Background In rheumatoid arthritis (RA), biological medications are marginally better than combination of conventional non-biological drugs such as methotrexate (MTX) with sulfasalazine and hydroxychloroquine (triple therapy [TT]) at group level [1–3]. Previously we have reported that multi-biomarker disease activity (MBDA) score measured after MTX monotherapy in MTX incomplete responders (MTX-IR) or the change of the MBDA score (ΔMBDA) from baseline (BL) to month 3 (M3) was predictive for a subset of patients with low versus high likelihood of subsequent response to TT or TNF inhibitor (TNFi) [4, 5].

Objectives To evaluate a combination of the MBDA score at M3 and ΔMBDA (BL-M3) as a predictor of response to TT or TNFi in MTX-IR in early RA patients from the SWEFOT trial.

Methods In the SWEFOT trial, patients started MTX monotherapy for 3 months and MTX-IR were randomised to TT or TNFi. We analysed 157 MTX-IR patients with complete data on the MBDA score at BL and M3, and DAS28 at year 1. The MBDA score between BL and M3 was compared by Wilcoxon Signed Rank test. Proportions of clinical responders (DAS28≤3.2) at year 1 among patients with high (>44 [validated cut-off] or >38 [non-validated, ROC curve-based cut-off]) MBDA score at M3 AND non-big decrease from BL to M3 (ΔMBDA≤20) were compared with other patients (MBDA≤44/≤38 OR/AND ΔMBDA>20) by χ² test. Overall difference of the responses in the two therapy arms was analysed by Breslow-Day test (for homogeneity of odds ratio).

Results Median (interquartile range) of the MBDA score at BL and M3 were 59 (49–73) and 46 (37–60), respectively (p<0.001). For patients with a high MBDA score (>44 or >38) and ΔMBDA≤20, the likelihood of response to TNFi was significantly greater than to TT (60% vs 30%, p=0.006, Figure 1A and 60% vs 33%, p=0.006, Figure 1B), whereas for other patients the likelihood of response was greater for TT than TNFi (63% vs 46%, p=0.134, Figure 1A, and 69% vs 41%, p=0.035, Figure 1B). The overall differences of the responses to the treatments based on >44 or >38 cut-offs were highly significant (p=0.003 and p=0.001, respectively; Figure 1A, B).

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Conclusions In patients with early RA and incomplete response to MTX, MBDA score predicted the relative efficacy of subsequent treatment with triple therapy versus anti-TNF. Patients with high MBDA score after MTX monotherapy AND change in the MBDA score ≤20 had higher likelihood of responding to TNFi and the other patients had higher likelihood of responding to TT.

1. van Vollenhoven RF, et al. Lancet. 2012 May 5;379(9827):1712–20.

2. Moreland LW, et al. Arthritis Rheum. 2012 Sep;64(9):2824–35.

3. O'Dell JR, et al. N Engl J Med. 2013 Jul 25;369(4):307–18.

4. Hambardzumyan K, et al. Arthritis Rheumatol. 2015; 67 (suppl 10).

5. Hambardzumyan K, et al. Ann Rheum Dis. 2014 June 1, 2014;73(Suppl 2):382–3.

Disclosure of Interest K. Hambardzumyan: None declared, R. Bolce Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience, S. Saevarsdottir: None declared, K. Forslind: None declared, J. Wallman: None declared, R. van Vollenhoven Grant/research support from: Abb Vie, BMS, GSK, Pfizer, Roch, UCB, Consultant for: Abb Vie, Biotest, BMS, Crescendo Bioscience, GSK, Janssen, Lilly, Merck, Pfizer, Roch, UCB, Vertex