Pretreatment CRP levels could ‘inform clinical decision-making’ in RA
medwireNews: Rheumatoid arthritis (RA) patients with high pretreatment levels of C-reactive protein (CRP) may be more likely to respond positively to tocilizumab and negatively to rituximab or methotrexate than those with lower CRP levels, suggest study findings published in the Annals of the Rheumatic Diseases.
The researchers found that patients with baseline CRP levels of 4 mg/dL or above fared much better on tocilizumab than rituximab or methotrexate, and a non-response to tocilizumab based on CRP levels lessened the chances of reaching treatment target.
Also, if after 4 weeks of taking tocilizumab, the reduction in CRP is less than 20%, the chances of low disease activity or remission remain low regardless of pretreatment CRP levels, note Daniel Aletaha (University of Vienna, Austria) and colleagues, who recommend switching treatment in this case.
They say that “in the absence of any useful markers for preferential treatment to a specific mode of action in RA,” these findings are “important” and “may be used to inform clinical decision-making.”
Among the 1126 study participants who received tocilizumab 8 mg/kg, 7% achieved CDAI remission after 24 weeks, while 31% still had high disease activity. The patients achieving remission had the highest mean baseline CRP levels, at approximately 3.2 mg/dL versus 2.3 mg/dL for those whose disease activity remained high.
The converse was seen for the 250 and 249 patients who received rituximab and methotrexate, respectively, with those in remission at 24 weeks having the lowest mean baseline CRP levels (approximately 2.2 and 2.3 mg/dL, respectively), while those with high disease activity had the highest (approximately 3.8 and 3.5 mg/dL, respectively).
The researchers point out that the differences reached significance for rituximab but not for tocilizumab or methotrexate.
They also looked at the 24-week outcomes associated with different cutoff points of pretreatment CRP and found that 26% of tocilizumab-treated patients who had remitted by this time had pretreatment CRP levels above 4 mg/dL. This was fourfold more than the 6% of methotrexate-treated patients. Conversely, 17% of patients in the tocilizumab group with high disease activity levels at 24 weeks had pretreatment CRP levels above 4 mg/dL, compared with 24% of those in the methotrexate group.
But, “[i]t is important to note that these comparisons are partly not head to head,” emphasize Aletaha et al, since multiple clinical trials were evaluated within this study.
They note that patients with a greater CRP reduction within the first 4 weeks of receiving tocilizumab were significantly more likely to attain CDAI remission by week 24 than those with smaller reductions.
Indeed, patients with a CRP reduction of less than 20% within the first 4 weeks were significantly less likely than those with greater reductions to achieve remission on tocilizumab; by week 24, 27.5% had moderate disease activity, 20.3% had low disease activity, and 4.3% achieved remission.
“[A] CRP reduction <20% from baseline by 4 weeks of treatment on tocilizumab is a poor prognostic marker and should elicit considerations for changing treatment to another agent,” the researchers conclude.
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