Safety and Effectiveness of Indacaterol/Glycopyrronium/Mometasone Dry Powder Inhaler in Asthma: A Prospective Multicenter Phase IV Study.
Karmakar Saurabh S, Bhate Amit S AS, Prashanth C C, Kadam Dilip D et al.
Asthma remains a major public health challenge in India, characterized by high disease burden, poor adherence, and suboptimal control despite therapeutic advances. Fixed-dose combination therapy with indacaterol/glycopyrronium/mometasone furoate (IND/GLY/MF; DIFIZMA®), a single-inhaler triple therapy (SITT), offers the potential for improved symptom control and adherence through once-daily dosing. However, real-world and postmarketing surveillance data on the effectiveness and safety of IND/GLY/MF in Indian asthma patients remain limited, underscoring the need for local evidence to guide clinical practice. To evaluate the safety and effectiveness of once-daily IND/GLY/MF dry powder inhaler (DPI) in Indian adults with asthma inadequately controlled on inhaled corticosteroid (ICS)-long-acting β2-agonist (LABA) therapy. This was a prospective, open-label, multicenter, single-arm, phase IV postmarketing study conducted across multiple centers in India. Adults (18-65 years) with persistent asthma symptoms despite ICS ± LABA therapy received IND/GLY/MF DPI (160 µg mometasone furoate, 46 µg glycopyrronium bromide, 114 µg indacaterol acetate) once daily for 24 weeks. The primary endpoint was safety, based on treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations. Secondary endpoints included changes from baseline in the asthma control questionnaire (ACQ-7) score, FEV1, FVC, and FEV1/FVC ratio at weeks 4, 12, and 24. A total of 200 patients were enrolled (safety set), of whom 196 were included in the modified intent-to-treat (mITT) analysis and 189 in the per-protocol (PP) population. TEAEs occurred in 9.5% of participants, with 6.5% considered drug-related; all events were mild or moderate in severity. No serious adverse events, severe TEAEs, or deaths were reported. Clinically meaningful and progressive improvements were observed in asthma control and lung function over 24 weeks. The ACQ-7 score decreased from 3.00 ± 0.59 at baseline to 2.36 ± 0.54 at week 4, 1.86 ± 0.54 at week 12, and 1.39 ± 0.61 at week 24, corresponding to mean change of -0.64 ± 0.50, -1.14 ± 0.74, and -1.62 ± 0.89, respectively (all p < 0.0001). Mean FEV1 increased from 1.49 ± 0.51 L at baseline to 1.73 ± 0.60 L at week 4, 1.81 ± 0.53 L at week 12, and 1.95 ± 0.51 L at week 24, with corresponding mean changes of +0.24 L, +0.32 L, and +0.46 L (all p < 0.0001). Mean FVC improved from 2.13 ± 0.63 L at baseline to 2.30 ± 0.70 L, 2.33 ± 0.62 L, and 2.38 ± 0.59 L at weeks 4, 12, and 24, respectively (all p < 0.0001). The FEV1/FVC ratio increased from 71.63 ± 12.76 at baseline to 76.71 ± 11.33, 80.86 ± 12.67, and 84.00 ± 8.93 at weeks 4, 12, and 24, with mean changes of +4.99, +8.91, and +12.10, respectively (all p < 0.0001). No hospitalizations or rescue medication use were reported. Compliance with study medication was 100%, and both patients and physicians reported marked symptom improvement and high treatment satisfaction. Once-daily IND/GLY/MF DPI demonstrated a favorable safety profile and significant, sustained clinical benefits in adults with asthma inadequately controlled on ICS-LABA therapy. The triple combination provided rapid onset and sustained improvement in asthma control and lung function, with excellent adherence and tolerability in real-world Indian clinical practice. These findings support IND/GLY/MF as an effective and practical single-inhaler triple therapy option for optimized asthma management.