Introduction 1 5 6 10 11 In this RECONFIRM-2 study, we assessed the clinical efficacy and safety of infliximab and MTX over a 54-week study period when used in 410 RA patients in the same group, in order to reconfirm not only its clinical efficacy but also demographic factors related to the efficacy. Patients and methods Data and information on RA patients that fulfilled the diagnostic criteria of the American College of Rheumatology (ACR) were collected from three major rheumatology centers in Japan, including the First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu; the Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Saitama Medical Center, Saitama Medical University, Saitama; and the Institute of Rheumatology, Tokyo Women’s Medical University. All patients that received infliximab treatment in each institution by December 2005 were registered with this retrospective study. Demographic data, including disease duration and concomitant therapy, were collected from medical charts. The following parameters were evaluated before and at 54 weeks after the initial infliximab infusion: tender joint count (TJC) 28, swollen joint count (SJC) 28, patient’s assessment of pain on a visual analog scale (patient’s pain VAS), patient’s global assessment of disease activity (patient’s global VAS), physician’s global assessment of disease activity (physician’s global VAS), and C-reactive protein (CRP). Infliximab therapy 12 Therapeutic response http://www.das-score.nl/ 9 13 Discontinued subjects The continuation rate of infliximab therapy was calculated by all causes of discontinuation. Cumulative hazards and associated factors were analyzed in relation to three types of discontinuation: adverse events, inefficacy, and remission. Statistical analysis 1  P P Table 1 Baseline characteristics of patients in three institutions of rheumatology in Japan  Mean SD Min 25% Median 75% Max Female (%) 87.6 – – – – – – Age 53.1 12.7 19 46 55 62 80 Duration 9.4 8.8 0 3 6.6 13 54 Stage 3.0 1.0 1 2 3 4 4 Class 2.2 0.5 1 2 2 2 4 RF positive (%) 87.6 – – – – – – RF (titer) 213 331 1 39 96 241 2980 MTX dose 7.8 2.0 0 6 8 8 20 PSL dose 3.8 3.7 0 0 4 5 22.5 CRP 3.3 2.8 0 1.18 2.7 4.7 13.7 TJC28 10.5 7.3 0 5 9 15 28 SJC28 10.6 6.1 0 6 10 14 28 GH 63.1 21.9 0 49.3 66 80 100 DAS28-CRP 5.5 1.1 1.9 4.8 5.6 6.3 8.0 MTX PSL RF CRP GH TJC SJC DAS Results Baseline demographic and clinical characteristics  1 Continuation of infliximab therapy 1 1 2 Fig. 1 a n b  Table 2 Results from a Cox regression analysis performed to examine the factors related to the discontinuation of infliximab therapy Variable n n n Coef. HR CL CU P Coef. HR CL CU P Coef. HR CL CU P Age 0.037 1.038 1.006 1.070 0.020 −0.014 0.987 0.957 1.017 0.38 −0.021 0.980 0.888 1.081 0.68 Gender −0.940 0.391 0.177 0.863 0.020 0.160 1.173 0.352 3.910 0.79 – – – – – RA duration 0.018 1.018 0.983 1.054 0.320 0.005 1.005 0.964 1.046 0.83 −0.114 0.893 0.622 1.280 0.54 RF (±) −0.949 0.387 0.171 0.878 0.023 1.545 4.686 0.635 34.573 0.13 −1.150 0.317 0.023 4.291 0.39 MTX dose 0.096 1.101 0.920 1.318 0.290 −0.142 0.867 0.709 1.060 0.16 0.339 1.403 0.799 2.465 0.24 PSL dose −0.066 0.936 0.848 1.033 0.190 0.003 1.003 0.908 1.109 0.95 −0.636 0.529 0.187 1.500 0.23 DAS (0 week) 0.205 1.227 0.890 1.692 0.210 0.113 1.120 0.815 1.537 0.49 −0.474 0.623 0.164 2.367 0.49 Coef. HR CL CU Efficacy of infliximab therapy 2 3 4 5 Fig. 2 Line box upper lower box  Fig. 3 a b c d  Line box upper lower box  Fig. 4 Changes in DAS28 values during the 54-week study of patients using infliximab. The ratios of patients who demonstrated high disease activity (defined as DAS28-CRP >4.1), moderate activity (2.7–4.1), low activity (<2.7) and remission (<2.3) at each observation point during the 54-week study are shown  Fig. 5 The response to infliximab therapy during the 54-week study. The ratios of patients whose responses were evaluated by the European League Against Arthritis (EULAR) response criteria are shown  Demographic factors related to the clinical efficacy of infliximab therapy 3 4 Table 3 Results from the logistic regression analysis used to examine the factors related to clinical remission at weeks 22 and 54 induced by infliximab therapy Variables n n Coef. OR SE CL CU P Coef. OR SE CL CU P Intercept 1.530 4.617 1.034 0.608 35.067 0.139 1.770 5.868 1.010 0.811 42.445 0.080 Center 2 vs. Center 1 0.174 1.190 0.359 0.588 2.405 0.629 0.564 1.758 0.350 0.886 3.488 0.107 Center 3 vs. Center 1 1.072 2.922 