Despite Research, Utility of Calprotectin as Biomarker in Rheumatoid Arthritis Still Unclear

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A meta-analysis with data from more than 30 published articles provides an overview of associations between calprotectin levels and disease activity, treatment response, and inflammation among patients with rheumatoid arthritis.

Despite research efforts, disagreement still exists in regard to the utility of calprotectin levels for predicting or assessing inflammation and disease activity in people with rheumatoid arthritis, but a new study is shedding further light on these associations.

With a more significant emphasis on the identification of biomarkers for disease activity in recent years, results of the systematic review and meta-analysis, which leveraged data from more than 30 published articles, suggest calprotectin levels were associated with C-reactive protein and disease activity score, but failed to predict treatment outcomes in patients with rheumatoid arthritis.

“After integrated analyses, it was observed that blood calprotectin levels were higher in RA patients compared with healthy subjects; calprotectin was positively related to systemic inflammation and disease activity in RA patients. However, blood calprotectin levels failed to predict treatment outcomes in RA patients,” wrote investigators.

With an interest in leveraging advanced technologies to identify biomarkers for improving management of multiple conditions, numerous research endeavors have been launched in recent years, particularly in rheumatic disease. An inflammatory biomarker proven to reflect disease activity in multiple autoimmune inflammatory diseases, previous research has drawn mixed conclusions related to its specific utility as a biomarker in rheumatoid arthritis. With this in mind, a team of investigators from the Department of Immunology and Rheumatology at the Affiliated Hospital of Guizhou Medical University designed the current study to provide the field with an updated overview of data from studies investigating associations of calprotectin with inflammation, activity, and treatment response in rheumatoid arthritis patients.

For the purpose of analysis, investigators performed a search of relevant published works within the PubMed, Emboss, Web of Science, Cochrane databases, and their cited references from inception up to November 2021. A total of 38 articles were reviewed, 36 were assessed for further eligibility, and 31 were identified for inclusion in the investigators’ analyses. The primary outcomes of interest for the study were the standardized mean differences (MD) in calprotectin level among people with rheumatoid arthritis and healthy controls and associations between calprotectin levels with C-reactive protein, disease activity score, and treatment response, which was measured using pooled correlation coefficients (CC). Of the 31 articles included in the meta-analysis, 13 were included in the analysis of calprotectin levels between patients with rheumatoid arthritis and healthy controls, 19 were included in the analysis of the correlation between calprotectin levels and C-reactive protein, 4 were used in the analysis of the correlation between calprotectin levels and treatment response.

Upon analysis, results of the meta-analysis suggested levels of calprotectin were greater among those with rheumatoid arthritis compared to healthy controls (MD, 1.48 [95% CI, 1.16 to 1.79]). Further analysis of primary outcomes of interest revealed increased calprotectin levels were positively associated with C-reactive protein (CC, 0.58 [95% CI, 0.53 to 0.63]) and disease activity score (CC, 0.48 [95% CI, 0.38 to 0.58]) in patients with rheumatoid arthritis. Investigators noted results of their analyses demonstrated calprotectin showed an increased trend in rheumatoid arthritis responders compared to nonresponders, but this trend failed to reach statistical significance (MD, 0.38 [95% CI, -0.09 to 0.85]).

“This meta-analysis shows that calprotectin relates to disease risk, inflammation and activity in rheumatoid arthritis patients. It may also predict treatment response to some extent, but this issue needs further validation,” investigators concluded.

This study, “Linkage of calprotectin with inflammation, activity and treatment response of rheumatoid arthritis: a meta-analysis,” was published Biomarkers in Medicine.