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Response to ‘Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis’
Arthritis Research & Therapy volume 17, Article number: 166 (2015)
Markusse and colleagues recently investigated whether rheumatoid arthritis patient subgroups formed according to the presence of poor prognostic factors respond differently to initial monotherapy or combination therapy . Since both poor- and good-prognosis subgroups experienced a better response to initial combination therapy, the authors concluded that patient-tailored treatment based on prognosis as suggested by the European League Against Rheumatism (EULAR) recommendations  is currently not feasible.
As a general remark, the authors should be reminded that the EULAR recommendations primarily suggest combination of methotrexate with low-dose glucocorticoids because its efficacy is not surpassed by biologicals and it prevents overtreatment in 20 to 25 % of patients [3, 4]; delaying tumor necrosis factor-inhibitor initiation by 6 months does not affect outcomes . Moreover, the definitions of poor prognosis (PP) used by Markusse and colleagues contrast with the stratification suggested by EULAR, which, as their paper’s supplementary files highlight, influences outcomes . We therefore recommend that readers look at the supplementary information before drawing conclusions.
Markusse and colleagues propose the presence of three of four characteristics as the definition of PP (erosions, rheumatoid factor/anti-citrullinated protein antibody combination, swollen joint count, elevated Disease Activity Score). In contrast, the definition of PP established by Visser and colleagues in the same trial population (sic) uses a different approach, namely C-reactive protein, erosion score and rheumatoid factor/anti-citrullinated protein antibody combination, to determine who had >50 % chance of rapid radiographic progression (≥5 Sharp–van der Heijde Score (SHS) units/year) . The median SHS progression between initial combination therapy and initial monotherapy in PP patients differed only 1.5 SHS units in Markusse and colleagues’ model, but by 3.5 units in that of Visser and colleagues. Of the initial monotherapy patients in Visser’s and Markusse’s models, 64 % and 26 %, respectively, had rapid radiographic progression whereas this proportion was only 12 % and 10 % for initial combination therapy. This observation highlights that the definition of PP used by Visser and colleagues (provided only as supplementary material), in line with other work , is much better at identifying a PP population.
The odds of response to initial combination therapy versus initial monotherapy in the PP versus non-PP populations were much higher when using Visser and colleagues’ approach versus Markusse and colleagues’ approach (odds ratio of American College of Rheumatology 20/50/70: 10.0, 9.74, 9.33 vs. 2.72, 5.39, 4.22, respectively). Separation of the Health Assessment Questionnaire score between PP and non-PP patients treated with initial combination therapy is only seen with Visser and colleagues’ definition. This highlights that definition of PP influences the effect of clinical outcomes.
In accordance with the EULAR research agenda , we also believe it is important to study what effect patient stratification based on poor prognosis parameters has on clinical outcomes. Alas, we feel that Markusse and colleagues’ study did not address the question appropriately and therefore does not provide a good answer.
European League Against Rheumatism
Sharp–van der Heijde Score.
Markusse IM, de Vries-Bouwstra JK, Han K, van der Lubbe PA, Schouffoer AA, Kerstens PJ, et al. Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis. Arthritis Res Ther. 2014;16:430.
Smolen JS, Landewé R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73:492–509.
Wevers-de Boer K, Visser K, Heimans L, Ronday HK, Molenaar E, Groenendael JH, et al. Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study). Ann Rheum Dis. 2012;71:1472–7.
Smolen JS, Emery P, Fleischmann R, van Vollenhoven RF, Pavelka K, Durez P, et al. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet. 2014;383:321–32. Erratum. Lancet. 2014;383:308.
Visser K, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Ronday HK, Seys PE, Kerstens PJ, et al. A matrix risk model for the prediction of rapid radiographic progression in patients with rheumatoid arthritis receiving different dynamic treatment strategies: post hoc analyses from the BeSt study. Ann Rheum Dis. 2010;69:1333–7.
Vastesaeger N, Xu S, Aletaha D, St Clair EW, Smolen JS. A pilot risk model for the prediction of rapid radiographic progression in rheumatoid arthritis. Rheumatology (Oxford). 2009;48:1114–21.
JS is the convener of the EULAR Rheumatoid Arthritis recommendations Task Force. NV, JS and BF have published on models predicting PP.
NV, JS and BF were involved in drafting this letter and gave final approval of the version to be published.
See related research by Markusse et al., http://arthritis-research.com/content/16/5/430 and related letter by Markusse et al.,
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Vastesaeger, N., Fautrel, B. & Smolen, J. Response to ‘Feasibility of tailored treatment based on risk stratification in patients with early rheumatoid arthritis’. Arthritis Res Ther 17, 166 (2015). https://doi.org/10.1186/s13075-015-0680-8
- Early Rheumatoid Arthritis
- Health Assessment Questionnaire
- Swell Joint Count
- Health Assessment Questionnaire Score
- Poor Prognosis Patient