Little Evidence for Usefulness of Biomarkers for Predicting Successful Dose Reduction or Discontinuation of a Biologic Agent in Rheumatoid Arthritis: A Systematic Review

Abstract

ObjectiveTo systematically review studies addressing prediction of successful dose reduction or discontinuation of a biologic agent in rheumatoid arthritis (RA).MethodsPubMed, Embase, and Cochrane Library databases were searched for studies that examined the predictive value of biomarkers for successful dose reduction or discontinuation of a biologic agent in RA. Two reviewers independently selected studies, and extracted data and assessed the risk of bias. A biomarker was classified as a “potential predictor” if the univariate association was either strong (odds ratio or hazard ratio >2.0 or <0.5) or statistically significant. For biomarkers that were studied multiple times, qualitative best‐evidence synthesis was performed separately for the prediction of successful dose reduction and discontinuation. Biomarkers that were defined in ≥75% of the studies as potential predictors were regarded as “predictor” for the purposes of our study.ResultsOf 3,029 nonduplicate articles initially searched, 16 articles regarding 15 cohorts were included in the present study. Overall, 17 biomarkers were studied multiple times for the prediction of successful dose reduction, and 33 for the prediction of successful discontinuation of a biologic agent. Three predictors were identified: higher adalimumab trough level for successful dose reduction and lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of a biologic agent for successful discontinuation.ConclusionThe predictive value of a wide variety of biomarkers for successful dose reduction or discontinuation of biologic treatment in RA has been investigated. We identified only 3 biomarkers as predictors, in just 2 studies. The strength of the evidence is limited by the low quality of the included studies and the likelihood of reporting bias and multiple testing.

Tapering biologic therapy for people with rheumatoid arthritis in remission: A review of patient perspectives and associated clinical evidence

“…The strongest predictors of loss of DAS28 remission included failure to achieve sustained remission (DAS28 <2.6 at weeks 12, 20, 28 and 36) with induction therapy, a higher DAS28 at randomization and at 1 month, and an increase in DAS28, DAS28 components and patient‐reported outcomes at 1 month (Smolen, Szumski, Koenig, Jones, & Marshall, ). A recent systematic review which included data from 16 studies reported that only three factors from two studies were potential biomarkers, defined as being shown to be a predictor in ≥75% of studies in which the factor was examined (Tweehuysen et al, ). The factors identified were a higher adalimumab trough concentration associated with successful dose reduction, and a lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of biologic therapy associated with successful discontinuation (Tweehuysen et al, ).…”

“…A recent systematic review which included data from 16 studies reported that only three factors from two studies were potential biomarkers, defined as being shown to be a predictor in ≥75% of studies in which the factor was examined (Tweehuysen et al, ). The factors identified were a higher adalimumab trough concentration associated with successful dose reduction, and a lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of biologic therapy associated with successful discontinuation (Tweehuysen et al, ). Of note, the number of previous DMARDs and number of previous biologics were not identified as useful predictors (Tweehuysen et al, ).…”

“…The factors identified were a higher adalimumab trough concentration associated with successful dose reduction, and a lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of biologic therapy associated with successful discontinuation (Tweehuysen et al, ). Of note, the number of previous DMARDs and number of previous biologics were not identified as useful predictors (Tweehuysen et al, ). In summary, a range of clinical factors predict the successful tapering of biologics in RA.…”

Upcoming value of gene expression analysis in rheumatology

“…Число эрозий кости положительно коррелирует с тяжестью заболевания и с длительной инвалидностью больных РА [101]. Более того, увеличение числа эрозий по Шарпу-ван дер Хейде (Sharp & van der Heijde) считается наиболее важным показателем для уменьшения дозы или прекращения приёма биологического лекарственного средства [102]. Поэтому, предотвращение эрозий кости является наиболее значимым маркером эффективности терапии РА.…”

Rheumatoid Arthritis: The Problems of Remission and Therapy Resistance

“…Од-нако данные, касающиеся возможности лекарственного мониторинга эффективности терапии ГИБП, противоре-чивы [88].…”