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

Abstract

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.

Keywords: Anti-TNF; Methotrexate; Rheumatoid Arthritis.

Figure 1

Patient disposition through week 26. *Three adalimumab+MTX patients and one MTX alone patient discontinued from the study by week 26; however, they were included in the efficacy analyses at week 26. AE, adverse event; MTX, methotrexate.

Figure 2

(A) Box plot of change from baseline in mTSS at week 26 with adalimumab+MTX versus MTX alone and (B) cumulative probability plot of mean change from baseline to week 26 in mTSS score (LE). Thickened horizontal lines in (A) indicate median values, the boxes mark the interval between the 25th and 75th percentiles, whiskers indicate the IQR and mean values are reported in the boxes. No radiographic progression (change from baseline in mTSS≤0.5) was reported in 62.0% (106/171) of adalimumab+MTX patients versus 35.4% (57/161) of MTX alone patients (p<0.001). No clinically relevant radiographic progression (change from baseline mTSS≤3) was reported in 86.0% (147/171) of adalimumab+MTX patients versus 62.7% (101/161) of MTX alone patients (p<0.001) (B). LE, linear extrapolation; mTSS, modified total Sharp score; MTX, methotrexate. p Value determined using Wilcoxon rank sum test.

Figure 3

Percentage of patients with an (A) ACR20 response, (B) ACR50 response or (C) ACR70 response over time; (D) the percentage of patients with a EULAR response at week 26; (E) the percentage of patients with low, medium or high disease activity at week 26; and (F) the percentage of patients achieving functional remission (HAQ-DI score<0.5) at week 26. The following values were used to identify remission, low, medium and high disease activity for each clinical assessment in (E): DAS28-ESR or DAS-CRP (<2.6, ≥2.6–<3.2; ≥3.2–≤5.1, >5.1, respectively), SDAI (≤3.3, >3.3–≤11.0, >11.0–≤26.0, >26.0, respectively), and CDAI (≤2.8, >2.8–≤10.0, >10.0–≤22.0, >22.0, respectively). *p<0.001 versus MTX alone. †p=0.03 versus MTX alone. ACR, American College of Rheumatology; ADA, adalimumab; CDAI, clinical disease activity index; DA, disease activity; DAS28-CRP, disease activity score using a 28-joint count and C reactive protein level; DAS28-ESR, disease activity score using a 28-joint count and erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; HAQ-DI, Health Assessment Questionnaire disability index; MTX, methotrexate; SDAI, simplified disease activity index.