SUPPLEMENTARY MATERIAL
Supplementary Table S1. Baseline characteristics of patients with rheumatoid arthritis for the overall population, according to treatment.
Abatacept csDMARDs Total
Overall (n=114) Overall (n=88) (n=202)
Age (years) 65.6±13.7 64.1±13.5 64.9±13.6
Female sex 91 (79.8) 76 (86.4) 167 (82.7)
Disease duration (years) 8.6±10.6 7.5±9.2 8.1±10.0
Steinbrocker Stage / / / Ⅰ Ⅱ Ⅲ Ⅳ 33/33/28/20 41/24/16/7 * 74/57/44/27 Steinbrocker Class / / / Ⅰ Ⅱ Ⅲ Ⅳ 19/79/15/1 56/27/5/0 * 75/106/20/1
Swollen joint count 6.0±4.3 3.7±2.6 * 5.0±3.8
Tender joint count 5.9±4.8 2.3±3.1 * 4.3±4.5
CRP level (mg/dL) 1.9±2.8 0.5±0.9 * 1.3±2.3
ESR (mm/h) 41.7±29.2 21.9±17.3 * 33.1±26.6
Patient’s global VAS score (mm) 50.7±24.4 34.3±25.4 * 43.6±26.1 Physician’s global VAS score (mm) 46.2±19.9 29.6±14.4 * 39.0±19.5
DAS28-ESR 5.0±1.2 3.6±1.1 * 4.4±1.3
DAS28-CRP 4.4±1.2 3.0±0.9 * 3.8±1.2
SDAI 23.5±11.1 12.8±6.9 * 18.8±10.9
CDAI 21.6±10.1 12.3±6.6 * 17.5±9.9
HAQ score 0.8±0.7 0.4±0.7 * 0.7±0.7
RF-positive 97 (85.1) 63 (71.6) * 160 (79.2)
Anti-CCP-positive 96 (84.2) 65 (73.9) 161 (79.7)
Interstitial pneumonia 15 (13.2) 6 (6.8) 21 (10.4)
Steroid use 52 (45.6) 27 (30.7) * 79 (39.1)
Prednisolone (mg) 5.5±4.2 3.9±1.4 * 4.9±3.5
MTX use 75 (65.8) 51 (57.8) 126 (62.4)
Salazosulfapyridine 26 (22.8) 12 (13.6) 38 (18.8)
Bucillamine 10 (8.8) 20 (22.7) * 30 (14.9)
Tacrolimus 15 (13.2) 5 (5.7) 20 (9.9)
Iguratimod 12 (10.5) 3 (3.4) 15 (7.4)
Mizoribine 1 (0.9) 0 (0) 1 (0.5)
Additional treatment initiated during this study
Abatacept 114 (100) -
1 2 3 4 5
MTX - 20 (22.7)
Salazosulfapyridine - 9 (10.2)
Bucillamine - 21 (23.9)
Tacrolimus - 7 (8.0)
Iguratimod - 28 (31.8)
Leflunomide - 3 (3.4)
Results are shown as mean standard deviation or n (%). Student’s t-test was used for continuous variables. The chi-squared test was used for categorical variables. * p<0.05, abatacept vs csDMARDs
Abbreviations: CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; DAS28, disease activity score in 28 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; MTX, methotrexate; RF, rheumatoid factor; SDAI, Simple Disease Activity Index; VAS, visual analog scale
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Supplementary Table S2. Detailed efficacy results for the abatacept and csDMARDs overall groups.
