Potential Predictors of Successful Biologic or Targeted Synthetic DMARD Discontinuation

Successful discontinuation of disease-modifying antirheumatic drugs (DMARDs) may be predicted by better physical function, low activity of disease, low C-reactive protein (CRP) levels, shorter duration of disease, and low or no rheumatoid factor or anticitrullinated protein antibodies, according to a study recently published in Rheumatology. 

This systematic literature review included 34 studies of 5724 adults with rheumatoid arthritis treated with biologic or targeted synthetic DMARDs (b/tsDMARDs). Inclusion criteria were discontinuation among individuals with low disease activity or remission as well as an observational cohort, single-arm trial, or randomized controlled trial study design. All studies were found on MEDLINE and Cochrane Library databases, with American College of Rheumatology and European League Against Rheumatism abstracts from the past 5 years searched by hand. Data were extracted in a standardized form and identified information based on study design, number and characteristics of participants, type of treatment, whether tapering took place before b/tsDMARD discontinuation, disease activity and length of remission/low disease activity preceding discontinuation, length of follow-up time after discontinuation, and proportion of participants who maintained remission or low disease activity. Cohen’s d was used to compare pooled baseline characteristics, with small, medium, and large effect sizes defined as d≥0.2, d≥0.5, and d≥0.8, respectively. 

Despite significant heterogeneity, 19 studies reported ≥1 predictor of successful b/tsDMARD discontinuation: low disease activity in 13 studies, better physical function in 6 studies, participant demographics in 6 studies, low or no rheumatoid factor in 5 studies, low or no anticitrullinated protein antibodies in 3 studies, low C-reactive protein or erythrocyte sedimentation rate in 3 studies each, a shorter duration of disease in 3 studies, and low disease activity detected by imaging in 5 studies. 

Limitations to this study included heterogeneous studies and a consequent lack of meta-analysis, as well as the combination of different types of bDMARDs.

Study researchers concluded, “Several predictors of successful bDMARD discontinuation were identified. Although studies are heterogeneous and therefore no definite conclusions can be drawn, these predictors may inform clinicians in their decision making in patients who are considered for a potential bDMARD discontinuation. For tsDMARD discontinuation, only one study with high risk of bias could be found, limiting interpretation of results.”

Reference

Schlager L, Loiskandl M, Aletaha D, Radner H. Predictors of successful discontinuation of biologic and targeted synthetic DMARDs in patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review [published online July 19, 2019]. Rheumatology (Oxford). doi: 10.1093/rheumatology/kez278