Positioning new pharmacotherapies for COPD

Figures & data

Table 1 New pharmacotherapies in COPD management

	Agency approval	Indication GOLD grade	Efficacy				Safety and adverse effects	General remarks
			FEV1 improvement	Exercise	Exacerbations	Health status and symptoms
New LAMA monotherapy
Aclidinium	US, EU	GOLD B, C, D	++	++	++	++	Bronchospasm, nasopharingitis (6%), headache (5%), dry mouth (<2%)	Faster onset of action to tiotropium, better nighttime FEV1, BID dosing
Glycopyrronium	EU	GOLD B, C, D	+++	++	++	++	Antimuscarinic and cardiac side effects similar to placebo	Rapid onset, very good safety profile
Umeclidinium	US, EU	GOLD B, C, D	++	++,•	++,•	++,•	Minimal antimuscarinic side effects	Combined with vilanterol
New LABA monotherapy
Indacaterol	US, EU	GOLD B, C, D	+++	++	++	++	Cough (6.5%), headache (5.1%), nausea (2.4%)	Improved cardiovascular safety profile and lung function compared to salmeterol
Vilanterol	US, EU	GOLD B, C, D	++	++,•	++,•	++	Nasopharingitis (10%), headache (9%), dry mouth (< 10%)
Olodaterol	US	GOLD B, C, D	++	++	−	++	Nasopharyngitis (11%), dizziness (>2%), rash (>2%), arthralgia (>2%)
Abediterol	−		+++					Better lung function impact in comparison to indacaterol
New LAMA-LABA combination therapy
Umeclidinium and vilanterol	US, EU	GOLD C, D	+++		++	++	No increase in adverse events compared to placebo	First LAMA-LABA approved by the US FDA for maintenance treatment
Glycopyrronium and indacaterol	EU	GOLD C, D	+++		+++	+++	No increase in adverse events compared to tiotropium or glycopyrronium alone	Significantly better FEV1 and SGRQ compared to tiotropium and glycopyrronium alone
Tiotropium and olodaterol	−	GOLD C, D	+++		+	+++	No significant difference in adverse events compared to monocomponents	Significant improvement in SGRQ score was only seen in the 5/5 μg dosing
Aclidinium and formoterol	EU	GOLD C, D	+++		−	−/++	Nasopharingitis (7.8%), headache (7.5%)	Significant improvement in FEV1 1-hour postdosing compared to monocomponents
Glycopyrrolate and formoterol		GOLD C, D	+++					Improvement in FEV1 from 0 hours to 12 hours versus monotherapy with glycopyrrolate, formoterol, or tiotropium
New LABA-ICS combination therapies
Vilanterol and fluticasone	US, EU	GOLD C, D	+		+++		Compared to vilanterol alone, FDC leads to an increased risk of pneumonia	Once-daily FDC of LABA-ICS
Indacaterol and mometasone	−	GOLD C, D	++
Formoterol and ciclesonide	−	GOLD C, D	++			++	Oral candidiasis was the most common adverse event	Noninferiority comparison to combined fluticasone propionate/salmeterol in asthma
Formoterol and fluticasone	EU, Japan	GOLD C, D	+++				Approved for asthma, but in Phase III clinical trials for moderate to severe COPD	More rapid bronchodilator effect than fluticasone propionate/salmeterol
Triple LABA-LAMA-ICS therapy	−	GOLD C, D	++		−	++	No significant difference in adverse events compared to dual or monocomponents	A 40% reduction in mortality compared with ICS/LABA in a retrospective analysis
Dual muscarinic antagonist-β2-agonists	−		++a				Transient hypokalemic effect in 3/41 patients receiving additional high-dose salbutamol	GSK961081 has demonstrated effective bronchoprotection in early trials
Oral medications
Roflumilast	US, EU	GOLD C, D	++a		++	−	Weight loss, nausea, diarrhea, and psychiatric symptoms	Recommended use only in advanced COPD as an add-on therapy
Azithromycin	US, EU	GOLD C, D			++		QT interval prolongation, ototoxicity, and drug-drug interactions	Careful risk-benefit assessment given the side-effect profile
Moxifloxacin	US, EU	GOLD C, D			++	−/++	Significant Gl side effects compared to the placebo group	Intermittent pulsed therapy with 5 days of moxifloxacin every 8 weeks for six courses
Simvastatin	US, EU	GOLD C, D			−	−	No significant difference in fatal or nonfatal adverse events	No significant difference in exacerbations in one randomized, placebo-controlled trial

Notes: ⁻No improvement in the published literature; ⁺nonsignificant improvement; ⁺⁺significantly improved compared to placebo; ⁺⁺⁺significantly improved to other drugs of the same class;

• in combination therapy;

a improved FEV₁ from baseline.

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; LAMA, long-acting muscarinic antagonist; US, United States; EU, European Union; BID, twice daily; LABA, long-acting β-2 sympathomimetic agonist; FDA, Food and Drug Administration; FEV₁, forced expiratory volume in I second; SGRQ, St George’s Respiratory Questionnaire; ICS, inhaled corticosteroid; FDC, fixed-dose combination; Gl, gastrointestinal.