Calprotectin vs Acute-Phase Reactants to Discriminate RA, PsA Activity

Calprotectin discriminate disease activity in patients with RA receiving tumor necrosis factor inhibitors more effectively than acute-phase reactants.

Calprotectin may discriminate disease activity in patients with rheumatoid arthritis (RA) who are receiving tumor necrosis factor inhibitors (TNFi) more effectively than acute-phase reactants, according to recent data published in Arthritis Care & Research.

Researchers sought to compare the accuracy of calprotectin and acute-phase reactants in stratifying disease activity in 87 patients receiving adalimumab, etanercept, or infliximab. They also selected 56 patients with psoriatic arthritis (PsA)  and 40 healthy blood donors to be included as controls.

They used correlation and linear regression to analyze the association between calprotectin, C-reactive protein, and erythrocyte sedimentation rate and composite articular indices. They also measured the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves.

High Yield Data Summary

  • Serum calprotectin more accurately stratified RA disease activity in patients receiving TNFi therapy than the other acute phase reactants evaluated

The results showed that calprotectin levels correlated better with composite activity indices than C-reactive protein and erythrocyte sedimentation rate (all r coefficients >.70). Calprotectin levels were also lower among RA and PsA patients in clinical remission compared with individuals with low disease activity for all articular indices.

Among RA patients, erythrocyte sedimentation rate discriminated between remission and low disease activity only when using the Disease Activity Score in 28 joints, and C-reactive protein distinguished the two when using Simplified Disease Activity Index.

Patients in remission or with low disease activity, calprotectin distinguished between patients with no swollen joints and those with more than one swollen joint (1.74 µg/ml vs 3.04 µg/ml; =.010). Calprotectin serum levels were also inversely correlated with trough serum drug levels of etanercept (p= -0.671; <.001) and infliximab (p= -0.729; =.017).

“The results of this study show that serum levels of calprotectin stratify disease activity in RA patients receiving TNFi more accurately than the APR, whichever composite index was assessed,” the authors of the study wrote.

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“Only calprotectin distinguished between RA patients in clinical remission and those with low disease activity according to all indices analyzed, a finding that was also observed in PsA.  Calprotectin serum levels correlated inversely with TNFi trough serum levels, which are known to be associated with a good therapeutic response.”

Summary and Clinical Applicability

The researchers concluded that calprotectin may be considered an accurate biomarker for the assessment of disease activity in RA patients receiving TNFi.

“A potential clinical benefit of using calprotectin in daily practice could be the ability to differentiate between these 2 groups of patients, guiding therapeutic decisions toward more cost-effective and safer strategies, especially as greater disease progression is observed in patients with low disease activity than in those in remission,” the authors noted.

Limitations and Disclosures

The criteria of remission and low disease activity were defined by clinical criteria without imaging techniques that may be more sensitive in detecting active synovitis. In addition, the clinical value of calprotectin measurements in some patients may be affected by overlap values between patients with various degrees of disease activity.


Inciarte-mundo J, Victoria hernández M, Ruiz-esquide V, et al. Serum calprotectin versus acute-phase reactants in the discrimination of inflammatory disease activity in rheumatoid arthritis patients receiving tumor necrosis factor inhibitors. Arthritis Care Res (Hoboken). 2016;68(7):899-906.