Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials
New England Journal of Medicine, 2014 · paper · Clinical trials
Two phase 3 trials of secukinumab, an anti-interleukin-17A antibody, in 2044 patients with moderate-to-severe plaque psoriasis. At week 12, both doses cleared skin more often than placebo or etanercept, with higher infection rates than placebo.
1 finding
Substance The FIXTURE immunogenicity denominator "0.4% of the 980 secukinumab-treated patients tested" (Results) / "4 of 980 (0.4%)" (Discussion) is larger than the total of the Table 4 "Any Secukinumab, 300 mg (N=467)" and "Any Secukinumab, 150 mg (N=469)" columns (936).
- p. 12 Discussion, paragraph on anti-secukinumab antibodies
in 4 of 980 (0.4%) in the FIXTURE study
- p. 10 Results, immunogenicity paragraph
0.4% of the 980 secukinumab-treated patients tested
- p. 11 Table 4, Entire Study Period column headers
Any Secukinumab, 300 mg (N=467)
- p. 11 Table 4 column headers, entire study period
(N = 467)
Only the authors can say what is right here.
Judge's note: The Table 4 entire-period columns on p11 (upright image) already include the re-randomized placebo nonresponders (footnote †), so 936 is the total number of FIXTURE patients exposed to secukinumab. Etanercept patients did not switch to secukinumab. The text on p10 and p12 says 980 secukinumab-treated patients were tested, which is more than were exposed. I found no explanation in the article. The percentage is unchanged after rounding. Only the authors can say which figure is right.
Second check: another model agreed
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3 minor (typos and the like; most checked by the judge only)
Reference or label The sentences on the proportion with "a DLQI score of 0 or 1" (P<0.001) cite "(Table 2, and the Supplementary Appendix)" and "(Table 3, and the Supplementary Appendix)", but Tables 2 and 3 report only "DLQI — mean score" (baseline, wk 12, absolute change).
- p. 6 Secondary end points, ERASURE
group (P<0.001 for both comparisons) (Table 2, and the Supplementary Appendix)
- p. 6 Secondary end points, FIXTURE
sons) (Table 3, and the Supplementary Appendix)
- p. 7 Tables 2 and 3, DLQI rows
DLQI — mean score
- p. 6 Results, ERASURE secondary end points
The proportion of patients with a DLQI score of 0 or 1
Judge's note: On p7 I confirmed that Tables 2 and 3 contain only mean DLQI rows, with no 0/1 proportions or P values. The text on p6 cites the tables together with the Supplementary Appendix, which is not among the files. The tables hold related DLQI data, so the citation is loosely defensible, but the reported proportions cannot be found where the citation points. This is a minor pointer issue. The two reviewer notes describe the same defect.
Second check: another model agreed
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Wording The methods say the efficacy analyses "included all the patients who underwent randomization", and the text says 737 (ERASURE) and 1305 (FIXTURE) were included. The Table 2 denominators (e.g. PASI 75: 245, 243, 246) and Table 3 denominators (323, 327, 323, 324) add up to fewer patients, and the tables do not explain the gap.
- p. 4 Statistical Analysis
the analyses of the efficacy end points included all the patients who underwent randomization
- p. 6 Results, Characteristics of the Patients
A total of 1305 patients were included in the efficacy analyses
- p. 7 Table 2, PASI 75 row
174/243 (71.6)
- p. 7 Table 3, PASI 75 row
249/323 (77.1)
Only the authors can say what is right here.
Judge's note: Checked p4 (Statistical Analysis), p5 (Table 1 arm sizes: ERASURE 245/245/248; FIXTURE 327/327/326/326), p6 (737 and 1305 included in the efficacy analyses) and p7 (Tables 2 and 3). The Table 2 and 3 footnotes say only that missing data were imputed as nonresponses. The only statement that could explain the gap is the Figure 2 caption on p10 ("Only patients who could be evaluated for a response were included"), which is not referenced from the tables or the methods. The denominators therefore differ from the stated full analysis set, and only the authors can say which patients were excluded and why.
Second check: another model agreed
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Wording The text says response rates "increased during the period from week 12 to week 16 and then stabilized after week 16 (Fig. 2)", but in Fig. 2A the ERASURE 150-mg curves fall visibly after week 16 (e.g. IGA 0/1 from about 58% to about 41% and PASI 75 from about 77% to about 60% by week 52).
- p. 6 Response over Time
week 16 and then stabilized after week 16 (Fig. 2)
- p. 9 Figure 2A
Secukinumab, 150 mg (N=244)
Judge's note: On p9 (Figure 2) the ERASURE 150-mg curves for IGA 0/1, PASI 75 and PASI 90 each fall by about 15 to 17 points between week 16 and week 52, and the 300-mg curves also drift down (IGA from about 74% to about 60%). The FIXTURE curves are flatter. The sentence is hedged ("Inspection of the curves ... suggests"), but "stabilized" overstates the plateau for ERASURE. The values are approximate readings from the plot.
Second check: another model agreed