New data for the use of patient-reported outcomes (PRO) in patients with mycobacterium avium complex lung disease (MACLD) and two monoclonal antibodies in the treatment of chronic obstructive lung disease (COPD) were presented during Monday’s Clinical Trials Symposium at the ATS 2024 International Conference. The symposium highlighted novel trial results with the potential for great clinical impact.

QOL-B RD Validated for Assessing Respiratory Symptoms in Patients with MACLD

Charles L. Daley, MD, professor of medicine and chief of the division of mycobacterial and respiratory infections at National Jewish Health and professor of medicine-pulmonary sciences & critical care at the University of Colorado School of Medicine, presented results from the ARISE study, a randomized, double-blind trial to evaluate the quality of life-bronchiectasis questionnaire respiratory domain (QOL-B RD) in patients with MACLD.

“There are no validated PRO instruments to evaluate symptoms in patients with MACLD,” said Dr. Daley. “We know that respiratory symptoms and fatigue are most important to patients. These are covered in current instruments like the QOL-B RD.”

Adult patients with new or recurrent MACLD were randomized to receive either amikacin liposome inhalation suspension (ALIS) or placebo for six months. Patients in both groups also received azithromycin and ethambutol.

QOL-B RD showed strong reliability, validity, and responsiveness to assessing respiratory symptoms. The study identified 14.8 points as the threshold for meaningful symptom improvement.

Based on this threshold, 43.8 percent of patients in the ALIS group and 33.3 percent of patients in the comparator group achieved a meaningful improvement in symptoms after seven months. Patients in the ALIS group also had numerically greater rates of culture conversion.

Phase 2a COURSE Study of Tezepelumab in COPD Shows Increased Benefit in Those With High Baseline BEC

Dave Singh, MD, professor of respiratory pharmacology at the University of Manchester, presented the results of the COURSE trial, a Phase 2a study of tezepelumab in adults with moderate-to-very-severe COPD who had two or more exacerbations in the previous 12 months despite receiving stable triple inhaled therapy.

Patients were randomized to receive tezepelumab with triple therapy or triple therapy alone for 52 weeks.

Tezepelumab resulted in a nonsignificant 17 percent reduction in the annualized rate of moderate or severe COPD exacerbations. Pre-planned subgroup analyses showed that the benefit of tezepelumab was higher in those with higher baseline blood eosinophil count (BEC). In those with BEC greater than 150 cells/μL at baseline, tezepelumab reduced the annualized rate of moderate or severe COPD exacerbations by 37 percent.

“COPD is very heterogeneous, both in terms of clinical and biological characteristics,” said Dr. Singh. “In terms of therapy, a one-size-fits-all approach won’t work. The BEC greater than 150 subgroup is a potential responder population for tezepelumab.”

Phase 3 NOTUS Trial Confirms Efficacy of Dupilumab in Patients with COPD and Type 2 Inflammation

Surya P. Bhatt, MD, MSPH, professor of pulmonary, allergy & critical care medicine and medical director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham, presented the results of NOTUS, a randomized, double-blind phase 3 trial of dupilumab versus placebo in adult patients with moderate or severe COPD and type 2 inflammation.

“A substantial number of patients have predominant type 2 inflammation, which is evidenced by elevated sputum eosinophils and elevated Th2 cells, among other characteristics,” said Dr. Bhatt. “Patients continue to have exacerbations even when on therapy. Preventing these exacerbations is an important unmet need and target for new therapies.”

Dupilumab is a monoclonal antibody that blocks the receptor for interleukin-4 and interleukin-13, key drivers of type 2 inflammation.

At the end of 52 weeks of treatment, the annualized rate of moderate or severe COPD exacerbations was 34 percent lower in the dupilumab group than in the placebo group. This benefit was seen across subgroups, including gender, age, and smoking status. Dupilumab also improved markers of lung function and quality of life.