CE
Pharmacists: 1.00 contact hour (0.1 CEUs)
Released: January 29, 2024
Expiration: January 28, 2025
Monitoring and Follow-up of COPD
Anytime you see a patient with COPD, there are several things to consider. Certainly, pharmacologic therapy should be assessed and adjusted if warranted. HCPs also should consider nonpharmacologic therapy.1 Is the patient continuing to smoke? If the patient is continuing to smoke, encouraging smoking cessation is paramount. Another question to ask is, what is the patient’s degree of physical activity? HCPs should always refer our patients for pulmonary rehabilitation because of its benefit in those with COPD.
Other factors to consider are: Does the patient live at home? Does the patient need and does he or she have access to supplemental oxygen therapy? Is the patient up to date on recommended immunizations? Are the patient’s concomitant conditions well controlled? GOLD has done a good job recently of addressing comorbidities in patients with COPD, both physical, such as cardiovascular disease, and mental, such as depression and anxiety.1 It is crucial that HCPs recognize the need to manage those comorbidities.
Another question to ask is whether a patient has had spirometry performed recently. It is important that patients with COPD also have spirometry performed periodically.1 Fewer than 30% of patients with COPD have a spirometry-confirmed diagnosis.37 If pharmacists are properly trained and have the requisite resources, spirometry is something they can perform and for which they can bill. Alternatively, HCPs could refer patients to a pulmonologist. Patients should have spirometry from their initial diagnosis but also should have it done annually as part of their assessment and disease management.
Lastly, when patients come to you, you should always review their symptoms, specifically related to dyspnea.1 You should talk to them about any worsening symptoms and review their EHR for exacerbations, whether they have received corticosteroids and/or antibiotics, or whether they have been hospitalized for events related to COPD. You should assess access and adherence to therapy and inhaler technique, which is something pharmacists are uniquely equipped and situated to do. With all these factors considered, you can then adjust their regimen accordingly.1
Treatment of Patients With Persistent Dyspnea
GOLD now recognizes 2 treatable traits, or phenotypes.1 These include persistent dyspnea and frequent exacerbations. The report provides an algorithm for follow-up management for each treatable trait.
In patients with persistent dyspnea despite monotherapy with a long-acting bronchodilator, preferably a LAMA, you should first determine if they are optimally adhering to therapy.1 Once that is confirmed, you can escalate to a combination of LAMA/LABA. If you follow up with that patient and they voice and demonstrate adherence and have documented adherence to LAMA/LABA therapy but still have persistent dyspnea, you should consider switching their device or molecule. Escalating them to an ICS or triple therapy may not be warranted at this point, as they may not have a significant degree of eosinophilic-driven inflammation. You also should investigate and treat other causes and comorbidities.
Treatment of Patients With Consistent Exacerbations
For the treatable trait of persistent or frequent exacerbators, if a patient comes to you and they are receiving monotherapy, preferably a LAMA vs a LABA, you should assess their eosinophil count.1 If it is less than 300 cells/µL, which is a GOLD-specified and literature-dictated cutoff, you should escalate from monotherapy to a combination of a LAMA/LABA.
If the patient is receiving monotherapy and their serum eosinophil count is greater than 300 cells/µL, then you could consider escalating that patient to triple therapy.1 This is defined as a LAMA and LABA in combination, plus the ICS. If the patient is receiving dual bronchodilator therapy, the serum eosinophil threshold for adding an ICS is equal to or greater than 100 cells/µL. If it is less than 100 cells/µL, you may bypass the ICS.
It is important to point out that the mechanism of action of an ICS is decreasing eosinophilic-driven inflammation, and we know COPD to be associated with neutrophilic-driven inflammation.38 So, patients without a significant degree of—or an indication of—eosinophilic-driven inflammation will not benefit from ICS use. In these patients, the risks associated with this treatment most likely outweigh the benefits.
If a patient is receiving a LAMA/LABA in combination and their eosinophil count is less than 100 cells/µL, or they are receiving triple therapy and are continuing to experience exacerbations of COPD, you have a few options to consider. If the patient’s FEV1 is less than 50% and they fit the description of chronic bronchitis, you can use roflumilast.1 If they are a former smoker, you should consider prescribing chronic azithromycin. In the future, another option for these patients may be dupilumab. Recently, clinical trials showed that dupilumab improves symptoms and reduces exacerbations in these patients, although further trials are still needed to affirm these results before dupilumab can become widely used.39
ICSs: Withdrawal vs Continuation
As few as 3 years ago, approximately 50% to 60% of patients who were diagnosed with COPD were taking an ICS, although very few of them had an indication for one.40 On the left, you can see recommendations for considering withdrawal vs continuation of a prescribed ICS based on a patient’s serum eosinophil count and exacerbation/hospitalization history.41 There is limited evidence to guide ICS use as the number of annual exacerbations increases.42
Considerations of Pneumonia Risk
We do not frequently think about potential risks associated with inhaled medications, but there are certainly risks to ICSs, despite there being limited systemic exposure to the corticosteroid itself. 40 The biggest risk to patients who use ICSs is pneumonia. In reviewing the forest plot on the right, the data show a significant increase in cases of pneumonia when an ICS is used as a part of therapy for patients with COPD.43
Should You Include an ICS?
