This study demonstrated that the fluticasone/formoterol combination is at least as effective as its components administered concurrently from separate inhalers. Fluticasone/formoterol (500/20 μg, b.i.d.) showed superior efficacy to its inhaled corticosteroid component alone and the efficacy of fluticasone/formoterol was dose-dependent for several clinically important parameters.

Background: A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations.Methods: The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs.Results: The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively.Conclusions: The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be readily explained by differences in features of the respective studies and may be related to the favorable pharmacological/mechanistic characteristics of the constituent components fluticasone and formoterol compared to other drugs in their respective classes.

Background and purpose: Spinal muscular atrophy (SMA) is caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations in the SMN1 gene. Risdiplam is an orally administered molecule that modifies SMN2 pre-mRNA splicing to increase functional SMN protein.Methods: SUNFISH Part 1 was a dose-finding study conducted in 51 individuals with types 2 and 3 SMA aged 2-25 years. A dose-escalation method was used to identify the This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Fluticasone/formoterol combination therapy had comparable efficacy to its individual components administered concurrently, when measured by post-dose FEV1 in patients aged ≥ 12 years with mild to moderate-severe asthma. The safety and tolerability profile of fluticasone/formoterol combination therapy was similar to that of its individual components administered concurrently. Although this was an open-label study, the results remain compelling: the primary efficacy measure was a physical endpoint and study statisticians were blinded to treatment allocations until analysis was completed.

Risdiplam is an oral, survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67–4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI – 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment.