Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis
2000 · paper · Clinical trials
A 54-week trial of 428 rheumatoid arthritis patients with active disease despite methotrexate, adding infliximab or placebo. Combination therapy gave greater clinical response (51.8% vs 17.0%) and halted progression of joint damage.
7 findings
Substance Table 4, 10 mg every 4 wk column (N=66): subgroup changes are printed as "1.4±4.0" (clinical response, n=44) and "0.7±3.2" (no clinical response, n=22), both positive, but the whole-group total score change is "−0.7±3.8"; a minus sign appears to be missing on 1.4.
- p. 7 Table 4, Clinical response, Total radiographic score, last column
1.4±4.0
- p. 7 Table 4, No clinical response, Total radiographic score, last column
0.7±3.2
- p. 7 Table 4, Total score, last column (N=66)
0.7±3.8
Only the authors can say what is right here.
Judge's note: Read Table 4 on the p7 image. The minus sign is printed on −0.7±3.8, −0.7±3.0 and −1.1±6.4 but not on 1.4±4.0, so this is not an extraction loss. 44+22 = 66, so the subgroups partition the column. Weighted mean as printed is +1.17, against a printed −0.7; with −1.4 it is exactly −0.70. The same check reproduces the totals in the other four columns (6.94 vs 7.0, 1.30 vs 1.3, 1.64 vs 1.6, 0.14 vs 0.2). The total of −0.7 is independently supported by the abstract's pooled infliximab mean of 0.6 (N-weighted mean of 1.3, 1.6, 0.2, −0.7 is 0.61). The row label for this row says only "increase from base line". No footnote or text explains it. The responder value is the likely error, but only the authors can confirm the correct figure.
Second check: another model agreed
Report a problem with this finding
Substance Table 4, 3 mg every 4 wk column: erosion score change "0.3±4.7" plus joint-space-narrowing change "0.7±4.3" gives 1.0, but the total score change is printed as "1.6±8.5".
- p. 7 Table 4, Total score, 3 mg every 4 wk column
1.6±8.5
- p. 7 Table 4, Erosion score, 3 mg every 4 wk column
0.3±4.7
- p. 7 Table 4, Joint-space–narrowing score, 3 mg every 4 wk column
0.7±4.3
Only the authors can say what is right here.
Judge's note: Read Table 4 on the p7 image. The footnote defines the total (0 to 440) as the sum of the erosion (0 to 280) and joint-space-narrowing (0 to 160) subscales, so mean changes are additive in the same patients. The other four columns reconcile within rounding: 4.0+2.9 = 6.9 vs 7.0; 0.2+1.1 = 1.3; 0.2+0.0 = 0.2; −0.7+0.0 = −0.7. Here the gap is 0.6, far beyond rounding. One N (71) is given for the column and no text describes a different set for the subscales. The total of 1.6 is supported by the responder/non-responder split (1.64) and by the abstract's pooled 0.6, so the erosion or joint-space-narrowing entry is the likely error; the authors must say which.
Second check: another model agreed
Report a problem with this finding
Reference or label Text cites Table 4 for a result it does not contain: "when erosions and joint-space narrowing were examined independently and when the hands and feet were examined separately (Table 4)"; Table 4 has no hand or foot rows.
- p. 6 Results, Radiographic Evaluation, left column
when the hands and feet were examined separately (Table 4)
- p. 7 Table 4
Joint-space–narrowing score
- p. 7 Table 4 row labels
Erosion score (increase or decrease
Only the authors can say what is right here.
Judge's note: Read the sentence on the p6 image and every row label of Table 4 on the p7 image: total score, erosion score, joint-space-narrowing score, major progression, improvement, clinical response, no clinical response, duration of disease 3 yr or less. Nothing by hands or feet. The pointer supports only the erosion/joint-space-narrowing clause; the hand/foot analysis is not shown anywhere and is not marked "data not shown", unlike other unreported analyses in the same paragraph.
Second check: another model agreed · checked by hand
Report a problem with this finding
Reference or label Reference 23 is printed as "Arthritis Rheum 1991;35:26-34.", while reference 31 gives "Arthritis Rheum 1991;34:660-8."; year and volume in reference 23 do not agree (volume 35 corresponds to 1992).
- p. 9 Reference 23 (continued from previous page)
1991;35:26-34.
