Efficacy and Safety of Ustekinumab, a Human Interleukin-12/23 Monoclonal Antibody, in Patients with Psoriasis: PHOENIX 1
2008 · paper · Clinical trials
A phase III trial of ustekinumab, an interleukin-12/23 antibody, in 766 patients with moderate-to-severe psoriasis. About 67% reached PASI 75 at week 12 versus 3% on placebo, and every-12-week dosing maintained response for at least a year in most.
2 findings
Substance The Discussion says ustekinumab "is efficacious for the treatment of mild-to-moderate psoriasis", but the trial enrolled moderate-to-severe psoriasis (PASI ≥12, BSA ≥10%), as the Summary states.
- p. 7 Discussion, first paragraph
of mild-to-moderate psoriasis
- p. 1 Summary, Methods and Interpretation
efficacious for the treatment of moderate-to-severe psoriasis
- p. 1 Summary, Interpretation
Ustekinumab seems to be efficacious for the treatment of moderate-to-severe psoriasis
- p. 7 Discussion, first paragraph
is efficacious for the treatment of mild-to-moderate psoriasis
Judge's note: p7 image, Discussion first paragraph: the sentence reads 'mild-to-moderate psoriasis'. The Summary (p1), the introduction and eligibility criteria (p2), and the Discussion on p8 all say moderate-to-severe. PHOENIX 2 is also described as moderate-to-severe.
Second check: another model agreed
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Substance "Cytokines produced by Th17 cells, including interleukin 20 and interleukin 22" is cited to refs 25–26, whose titles concern IL-17 and IL-22, not IL-20.
- p. 8 Discussion, first column, first paragraph
interleukin 20 and interleukin 22, have been implicated
- p. 10 Reference 25
IL-23 upregulates IL-10 and induces IL-17 synthesis
- p. 8 Discussion, paragraph 1
Cytokines produced by Th17 cells, including interleukin 20 and interleukin 22
- p. 10 Reference 25
IL-23 upregulates IL-10 and induces IL-17 synthesis by polyclonally activated naïve T cells in human
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that IL-20 is not a Th17-derived cytokine. In the files, the preceding sentence names IL-17 as the Th17 cytokine. Ref 25 is 'IL-23 upregulates IL-10 and induces IL-17 synthesis…' and ref 26 is 'Interleukin-22, a TH17 cytokine…' (p10). Neither cited title mentions IL-20, so 'interleukin 20' is probably a slip for 'interleukin 17'.
Second check: another model agreed
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6 minor (typos and the like; most checked by the judge only)
Wording The Discussion says response "was generally maintained for at least a year and a half", but follow-up ended at week 76 (about 1.46 years), and the Summary and Results say 'at least a year'/'at least 1 year'.
- p. 8 Discussion, first column, end
generally maintained for at least a year and a half
- p. 1 Summary, Interpretation
maintains efficacy for at least a year in most patients
- p. 6 Results, randomised withdrawal
through at least 1 year
- p. 8 Discussion, paragraph 2
generally maintained for at least a year and a half in patients who received the drug every 12 weeks
Only the authors can say what is right here.
Judge's note: p8 Discussion. Data run only to week 76 (Figure 4, p7), which is less than 78 weeks. The p1 Summary and p6 Results both say at least 1 year. 'At least' a year and a half goes beyond the observed follow-up.
Second check: another model agreed
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Wording Table 3 (weeks 0–12) gives adverse events leading to withdrawal as "1 (0·4%)" for 45 mg and "4 (1·6%)" for 90 mg, while Figure 2 shows 0 and 2 adverse-event discontinuations before week 12.
- p. 8 Table 3, row 'Adverse events leading to withdrawal of study agent'
1 (0·4%)
- p. 3 Figure 2, discontinuations before week 12
0 adverse event
Only the authors can say what is right here.
Judge's note: p3 Figure 2: 45 mg 0 adverse event; 90 mg 2 adverse event; placebo 6. p8 Table 3: 1, 4, 6. The crossover phase also differs (Figure 2 gives 11 AE for 45 mg, Table 3 gives 7). The counts may be defined differently (an AE occurring in the phase versus the time of discontinuation), but no definition is given, so this is a query for the authors.
Second check: another model agreed
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Wording Table 2, DLQI score of 0 or 1, 90 mg: "131 (52·4%)" at week 12 (DLQI n=249) and "167 (69·0%)" at week 28 (n=241). These match denominators of 250 and 242, not the stated n.
- p. 5 Table 2, DLQI score of 0 or 1, week 12, 90 mg
131 (52·4%)*
- p. 5 Table 2, DLQI score of 0 or 1, week 28, 90 mg
167 (69·0%)
Only the authors can say what is right here.
Judge's note: Checked Table 2 on the p5 image. The other five DLQI 0/1 cells match their n row: 135/254=53.1, 15/252=6.0, 146/249=58.6, 74/123=60.2, 90/118=76.3. The two 90 mg cells instead match an n one higher than shown. No footnote gives a different denominator for the responder row, so only the authors can say which denominator applies.
Second check: another model agreed
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Wording The text says median PASI improvement in the withdrawal groups fell "to about 40% at week 64", but in Figure 4A/B the week-64 placebo medians sit at about 47–48%. Values near 40% appear only at weeks 68–76.
- p. 6 Results, second column bottom
about 40% at week 64
- p. 7 Figure 4A and 4B, placebo curves
Median percentage
Judge's note: On the p7 Figure 4 image, the week-64 placebo markers in both panels are clearly above the 40 gridline, close to 47–48%. The curves reach about 40–43% at weeks 68–76. This is a plot reading and the text says 'about', so it is a minor mismatch.
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Typo Conflict of interest statement: "Perrigo Isreal" should read "Perrigo Israel".
- p. 9 Conflict of interest statement
Perrigo Isreal
- p. 9 Conflict of interest statement, CLL
Perrigo Isreal Pharamceutical
Judge's note: The p9 crop shows 'Perrigo Isreal Pharamceutical' as printed, so this is not an extraction artefact.
Second check: none (judge only)
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Typo Conflict of interest statement: "Pharamceutical" should read "Pharmaceutical".
- p. 9 Conflict of interest statement
Pharamceutical
Judge's note: Visible on the p9 image in 'Perrigo Isreal Pharamceutical'. This is a separate misspelling from C013.
Second check: none (judge only)