Abatacept csDMARDs OR (95% CI)
p-value Overall (n=114) Overall (n=88)
Week 12
Proportion of patients with good
EULAR response (%) 31.6 22.7 1.569 (0.831–
2.964) 0.2168
Proportion of patients with good or
moderate EULAR response (%) 71.1 47.7 2.688 (1.502–
4.811) 0.0013
Change in DAS28-ESR from
baseline −1.565±1.325 −0.600±0.876 <0.0001
Change in SDAI from baseline −12.826±11.232 −4.018±5.356 <0.0001
Change in DAS28-CRP from
baseline −1.520±1.263 −0.537±0.821 <0.0001
Change in CDAI from baseline −11.729±10.473 −3.882±5.350 <0.0001
Week 24
Proportion of patients with good
EULAR response (%) 38.6 23.9 2.005 (1.081–
3.722) 0.0384
Proportion of patients with good or
moderate EULAR response (%) 81.6 43.2 5.827 (3.091–
10.987) <0.0001 Change in DAS28-ESR from
baseline −1.808±1.319 −0.674±1.002 <0.0001
Change in SDAI from baseline −14.520±11.930 −4.669±6.769 <0.0001
Change in DAS28-CRP from
baseline −1.784±1.287 −0.633±0.920 <0.0001
Change in CDAI from baseline −13.195±10.995 −4.479±6.480 <0.0001
Overall change in steroid dose
(mg/day) −1.332±3.081 −0.173±0.373 0.0123
Results are shown as mean standard deviation unless otherwise stated. Student’s t-test was used for continuous variables. The chi-squared test was used for categorical variables.
Abbreviations: CDAI, Clinical Disease Activity Index; CI, confidence interval; CRP, C-reactive protein; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; DAS28, disease activity score in 28 joints; ESR, erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; SDAI, Simple Disease Activity Index; SDAI, Simple Disease Activity Index 1
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Supplementary Table S3. Baseline characteristics of the patients with rheumatoid arthritis after propensity-score matching to compare between AY and CY, and AO and CO.
AY; n=25 CY; n=25 p-value AO; n=31 CO; n=31 p-value
Age (years) 54.3±9.6 51.7±8.8 0.3222 74.4±6.1 74.5±5.8 0.9157
Female sex 22 (88.0) 22 (88.0) 1.0000 24 (77.4) 27 (87.1) 0.5061
Disease duration (years) 8.0±10.8 6.4±7.7 0.5340 9.0±9.5 9.3±11.3 0.8901
Steinbrocker Stage / / / Ⅰ Ⅱ Ⅲ Ⅳ 6/10/4/5 14/7/2/2 0.1282 10/8/7/6 11/9/8/3 0.7595
Steinbrocker Class / / / Ⅰ Ⅱ Ⅲ Ⅳ 5/18/2/0 15/9/1/0 Not calculable
7/18/5/1 15/12/4/0 0.1564
Swollen joint count 4.3±2.9 4.1±3.1 0.8140 4.5±4.4 4.0±3.0 0.5932
Tender joint count 2.9±2.6 2.8±3.1 0.9213 4.4±4.3 3.1±4.1 0.2326
CRP level (mg/dL) 0.5±0.8 0.5±0.5 0.9559 0.9±1.0 0.9±1.3 0.9779
ESR (mm/h) 20.3±13.7 20.1±16.8 0.9707 30.5±20.5 31.7±19.4 0.8113
Patient's global VAS score (mm) 37.5±22.9 35.3±21.4 0.7273 44.2±26.3 42.2±28.6 0.7688
Physician's global VAS score (mm) 32.1±15.0 35.2±15.7 0.4880 36.2±17.1 33.8±14.3 0.5446
DAS28-ESR 3.9±0.7 3.7±0.9 0.4125 4.4±1.2 4.2±1.1 0.4708
DAS28-CRP 3.3+0.7 3.2±0.8 0.7199 3.8±1.1 3.5±1.0 0.2335
SDAI 14.6±5.0 14.4±5.8 0.8933 17.8±9.6 15.6±8.3 0.3249
CDAI 14.2±5.0 14.0±5.7 0.8980 16.9±9.3 14.7±8.1 0.3105
HAQ score 0.5±0.6 0.3±0.5 0.2167 0.8±0.8 0.8±0.9 0.8422
RF positive 20 (80.0) 20 (80.0) 1.0000 25 (80.6) 23 (74.2) 0.7613
anti-CCP antibody positive 21 (84.0) 22 (88.0) 1.0000 25 (80.6) 24 (77.4) 1.0000
1 2 3
steroid use 8 (32.0) 6 (24.0) 0.7528 14 (45.2) 11 (35.5) 0.6046
prednisolone (mg) 5.2±3.3 3.3±2.0 0.2114 6.6±6.2 4.2±1.4 0.1957
MTX use 20 (80.0) 19 (76.0) 1.0000 20 (64.5) 18 (58.1) 0.7943
Results are shown as mean standard deviation or n (%). Student’s t-test was used for continuous variables. The chi-squared test was used for categorical variables.
