Formoterol mono- and combination therapy with tiotropium in patients with COPD: A 6-month study

Abstract

Although guidelines recommend combining long-acting bronchodilators in COPD, data are limited. We examined the clinical efficacy and safety of formoterol, tiotropium and the combination in patients with COPD. Eight hundred and forty-seven patients with COPD (mean FEV(1) 52% predicted; FEV(1)/FVC 53%) were randomized to receive one of the following four treatments for 24 weeks: formoterol 10 microg b.i.d. plus tiotropium 18 microg o.d.; formoterol 10 microg b.i.d.; tiotropium 18 microg o.d., or placebo. The study was partially blinded (formoterol and placebo). For the primary endpoint, FEV(1) 2h post-dose after 24 weeks, there were small differences in favour of the combination therapy versus formoterol (0.07 L, p=0.044) or tiotropium (0.06 L, p=0.066). All three treatments were superior to placebo (p<0.001). The combination was statistically superior to monotherapy for: the primary endpoint (p=0.044 vs. formoterol); FEV(1) 5 min after the first dose (p<0.001) and at 12 weeks (p<0.05 vs. tiotropium); and peak expiratory flow averaged over the first 6 weeks (p<0.001 vs. both). The three active treatments were significantly more effective than placebo for secondary endpoints: COPD-related 'bad days', symptoms, use of rescue medication and peak expiratory flow, and aspects of health-related quality of life. The overall incidence of adverse events was similar with all active treatments, although COPD-related adverse events were more common with tiotropium. Combined bronchodilator therapy may be a valuable treatment option for patients with COPD.

Effect of tiotropium on quality of life in COPD: a systematic review

“…[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] Of the 24 publications that met the inclusion criteria for this systematic review (see Table 1), 16 compared tiotropium with placebo, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] seven compared tiotropium with an active comparator, [66][67][68][69][70][71][72] and one compared tiotropium with both placebo and an active comparator. 73 The QoL outcomes reported in the 24 included publications were mostly SGRQ and/or TDI (Tables 2 and 3).…”

Cardiovascular safety of new inhaled medications for asthma and chronic obstructive pulmonary disease: a critical review from pharmacist perspective

“…51,[53][54][55] An earlier semi-open label study has reported a decrease in serum potassium levels in ~5% of subjects treated with LABAs, but no statistically significant difference was observed in laboratory values, ECG and vital signs. 38 In addition, one study has found that serum potassium and glucose levels were slightly increased without reaching significance, and incidences of other AEs were lower in the treatment group. 59 Although these agents were administered via an inhaler device, small amounts of the drug were absorbed systematically, and it is believed that high plasma levels can contribute to greater extra-pulmonary effects.…”

“…5,26,37 However, the use of SABAs was permitted in many studies, and it may mask the true effect of LABAs. [38][39][40][41] Some studies also suggested that ICSs can contribute to dose-dependent reduction of cardiotoxicity from LABAs. 5,29,38,42,43 Increased efficacy is believed to be a result of molecular interaction, where ICSs activate the beta2-receptor gene.…”

“…[38][39][40][41] Some studies also suggested that ICSs can contribute to dose-dependent reduction of cardiotoxicity from LABAs. 5,29,38,42,43 Increased efficacy is believed to be a result of molecular interaction, where ICSs activate the beta2-receptor gene. In turn, LABAs modulate phosphorylation of glucocorticosteroid receptors, priming them for steroiddependent activation.…”

Efeito agudo do indacaterol mais tiotrópio versus formoterol mais tiotrópio sobre hiperinsuflação pulmonar (Estudo EFINTH) na DPOC: protocolo de estudo para um ensaio randomizado

“…1,5,6 Achados reforçam a ideia de que broncodilatadores com mecanismos de ação diferentes podem melhorar a eficácia no manejo dos sintomas e diminuir o risco de eventos adversos comparados ao aumento de dose de um agente isolado. [7][8][9] Adicionalmente, evidências de estudos prospectivos tem demonstrado significante melhora na função pulmonar da combinação em dose fixa LABA/LAMA comparada aos seus monocomponentes ou a outro LAMA. [10][11][12] Recentemente, os LABAs de ação ultralonga (ultra-LABAs) com ação terapêutica de 24 horas foram lançados no mercado brasileiro.…”