MBDA Score Shouldn’t be Overlooked in RA

Multi-biomarker disease activity (MBDA) predicts radiographic progression in rheumatoid arthritis patients up to two years past diagnosis, even for patients previously treated with disease-modifying anti-rheumatic drugs, new research finds.

The results, published in the journal RMD Open, come from the Swedish Farmacotherapy (SWEFOT) trial. Data from this trial published in 2015 had shown that Vectra's proprietary MBDA test predicts the risk of rapid radiographic progression for up to a year in patients naïve to disease-modifying anti-rheumatic drugs (DMARDs). But many patients who might benefit from biomarker screening are not DMARD-naive, wrote lead author Karen Hambardzumyan of Karolinska University Hospital in Sweden and her colleagues.

In the new study, the researchers focused on a subset of 220 SWEFOT patients who all had baseline MBDA scores, C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR) and DAS28 scores on record. Seventy-six of these patients were responders to methotrexate.

The non-responders were randomly assigned after three months to either non-biologic DMARD triple therapy (methotrexate, MTX+sulfasalazine and hydroxychloroquine, a total of 144 patients) or to biological therapy plus methotrexate (the anti-TNF infliximab, a total of 71 patients). For 205 of this subset, the same set of disease activity scores were taken at three months; 133 participants had that data after a 1-year follow-up as well. Finally, modified Sharp/van der Heijde scores (SHS) were evaluated from hands and feet radiographs at baseline, year one and year two.

At three months, there were significant associations between MBDA score (p=0.002), CRP levels (p=0.003) and ESR (p=0.002) and the proportion of rapid radiographic progression. (Rapid radiographic progression, or RRP, was defined as an increase of SHS by more than 5 at any time during the study period.) DAS28 was not significantly associated with rapid radiographic progression at three months, but was at one-year follow-up (p=0.005), as were the three other disease activity markers (p<0.001, p=0.008 and p=0.004 respectively).

"MBDA score at [baseline] month 3 and year 1 was associated with the status of subsequent RRP," the researchers wrote. "Thus, having a low MBDA score at [baseline], or a score reducing to a low level at any of the later time-points, was associated with a lower risk of subsequent RRP."

A low MBDA score was non-significantly more predictive of lower proportions of rapid radiographic progression than low CPR, ESR or DAS28, they wrote. For example, patients who had a high baseline score that shifted to low at three months, or low to moderate at one year, had lower frequencies of rapid radiographic progression than those who had a high MBDA score throughout. Among those whose CRP or ESR moved into the low category at month 3 or year 1, there was still an elevated risk of rapid radiographic progression over the next year, ranging from percent to 24 percent.

"Some patients at very low CRP levels at all three time-points have RRP over 2 years, while those with low or moderate MBDA scores have lower proportions with RRP," the researchers wrote. "Moreover, when comparing proportions of patients with RRP from [baseline] to year 2 between the TT and anti-TNF treated groups, patients with a high MBDA score at [baseline] or month 3 differed significantly, whereas those with high CRP did not."

The study is limited by a lack of MBDA data for methotrexate responders at year one, and by the fact that this subgroup of the SWEFOT patients was not representative of rheumatoid arthritis patients as a whole, the researchers wrote. But data on multiple time-points offers a comprehensive look at MBDA's predictive value at disease onset, they wrote. The expense of MBDA testing might also be offset by the opportunity to target treatment, they wrote. Patients with a high MBDA score who were treated with anti-TNF therapy were less likely to experience rapid radiological progression by year two than patients treated with triple therapy, the researchers found.

"Thus, while MBDA is more expensive than using conventional biomarkers (ie, ESR and CRP), targeting (biological) therapies to patients with the greatest potential benefit may generate considerable savings," the researchers wrote.

References:

Hambardzumyan K, Bolce RJ, Saevarsdottir S, et al. "Association of a multibiomarker disease activity score at multiple time-points with radiographic progression in rheumatoid arthritis: results from the SWEFOT trial." RMD Open 2016;2(1). doi:10.1136/rmdopen-2015-000197