AO, older patients receiving abatacept; AY, younger patients receiving abatacept; CCP, cyclic citrullinated peptide; CDAI, Clinical Disease Activity Index;
CO, older patients receiving conventional synthetic disease-modifying antirheumatic drugs; CRP, C-reactive protein; CY, younger patients receiving conventional synthetic disease-modifying antirheumatic drugs; DAS28, disease activity score in 28 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; MTX, methotrexate; RF, rheumatoid factor; SDAI, Simple Disease Activity Index; VAS, visual analog scale
1 2 3 4 5 67
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Supplementary Table S4. Baseline characteristics of patients with rheumatoid arthritis for the overall population after propensity-score matching to compare abatacept and csDMARDs.
Abatacept Overall (n=58)
csDMARDs Overall (n=58)
p value
Age (years) 63.5±12.7 65.7±13.2 0.3618
Female sex 49 (84.5) 51 (87.9) 0.7877
Disease duration (years) 8.2±9.5 7.5±9.3 0.6892
Steinbrocker Stage / / /Ⅰ Ⅱ Ⅲ Ⅳ 20/16/12/10 26/14/13/5 0.4535
Steinbrocker Class / / /Ⅰ Ⅱ Ⅲ Ⅳ 13/40/4/1 31/23/4/0 0.0047
Swollen joint count 3.9±3.3 4.1±2.8 0.7387
Tender joint count 3.4±2.9 2.8±3.6 0.3681
CRP level (mg/dL) 0.7±1.2 0.7±1.0 0.7782
ESR (mm/h) 25.9±17.8 25.7±19.2 0.9453
Patient's global VAS score (mm) 40.9±23.6 39.9±25.9 0.8198
physician's global VAS score (mm) 33.8±15.3 33.4±14.9 0.8733
DAS28-ESR 4.1±0.9 3.9±1.1 0.3528
DAS28-CRP 3.5±0.8 3.4±0.9 0.3028
SDAI 15.6±5.9 15.0±7.1 0.6406
CDAI 14.8±6.0 14.3±6.9 0.6699
HAQ score 0.6±0.6 0.6±0.8 0.8444
RF positive 44 (75.9) 43 (74.1) 1.0000
anti-CCP antibody positive 46 (79.3) 46 (79.3) 1.0000
steroid use 21 (36.2) 23 (39.7) 0.8482
prednisolone (mg) 5.5±5.3 3.7±1.5 0.1654
MTX use 44 (75.9) 39 (67.2) 0.4104
Results are shown as mean standard deviation or n (%). Student’s t-test was used for continuous variables. The chi-squared test was used for categorical variables.
CCP, cyclic citrullinated peptide; CDAI, Clinical Disease Activity Index; CRP, C-reactive protein;
DAS28, disease activity score in 28 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; MTX, methotrexate; RF, rheumatoid factor; SDAI, Simple Disease Activity Index; VAS, visual analog scale
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4 5 6 7 8 9 10
Supplementary Table S5. Baseline characteristics of AO and AY groups adjusted after propensity- score matching.
