Background/Purpose: Tapering of biologics in rheumatoid arthritis (RA) is based on a trial-and-error disease activity guided strategy, because it is not known in advance which patient can successfully taper. Prediction of successful dose reduction or discontinuation of a biologic could prevent flares and save drug exposition. In the last years, several cohort studies have investigated biomarkers for predicting successful tapering. However, these results have not yet been systematically summarized. The objective of our study was to systematically review studies that address prediction of successful dose reduction or discontinuation of a biologic in RA patients.

Methods: A broad literature search was performed in PubMed, EMBASE and Cochrane Library (November 2015). Studies that examined the predictive value of biomarkers for successful dose reduction or discontinuation of a biologic in RA patients were included. Two reviewers independently selected studies, extracted data and assessed risk of bias. A biomarker was classified as potential predictor if the univariate association was either strong (odds ratio or hazard ratio > 2.0 or < 0.5) or statistically significant. If these data were not provided, other association measures or textual conclusions were used. Qualitative best-evidence synthesis for biomarkers studied multiple times was performed separately for the prediction of successful dose reduction and discontinuation. Biomarkers that were defined in ≥ 75% of the studies as potential predictor were regarded as ‘Predictor’.

Results: Out of 3029 non-duplicate articles, 16 articles on 15 cohorts were included. In total, 17/52 and 33/64 biomarkers were studied multiple times for the prediction of successful dose reduction and successful discontinuation of a biologic. Three predictors were identified: higher adalimumab trough level for successful dose reduction (Figure 1); and lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of a biologic for successful discontinuation. Noteworthy, those three biomarkers were only studied twice, meaning that more frequently investigated biomarkers yielded no consistent predictors.

Conclusion: The predictive value of a wide variety of biomarkers for successful dose reduction or discontinuation of a biologic in rheumatoid arthritis has been investigated. We identified only three biomarkers as predictor in just two studies. The strength of the evidence is limited by the low quality of included studies and the likelihood of reporting bias and multiple testing. Figure 1  Biomarkers for the prediction of successful dose reduction of a biologic