Although radiographic progression was found to be minimal in patients with rheumatoid arthritis (RA) being treated with tumor necrosis factor (TNF) inhibitors, physicians should treat toward a goal of low disease activity or remission during the early stages of therapy, according to results published in RMD Open.
Researchers conducted a pooled analysis of three phase 3 clinical trials (ClinicalTrials.gov Identifier: NCT01895309, NCT01936181, and NCT02167139) of biosimilars in order to assess 1-year radiographic progression by disease activity state over different time points in patients who were treated with TNF inhibitors. Each trial was a multicenter, randomized, double-blind, parallel-group designed trial and included patients with moderate or severe active RA, despite methotrexate treatment.
Participants in the study were pooled and grouped per disease activity state of remission — remission, low disease activity, moderate disease activity, and high disease activity — based on disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index, and Simplified Disease Activity Index at weeks 12/14, 24/30, and 52/54, depending on treatment.
The total cohort included 1580 patients across the 3 trials; 80.1% of patients (n=1265; mean age 51.3 years; disease duration 5.9 years) had available modified Total Sharp Score (mTSS) assessment at both baseline and week 52/54 and were therefore included in the analysis. At baseline, the mean mTSS was 37.1. In all treatment groups, mean mTSS change from week 0 to 52/54 was 0.4±2.8, with 72.7% of patients identified as radiographic nonprogressors.
In all treatment groups, 1-year mean radiographic progression was highest in the high disease activity group and lowest among patients in the remission group, with a 1-year mean change in mTSS of 0.03±2.1, 0.4±2.2, 0.3±2.2, and 1.3±4.4 in the remission, low, moderate, and high disease activity groups, respectively. The estimated difference of the 1-year mean change in mTSS, determined by DAS28-ESR, was “significantly larger” in the high disease activity group (1.3; 95% CI, 0.7-1.8) compared with the moderate and low disease activity groups (0.2 and 0.4, respectively).
In each group, the corresponding proportions of radiographic nonprogressors were 79.8% in the remission group, and 78.1%, 74.1%, and 58.4% in the low, moderate, and high disease activity groups, respectively. A higher proportion of patients demonstrated no rapid radiographic progression at year 1 compared with patients who demonstrated ≤1 change in mTSS at year 1 (96.1% vs 83.9%).
Investigators evaluated 1-year radiographic progression based on DAS28-ESR at week 24/30, and found that across all treatments combined, the odds ratio of the proportion of radiographic nonprogressors was lowest in the high disease activity group (0.35; 95% CI, 0.23-0.54) compared with the moderate and low disease activity groups (0.72 and 0.90). Similar results were noted at week 12/14.
Study limitations included differences between the 3 studies: differences in disease duration and baseline mTSS; the use of disparate but qualified X-ray readers; no evaluation of differences in radiographic progression by product or between biosimilars.
“Our pooled radiographic assessment data…showed that radiographic progression is minimal overall but increases as disease activity worsens, despite using TNF inhibitors,” the researchers concluded. “Thus, in line with treat-to-target recommendations, [moderate or high disease activity] are unacceptable states when treating patients with TNF inhibitors, even from the standpoint of radiographic progression of joint damage.”
Disclosure: This clinical trial was supported by Samsung Bioepis Co, Ltd. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Smolen JS, Choe J-Y, Weinblatt ME, et al. Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis. 2020;6(1):e001096.