AY; n=38 AO; n=38 p-value
Age (years) 52.2±10.4 74.2±5.7 <0.0001
Female sex 29 (76.3) 26 (68.4) 0.6079
Disease duration (years) 6.7±8.6 5.8±6.1 0.6245
Steinbrocker Stage / / / Ⅰ Ⅱ Ⅲ Ⅳ 14/12/7/5 13/11/8/6 0.9712 Steinbrocker Class / / / Ⅰ Ⅱ Ⅲ Ⅳ 7/28/3/0 9/28/1/0 NaN
Swollen joint count 5.4±3.3 5.8±5.4 0.6995
Tender joint count 5.4±4.3 4.6±4.3 0.3940
CRP level (mg/dL) 1.7±3.5 1.7±2.3 0.9997
ESR (mm/h) 33.2±29.3 37.7±24.8 0.4778
Patient's global VAS score(mm) 50.1±25.0 46.5±22.6 0.5141 Physician's global VAS score
(mm)
43.7±21.2 42.4±18.7 0.7663
DAS28-ESR 4.7±1.1 4.6±1.3 0.7080
DAS28-CRP 4.1±1.1 4.1±1.1 0.7481
SDAI 22.0±10.2 21.0±11.5 0.7074
CDAI 20.2±9.0 19.3±10.7 0.6796
HAQ score 0.7±0.6 0.7±0.5 0.9801
RF positive 30 (78.9) 30 (78.9) 1.0000
anti-CCP antibody positive 32 (84.2) 31 (81.6) 1.0000
steroid use 14 (36.8) 13 (34.2) 1.0000
prednisolone (mg) 5.3±4.0 5.7±6.1 0.8417
MTX use 29 (76.3) 31 (81.6) 0.7784
Results are shown as mean standard deviation or n (%). Student’s t-test was used for continuous variables. The chi-squared test was used for categorical variables.
AO, older patients receiving abatacept; AY, younger patients receiving abatacept; CCP, cyclic citrullinated peptide; CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; DAS28, disease activity score in 28 joints; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; MTX, methotrexate; RF, rheumatoid factor; SDAI, Simple Disease Activity Index;
VAS, visual analog scale 1
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4 5 6 7 8 9 10
Supplementary Figure S1. Changes in absolute number of DAS28-ESR and SDAI.
Error bars represent standard deviations.
Abbreviations: csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; DAS28- ESR, disease activity score in 28 joints using erythrocyte sedimentation rate; SDAI, Simple Disease Activity Index
1 2 3 4 5
1
2
Supplementary Figure S3. Proportions of EULAR responses at week 24 (a) and changes in DAS28-ESR (b) and SDAI (c) from baseline at week 24 during treatment of older and younger patients with rheumatoid arthritis after propensity-score matching. Proportions of patients with a EULAR good response vs those with a EULAR moderate or no response were compared using the chi-squared test. Error bars represent standard deviations. Comparisons 12
3 4 5
between groups were performed using Student’s t-test.
Abbreviations: DAS28-ESR, disease activity score in 28 joints using erythrocyte sedimentation rate; EULAR, European League Against Rheumatism;
SDAI, Simple Disease Activity Index 1
2 3 4
Supplementary Figure S4. Proportions of EULAR responses at week 24 (a) and changes in DAS28-ESR (b) and SDAI (c) from baseline at week 24 during treatment of overall patients with rheumatoid arthritis after propensity-score matching. Proportions of patients with a EULAR good response vs those with a EULAR moderate or no response were compared using the chi-squared test. Error bars represent standard deviations. Comparisons between groups were performed using Student’s t-test.
Abbreviations: csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; DAS28-ESR, disease activity score in 28 joints using erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; SDAI, Simple Disease Activity Index
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Supplementary Figure S5. Proportions of EULAR responses at week 24 (a) and changes in DAS28-ESR (b) and SDAI (c) from baseline at week 24 12
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Supplementary Figure S6. Proportions of EULAR responses at week 12 and 24 (a) and changes in DAS28-ESR (b) and SDAI (c) from baseline at weeks 12 and 24 during treatment of A-EO and A-YO groups. Proportions of patients with a EULAR good response vs those with a EULAR moderate or no response were compared using the chi-squared test. Error bars represent standard deviations. Comparisons between groups were performed using Student’s t-test.
