Supplementary tables
Table S1Baseline characteristics of the patients enrolled inthe RISING study.
Characteristics / DataN=327
Gender (female), % / 81.7
Mean age, years / 49.9 ± 12.0
Mean disease duration, years / 8.2 ± 8.0
IP as comorbidity, % / 0.3*
Rheumatoid factor positive, % / 85.9
Anti-CCP antibody positive, % / 91.4
Mean DAS28-ESR at week 0 / 6.2 ± 0.9
Mean HAQ at week 0 / 1.21 ± 0.65
Mean modified total Sharp score at week 0 / 49.9 ± 50.6
Mean dose of MTX at week 0, mg/week / 7.8 ± 1.7
Corticosteroid use at week 0, % / 68.2
DMARDs other than MTX use at week 0, % / 30.9
Serum KL-6 at week 0, U/ml / 254.4 ± 135.8
Serum KL-6 >=500 U/ml at week 0, % / 3.1
Baseline data from 327 patients who received open-label treatment with 3mg/kg of infliximab (IFX) are shown. Data are shown as mean +/- SD if not otherwise mentioned.
*Two other patients had rheumatoid lung as a comorbidity.IP = interstitial pneumonia, CCP = circulated citrullinated peptide, DAS28-ESR = disease activity score with 28 joint counts and erythrocyte sedimentation rate, HAQ = health assessment questionnaires, MTX = methotrexate, DMARDs = disease-modifying antirheumatic drugs
Table S2Baseline characteristics of the patients enrolled inthe HIKARI and J-RAPID studies.
(without MTX)
N=230 / J-RAPID
(MTX combination)
N=316
Gender (female), % / 74.3 / 82.9
Mean age, years / 55.7 / 53.0
Mean disease duration, years / 5.6 / 5.8
IP as comorbidity, % / 12.2 / 2.2
Rheumatoid factor positive, % / 87.4 / 88.0
Mean DAS28-ESR at week 0 / 6.2 / 6.3
Mean HAQ at week 0 / 1.13 / 1.15
Mean modified total Sharp score at week 0 / 41.3 / 51.8
Mean dose of MTX at week 0 (mg/week) / N/A / 7.5
Corticosteroid use at week 0, % / 68.7 / 65.8
DMARDs other than MTX at week 0, % / 55.2 / N/A
Baseline characteristics of full analysis set patients (FAS patients) with available serum. KL-6 data are shown.
Anti-citrullinated peptide antibody was not measured in these trials. Because patients were randomized in both clinical trials, baseline characteristics in the total patient population aresummarized.
IP = interstitial pneumonia, DAS28-ESR = disease activity score with 28 joint counts and erythrocyte sedimentation rate, HAQ = health assessment questionnaire, MTX = methotrexate, DMARDs = disease-modifying antirheumatic drugs
Table S3Baseline data for serum KL-6 levels in the HIKARI and J-RAPID studies.
Treatment group* / Number of patients / KL-6 (U/ml)
Mean+/-SD / KL-6>=500U/ml
Number (%) / Number of patients / KL-6 (U/ml)
Mean+/-SD / KL-6>=500 U/ml
Number (%)
100mg / N/A / N/A / N/A / 72 / 244.6+/-110.5 / 3 (4.2)
200mg / 116 / 312+/-185.1 / 13 (11.2) / 82 / 261.0+/-108.9 / 5 (6.1)
400mg / N/A / N/A / N/A / 85 / 251.4+/-98.1 / 2 (2.4)
Placebo / 114 / 305.1+/-179.7 / 10 (8.8) / 77 / 252.2+/-96.1 / 2 (2.6)
*In J-RAPID, patients received placebo, certolizumab pegol 100mg, 200mg, or 400mg with concomitant methotrexate (MTX).
N/A = not applicable, SD = standard deviation
Table S4Baseline characteristics of patients enrolled inthe GO-MONO and GO-FORTH studies.
GO-MONO(monotherapy)
N=250 / GO-FORTH
(MTX combination)
N=212
Gender (female), % / 80.8 / 87.3
Mean age, years / 51.9 / 49.7
Mean disease duration, years / 9.1 / 8.3
IP as comorbidity, % / 0 / 0
Rheumatoid factor positive, % / 81.5 / 78.8
Anti-CCP antibody, U/ml / 87.2 / 88.2
Mean DAS28-ESR at week 0 / 5.8 / 5.5
Mean HAQ at week 0 / 0.98 / 0.94
Mean modified total Sharp score at week 0 / 54.8 / 54.7
Mean dose of MTX at week 0, mg/wk / N.A. / 7.5
Corticosteroid use* at week 0, % / 71.6 / 65.6
Use of DMARDs other than MTX at week 0, % / 0 / 0
Baseline characteristics of patients who gave consent to measure serum KL-6 levels and had available data are shown. Because patients were randomized in both clinical trials, baseline characteristics inthetotal patient population aresummarized. Rheumatoid arthritis patients with IP were excluded from both trials by the protocols. Use of disease-modifying antirheumatic drugs (DMARDs) other than MTX was not allowed by the protocols.* = oral or suppository, IP = interstitial pneumonia, CCP = circulated citrullinated peptide, DAS28-ESR = disease activity score with 28 joint counts and erythrocyte sedimentation rate, HAQ = health assessment questionnaires, MTX = methotrexate
Table S5Baseline data for serum KL-6 levels in the GO-MONO and GO-FORTH studies.
Number of patients* / KL-6 (U/ml)
Mean+/-SD / KL-6>=
500U/ml
Number (%) / Number of patients * / KL-6 (U/ml)
Mean+/-SD / KL-6 >=500 U/ml
Number (%)
50 mg / 79 / 271.8+/-103.7 / 3 (3.8) / 68 / 248.4+/-87.6 / 2 (2.9)
100 mg / 91 / 249.8+/-76.7 / 0 (0.0) / 72 / 234.7+/-74.7 / 0 (0.0)
Placebo / 80 / 252.7+/-92.4 / 1 (1.3) / 72 / 262.4+/-95.0 / 3 (4.2)
*: Number of patients who gave consent to measure serum KL-6 levels and had available data.
†: In GO-FORTH, patients received placebo, golimumab 50mg, or golimumab 100mg with concomitant MTX.
SD = standard deviation
Table S6Pulmonary events associated with elevated serum KL-6 levels (criteria B) by week 54 in all the patients or in each treatment group in the RISING study.
total / 3mg/kg / 6mg/kg / 10mg/kgNumber of patients meeting criteria B by week 54 / 51* / 14 / 16 / 17
Pneumocystisjirovecipneumonia / 1† / 0 / 0 / 0
Interstitial lung disease / 2‡ / 0 / 0 / 1
Pulmonary fibrosis / 0 / 0 / 0 / 0
Pulmonary interstitial emphysema syndrome / 0 / 0 / 0 / 0
No event / 48 / 14 / 16 / 16
Pathological events areclassified by the preferred terms (PTs) of MedDRA ver. 12.0.
*: including 4 patients who did not enter the double-blind phase.
†: a suspected case of Pneumocystisjirovecipneumonia
‡: one of the two patients had elevation of serum KL-6 level and diffuse micro-nodular opacity on thoracic computed tomography at week 6 and, and did not enter the double-blind period. Final diagnosis of this adverse event was interstitial pneumonia.
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