Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial

2020 ◽  
Vol 57 (1) ◽  
pp. 2000348 ◽  
Author(s):  
Susumu Sakamoto ◽  
Kensuke Kataoka ◽  
Yasuhiro Kondoh ◽  
Motoyasu Kato ◽  
Masaki Okamoto ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Combination Therapy ◽  
Acute Exacerbation ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Rate Of Change ◽  
Open Label ◽  
Multicentre Phase ◽  
Serial Change

BackgroundA randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown.MethodsThis 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (DLCO) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability.Results81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was −300 mL and −123 mL, respectively (difference −178 mL, 95% CI −324–−31 mL; p=0.018). Serial change in DLCO, 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups.ConclusionsCombination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.

scholarly journals FDA-approved Antitussive Dextromethorphan Enhances Antifibrotic Effectiveness of Pirfenidone in Bleomycin-induced Mice and Patients with Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Nana Liu ◽  
Yubao Wang ◽  
Jie Huang ◽  
Yunze Du ◽  
Luqing Wei ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Reactions ◽  
Controlled Trial ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Randomized Controlled ◽  
Model Study ◽  
One Year

Abstract Background: We aimed to investigate whether dextromethorphan (DM), an antitussive agent, could improve the antifibrotic efficacy of pirfenidone in treating idiopathic pulmonary fibrosis, a fatal interstitial lung disease characterized by progressive and irreversible respiratory failure.Methods: A bleomycin-induced mouse pulmonary fibrosis model study and an open-label randomized clinical trial were performed to evaluate the effectiveness of pirfenidone combined with DM.Results: In the animal study, pirfenidone combined with DM protected the mice against bleomycin-induced pulmonary fibrosis with better capabilities than pirfenidone or DM alone, as indicated by lung histologic analysis and hydroxyproline levels. In the clinical study, pirfenidone plus DM markedly mitigated pulmonary function (FEV1 and FVC) decline and ameliorated chest HRCT imaging scores (ground glass opacities and reticulation) of patients with IPF compared with pirfenidone alone at one year after administration. There were no significant differences in adverse reactions between the pirfenidone-DM group and the pirfenidone group.Conclusions: Pirfenidone plus DM may be a better strategy to modify IPF than pirfenidone alone. The efficacy and safety of the combination of pirfenidone and DM for patients with IPF warrants further verification by a double-blind randomized controlled trial (RCT).

scholarly journals Early combination therapy with etanercept and methotrexate in JIA patients shortens the time to reach an inactive disease state and remission: results of a double-blind placebo-controlled trial

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ekaterina Alexeeva ◽  
Gerd Horneff ◽  
Tatyana Dvoryakovskaya ◽  
Rina Denisova ◽  
Irina Nikishina ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Controlled Trial ◽  
Randomized Study ◽  
Primary Objective ◽  
Disease State ◽  
Inactive Disease ◽  
Open Label ◽  
Standard Regimen ◽  
Double Blind ◽  
Early Combination Therapy

Abstract Background Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease. Methods A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit. Results By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/−IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14–32) and 32 (24–40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients. Conclusions Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.

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