Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
2018 · paper · Clinical trials
A 52-week randomized trial of add-on dupilumab versus placebo in 1,902 patients with uncontrolled asthma. Dupilumab lowered severe exacerbation rates by about 48% and improved lung function, with larger benefits at higher eosinophil counts; some patients developed raised blood eosinophils.
1 finding
Reference or label The ACQ-5 MCID statement is cited as "portant difference is 0.5)16,17" in the Methods but as "The minimal clinically important difference is 0.5.17,18" in the Table 1 footnote.
- p. 2 Methods, Patients
portant difference is 0.5)16,17
- p. 5 Table 1, footnote †
The minimal clinically important difference is 0.5.17,18
- p. 2 Methods, Patients
the minimal clinically im- portant difference is 0.5)16,17
Only the authors can say what is right here.
Judge's note: Both superscripts checked on the page images (p2 crop and the p5 footnote). In the reference list, ref 16 is Juniper 2005 on the shortened ACQ versions, ref 17 is Juniper 1999 on AQLQ validation (cited elsewhere for the AQLQ), and ref 18 is the Reddel ATS/ERS exacerbation-endpoints statement (cited elsewhere for the severe-exacerbation definition). The same claim carries two different reference pairs, and the footnote leaves out the ACQ paper (ref 16). Only the authors can say which pair they intended.
Second check: another model agreed
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4 minor (typos and the like; most checked by the judge only)
Reference or label The text says "according to the Global Initiative for Asthma 2014 guidelines,15" but ref 15 is the GINA 2015 report ("Global strategy for asthma management and prevention. 2015 ... GINA_Report_2015_Aug11-1.pdf").
- p. 2 Methods, Patients
Asthma 2014 guidelines,15
- p. 11 Reference 15
and prevention. 2015 (http://ginasthma.org/
Judge's note: Checked on the p2 crop and the p11 reference list. The year named in the text (2014) does not match the cited document (2015). The protocol may have used the 2014 criteria while the newest report was cited, so this is a minor consistency point.
Second check: another model agreed
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Wording The Table 2 title reads "Adverse Events That Emerged during the Intervention Period", while the Methods and Safety text count adverse events over the "trial period" (first dose to last dose plus 98 days).
- p. 8 Table 2 title
Adverse Events That Emerged during the Intervention Period (Safety Population).
- p. 8 Results, Safety
The incidence of adverse events that emerged during the trial period was similar
- p. 3 Methods, End Points
the last administration of the trial regimen plus 98 days
Judge's note: Checked on the p8 page image and the p3 Methods crop. The Methods define the AE reporting window as the trial period, the Safety text cites Table 2 for events "during the trial period", and the table title says "Intervention Period", a term the paper uses for the 52-week treatment phase. The label is ambiguous; either wording could be what was meant.
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Wording "All 1902 randomly assigned patients were included in the final analysis: 1434 patients completed the 52-week intervention period, 235 had treatment ongoing, and 228 discontinued the intervention". These sum to 1897, not 1902.
- p. 4 Results, Trial Patients
1434 patients completed the 52-week intervention peri- od, 235 had treatment ongoing, and 228 dis- continued the intervention
Only the authors can say what is right here.
Judge's note: Checked on the p4 crop. The three categories sum to 1897, the number who received the intervention (stated just before). The 5 randomised but untreated patients are not placed in any category, although the sentence presents the split as covering all 1902. The article gives no explicit account of them; Fig. S2 is not among the files.
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Wording The Discussion says the hospitalization/ED exacerbation rate "was also significantly lower with dupilumab than with placebo", but the Results report only group rates of 0.035 (0.025 to 0.048) and 0.065 (0.047 to 0.090) and "46.8% lower", with no test or CI for the comparison.
- p. 9 Discussion, first paragraph
was also significantly lower with dupilumab than with placebo
- p. 7 Results, Additional Secondary Outcomes
was 0.035 (95% CI, 0.025 to 0.048) in the combined dupilumab groups and 0.065 (95% CI, 0.047 to 0.090)
Only the authors can say what is right here.
Judge's note: Checked p9 (Discussion) and p7 (Results). The Methods (p3/4) say endpoints after the hierarchy break, or outside it, are shown with 95% CIs only and without multiplicity control. The article does not say whether this endpoint was in the hierarchy (Table S1/S6, not among the files), so the article text does not support the word "significantly". Query for the authors: which test and which hierarchy position underlie this claim.
Second check: another model agreed