Baseline C-reactive protein (CRP) levels may predict response to tocilizumab and clinical success with this therapy in patients with rheumatoid arthritis (RA), according to study results published in the Annals of Rheumatic Diseases.
To examine whether the direction of the association between CRP level and treatment response to tocilizumab differs from that of other compounds, information from a total of 4 randomized controlled trials was used to obtain data comprising 1126 treatment courses with tocilizumab, 250 courses of rituximab, and 249 courses of methotrexate. In 3 trials, researchers examined tocilizumab in patients with active disease despite the use of methotrexate therapy (n=2) or methotrexate and other conventional synthetic disease-modifying antirheumatic drugs (n=1). The fourth trial examined methotrexate-naive patients with early RA who were treated with methotrexate monotherapy or methotrexate plus rituximab.
Baseline values and changes in the clinical disease activity index (CDAI) over 24 weeks of follow-up were compared with CRP values at baseline and early CRP changes (4 weeks). A separate trial that investigated tocilizumab in early RA was used to validate the findings from this analysis.
In the group of patients who were treated with tocilizumab, the levels of CRP dropped by an average of 74% from baseline within a 4-week period. A further reduction to 85% from baseline was observed thereafter. Patients who achieved CDAI remission on tocilizumab at 24 weeks had the highest CRP levels (≥4 mg/dL) at baseline compared with patients who continued to have high disease activity. For rituximab and methotrexate, the opposite was true: patients with the highest levels of CRP at baseline had worse clinical outcomes at week 24.
The largest reductions in CRP levels by week 4 were observed in tocilizumab-treated patients who attained remission at 24 weeks vs patients who reached higher disease activity states. Early CRP nonresponse was significantly associated with patients not achieving their clinical treatment goals compared with the CRP responders (P =.038).
Limitations to this analysis were the use of prior trial data and the lack of adjustment for infections, which could have influenced CRP levels.
“[I]n the absence of any useful markers for preferential treatment response to a specific mode of action in RA, the finding of an inverse relationship of CRP with response to [tocilizumab] (higher→good response more likely) as opposed to its relationship with other treatments (higher→good response less likely) constitutes an important information and may be used to inform clinical decision-making,” wrote the study authors. They added that a CRP reduction of <20% from baseline by 4 weeks of tocilizumab treatment was indicative of poor prognosis and “should elicit considerations for changing treatment to another agent.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Shafran IH, Alasti F, Smolen JS, Aletaha D. Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab [published online May 5, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-215987