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.

[RANKL inhibition as therapy for joint damage].

RANK ligand (RANKL) is a key mediator of osteoclast formation, function, and survival. Therefore, RANKL is thought to be responsible for osteoclast-mediated bone resorption in a broad range of disorders such as postmenopausal osteoporosis and cancer-induced bone disease. Moreover, RANKL has been implicated as a primary mediator of bone erosions, a hallmark of rheumatoid arthritis (RA). Denosumab is a fully human monoclonal antibody. This antibody binds to RANKL with high affinity and specificity, and inhibits RANKL-RANK interaction, mimicking the endogenous effects of osteoprotegerin (OPG), a soluble RANKL decoy receptor. Clinical trial data support the continued development of denosumab for the inhibition of bone erosions in RA.

[Antibody to IL-1 or IL-15].

There have recently been fewer publications written in Japanese describing inflammatory cytokines in rheumatoid arthritis (RA) other than tumor necrosis factor and interleukin (IL) -6. Interleukins such as IL-1 and IL-15 are thought to play an important role, at least in part, in pathogenesis of RA. In this review, the two interleukins above were mentioned from mainly RA point of view, respectively. Monoclonal antibody to each cytokine might be brought to the clinic in the future.