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Response to: ‘Comment on ‘Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab’’ by Pethoe-Schramm et al
  1. Inbal Haya Shafran1,2,
  2. Farideh Alasti1,
  3. Josef S Smolen1,
  4. Daniel Aletaha1
  1. 1Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  2. 2Internal Medicine D, Chaim Sheba Medical Center, Tel Hashomer, Israel
  1. Correspondence to Professor Daniel Aletaha, Department of Rheumatology, Medical University of Vienna, 1090 Wien, Austria; daniel.aletaha{at}

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We would like to thank Dr Pethoe-Schramm and colleagues for their comment on our paper1 and the diligent assessment of the data we presented.2 The authors addressed each of our Figures sequentially and, therefore, it will be a pleasure to respond here accordingly.

Before doing so, we would like to mention that in contrast to other studies, like the one by Wang et al3 which we also referred to in our paper, we approached the analyses by using Clinical Disease Activity Index (CDAI) remission criteria (endorsed by ACR-EULAR for this purpose) rather than "remission" criteria by the Disease Activity Score using 28 joint counts (DAS28) .4 5 As often described, DAS28 <2.6 is an inappropriate remission endpoint because many patients still have residual swollen joints which are drivers of joint damage.6 7 Moreover, acute phase reactants are highly weighted in the formula.8 9 Consequently, DAS28 remission rates are exaggerated and misleading in the context of interleukin-6 (IL-6) inhibition by cytokine receptor inhibitors like tocilizumab or pathway inhibitors like Janus kinase inhibitors;10 11 moreover, these issues cannot be overcome by lowering the threshold for the remission cutpoint.5 12 Finally, since DAS28 includes an acute phase reactant, using it as an outcome to evaluate the role of C-reactive protein (CRP) cannot be seen as independent of CRP and, therefore, may be circular.

Equally importantly, we did not start by asking the question of the ‘distribution of baseline… concentrations of…CRP’ in relation to achieving DAS28 <2.6 or not, but rather asked the question, which CRP-levels those patients who achieved stringent remission at endpoint had at baseline and compared this with baseline CRP levels in patients who had other disease activity states at endpoint and not just non-remission. Thus, …

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