yet questions regarding their economic value remain. Ensifentrine is currently the only new therapy scrutinized in a US-based cost-effectiveness analysis, which demonstrated ICER values exceeding typical thresholds.²⁹ Similarly, biologics such as mepolizumab and dupilumab carry high up-front costs that may hinder patient access.³² Innovative reimbursement models, including value-based contracting, may help address affordability concerns and align payment with patient outcomes.³⁵ Beyond cost, successful therapeutic integration depends upon ensuring that patients are appropriately trained and supported by prescribers and care teams to optimize adherence, dosing, and administration.⁹ Collectively, these considerations highlight the promise of new COPD therapies while stressing the need for thoughtful implementation strategies to ensure access and improve outcomes.

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