0.324 1.549 5.510 0.001 0.989 2.689 0.325 1.423 5.082 0.002 Age −0.014 0.986 0.010 0.967 1.006 0.168 −0.024 0.976 0.010 0.957 0.995 0.014 Gender 0.563 1.755 0.392 0.813 3.787 0.152 0.154 1.166 0.370 0.565 2.409 0.677 RA duration −0.007 0.993 0.015 0.964 1.023 0.640 0.010 1.010 0.014 0.982 1.039 0.491 RF (±) −0.413 0.662 0.339 0.340 1.287 0.224 −0.742 0.476 0.329 0.250 0.908 0.024 MTX dose 0.042 1.043 0.068 0.913 1.193 0.535 0.005 1.005 0.066 0.884 1.143 0.936 PSL dose −0.063 0.939 0.035 0.876 1.005 0.070 −0.058 0.944 0.034 0.882 1.009 0.092 DAS28-CRP −0.464 0.629 0.116 0.501 0.789 0.000 −0.276 0.759 0.112 0.609 0.945 0.014 Coef. OR SE CL CU Table 4 Results from the logistic regression analysis used to examine the factors related to the secondary inefficiency from week 22 to 54 during infliximab therapy Variables n n Coef. OR SE CL CU P Coef. OR SE CL CU P (Intercept) −1.461 0.232 1.079 0.028 1.923 0.176 −4.331 0.013 1.439 0.001 0.221 0.003 Center 2 vs. Center 1 −0.008 0.992 0.350 0.499 1.970 0.981 0.074 1.077 0.440 0.455 2.549 0.866 Center 3 vs. Center 1 0.071 1.073 0.333 0.559 2.060 0.831 0.054 1.056 0.426 0.458 2.433 0.899 Age 0.019 1.019 0.011 0.998 1.042 0.079 0.032 1.032 0.014 1.004 1.062 0.028 Gender −0.283 0.753 0.358 0.373 1.520 0.429 0.250 1.284 0.511 0.471 3.500 0.625 RA duration −0.029 0.972 0.017 0.941 1.004 0.083 −0.020 0.980 0.020 0.942 1.019 0.313 RF (±) −0.233 0.792 0.366 0.387 1.622 0.524 0.164 1.178 0.512 0.432 3.212 0.749 MTX dose −0.001 0.999 0.069 0.873 1.144 0.990 0.039 1.040 0.086 0.879 1.230 0.649 PSL dose −0.015 0.985 0.036 0.918 1.057 0.682 0.019 1.019 0.045 0.934 1.112 0.676 DAS28-CRP (0 week) −0.033 0.967 0.118 0.767 1.219 0.779 −0.011 0.989 0.148 0.739 1.323 0.941 Coef OR SE CL CU Discussion 14 7 15 16 N pneumocystis jirovecii In this study, to clarify how predisposing factors from the demographic characteristics of RA patients were related to the clinical efficacy of infliximab therapy, a multivariate analysis using a logistic regression was performed. In this study, multiple variables including sex, age, duration of disease, stage, class, positive/negative RF, concomitant MTX dose, concomitant PSL dose, and initial levels of CRP, TJC, SJC and GH were assessed. It is worth noting that, among multiple variables, younger age, RF-negativity and lower levels of DAS28-CRP at the baseline were significantly correlated with the clinical remission induced by infliximab therapy at week 54. These results imply that the timely use of MTX and infliximab can be strongly recommended for younger RA patients that show RF-negativity in order to efficiently achieve clinical remission. On the other hand, male gender, older age and RF-negativity were significantly correlated with discontinuation of infliximab due to adverse reactions, whereas there was no significant factor responsible for discontinuation as a result of inefficacy, and only older age affected secondary insufficiency from week 22 to 54 after the infliximab therapy. Although it is intriguing that male gender predisposes for discontinuation as a result of adverse events, these results provide the first information that can be used to facilitate the more efficacious use of infliximab and MTX in the daily practice of rheumatologists. Taken together, this REOCNFIRM-2 study reconfirms the clinical efficacy of treatment with infliximab and MTX in Japanese RA patients using the DAS28-CRP and EULAR response criteria. Among 410 patients with active RA, approximately 28% and 39% of the patients satisfied the remission and low disease activity criteria, and good response according to the EULAR criteria was achieved in 37% of the patients treated with infliximab plus MTX during the 54-week study period. The clinical efficacy of infliximab was maintained from week 22 to 54 after the treatment, and secondary insufficiency after week 22 was marginal after the appropriate treatment in this study group. Several demographic factors, including male gender, RF-negativity and lower scores of DAS28-CRP, were significant predisposing factors for remission. The promising effectiveness of infliximab at improving measures of disease activity in RA patients has led to this therapy becoming one of the key advances in the management of RA. Thus, this study is important because it provides obvious and invaluable evidence concerning the efficacy of the combinational use of infliximab and MTX, and can guide the real clinical use of infliximab in the future.