Background/Purpose:  For the treatment of rheumatoid arthritis (RA) a therapeutic window of opportunity exists– patients treated early have favorable outcomes compared with patients treated after they have progressed radiographically. This study investigated the impact of time of radiographic inhibition on the long-term outcomes of patients who achieved early disease control.

Methods:  This analysis studied ten-year data from PREMIER (a phase 3, randomized clinical trial of adalimumab in patients with recent onset RA), and DE-019 (a phase 3, randomized clinical trial of adalimumab in patients with long-standing RA). Radiographic progression was defined as an increase of modified total Sharp score (mTSS) of at least 0.5 units relative to baseline. Patients who achieved remission at year 1 (defined as disease activity score 28-joint count [DAS28] < 2.6) were categorized into four groups according to the time of first recorded radiographic progression: (1) progressed within year 1, (2) progressed between year 2 and 3, (3) progressed between year 5 and 10, and (4) never progressed before the end of 10-year follow-up. Outcomes at year 10 were summarized for each of the groups, including health assessment questionnaire disability index (HAQ-DI), DAS28, simple disease activity index (SDAI), and proportion of patients in remission at the end of follow-up. Tests for trend were conducted for each outcome. A sensitivity analysis imputing year 10 outcomes was conducted using last observation carried forward for patients who did not complete all 10 years of follow-up.

Results:  A total of 314 RA patients included in the two trials achieved remission at year 1, among whom 149 completed 10 years of follow-up. Delaying radiographic progression was associated with lower levels of physical dysfunction, as measured using HAQ-DI. The average HAQ-DI at year 10 was 0.53 for progressions within the first year, 0.39 for progressions between year 2 and 3, 0.31 for progressions between year 5 and 10, and 0.14 for patients did not progress before the end of follow-up. The incremental HAQ-DI score between the first year progressions and the no progression groups is approximately 1.8 times the minimal clinically important difference of 0.22. In addition, a linear trend of HAQ-DI was observed across different times to radiographic progression (p-for-trend = 0.01). Disease activity, measured using DAS28, SDAI, and remission at the end of follow-up, was not statistically different across the four groups. Results were consistent in the sensitivity analysis where year 10 outcomes were imputed for patients who did not complete the follow-up.

Conclusion:  RA patients achieving early remission experienced normalized physical function. Patients who additionally delayed radiographic progression had an incremental benefit in terms of long-term physical function.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incremental-benefit-of-radiographic-inhibition-on-long-term-outcomes-in-patients-with-rheumatoid-arthritis/