ERS 2024: Remission in COPD, Is It Feasible?
Speaker: Dave Singh
Personalized medicine seeks to enhance treatment outcomes through tailored strategies for individual patients. In chronic obstructive pulmonary disease (COPD), the feasibility of achieving remission necessitates precise definitions of key terms such as "remission," "stability," and "disease activity."
To establish a consistent framework, examining definitions used in other chronic conditions, such as rheumatoid arthritis (RA) and multiple sclerosis, is essential. RA treatment guidelines, as outlined in both European and American recommendations, start with non-biological therapies, including corticosteroids and methotrexate, with a re-evaluation at three to six months. If remission is not achieved, biologics are introduced. Remission in RA is characterized by the absence of swelling or tender joints, a C-reactive protein (CRP) level below 1 mg/L, and the patient’s overall well-being. "Low disease activity" refers to reduced symptoms rather than a complete absence. Applying these definitions to COPD involves determining if similar criteria for remission can be established. While COPD does not traditionally use the term "remission," concepts of stability and controlled disease activity can be adapted to this condition. Defining treatment goals and evaluating responses in both responders and non-responders can provide insights into the potential for achieving remission or equivalent outcomes in COPD.
The success of treatment strategies in chronic diseases such as COPD and asthma can be attributed to the implementation of earlier treatment interventions. This approach aims to prevent damage and long-term disability, which has been a key factor in improving patient outcomes. In contrast, current practices often allow for flare-ups and high disease burden before adjusting treatment, a standard that is not followed in disciplines like rheumatology. Rheumatologists have demonstrated success by initiating earlier treatment and striving for remission, utilizing disease-modifying drugs and biologics, and frequently employing combination therapies. This proactive approach to achieving remission serves as a model for COPD management, highlighting the need for similar strategies in obstructive lung diseases.
In multiple sclerosis (MS), a disease often diagnosed with significant delays, the treatment goal has evolved to "no evidence of disease activity" (NEDA). This includes the absence of disability progression, objective measurements from magnetic resonance imaging (MRI), and no clinical relapses. The concept of NEDA allows for a degree of pathology and symptoms but emphasizes that disease progression should not worsen. This approach offers a valuable parallel for COPD, suggesting that targets such as no worsening of symptoms, no progression in objective measures like forced expiratory volume in 1 second (FEV1) or computed tomography (CT) imaging, and no exacerbations could be adopted. According to a study evaluating the efficacy, safety, and patient-reported outcomes in patients with active relapsing multiple sclerosis treated with Ocrelizumab, 247 out of 422 patients (58.5%) achieved NEDA at week 48. This proportion was higher in secondary progressive multiple sclerosis (SPMS) patients.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations for COPD treatment focus on symptom improvement, disease progression prevention, exacerbation reduction, and mortality reduction. Despite these goals, there is a tendency toward pessimism regarding the achievable outcomes. This perspective could shift with the adoption of clearly defined treatment targets, which could enhance clinical practice and patient management. Understanding the interplay between disease activity, progression, and symptoms is crucial. For instance, ongoing smoking can accelerate disease progression, making smoking cessation a fundamental intervention to slow down disease progression. By defining and targeting specific goals, it is possible to improve practice standards and patient conversations, ultimately enhancing disease management and outcomes.
In COPD, disease progression is a key factor leading to damage, which is often referred to as severity. Once a high level of damage is established, persistent symptoms and an inability to achieve remission become common. Thus, early intervention to prevent progression and damage is crucial. Symptoms arise from both the extent of damage and the current level of disease activity. Therefore, the focus should be on managing disease activity to prevent further severity, rather than solely addressing severity itself. Unlike in rheumatoid arthritis, where objective biomarkers like CRP are available to gauge disease activity, COPD lacks a similar objective biomarker. Currently, the number of exacerbations serves as a clinical marker of disease activity. Traditional definitions that consider two exacerbations as indicative of disease activity are insufficient. Even a single exacerbation is associated with worse outcomes, including increased mortality. Therefore, the optimal target should be to achieve zero exacerbations.
In managing COPD, improvement in symptoms is often the primary goal. However, once a patient reaches their personal best, the treatment target should shift towards maintaining that optimal state and preventing any further deterioration. This approach mirrors the strategy used in multiple sclerosis, where the aim is to prevent worsening rather than simply addressing existing symptoms. Patients often value the goal of maintaining their current level of functioning and avoiding hospitalizations. This shift in treatment targets can lead to more meaningful outcomes for patients, such as maintaining their ability to engage in daily activities and social functions. Data from recent studies underscore that achieving low disease activity is feasible. For instance, in clinical trials, over half of patients using standard inhalers experienced no exacerbations over a year. Similarly, studies involving biological therapies demonstrate that a significant proportion of patients on triple therapy with a placebo biological agent achieved the same outcome. These findings suggest that with proper management and adherence to treatment, maintaining low disease activity is achievable for many patients with COPD.
In randomized controlled trials, maintaining lung function stability over the short term is a significant challenge, particularly given the progressive nature of COPD. For instance, dupilumab has shown that patients in both treatment arms generally maintained stable lung function over a year. In the IMPACT (Informing the Pathway of COPD Treatment) study, a decrease in lung function was associated with poorer quality of life. Conversely, patients who maintained stable lung function experienced substantial improvements in quality of life. Comparing to other diseases, such as multiple sclerosis and rheumatoid arthritis, achieving low disease activity coupled with low symptoms aligns with the concept of remission. The term “immune remission,” introduced by Celeste, also holds value, especially if patients experience some symptoms but still achieve significant disease control.
Currently, the treatment of COPD allows for the possibility of achieving periods without symptom worsening, no FEV1 decline, and no exacerbations. This level of control, termed stable COPD, reflects a shared treatment goal and a more optimistic outlook than traditionally considered. To reach remission, earlier diagnosis and the use of emerging disease-modifying drugs, potentially in combination, will be crucial. Precision medicine approaches may eventually enable some patients with COPD to achieve remission.
European Respiratory Society Congress 2024, 7–11 September, Vienna, Austria.
