An Overview of the Safety and Efficacy of Monoclonal Antibodies for the Chronic Obstructive Pulmonary Disease

Figures & data

Table 1 Trials That Have Evaluated or are Evaluating mAbs in COPD

Classes of mAbs	mAbs	Effects	Ongoing Studies
Targeting specific pro-inflammatory and pro-neutrophilic cytokines and chemokines in COPD
TNF-α inhibitors	Etanercept Infliximab	Reduction in COPD hospitalizations. No beneficial effect for the treatment of AECOPDs but in patients with <2% eosinophils at baseline showed a possible better response than with prednisone. No beneficial effects.
Anti–CXCL8	ABX-CXCL8	Improvement in dyspnoea, but not in lung function or health status.
Anti–IL-1β	Canakinumab MEDI8986	Lack of efficacy on the risk of AECOPDs, lung function, and health status. Lack of efficacy on the risk of AECOPDs, lung function, and health status.
Anti–IL-17A	CNTO 6785	Only a small improvement in FEV1% predicted.
Targeting T2-mediated inflammation
Anti–IL-5	Mepolizumab Benralizumab	Reduction of the rate of moderate and severe AECOPDs in those with higher levels of blood eosinophils. In individuals with blood eosinophil counts ≥150 cells/µL at screening or ≥300 cells/µL in the prior year, reduction of AECOPDs requiring corticosteroid treatment especially in the presence of increased blood eosinophil counts, but not of those requiring antibiotics. Reduction of the rate of moderate and severe AECOPDs in those with higher levels of blood eosinophils. A history of three or more AECOPDs in the past 12 months, baseline postbronchodilator FEV1 less than 40% and postbronchodilator response of 15% or more predict the treatment effect in individuals with baseline blood eosinophil count ≥220 cells/μL under triple therapy.	A Phase III trial ongoing to confirm the benefits of mepolizumab as add-on treatment to optimized maintenance COPD therapy in COPD patients experiencing frequent AECOPDs and characterized by eosinophil levels. A Phase II study evaluating whether starting mepolizumab at the time of a hospitalisation for an AECOPD in patients with significant eosinophilia will result in a reduction in readmission to hospital in a high-risk population. A Phase III trial evaluating the efficacy and safety of benralizumab on annualized rate of moderate or severe AECOPDs in patients with moderate to very severe COPD with a history of ≥2 moderate and/or severe AECOPDs in the previous year and elevated peripheral blood eosinophils (≥300/μL) despite receiving triple therapy for at least 3 months and ICS-based dual inhaled treatment for the rest of the year. A Phase II trial testing whether in patients who have an elevated eosinophil count at the time of exacerbation, a single injection of benralizumab alone or in combination with prednisolone will improve clinical response compared with prednisolone alone.
Anti–IL13/anti–IL4	Dupilumab Lebrikizumab	It does not influence AECOPD rate versus placebo in patients with COPD and a history of exacerbations despite ICS and at least one long-acting bronchodilator inhaler medication.	A Phase III trials assessing its efficacy, safety, and tolerability in patients with moderate-to-severe COPD with type 2 inflammation.
Anti–TSLP	Tezepelumab		A Phase IIa trial assessing its safety and efficacy in patients with moderate to very severe COPD receiving triple maintenance therapy, and having had 2 or more documented AECOPDs in the 12 months prior the enrolment.
Anti–IL-33	Itepekimab MSTT1041A MEDI 3506	No reduction of the annualized rate of moderate-to-severe AECOPDs but in former smokers with COPD significant reduction of the frequency of AECOPDs and improvement of lung function.	Phase III trials evaluating its efficacy compared with placebo on the annualized rate of moderate-or-severe AECOPDs over a 52-week placebo-controlled treatment period in former smokers with moderate-to-severe COPD. A Phase II trial evaluating its impact on the rate of AECOPDs. A Phase II proof of concept trial assessing its effects compared with placebo on pulmonary function after 12 week-treatment in patients with moderate to severe COPD and chronic bronchitis.