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
- disease activity
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Handling editor Dimitrios T Boumpas
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.