Background/Purpose

Clinical trials in rheumatoid arthritis (RA) often require elevated C-reactive protein (CRP) as an inclusion criterion, which may limit recruitment by excluding some patients with active disease. The multi-biomarker disease activity (MBDA) score (Vectra® DA) quantifies disease activity with a score of 1 to 100 and can be high (>44) when CRP is low, e.g., ≤1 mg/dL.  This study explored the hypothesis that, by using MBDA score >44 as a clinical trial inclusion criterion complementary to CRP >1 mg/dL, the number of eligible patients can be increased while maintaining ability to detect treatment responses and radiographic progression.

Methods

The Swedish Farmacotherapy (SWEFOT) trial, disease modifying anti-rheumatic drugs (DMARD)-naïve patients with early RA were enrolled without a CRP requirement, and received methotrexate (MTX) monotherapy from baseline (BL); at 3 months, non-responders to MTX (NR, DAS28 >3.2) received treatment intensification with triple therapy or MTX plus infliximab. For the present study, we analyzed two populations from SWEFOT: 1) DMARD-naïve patients, based on enrollment at BL, and 2) MTX non-responders, based on the Month 3 assessment.  In both analyses, patients were grouped according to CRP (≤1 vs. >1 mg/dL) and MBDA score (≤44 vs. >44) at the defining time point, and clinical outcomes were assessed from BL to 3 months for DMARD-naïve patients treated with MTX; and from 3 to 12 months for MTX NRs receiving triple therapy or anti-TNF.  Radiographic progression was assessed by change (Δ) in Sharp van der Heijde score (SHS) from BL to 1 year for both analyses.

Results

In the DMARD-naïve population (N=220), BL values, changes in clinical disease activity from BL to Month 3, and DSHS from BL to year 1 were similar for patients with MBDA score >44 and CRP ≤1 mg/dL (n=37) vs. patients with CRP >1 mg/dL (n=154).  If the two groups are combined, the resulting group (n=191) has 24% more patients and similar clinical and radiographic outcomes, compared with the CRP >1 mg/dL group.  For the MTX NRs (N=127), values at Month 3 and their changes to Month 12 were also similar for patients with MBDA score >44 and CRP ≤1mg/dL (n=23) vs. those with CRP >1 mg/dL (n=49). Combining these two groups results in a group with 47% more patients (n=72) and similar outcomes, compared with the CRP >1 mg/dL group. (See table) In comparison, for patients with MBDA score ≤44 and CRP ≤1 mg/dL, there is less change in clinical disease activity at Month 12 for the MTX NRs, and less radiographic progression at Month 12 for the DMARD-naïve and MTX NR groups.

Conclusion

These analyses suggest that if a clinical trial of DMARD-naïve or MTX-NR patients with RA were to include patients with MBDA score >44 even though CRP was ≤1mg/dL, the number of eligible patients would be increased by 24% and 47%, respectively, compared with the conventional approach to enrollment based on   CRP >1 mg/dL alone, while maintaining clinical and radiographic outcomes.