Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial.

OBJECTIVE: The aim of this study was to compare efficacy outcomes of initial treatment with adalimumab + MTX vs adalimumab addition following 26 weeks of MTX monotherapy in Japanese early RA patients naive to MTX with high disease activity. METHODS: Patients completing the 26-week, randomized, placebo-controlled trial of adalimumab + MTX were eligible to receive 26 weeks of open-label adalimumab + MTX. Patients were assessed for mean change from baseline in the 28-joint DAS with ESR (DAS28-ESR) and modified total Sharp score (mTSS), and for the proportions of patients achieving clinical, functional or radiographic remission. RESULTS: Of 333 patients assessed, 278 (137 from the initial adalimumab + MTX and 141 from the initial placebo + MTX groups) completed the 52-week study. Significant differences in clinical and functional parameters observed during the 26-week blinded period were not apparent following the addition of open-label adalimumab to MTX. Open-label adalimumab + MTX slowed radiographic progression through week 52 in both groups, but patients who received adalimumab + MTX throughout the study exhibited less radiographic progression than those who received placebo + MTX during the first 26 weeks (mean ΔmTSS at week 52 = 2.56 vs 3.30, P < 0.001). CONCLUSION: Delayed addition of adalimumab in Japanese MTX-naive early RA patients did not impact clinical and functional outcomes at week 52 compared with the earlier addition of adalimumab. However, the accrual of significant structural damage during blinded placebo + MTX therapy contributed to the persistence of differences between the treatment strategies, suggesting that Japanese patients at risk for aggressive disease should benefit from the early inclusion of adalimumab + MTX combination therapy. Trial registration. ClinicalTrials.gov (http://clinicaltrials.gov/), NCT00870467.

Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study.

OBJECTIVES: To evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics. METHODS: This randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6-8 mg every week versus MTX 6-8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26. RESULTS: A total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed. CONCLUSIONS: Adalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity.

Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus (FK506) in patients with active rheumatoid arthritis (RA) exhibiting resistance to disease modifying antirheumatic drug (DMARD) therapy, and to determine the optimal dosage. METHODS: A total of 212 patients with DMARD-resistant RA were enrolled in this double blind, multicenter, randomized, placebo controlled study and allocated to 3 groups. Patients were administered tacrolimus at a dosage of 1.5 mg/day (68 patients) or 3 mg/day (70 patients), or placebo (74 patients), for 16 weeks. They were allowed to continue taking prednisolone (< or = 5 mg/day) and/or one nonsteroidal antiinflammatory drug (NSAID) during the study. Clinical assessment was based on the American College of Rheumatology (ACR) 20% criteria. RESULTS: ACR 20% response rates were higher in both tacrolimus groups (3 mg: 48.3%; 1.5 mg: 24.6%) than in the placebo group (14.1%), with the rate in the 3 mg group significantly higher. There were no significant differences between the tacrolimus groups and placebo group in the incidence of adverse events. The main adverse events in the tacrolimus groups, especially in the 3 mg group, were renal function abnormalities and gastrointestinal symptoms. However, no significant differences were observed among the 3 groups in the incidence of any adverse event except decrease in serum Mg level. CONCLUSION: Our findings demonstrate excellent dose-dependent efficacy of tacrolimus in patients with DMARD-resistant RA and strongly suggest the usefulness of tacrolimus for treatment of RA. The optimal dosage appears to be 3 mg/day in terms of efficacy and safety.