Expanded analyses combining baseline characteristics with genetic/biologic markers are needed to increase the accuracy that outcomes can be predicted. Adalimumab + MTX treatment was generally well tolerated, and the security profile was consistent with previously reported studies of Japanese RA patients and consistent with global trials of TNF inhibitors in combination with Spectinomycin HCl MTX. As with all studies, important limitations exist. such individual populations [8C11], however, studies in Eastern populations are lacking, where environmental, genetic and medical and/or disease management differences may impact drug effectiveness and tolerability. The combination of adalimumab, a fully human monoclonal antibody against TNF-, with MTX has been shown in global clinical trials to significantly reduce disease activity, improve physical function and prevent structural damage more effectively than MTX monotherapy in MTX-naive patients with early RA and high disease activity [8, 12]. The HOPEFUL-1 trial (adalimumab, a human anti-TNF monoclonal antibody, end result study for the prolonged efficacy under allocation to treatment strategies in early RA) was conducted to assess the effect of adalimumab in combination with MTX MTX alone as a first-line therapy in Japanese patients not previously treated with MTX who experienced Spectinomycin HCl high disease activity and risk factors for aggressive disease. The trial consisted of a 26-week randomized controlled period (adalimumab + MTX placebo + MTX) followed by a 26-week open-label (OL) period (OL adalimumab + MTX). Adalimumab in combination with MTX was superior to placebo + MTX during the 26-week blinded period [13]; the current post hoc analysis assessed whether there was continued separation between the treatment strategies through week 52 (i.e. 26 weeks after all patients began receiving combination therapy). Methods Patients Adult patients 20 years of age with active RA, as defined by the 1987 revised ACR criteria [14], of 2 years duration and not previously treated with MTX were eligible for enrolment in this study. In addition, patients were required to have at least 10 tender joints (of 68 assessed), 8 swollen joints (of 66 assessed), CRP 1.5 mg/dl or ESR 28 mm/hour and at least one joint erosion (JE) or RF positivity. Exclusion criteria included prior exposure to more than two DMARDs, previous treatment with CYC, ciclosporin, AZA, tacrolimus or biologic DMARDs, and patients with a chronic contamination, interstitial pneumonia or a history of tuberculosis or malignancy. The study was conducted with the approval of the study site ethical review boards and in accordance with the ethical principles of the Declaration of Helsinki; all patients provided written informed consent. Study design This phase 3 trial (clinicaltrials.gov identifier “type”:”clinical-trial”,”attrs”:”text”:”NCT00870467″,”term_id”:”NCT00870467″NCT00870467 [13]) was conducted at 94 centres in Japan from 11 April 2009 through 1 August 2011 and consisted of two periods. During the first period (blinded period), patients were randomized 1:1 to receive 40 mg adalimumab every other week + weekly MTX (initiated at 6 mg/week) or placebo every other week + weekly MTX for the first 26 weeks. The dose of MTX could be increased to Spectinomycin HCl 8 mg/week at week 8 if a 20% improvement in the tender or swollen joint count from baseline was not achieved or at the discretion of the investigator, except in the case of a security concern. Reduction of MTX to 4 mg/week was also permitted and at the discretion of the investigator. For ethical reasons, patients were eligible to be rescued with OL adalimumab + MTX if they experienced a 20% increase from baseline in tender and swollen joint counts at week 12, 16 or 20 (rescue period). Patients completing 26 weeks of study drug, either during the blinded or rescue period, were eligible to receive OL adalimumab + MTX for an additional 26 weeks (OL period)(%)143 (84.1)128 (78.5)RA duration, years0.3 (0.4)0.3 (0.4)Excess weight, kg54.4 (9.7)56.1 (12.3)Previous DMARD use, (%)74 (43.5)87 (53.4)????1 DMARD57 (33.5)69 (42.3)????2 DMARDs17 (10.0)18 (11.0)Baseline corticosteroid use, (%)58 (34.1)49 (30.1)RF positive, (%)145 (85.3)136 (83.4)????Mean titre (s.d.), IU/ml154.6 (202.9)163.7 (362.8)Anti-CCP positive, (%)144 (84.7)136 (83.4)????Mean Spectinomycin HCl titre (s.d.), U/ml388.3 (695.7)241.3 (367.2)ESR, mm/h59.8 (30.2)61.8 (29.0)CRP, mg/dl2.9 (3.0)3.1 (3.3)Swollen joint count????0C2811.6 (4.7)11.8 (5.3)????0C6616.5 (6.2)17.3 (7.7)Tender joint count????0C2813.2 (5.9)13.2 (6.1)????0C6620.7 (9.3)21.1 (10.2)mTSS13.7 (22.3)13.6 (17.4)Erosion score7.5 (11.7)7.3 (9.2)Joint space narrowing score6.2 (11.4)6.2 (9.4)DAS28-ESR6.6 (0.9)6.6 (1.0)HAQ-DI score1.1 (0.7)1.3 (0.7)SDAI score40.7 (12.0)41.4 (13.8)CDAI score37.8 (10.9)38.3(12.4)Physicians global assessment of disease activity, mm65.9 (18.4)66.2 (18.8)Patients global assessment of disease activity, mm64.3 (24.8)66.4 (23.7) Open in a separate window aAll values are given as mean (s.d.), ACTB unless otherwise indicated. Clinical, functional and radiographic outcomes Treatment with adalimumab.