Advances in COPD Treatment: The Role of Biologics

A patient with COPD was struggling with two to three exacerbations per year, sometimes requiring hospitalization. Despite being on standard inhaled therapies, the patient remained highly symptomatic, experiencing shortness of breath even when engaging in routine chores around the house.

Since standard treatments had already been tried, Cleveland Clinic Pulmonologist Wajdy Abi-Saleh, MD, started the patient on dupilumab, a biologic therapy that targets the inflammatory pathways of COPD.

“Within a short time, the patient experienced symptomatic improvement; they felt better, and the exacerbation rate has been well controlled since then, with no exacerbations,” Dr. Abi-Saleh says.

Targeting inflammation with biologics

Even though COPD is preventable and treatable, many patients remain poorly controlled, with debilitating symptoms that lead to significant morbidity and mortality. For patients who continue to experience exacerbations with standard therapies, a new generation of biologic drugs can offer significant benefit, says Dr. Abi-Saleh, noting that even more new therapies are in the development pipeline.

Unlike standard therapies like bronchodilators that relieve obstructions to improve respiratory symptoms, biologics work by targeting the inflammatory pathways of COPD itself.

The primary goal is to reduce exacerbations. Dr. Abi-Saleh notes that, in addition to causing worsening symptoms, ER visits and hospital admissions, exacerbations can lead to long-term decline.

“When the patient’s lung function declines, it can take a long time to go back to their previous baseline, and sometimes they never do,” he says. “So, this is why reducing exacerbations has been such an important outcome for us to reach.”

The current landscape of biologics

Two biologics are currently approved for use in COPD, both for patients with type 2 inflammation.

Dupilumab (Dupixent) works by blocking IL-4 and IL-13, key drivers of the type 2 inflammatory pathway. It has been shown to reduce exacerbations, increase lung function, and improve quality of life.

Initial tests of mepolizumab (Nucala), a newer drug that blocks IL-5, initially failed to show efficacy in patients with COPD. However, when the study cohort was narrowed to COPD patients with type 2 inflammation, exacerbations were successfully reduced, Dr. Abi-Saleh says.

Both drugs have also been used to treat asthma, he noted.

Selecting patients appropriately

Providers should know that the ideal candidates for biologic drugs are patients who have already maximized standard inhaled therapies and are still having two, three, or more moderate-to-severe exacerbations per year. These patients are typically experiencing a high symptom burden despite treatment, and are compliant with medications, Dr. Abi-Saleh explains.

Providers should check eosinophil counts to identify patients with type 2 inflammation who could benefit from these therapies, he notes.

He adds that biologics are not appropriate as a first-line therapy, or for patients who haven’t exhausted standard treatment approaches.

“Some patients continue smoking, they don’t take their inhalers, or they have issues with reimbursement for their inhalers, so they put off the expensive ones and just use the reliever, unfortunately,” he says. “Those patients would not be a good candidate for a biologic agent.”

He notes that the Cleveland Clinic follows the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for patient stratification and a step-up approach to therapy.

More treatments in the pipeline

Dr. Abi-Saleh notes that there are more emerging COPD treatments in the pipeline. These include tezepelumab, an asthma drug that blocks the thymic stromal lymphopoietin (TSLP).

“That actually works further up and has even more downstream blockage of other interleukins than mepolizumab and dupilumab, including the IL-4, IL-5, and IL-13, which are all drivers of inflammation in asthma, but also in this type 2 inflammation COPD,” he says. “So that is potentially another agent that will be added to our armamentarium for COPD.”

Beyond biologics, research is also underway in other COPD treatments. He notes that Cleveland Clinic is participating in an ongoing multicenter study on a technique called airway scaffolding that works to decrease trapped air in patients with severe emphysema.

“There are multiple studies going on,” Dr. Abi-Saleh says. “So, the field is rapidly evolving, and we are looking forward to having more tools we can use to treat these patients.”