INSTEAD: a randomised switch trial of indacaterolversussalmeterol/fluticasone in moderate COPD

Abstract

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen).This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 mg once daily or SFC 50/500 mg twice daily. Patients had been receiving SFC 50/500 mg for o3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate noninferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV1) after 12 weeks (non-inferiority margin of 0.06 L).The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45-26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George's Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected.This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 mg with no efficacy loss. @ERSpublications Moderate COPD patients can switch from salmeterol/fluticasone to indacaterol with no efficacy loss

Progress and Prospects for Long-Acting Β 2 -Agonists in the Treatment of Chronic Obstructive Pulmonary Disease (Copd)

“…The crucial Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/ Fluticasone to Indacaterol (INSTEAD) trial, which enrolled COPD patients with moderate airflow limitation and without a history of exacerbations in the previous year, but on treatment with ICS/LABA combination therapy for ≥3 months, documented that these patients can be switched from ICS/LABA to indacaterol 150 μg with no efficacy loss [27].…”

Future treatment for asthma

“…The recently developed once-daily, very long-acting LABA (indacaterol, vilanterol, olodaterol and others [62][63][64][65][66]) potentially offer better bronchodilation patterns relevant to treating severe asthma with persistent airflow obstruction. Whether these drugs will also synergistically improve asthma control and reduce exacerbation rates is unknown at present.…”

And Then There Were Three: Time to Move Onward in COPD Drug Development Beyond LAMA/LABA/ICS at Last?

“…Although ever since there have been countless review papers, workshops and conferences about ''who needs ICS in COPD'', it appeared that the overuse of ICS in COPD was indeed a hard habit to break. Even when well-designed clinical trials confirmed the effectiveness of non-ICS containing combinations for COPD exacerbation prevention [6], and the feasibility of weaning off ICS in subjects with a questionable indication for this type of drug [7,8], change was reluctant and slow. Why were doctors so persistent with their prescription habits?…”

“…Indeed, I got it wrong: the drug industry (as well as clinical researchers and expert committees) has spent (wasted?) over 20 years with the question of searching for often marginal differences in outcomes with ''optimal'' treatment regimes comparing one, two or three single or combined (pharmacologically old) components, often following their canonical imperatives of ''maximized'' bronchodilation versus ICS-containing combos: LAMA versus ICS/LABA [10], ICS/LABA versus LABA [11], LABA/LAMA versus LAMA [12,13], LABA/LAMA versus ICS/LABA [6], plus a number of studies circling around the question if it was possible to withdraw ICS safely or not [7,8,14]. Tellingly, the only study that ignored the ''one-or-another'' agenda and looked at the effects of combining all three (ICS/LABA plus LAMA) compounds together (the Canadian OPTIMA trial) [15], mimicking usual practice of clinicians, particular in more severe forms of COPD, was non-industry sponsored.…”