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


Background Rheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant, except for inhibition of IL-6, which often disproportionally reduces the CRP due to direct inhibition of its hepatic production. We investigated whether pre-treatment CRP is a useful marker that can guide a preferential treatment choice towards IL-6 inhibition.

Methods Data of 1126 treatment courses with tocilizumab (TCZ; early RA), 250 courses of rituximab (RTX; established RA) and 249 courses of methotrexate (MTX; established RA) were analysed. We compared clinical disease activity index (CDAI) values and change along 24 weeks’ follow-up to CRP values at baseline or its early change. We validated the results using data from a separate TCZ trial in early RA.

Results CRP levels in the TCZ group on average dropped by 74% within 4 weeks. Patients who attained CDAI remission at 24 weeks on TCZ had the highest baseline CRP levels while patients in high disease activity had the lowest; this association was reverse in the RTX and MTX groups. TCZ patients who achieved remission at 24 weeks showed the largest reductions of CRP levels by week 4 compared with those reaching higher disease activity states. Early CRP non-response was indicative of a risk of not achieving clinical treatment goals (p=0.038).

Conclusion Baseline CRP appears to have a positive association with reaching the therapeutic target on TCZ treatment, but is a negative predictor for RTX and MTX. Patients on TCZ without an early CRP response have a lower chance of achieving remission. CRP and its early course may inform, to some extent, the estimation of potential therapeutic success in patients with RA.

  • rheumatoid arthritis
  • treatment
  • disease activity

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  • Handling editor Dimitrios T Boumpas

  • Correction notice This article has been corrected since it published Online First. The acknowledgement section has been added.

  • Contributors IHS: planning of the project, analysis and interpretation of data, drafting the work. FA: analysis and interpretation of data. JSS: planning of the project, interpretation of data, critical revisions of the work. DA: project plan and design, interpretation and reporting the data, critical revisions of the work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests DA reports grants and personal fees from Roche, outside the submitted work. JSS received grants to his institution from AbbVie, AstraZeneca, Janssen, Lilly, Merck Sharpe & Dohme, Pfizer and Roche, and provided expert advice for, or had symposia speaking engagements with, AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, Glaxo, ILTOO Pharma, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB.

  • Patient and public involvement It was not possible to involve patients or the public in this work.

  • Patient consent for publication Not required.

  • Ethics approval Secondary analysis of existing data.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available. This is a secondary analysis of deidentified participant data which was provided by ‘F. Hoffmann-La Roche AG’. Any request for the data should be addressed to the providing company.