- p. 9 Reference 31
Arthritis Rheum 1991;34:660-8.
Judge's note: Read references 23 to 31 on the p9 image and references 5, 11, 13, 14 on the p8 image. Within this reference list Arthritis Rheum runs one volume per year: 1980;23, 1986;29, 1991;34, 1993;36, 1996;39, 1998;41. Volume 35 therefore falls in 1992, so reference 23 is internally inconsistent with the rest of the list. Pages 26-34 are from the start of a volume, which fits volume 35 (1992) and not volume 34, so the year is the likely error. The inconsistency is established from the file; the exact correct year should be confirmed against the cited article.
Second check: another model agreed
Report a problem with this finding
Wording Methods list "the health assessment questionnaire estimate of disability" among measures "all of which were assessed with the use of visual-analogue scales (range, 0 to 10 cm, with higher scores indicating poorer status or more severe pain)", but the next paragraph says the Health Assessment Questionnaire is scored "on a scale ranging from 0 (no difficulty) to 3 (unable to perform the activity)".
- p. 2
were assessed with the use of visual-analogue scales (range, 0 to 10 cm,
Judge's note: Viewed the crop of PDF page 2. The sentence defining ACR 20 names four measures (patient's global assessment, patient's pain, HAQ disability estimate, physician's global assessment) and says all were assessed on 0 to 10 cm visual-analogue scales. The paragraph immediately below describes the HAQ as a self-administered questionnaire scored 0 to 3, and Table 1 reports baseline HAQ scores of about 1.7 to 1.8, consistent with the 0 to 3 scale. The 'all of which' wording therefore misdescribes the HAQ; no statement elsewhere says a visual-analogue version of the HAQ was used. A wording defect only, the data are unaffected.
Second check: another model agreed
Report a problem with this finding
Wording Between-group radiographic comparison is reported as "(P<0.001, by Wilcoxon's signed-rank test)", a test that the Statistical Analysis section does not mention (it specifies chi-square, analysis of variance, Fisher's exact test and linear contrasts).
- p. 5 Results, Radiographic Evaluation of Joint Damage
(P<0.001, by Wilcoxon’s signed-rank test)
- p. 2 Methods, Statistical Analysis
analysis of variance to evaluate continuous variables
- p. 5 Results, Radiographic Evaluation
by Wilcoxon’s signed-
Only the authors can say what is right here.
Judge's note: Read the Results sentence on the p5 image and the Statistical Analysis section on the p2 image. Methods say "analysis of variance to evaluate continuous variables" and "pairwise comparisons using linear contrasts"; no Wilcoxon or other rank test is described anywhere in the article. That inconsistency is verifiable in the file. The further point that a signed-rank test is a paired test, so a comparison of independent groups would use the rank-sum test, is a statistical-methods point the authors would need to clarify (the name may be a slip for rank-sum).
Second check: another model agreed
Report a problem with this finding
Wording Text lists serum C-reactive protein among components for which "all dosages of infliximab plus methotrexate were superior to methotrexate and placebo (P<0.001, except in the case of pain in the group given 3 mg per kilogram every eight weeks, for which P=0.016)", but Table 2 gives P=0.006 for C-reactive protein in the 3 mg every 8 wk group.
- p. 3 Results, Efficacy, left column
(P<0.001, except in the case of pain in the group given 3 mg per kilogram every eight weeks, for which P=0.016)
- p. 4 Table 2, Serum C-reactive protein, P value, 3 mg every 8 wk column
0.006
- p. 3 Results, Efficacy
superior to methotrexate and placebo (P<0.001, except in the case of pain in the group given 3 mg per kilogram every eight weeks, for which P=0.016)
- p. 3 Results, Efficacy
all dosages of infliximab plus methotrexate were superior to methotrexate and placebo (P<0.001, except in the case of pain in the group given 3 mg per kilogram every eight weeks
Only the authors can say what is right here.
Judge's note: Checked the sentence on the p3 image and Table 2 on the p4 image: the CRP P-value row reads 0.006 / <0.001 / <0.001 / <0.001. Swollen and tender joints are <0.001 in all four columns, so CRP at 3 mg every 8 wk is a second, unstated exception. Searched the text for another CRP analysis (e.g. percent change) that could carry P<0.001; none is described, and Table 2 is the only CRP comparison shown. The result is still significant, so the direction is unaffected; the text misdescribes the table. Authors could say whether the text refers to a different CRP analysis.