Abbreviations: A-EO, elderly-onset patients receiving abatacept; A-YO, young-onset patients receiving abatacept; DAS28-ESR, disease activity score in 28 joints using erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; SDAI, Simple Disease Activity Index
12 3 4 5 6 7 8
1
Abbreviations: csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; DAS28-ESR, disease activity score in 28 joints using erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; SDAI, Simple Disease Activity Index
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Appendix List of collaborators
ABT-ATS study group: Z. Yamada, S. Masuoka, S. Mizutani, S. Yamada, M. Kawazoe, H. Sato, M.
Kaburaki, S. Muraoka, K. Kaneko, T. Nanki, Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine (Omori), Tokyo, Japan; W. Hirose, Hirose Clinic of Rheumatology, Saitama, Japan; Y. Kimura, K. Asako, H. Kikuchi, H. Kono, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan; K. Nishimura, Department of Orthopaedic Surgery, Teikyo University School of Medicine, Tokyo, Japan; N. Abe, S. Tanimura, S.
Yasuda, T. Atsumi, Department of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Hokkaido, Japan; Y. Komano, Department of Rheumatology, Jujo Takeda Rehabilitation Hospital, Kyoto, Japan; H. Kawano, J.
Kishi, Y. Nishioka, Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan; T Hidaka, Insutitute of Rheumatology, Zenjinkai Miyazaki-Zenjinkai Hospital, Miyazaki, Japan; S. Nakashima, Y.
Takeuchi, H. Dobashi, Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan; T Kasama, Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan; D. Kanai, A. Ihata, Department of Rheumatology, Yokohama Minami Kyosai Hospital, Kanagawa, Japan; M. Inoo, Utazu Hospital, Ayauta-gun, Kagawa, Japan; K. Suemori, H. Hasegawa, Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Ehime, Japan; T. Okano, M. Tada, Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan; S. Tsuboi, Department of Rheumatology, Shizuoka Kosei Hospital, Shizuoka, Japan; K. Kubo, T. Sugihara, Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan; S. Tsunoda, H.
Sano, Division of Rheumatology, Department of Internal Medicine Hyogo College of Medicine, Hyogo, Japan; R. Yoshimi, Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Kanagawa, Japan; Y. Shimizu, S. Fukaya, T. Odani, Third Department of Internal Medicine, Obihiro-Kosei General Hospital, Hokkaido, Japan; K. Amano, Department of Immunology and Rheumatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan; Y. Inoue, H. Kameda, Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine (Ohashi), Tokyo, Japan; T. Nagai, Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan (Currently, T. Nagai, Department of Rheumatology, Minaminagano Medical Center Shinonoi General Hospital, Nagano, Japan) ; K. Ohmura, Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; S. Hirata, Department of Clinical Rheumatology, Kumamoto University Graduate School of Medicine, Kumamoto, Japan; K. Takagi, Department of Rheumatology, Sainokuni Higashi Omiya Medical Center, Saitama, Japan; Y. Inoue, K. Nakano, K. Saito, Y. Tanaka, The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan; Y. Takahashi, Yu-Family Clinic, Miyagi, Japan; Y. Okano, Department of Internal Medicine and Center for Arthritis and Rheumatic Disease, Kawasaki Municipal Kawasaki Hospital, kanagawa, Japan; N. Hagino, Department of Rheumatology, Teikyo University Chiba Medical Center, Chiba, Japan; T. Sawada, Department of Rheumatology, Tokyo Medical University Hospital, Tokyo, Japan; T. Tsuru, PS Clinic, Fukuoka, Japan; H. Hagiyama, Department of Rheumatology, Yokohama City Minato Red Cross Hospital, Kanagawa, Japan.
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