Inhaled Corticosteroids for Chronic Obstructive Pulmonary Disease—The Shifting Treatment Paradigm

Figures & data

Table 1.  COPD treatment algorithm employed by NHS Tayside. The algorithm recommends that a combined inhaled steroid and long-acting bronchodilator should be prescribed only if the patient has persistent breathlessness or repeated exacerbations despite optimal bronchodilator therapy (defined in step 3 as LABA and LAMA co-prescribing, coloured blue) and should be discontinued if no benefit after 4 weeks

	Symptoms	Inhaled Medication^1
Step 1	Breathlessness and exercise limitation	SABA or SAMA as required
Step 2	Persistent breathlessness and/or repeated exacerbations	SABA or SAMA as required	+	LABA
			Or
		SABA as required	+	LAMA
Step 3^2	Persistent breathlessness and/or repeated exacerbations despite treatment at step 2	SABA as required	+	LABA + LAMA
Step 4	Persistent breathlessness and/or repeated exacerbations despite treatment at step 3	SABA as required	+	ICS/LABA + LAMA

ICS, inhaled corticosteroids; LABA, long-actingβ2-agonist bronchodilator; LAMA, long-acting anti-cholinergic; SABA, short-acting β2-agonist bronchodilator; SAMA, short acting anti-cholinergic.

¹Consider administration via an MDI and spacer at each step when:

The inspiratory flow rate is < 30 L/min.

Poor technique with dry powder device.

Recurrent candidiasis of the mouth or throat.

Medication is carer administered.

Unlikely to generate sufficient inspiratory flow when exacerbating.

²Theophylline use.

Oral slow release theophylline (Uniphyllin® m/r tablets) may be useful after a trial of short-acting bronchodilators and long-acting bronchodilators, or in patients who are unable to use inhaled therapy. Monitoring plasma levels of theophylline is not routinely necessary in stable patients but may be warranted in certain circumstances, eg, a change in clinical status, where toxicity is suspected or during concomitant use of interacting drugs.

Table 2.  LABA/LAMA fixed-dose combinations in late-stage clinical development

Combination	Development phase	Company	Pivotal trials
Indacaterol/glycopyrronium (QVA149)	110/50 μg approved (EU, Japan)	Novartis	IGNITE program 11 trials, 11,000 patients
Umeclidinium/vilanterol	62.5/25 μg approved (US, EU, Japan)	GSK, Theravance	Phase III program 7 trials, 6000 patients
Olodaterol/tiotropium	5 /5 μg filed in EU, US	Boehringer Ingelheim	TOviTO program Several trials, 5000 patients
Aclidinium/formoterol	400/12 μg (bid) Filed in EU	Almirall, Forest	ACLIFORM (NCT01462942), AUGMENT (NCT01437397) LAC-MD-32; LAC-MD-36
Formoterol/glycopyrronium	Phase III	AstraZeneca	PINNACLE 1 (NCT01854645) PINNACLE 2 (NCT01854658) Safety extension (NCT01970878)

Figure 1. Comparison of FEV₁ for QVA149 versus fluticasone/salmeterol. The ILLUMINATE double-blind, randomised trial of 523 patients. The primary study endpoint was FEV₁ AUC_{0–12 h} at 26 weeks for QVA149 vs. salmeterol/fluticasone (40). At Week 26, FEV₁ AUC_{0–12 h} was significantly higher with QVA149 compared with fluticasone/salmeterol combination, with a significant and clinically meaningful treatment difference of 138 mL (95% CI 100–176; p < 0.0001).

Vogelmeier CF, Bateman ED, Pallante J, Alagappan VKT, D’Andrea P, Chen H, Banerji D. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol–fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respir Med 2013; 1:51–60.

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