Natalizumab for Relapsing Multiple Sclerosis
2006 · paper · Clinical trials
A two-year placebo-controlled trial of natalizumab in 942 patients with relapsing multiple sclerosis. Natalizumab reduced sustained disability progression by 42% and relapse rate by 68%, and sharply cut new MRI lesions.
1 finding
Substance "had 27 hypersensitivity reactions: 12 cases of urticaria or generalized urticaria, 1 of allergic dermatitis, 8 of a reaction called hypersensitivity, and 5 of anaphylactic or anaphylactoid reactions": the categories sum to 26, not 27.
- p. 8 Safety, hypersensitivity paragraph
had 27 hypersensitivity reactions: 12 cases of urticaria or generalized urticaria, 1 of allergic dermatitis, 8 of a reaction called hypersensitivity, and 5 of anaphylactic or anaphylactoid reactions
- p. 8 Safety, hypersensitivity paragraph (left column below Figure 1)
had 27 hypersensitivity reactions: 12 cases of urticaria or generalized urticaria, 1 of allergic dermatitis, 8 of a reaction called hypersensitivity, and 5 of anaphy-
- p. 8 Safety, hypersensitivity paragraph
Twenty-five patients receiving natalizumab (4 percent) had 27 hypersensitivity reactions: 12 cases of urticaria or generalized urticaria, 1 of allergic dermatitis, 8 of a reaction called hypersensitivity, and 5 of anaphylactic or anaphylactoid reactions
- p. 8 Safety, hypersensitivity paragraph
had 27 hypersensitivity reactions: 12 cases of urticaria or generalized urticaria, 1 of allergic dermatitis, 8 of a reaction called hypersensitivity, and 5 of anaphylactic
Only the authors can say what is right here.
Judge's note: Read the p8 page image and crop; the digits are as quoted. The categories are listed as exhaustive and there is no 'other' category. The patient with two reactions (7th and 13th infusions) explains 25 patients versus 27 reactions, not the 26-versus-27 gap. Either the total or one category count is wrong, and only the authors can say which.
Second check: another model agreed
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5 minor (typos and the like; most checked by the judge only)
Wording Methods require "at least one medically documented relapse within the 12 months before the study began", yet Table 1 lists "0 — 6 (<1) / 6 (2) / 12 (1)" patients with no relapses in the past year, and the paper does not explain this.
- p. 2 Methods, Patients
had had at least one medically documented re-lapse within the 12 months before the study be-gan
- p. 6 Table 1, No. of relapses in past yr, row 0
12 (1)
Judge's note: Checked the inclusion criterion on p2 and the Table 1 row on p6 in the page images. 6+6=12 patients have 0 relapses, which the stated criterion should exclude. I found nothing in the text about protocol deviations or a different look-back window. These are probably eligibility deviations, so I file it as an observation, not an error.
Second check: another model agreed
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Wording Methods require "a score of 0 to 5.0 on the Expanded Disability Status Scale", but Table 1 reports EDSS "≥5.5 — 2 (<1) / 2 (<1) / 4 (<1)" and a range of "0–6" in both arms, with no explanation.
- p. 2 Methods, Patients
who had a score of 0 to 5.0 on the Expand-ed Disability Status Scale (EDSS)
- p. 6 Table 1, EDSS score
4 (<1)
Judge's note: Checked p2 (entry criterion) and Table 1 on p6 in the page images. Four patients had a baseline EDSS above the stated maximum. The paper does not say whether this is a screening-versus-baseline difference or a protocol deviation.
Second check: another model agreed
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Wording Conclusion: "Within the 30-month evaluation period of this trial", whereas elsewhere the trial is a two-year study with dosing "for up to 116 weeks" and patients who "completed the 120-week study".
- p. 11 Discussion, concluding paragraph
Within the 30-month evaluation period of this trial
- p. 4 Results, Study Population
completed the 120-week study
- p. 9 Discussion
natalizumab was safe as monotherapy over two years
- p. 2 Study Design
for up to 116 weeks
Only the authors can say what is right here.
Judge's note: Checked p11 (conclusion), p2 (116 weeks), the text on p4 (120-week study) and p9 ('safe as monotherapy over two years'). The paper defines no 30-month period anywhere. 120 weeks is about 27.6 months. The authors need to say what the 30 months refers to.
Second check: another model agreed
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Wording "Because of adverse effects ... 3 percent of patients receiving natalizumab and 2 percent receiving placebo withdrew from the study", while Figure 1 shows "15 Had adverse event" of 627 natalizumab patients (2.4%).
- p. 8 Safety, last paragraph
and 3 percent of patients receiving natali-zumab and 2 percent receiving placebo withdrew from the study
- p. 8 Figure 1, natalizumab withdrawals
15 Had adverse event
- p. 8 Safety, last paragraph (right column)
3 percent of patients receiving natali-zumab and 2 percent receiving placebo withdrew
- p. 8 text after hypersensitivity paragraph
3 percent of patients receiving natali-
Only the authors can say what is right here.
Judge's note: Checked the p8 text and Figure 1 in the image. 15/627 rounds to 2%, not 3%. The placebo figure matches (6/312 or 6/315 is about 2%). Counting the 2 deaths as adverse events would give 17/627 = 2.7%, which rounds to 3%, but the paper does not say this. Figure 1 may also list only the primary reason for withdrawal. I file this as a query.
Second check: another model agreed
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Typo Dr. Polman's disclosure: "grant support from Biogen Idec and Schering, Wyeth, and GlaxoSmithKline": the 'and' after the first item breaks the series.
- p. 11 Disclosures, Dr. Polman
grant support from Biogen Idec and Schering, Wyeth, and GlaxoSmithKline
Judge's note: Confirmed in the p11 image. This is a cosmetic list-punctuation inconsistency; the authors may have meant to group the first two companies.
Second check: none (judge only)