This slide depicts simplified criteria to consider when deciding whether to include an ICS in the care of a patient with COPD.1
In essence, an ICS should be included in treatment if a patient has a history of severe exacerbations and frequent exacerbations, defined as greater than 2 per year, and their blood eosinophil count is greater than 300 cells/µL, or if the patient has a history of asthma.1 This includes patients who receive an eventual diagnosis of COPD-A or who had a diagnosis at one point in time of asthma or ACOS, and uncontrolled or poorly controlled pediatric or childhood asthma or adult asthma.
The simplified criteria also indicate that you could consider ICSs if the patient has had 1 moderate exacerbation per year that did not require hospitalization. I would dare say that ICSs also should be considered for patients with 1 severe exacerbation per year that required hospitalization and a blood eosinophil count of greater than 100 cells/µL but less than 300 cells/µL, as spelled out by previously published literature.1
Lastly, patients do not need and will not benefit from an ICS if they have recurrent pneumonia; if they have no indication of eosinophilic-driven inflammation, defined as blood eosinophils of less than 100 cells/µL; or if they have a history of mycobacterial infection.1
Dupilumab: Investigational Agent
Dupilumab, an IL-4/IL-13 inhibitor that blocks many aspects of type 2 inflammation, currently is classified as investigational for COPD.39 It is being studied for the treatable trait of frequent exacerbation.
Although investigational, dupilumab is a well-known agent, as it is FDA-approved for the treatment of atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, prurigo nodularis, and eosinophilic esophagitis. Recently, the phase III BOREAS study was conducted in patients with COPD who were active or former smokers.39 Patients with chronic bronchitis, 2 moderate or 1 severe exacerbation, and a serum eosinophil level of 300 cells/µL or more were included. Of note, treatment with dupilumab was associated with reduced rates of moderate to severe exacerbation rates vs placebo. These results strongly support FDA approval of dupilumab for treatment of COPD.
Other Agents on the Horizon
Dupilumab is likely to be the first biologic approved for the treatment of COPD, but it is not the only novel agent in the pipeline. If you look at other agents on the horizon for the treatment of COPD, a number are likely to gain approval soon. Ensifentrine is a PDE3/PDE4 inhibitor—a novel mechanism of action in the treatment of COPD—that may be approved as early as 2024.44 Mepolizumab and benralizumab are anti–IL-5 biologics that have been mentioned in GOLD 2024 specifically, although there have been inconsistent results with phase III studies for these agents, with a trend toward a lack of benefit for most patients with COPD.1,45,46 However, there may be some nuance or niche where they exist in the treatment of these patients. In addition, several genetic therapies are targeting α-1 antitrypsin deficiency in their early stages.47
Billy, a 66-Year-Old Man
Back to our patient Billy: As a reminder, he is a 66-year-old male with known COPD who had a recent hospitalization for an exacerbation. His FEV1 as obtained last year was 40% predicted. His blood eosinophil level is not significantly elevated, and he is currently being treated with a LABA/LAMA fixed-dose inhaler.
The first question I would ask is related to his adherence to the LABA/LAMA. I would ask him: Are you taking it? Are you taking it consistently? Are there any issues or barriers to your obtaining your LABA/LAMA? Typically, the biggest hurdle or barrier to care for most patients is the out-of-pocket cost of inhalers because most of them are still a brand and not generic.
If he voices adherence, I also would ask questions to get more information about whether he is fully adherent to his treatment regimen. I would ask him to walk me through how he uses his inhaler, specifically his inspiratory maneuver. I would use the teach-back method. Some questions I would ask include: What inhaler do you use? Can you talk me through the steps of how you use it?
I would then ask him to demonstrate his inspiratory maneuver using the In-Check DIAL G16 device, or something similar, to assess his technique and make sure that it is correctly paired to the device from which he is receiving the LABA/LAMA.
Treating Billy: Considerations for Patients With Consistent Exacerbations
Billy is already receiving a LABA/LAMA combination, so you can start at the second step of this treatment algorithm.1
Although he has just had an exacerbation and he usually has 1-2 exacerbations per year, I do not think that he is a good candidate for an ICS.
Treating Billy: Considerations for Patients With Consistent Exacerbations
His blood eosinophils are below 100 cells/µL, which would suggest that an ICS is not the best option for escalation.1
You can then move on to consider if he is a good candidate for another adjunct agent, such as roflumilast, azithromycin, or even dupilumab.
Treating Billy: Considerations for Patients With Consistent Exacerbations
Billy’s FEV1 is only 40% predicted, and he has a history of chronic bronchitis. According to the treatment algorithm, roflumilast may be a good option to consider next for him.1 To be thorough, you should consider whether he is a candidate for the other options, as well.
Treating Billy: Considerations for Patients With Consistent Exacerbations
Billy is a current smoker, so counseling him to cease smoking and considering varenicline are paramount for him.1
The singular best thing you can do for any patient with COPD who continues to smoke is help them stop smoking.
Treating Billy: Considerations for Patients With Consistent Exacerbations
Because Billy is a current smoker as opposed to a former smoker and azithromycin is preferably used in former smokers, roflumilast still would be the preferred option.1 Because the data for use of dupilumab in COPD are still limited and there are other viable options for treatment escalation in this case, you should avoid that option at this time.
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