Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma
2014 · paper · Clinical trials
A randomized trial in 576 patients with severe eosinophilic asthma testing mepolizumab, an anti-interleukin-5 antibody, against placebo for 32 weeks. Mepolizumab cut exacerbation rates by 47% (intravenous) and 53% (subcutaneous) and improved symptom scores and lung function.
4 findings
Substance Results text says "Of the 802 patients who were screened, 576 underwent randomization and constituted the modified intention-to-treat population" and the abstract says "we assigned 576 patients", but Figure 1B shows "580 Underwent randomization", "4 Did not receive treatment", "576 Received treatment".
- p. 3 Results, Patients (continues on p. 5)
Of the 802 patients who were screened, 576 un-
- p. 4 Figure 1B
580 Underwent randomization
- p. 1 Abstract, Methods
we assigned 576 patients
Judge's note: Viewed page 3 and page 4 images. The flow diagram arithmetic is internally consistent and gives 580 randomized and 576 treated (191+191+194). The Methods define the modified intention-to-treat set as patients who received at least one dose, so 576 is the treated set, not the number randomized. No statement in the article reconciles the two; the text misstates the number randomized as 576.
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Reference or label Table 1 footnote "§ Reversibility was measured at baseline." is keyed to the row "Before bronchodilation — liters§"; the row "Reversibility — %" carries no marker.
- p. 6 Table 1, FEV1 rows and footnote §
Before bronchodilation — liters§
- p. 6 Table 1 footnote §
Reversibility was measured at baseline.
Only the authors can say what is right here.
Judge's note: Viewed the page 6 image. The § marker sits on the prebronchodilator FEV1 (liters) row, while the footnote text concerns reversibility, which is a separate unmarked row two lines below. Either the marker is on the wrong row or the footnote text is wrong (the next footnote, ¶, gives the timing of the percent-predicted value). Only the authors can say which.
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Reference or label Table 1 row "Geometric mean blood eosinophil count on loge scale — cells/µl" prints "320±938", "280±987", "290±1050"; SDs of that size cannot be on the loge scale (compare the IgE row, "150±1.5").
- p. 6 Table 1, Geometric mean blood eosinophil count on loge scale — cells/µl
320±938
Only the authors can say what is right here.
Judge's note: Viewed the page 6 image; the values are printed as quoted. The table footnote says plus–minus values are means (or geometric means) ±SD, and the row label says loge scale. The IgE row with the same label shows a log-scale SD of 1.5, whereas 938, 987 and 1050 are not possible as loge-scale SDs for geometric means near 300 cells/µl. Either a decimal point was lost (0.938, 0.987, 1.050) or the SDs are on a different scale from the label. The authors need to say which; rated as a label/scale problem because the fix is not determinable from the files.
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Reference or label "In a previous study,11 mepolizumab did not produce a significant benefit, but patients were not selected on the basis of frequent exacerbations, treatment with high doses of inhaled glucocorticoids, or a specific blood eosinophil count" cites ref. 11 (Nair et al., "Mepolizumab for prednisone-dependent asthma with sputum eosinophilia"); the description fits ref. 9 (Flood-Page et al., "...mepolizumab in patients with moderate persistent asthma").
- p. 8 Discussion, first paragraph
In a previous study,11 mepolizumab did not produce a significant ben-
- p. 9 Reference list, ref. 11
Mepolizumab for prednisone-dependent asthma with sputum eosino-
- p. 9 Reference list, entry 9
A study to evaluate safety and ef-
Only the authors can say what is right here.
Judge's note: Viewed the page 8 image for the citation; read the reference list on page 9 from the text layer. By its own title, ref. 11 enrolled a selected population (prednisone-dependent, sputum eosinophilia), and the Introduction cites refs 7-12 as showing reduced exacerbations and reduced need for systemic glucocorticoids. The description of an unselected population with no significant benefit matches the title of ref. 9. The mismatch is visible from the titles alone, but which reference the authors intended is for them to confirm.
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2 minor (typos and the like; most checked by the judge only)
Wording Missing responses "were included in the “significantly worse” category", but the 7-point scale is described with "7 indicating substantial worsening of asthma"; no category named "significantly worse" is defined.
- p. 3
patients with missing responses were included in the “significantly worse” category
Judge's note: Viewed page 3. The scale anchors are given as "substantial improvement" (1) and "substantial worsening" (7), while the quoted category name in the statistical analysis is "significantly worse". Presumably the same category (score 7), but the quoted label does not match the scale as described. A minor wording inconsistency; the category labels may be defined in the supplement, which is not among the files.
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Typo Discussion opens "In patients treated with high-dose inhaled oral glucocorticoids with or without maintenance oral glucocorticoids"; the first "oral" is a stray word.
- p. 7 Discussion, first sentence
In patients treated with high-dose inhaled oral
- p. 7 Discussion, first sentence
In patients treated with high-dose inhaled oral glucocorticoids with or without maintenance oral glucocorticoids
- p. 7 Discussion, first sentence
high-dose inhaled oral glucocorticoids with or without maintenance oral
- p. 7 Discussion, first sentence
treated with high-dose inhaled oral glucocorticoids with or without maintenance oral
Judge's note: Viewed the page 7 image; the text is printed as quoted. The abstract's parallel wording is "high-dose inhaled glucocorticoids with or without oral glucocorticoids", and the Methods require inhaled fluticasone or equivalent. "Inhaled oral" is self-contradictory next to "maintenance oral glucocorticoids"; the evident fix is to delete the first "oral".
Second check: none (judge only)