Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE

Abstract

Background: In the IMAGEstudy, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis.

Objective: The aim of this study was to assess joint damage progression and clinical outcomes over 2 years.

Methods: Patients (n=755) were randomised to receive rituximab 2×500 mg+MTX, 2×1000 mg+MTX or placebo+MTX. The placebo-controlled period continued to week 104. Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score (mTSS), total erosion score and joint space narrowing score from baseline to week 104. Clinical efficacy and physical function end points were also assessed.

Results: At 2 years, rituximab 2×1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone (mTSS change 0.41 vs 1.95; p<0.0001 (79% inhibition)), and a higher proportion of patients receiving rituximab 2×1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone (57% vs 37%; p<0.0001). Contrary to 1-year results, exploratory analysis of rituximab 2×500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61% versus placebo+MTX (mTSS, exploratory p=0.0041). Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2. Safety profiles were similar between groups.

Conclusions: Treatment with rituximab 2×1000 mg+MTX was associated with sustained improvements in radiographic, clinical and functional outcomes over 2 years. Clinical trials.gov identifier NCT00299104.

Figure 1

Change in radiographic end points at 2 years in the modified intention-to-treat population. Linear extrapolation used for missing values. Adjusted p-values comparing rituximab+MTX groups with the placebo+MTX group; values in parentheses are unadjusted, exploratory p-values. mTSS, total Genant-modified Sharp score; MTX, methotrexate; NS, non-significant.

Figure 2

Rate of radiographic progression (change in mTSS) over 2 years. (A) Mean change in mTSS. Linear extrapolation used for missing data. Error bars show ±1.96×standard error. (B) Annualised rate of progression of mTSS (all observed data). mTSS, total Genant-modified Sharp score; MTX, methotrexate.

Figure 3

Efficacy over 2 years. (A) ACR20, (B) ACR50, (C) ACR70 and (D) ACR90 responses. LOCF used for tender and swollen joint counts, HAQ score, CRP, ESR and VAS assessments. ACRn was set to ‘non-responder’ when the score was missing. Patients were classified as non-responders from the point of withdrawal or rescue use. (E) EULAR good response. LOCF used for tender and swollen joint counts, ESR and patient's Global Assessment of Disease Activity VAS. EULAR response was set to ‘non-responder’ when the DAS28 score was missing. Patients were classified as non-responders from the point of withdrawal or rescue use. (F) Mean change in DAS28. LOCF used for tender and swollen joint counts, ESR and patient's Global Assessment of Disease Activity VAS. Error bars show ±1.96×standard error. ACR, American College of Rheumatology; CRP, C reactive protein; DAS28, Disease Activity Score in 28 joints; ESR, erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; HAQ, Health Assessment Questionnaire; LOCF, last observation carried forward; MTX, methotrexate; VAS, visual analogue scale.

Figure 4

Mean change in HAQ-DI over 2 years. LOCF was used for missing data. Error bars show ±1.96×standard error. HAQ-DI, Health Assessment Questionnaire-Disability Index; LOCF, last observation carried forward; MTX, methotrexate.