A Multi‐Biomarker Disease Activity Score and the Choice of Second‐Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure

Abstract

ObjectiveTo investigate whether the Multi‐Biomarker Disease Activity (MBDA) score predicts optimal add‐on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX‐IRs).MethodsWe analyzed data from 157 MTX‐IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28‐ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who were randomized to receive triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) versus MTX plus infliximab. The MBDA score as a predictor of the subsequent DAS28‐based response to each second‐line treatment was analyzed at randomization with the Breslow‐Day test for 2 × 2 groups, using both validated categories (low [<30], moderate [30–44], and high [>44]) and dichotomized categories (lower [≤38] versus higher [>38]).ResultsAmong the 157 patients, 12% had a low MBDA score, 32% moderate, and 56% high. Of those with a low MBDA score, 88% responded to subsequent triple therapy, and 18% responded to MTX plus infliximab (P = 0.006); for those with a high MBDA score, the response rates were 35% and 58%, respectively (P = 0.040). When using 38 as a cutoff for the MBDA score (29% patients with lower scores versus 71% with higher scores), the differential associations with response to triple therapy versus MTX plus infliximab were 79% versus 44% and 36% versus 58%, respectively (P = 0.001). Clinical and inflammatory markers had poorer predictive capacity for response to triple therapy or MTX plus infliximab.ConclusionIn patients with RA who had an inadequate response to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post‐MTX biochemical improvements (lower MBDA scores) were more likely to respond to triple therapy than to MTX plus infliximab. If confirmed, these results may help to improve treatment in RA.

Correlation of the Multi‐Biomarker Disease Activity Score With Rheumatoid Arthritis Disease Activity Measures: A Systematic Review and Meta‐Analysis

“…Among RA patients with an inadequate response to MTX in the Swedish Pharmacotherapy trial (SWEFOT), more patients with low MBDA responded to triple therapy (MTX, hydroxychloroquine, and sulfasalazine) than the addition of infliximab (88% versus 18%; P = 0.006), defined as achieving a DAS28 <3.2 or a EULAR good response. Patients with high MBDA scores responded more frequently to the addition of infliximab rather than triple therapy (58% versus 35%; P = 0.040) . In a separate analysis from the SWEFOT trial, patients with high MBDA scores receiving triple therapy were more likely to have RP after 2 years of follow‐up than patients receiving MTX and infliximab .…”

“…Our search strategy identified an initial 718 studies, with 470 remaining after excluding duplicates (Figure ). Full‐text review of 121 studies was completed with exclusion of those reported only in abstract form (n = 98) or without original data (n = 1), resulting in 22 articles included in the systematic review . Eight studies showed correlations with RA disease activity measures and were included in the meta‐analyses .…”

Genotypes, phenotypes and treatment with immunomodulators in the rheumatic diseases

“…And indeed, our analyses showed that patients who had moderate or high MBDA levels despite MTX therapy stood to benefit significantly from anti‐TNF as compared to conventional therapy – with a clinical margin that was more convincing than in the overall study population – whilst for patients with a low MBDA under MTX treatment the addition of conventional agents was not only as effective, but in fact even more effective than the biological treatment (Fig. ) . Although these analyses still remain at the group level, it may be concluded that the MBDA analyses have the potential to guide therapy decisions in the MTX incomplete responder patient group, when both conventional therapies and TNF‐inhibitors are considered.…”

“…The multibiomarker disease activity score differentially predicts clinical responses to conventional agents and anti‐ TNF in the SWEFOT trial. Reproduced, with permission, from reference .…”

Precision medicine in rheumatoid arthritis: are we there yet?

“…A multi-biomarker disease activity (MBDA) score is available to rheumatologists too. This consists of 12 serum biomarkers and has been shown to predict response to tripletherapy in patients with early RA with moderate or high disease activity (per DAS28) after 3 months of methotrexate monotherapy [10]. However, unmet needs remain in the field, with regard to accurate prediction of the most effective treatment in individual RA patients.…”