Second check: another model agreed
Report a problem with this finding
6 minor (typos and the like; most checked by the judge only)
Wording Discussion (p. 1601) says "in 40 to 55 percent of the patients, the radiographic evidence of joint damage decreased", but Table 4 (Improvement row: 44, 48, 39, 55) and the Results (p. 1599, "39 to 55 percent vs. 14 percent") give a lower bound of 39 percent.
- p. 8 Discussion, paragraph on current therapies
but in 40 to 55 percent of the
- p. 6 Results, Radiographic Evaluation, right column
(39 to 55 percent vs. 14 percent)
- p. 7 Table 4, Improvement (% of patients)
39
- p. 8
in 40 to 55 percent of the patients,
Judge's note: I checked the page images. In Table 4 on p. 1600 (PDF p7), the 'Improvement (% of patients)' row reads 14 for methotrexate plus placebo, then 44, 48, 39 and 55 for the four infliximab groups. The lowest of these is 39, in the 10 mg/kg every 8 wk group. The Results crop (PDF p6) says "39 to 55 percent vs. 14 percent". The Discussion crop (PDF p8) says "40 to 55 percent" for the same quantity, population and 54-week timepoint. I found no definition of a different population or pooling that would explain the 40, and no erratum for this article among the files. The only erratum mentioned is inside reference entry 1696, which is about another paper. The 40 is probably 39 rounded loosely, but it disagrees with the paper's own Results and table, so it should read 39 to 55. I rate it minor because the difference is 1 percentage point.
Second check: another model agreed
Report a problem with this finding
Typo Affiliation footnote uses a comma where every other institution is separated by a semicolon: "Duke University Medical Center, Durham, N.C. (E.W.S.), Virginia Mason Research Center, Seattle (D.E.F.);".
- p. 1 Author affiliation footnote
(E.W.S.), Virginia Mason Research Center, Seattle (D.E.F.)
Judge's note: Read the footnote on the p1 image. All other affiliations end with "(initials);"; only the one after (E.W.S.) is followed by a comma. Punctuation slip, meaning recoverable.
Second check: none (judge only)
Report a problem with this finding
Typo Redundant qualifier in the eligibility criteria: "and at least two or more of the following: morning stiffness ..., an erythrocyte sedimentation rate ..., and a serum C-reactive protein concentration".
- p. 2 Methods, Patients (top of left column)
and at least two or more of the following
- p. 2 Methods, Patients
at least two or more of the following
Judge's note: Read on the p2 image, top of the left column. "at least two" and "two or more" are doubled. Meaning is unchanged (two of the three listed items); cosmetic only.
Second check: none (judge only)
Report a problem with this finding
Typo Reference 21 prints the third author as "Nuver-Zwat IH"; the surname is probably Nuver-Zwart.
- p. 8 Reference 21
Nuver-Zwat IH
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that the coauthor of the 1989 Lancet paper on hydroxychloroquine and sulphasalazine is Nuver-Zwart IH. The p8 image does print "Nuver-Zwat IH". Nothing in the files gives the correct spelling; it needs checking against the cited article.
Second check: none (judge only)
Report a problem with this finding
Typo Reference 16 prints the third author as "Keller SK"; the SF-36 summary scales manual is probably by Keller SD.
- p. 8 Reference 16
Keller SK
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that the authors of "SF-36 physical and mental health summary scales: a user's manual" (1994) are Ware JE Jr, Kosinski M, Keller SD. The p8 image does print "Keller SK". Not verifiable from the files; needs checking against the cited manual.
Second check: none (judge only)
Report a problem with this finding
Typo Reference 29 prints the authors as "Parker SL, Tong T, Bolder S, Wingo P."; the third author is probably Bolden S.
- p. 9 Reference 29
Parker SL, Tong T, Bolder S, Wingo P.
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: that the authors of "Cancer statistics, 1997" (CA Cancer J Clin 1997;47:5-27) are Parker SL, Tong T, Bolden S, Wingo PA. The p9 image does print "Bolder S, Wingo P." Not verifiable from the files; needs checking against the cited article.
Second check: none (judge only)