<p>Supplementary material for publication online only:</p><p>Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: postmarketing surveillance report of the first 3,000 patients</p><p>Table S1 summarizes reasons for and window of time for patient discontinuation. Table S2 provides an overview of adverse drug reactions (ADRs) and serious ADRs, including rates of these events in patients with and without biologic, disease-modifying antirheumatic drug </p><p>(DMARD), methotrexate (MTX), and glucocorticoid use. ADRs are also summarized by the </p><p>Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC). Table S3 illustrates Steinbrocker’s functional class-specific mean changes in 28-joint Disease Activity </p><p>Scores from baseline (DAS28) stratified by prior use of biologic and with and without concomitant MTX use. European League Against Rheumatism (EULAR) response rates are summarized in Fig. S1. Table S1 Discontinuation among all adalimumab-treated patients (N = 3,000) a</p><p>N % Total discontinued 962 33.2 Adverse event 321 10.7 Lack of efficacy 388 12.9 Withdrew consent 103 3.4 Lost to follow-up 111 3.7 Other 38 1.3 Window of discontinuationb <30 days 210 7.0 30 to <60 days 202 6.7 60 to <90 days 195 6.5 90 to <120 days 137 4.6 120 to <150 days 150 5.0</p><p>≥150 days 68 2.3 a 2,991 RA and 9 with other diseases b The duration from the start to discontinuation of adalimumab Table S2 Overview of adverse drug reactions (ADRs) during adalimumab therapy (% of </p><p> patients)</p><p>All ADRs Serious ADRs Total patients (N = 3,000) a 27.3 4.1 Biologic-naïve (n = 1,509) 26.2 3.6 Biologic-experienced (n = 1,491) 28.4 4.6 No concomitant DMARD (n = 540) 28.1 4.3 Concomitant DMARD (n = 2,460) 27.1 4.1 MedDRA SOC (N = 3,000) a Blood disorders 0.5 0.2 Cardiac disorders 0.1 0 Ear and labyrinth disorders 0.1 0 Eye disorders 0.3 0.1 Gastrointestinal disorders 2.0 0.2 General disorders 8.0 0.3 Hepatobiliary disorders 1.1 0.1 Immune system disorders 0.1 0 Infections 7.8 2.4b Injury and poisoning 0.1 0 Laboratory test abnormality 1.7 0.1 Metabolism disorders 0.1 0 Musculoskeletal disorders 0.5 0.1 Neoplasms 0.1 0.1 Nervous system disorders 1.0 0.1 Renal and urinary disorders 0.2 0 Reproductive system disorders 0.1 0 Respiratory disorders 3.3 0.6 Skin disorders 8.5 0.1 Vascular disorders 0.4 0 DMARD disease-modifying antirheumatic drug; MedDRA Medical Dictionary for Regulatory</p><p>Activities; SOC system organ class. a2,991 RA and 9 with other diseases bRespiratory infections, n = 42; other infections, n = 14; skin infections, n = 10; bone and joint infections, n = 5; sepsis, n = 5; digestive system infections, n = 5; urinary tract infections, n = 4. Table S3 Steinbrocker’s rheumatoid arthritis functional class-specific mean DAS28 </p><p> stratified by prior biologic and methotrexate (MTX) use</p><p>Steinbrocker’s</p><p>Functional Week 4 Week 12 Week 24</p><p>Class No MTX N 277 326 383 -0.96 ± -0.92 ± -1.08 ± DAS28 ± SD Classes 1.18 1.40 1.47 With MTX I and II N 726 842 953 -1.26 ± -1.35 ± -1.47 ± DAS28 ± SD 1.05 1.20 1.30 All Student's t-testa p < 0.001 p < 0.001 p < 0.001 No MTX patients N 109 132 148 -0.86 ± -0.98± -1.02 ± DAS28 ± SD Classes 1.15 1.30 1.37 With MTX III and IV N 230 268 299 -1.21± -1.39 ± -1.50 ± DAS28 ± SD 1.14 1.29 1.33 Student's t-testa p = 0.008 p = 0.003 p < 0.001 Biologic- No MTX N 148 166 191 naïve -1.35 ± -1.40± -1.53 ± DAS28 ± SD Classes 1.08 1.29 1.32 With MTX I and II N 424 479 546 -1.52 ± -1.63 ± -1.75± DAS28 ± SD 0.96 1.09 1.18 Student's t-testa p = 0.076 p = 0.021 p = 0.034 Classes No MTX N 52 60 66 III and IV -1.15 ± -1.41 ± -1.42 ± DAS28 ± SD 1.08 1.17 1.25 With MTX N 111 129 145 -1.47± -1.76 ± -1.90 ± DAS28 ± SD 1.18 1.19 1.24 Student's t-testa p = 0.096 p = 0.060 p = 0.009 No MTX N 129 160 192 -0.52± -0.43 ± -0.64± DAS28 ± SD Classes 1.14 1.34 1.47 With MTX I and II N 302 363 407 -0.91 ± -0.97± -1.10 ± DAS28 ± SD 1.07 1.23 1.36 Prior Student's t-testa p < 0.001 p < 0.001 p < 0.001 No MTX biologic N 57 72 82 -0.59 ± -0.62± -0.70 ± DAS28 ± SD Classes III 1.16 1.29 1.39 With MTX and IV N 119 139 154 -0.96± -1.04 ± -1.12 ± DAS28 ± SD 1.04 1.29 1.30 Student's t-testa p = 0.034 p = 0.024 p = 0.023 DAS28 change in 28-joint Disease Activity Score from baseline</p><p> ap-values comparing concomitant MTX use with no MTX use (Student's t-test). Fig. S1 European League Against Rheumatism (EULAR) response (28-joint Disease Activity</p><p>Score [DAS28]-4 [erythrocyte sedimenations rate (ESR)]). N = 1,342 at Week 4, N = 1,568 at</p><p>Week 12, and N = 1,783 at Week 24. ap < 0.001 (Cochran-Armitage test for trend). </p><p>No EULAR Response Moderate EULAR Response Good EULAR Response</p><p>19.6% 23.2% 27.5%</p><p>63.7% 65.9% 66.8%a</p><p>44.1% 42.7% 39.3%</p><p>36.3% 34.1% 33.2%</p><p>Week 4 Week 12 Week 24</p>