Jump to comment:

• Step up therapy remains an appropriate option
  Duncan R Porter
  Published on: 13 April 2016

• Published on: 13 April 2016

  Step up therapy remains an appropriate option

  • Duncan R Porter, Senior Lecturer

  Dear Editor,

  I congratulate the research team from Rotterdam for the high quality study design of the tREACH study, but their conclusions are over-stated [1]. Their quotation of the literature is incomplete, referring to studies that have studied initial combination DMARDs plus corticosteroid (BeSt, FinRACo, COBRA) but excluding those studies that do not support their conclusions. There have been two previously publ...

  Show More

  Dear Editor,

  I congratulate the research team from Rotterdam for the high quality study design of the tREACH study, but their conclusions are over-stated [1]. Their quotation of the literature is incomplete, referring to studies that have studied initial combination DMARDs plus corticosteroid (BeSt, FinRACo, COBRA) but excluding those studies that do not support their conclusions. There have been two previously published randomised controlled trials comparing step up and initial combination triple DMARD therapy which show no sustained benefit of initial triple therapy.

  Saunders et al found no superiority of triple therapy (MTX, SSZ and HCQ) when compared to step up therapy if delivered within the context of an intensive management strategy. This study recruited patients with high disease activity (DAS28>5.1) with a longer disease duration; patients were reviewed patients monthly, and given bridging IM corticosteroid and IA corticosteroid injections when required. The study was smaller (n=96) and did not have sufficient power to detect a small difference in mean change in DAS28, but the trend at 12 months favoured step-up therapy (difference [95%CI] in mean change in DAS28 = 0.5 [-0.2, 1.1]). [2]

  Within the context of a less intensive management strategy, Moreland et al demonstrated that early superiority of triple therapy over initial MTX monotherapy was not sustained following 'step up' to triple therapy in patients with a sub-optimal response to MTX monotherapy. Moreover, this study showed no clinical advantage to stepping up from MTX monotherapy to MTX/etanercept rather than to triple therapy. [3]

  The tREACH study demonstrated an early, statistically significant superiority with initial combination therapy but the authors do not discuss the clinical significance of this difference - they identified that on average the DAS fell by 0.39 more with initial combination therapy but this value is comfortably within the reported measurement error of DAS of 0.6 units [4]. Whether this very small difference in change in DAS is of any clinical significance may be answered by long term follow up of the tREACH study.

  It is important to assess all the evidence available before making recommendations based on a single study. The tREACH study suggests that initial triple therapy may yield a slightly larger reduction in DAS, but not all other studies support this conclusion. Given our current knowledge, it remains appropriate to offer patients with recently diagnosed RA either initial combination therapy or a step-up regimen. Crucially, whichever strategy is chosen by the patient, he/she should be reviewed frequently, assessed carefully and treated intensively with the aim of reaching low disease activity or remission.

  References

  1. P H de Jong, J M Hazes, P J Barenregt et al. Induction therapy with a combination of DMARDs is better than methotrexate therapy" first results of the tREACH trial. Ann Rheum Dis 2013;72:72-78

  2. S A Saunders, H A Capell, A Stirling et al. Triple therapy in Early Active Rheumatoid Arthritis. Arth Rheum 2008;58:1310-1317

  3. L W Moreland, J R O'Dell, H Paulus et al. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: The Treatment of Early Aggressive Rheumatoid Arthritis trial. Arth Rheum 2012;64:2824-2835

  4. AM van Gestel, M L L Prevoo, M A van't Hof, et al. Development and validation of the European League against Rheumatism response criteria for Rheumatoid Arthritis. Arth Rheum 1996;39:34-40

  Conflict of Interest:

  Research funding (Pfizer, Roche), consultancy fees (Pfizer, BMS, Roche), sponsorship (Pfzer, Abbott, Roche, BMS)

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top