Withdrawal of biologic agents in rheumatoid arthritis: a systematic review and meta-analysis

The aim of this study is to assess the efficacy of withdrawing biologics from patients with rheumatoid arthritis in sustained remission or low disease activity. This is a systematic review of clinical trials that randomized withdrawal or continuation of biologics. We searched MEDLINE, Embase, and other databases. Three authors independently selected and extracted the data from the studies. The GRADE approach was employed to assess the quality of the evidence. We calculated meta-analyses of random effects model and estimated the heterogeneity by I ². The number needed to treat (NNT) was calculated for significant outcomes. We included six trials (N = 1927 patients), most were industry-sponsored. Compared to withdrawing, continuing biologics increased the probability of low disease activity (relative risk [RR] = 0.66, 95 % CI 0.51–0.84, I ² = 91 %, NNT = 4, low quality), remission (0.57, 0.44–0.74, I ² = 82 %, NNT = 3, low quality), and radiographic progression (RR = 0.91, 95 % CI 0.85–0.98, I ² = 13 %, NNT = 12, moderate quality). No significant difference was detected in the incidence of serious adverse events, serious infection, malignancy, and scores of improvement of tender and swollen joints between these strategies (low quality). A worse profile of outcomes was experienced by those patients when compared to the ones that continued biologics, but almost half of patients maintained low disease activity after withdrawal. As the quality of evidence was low, the conclusions may change as new results become available. The potential harms and benefits of this decision must be discussed with patients.