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Arthritis Rheumatol. 2016 Dec 19. doi: 10.1002/art.40019. [Epub ahead of print]

A multi-biomarker disease activity score and the choice of second-line therapy in early rheumatoid arthritis after methotrexate failure.

Author information

  • 1Unit of Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • 2Unit of Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • 3Section of Rheumatology, Department of Clinical Sciences, Lund University, Helsingborg, Sweden.
  • 4Section of Rheumatology, Department of Medicine, Helsingborg's Lasarett, Helsingborg, Sweden.
  • 5Section of Orthopaedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
  • 6Section of Rheumatology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
  • 7Institution LIME Medical Management Centre, Karolinska Institutet, Stockholm, Sweden.
  • 8Crescendo Bioscience Inc., South San Francisco, California, USA.

Abstract

OBJECTIVE:

We investigated whether the multi-biomarker disease activity (MBDA) score predicts optimal add-on treatment in methotrexate-inadequate-responders (MTX-IR) in early rheumatoid arthritis (RA).

METHODS:

We analysed 157 MTX-IRs (28-joint disease activity score based on erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Farmacotherapy (SWEFOT) trial who were randomized to triple therapy (TT [MTX+sulfasalazine+hydroxychloroquine]) versus MTX+infliximab. The MBDA score was analysed at randomisation, using both validated categories (low<30, moderate 30-44 and high>44) and dichotomized as lower (≤38) versus higher (>38), as a predictor of the subsequent DAS28-based response to each second-line treatment by Breslow-Day test for 2x2 groups.

RESULTS:

Among 157 patients, 12% had low MBDA score, 32% moderate and 56% high. Of those with a low MBDA score 88% responded to subsequent TT, and 18% to MTX+infliximab (p=0.006), while for those with a high MBDA score, the response rates were 35% and 58%, respectively (p=0.040). When using 38 as a cut-off for the MBDA score (29% patients with lower and 71% with higher MBDA score), the differential associations with response to triple versus MTX+infliximab therapies were 79% versus 44% and 36% versus 58%, respectively; p=0.001. Clinical and inflammatory markers had poorer predictive capacity for response to triple or MTX+infliximab therapies.

CONCLUSION:

In patients with RA who responded insufficiently to MTX, the MBDA score categories were differentially associated with response to subsequent therapies. Thus, patients with post-MTX biochemical improvements (lower MBDA) were more likely to respond to TT than to MTX+infliximab. If confirmed, these results may help improve treatment in RA. This article is protected by copyright. All rights reserved.

PMID:
27992691
DOI:
10.1002/art.40019
[PubMed - as supplied by publisher]
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