Tapering and Withdrawal of Biologics or Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Patients with Inflammatory Arthritis: A Systematic Review and Meta-Analyses of Randomised Trials

Line Uhrenholt¹, Robin Christensen², Wilfred K Dinesen³, Caroline Liboriussen³, Stine Andersen³, Lene Dreyer¹, Annette Schlemmer⁴, Ellen-Margrethe Hauge⁵, Conni Skrubbeltrang⁶ and Salome Kristensen¹, ¹Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark, ²Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen & Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Copenhagen, Denmark, ³Department of Clinical Medicine, Aalborg University, Aalborg, Denmark, ⁴Department of Rheumatology, Randers Regional Hospital, Randers, Denmark, ⁵Aarhus University Hospital, Aarhus, Denmark, ⁶Medical Library, Aalborg University Hospital, Aalborg, Denmark

Meeting: ACR Convergence 2021

Keywords: Ankylosing spondylitis (AS), Biologicals, meta-analysis, rheumatoid arthritis, spondyloarthritis

Session Information

Date: Sunday, November 7, 2021

Title: RA – Treatments Poster I: Comparative Effectiveness, Biosimilars, Withdrawal, & the Real World (0813–0845)

Session Type: Poster Session B

Session Time: 8:30AM-10:30AM

Background/Purpose: Tapering and withdrawal of biological or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs or tsDMARDs) in patients with inflammatory arthritis (IA) in remission or low disease activity (LDA) are a topic of great interest. This systematic review aimed to assess the risk of flare after tapering or withdrawing b- or tsDMARDs compared to continuation of standard dosage.

Methods: The protocol was registered at PROSPERO (CRD42019136905). Predefined search terms identified relevant articles in Cochrane Library, EMBASE, PubMed, and Web of Science (search date: 13-14/06/2019, rerun 11/01/2021). Congress abstracts from ACR and EULAR after 01/01/2017 was evaluated for eligibility. Randomized trials comparing tapering or withdrawal of b- or tsDMARDs in patients with IA with continuation of standard dosage were included. Random-effects meta-analyses were performed to combine the risk ratio (RR) with 95% confidence interval (95%CI) for data on flare after either A) Tapering or B) Withdrawal of b- or tsDMARDs compared to continuation of standard dosage stratified by diagnosis. In trials with >1 tapering strategy, data for the different tapering strategies were combined initially before meta-analysis.

Results: 14,861 references were screened, and 22 trials were included in the meta-analyses of flare risk with data on 3,942 patients with RA and 828 patients with axSpA (Figure 1). An increased risk for developing flare(s) was demonstrated in the meta-analysis on 15 trials tapering of b- or tsDMARDs, RR = 1.45 (95%CI: 1.19 to 1.77; Figure 2). This corresponds to an absolute effect of number needed to treat (NNT [harm]) of 10 patients. Moreover, in 11 trials testing the effect of (abrupt) withdrawal of tumour necrosis factor inhibitors (TNFis), a highly evident increased risk was demonstrated, RR = 2.28 (95%CI: 1.78 to 2.93; Figure 2) with an absolute effect of NNT (harm) of 3 patients. As presented in Figure 2, no significant difference in the risk for flare was observed in subgroup meta-analyses when stratifying by diagnosis (i.e. axSpA or RA).

In summary, 431 patients (32.7%) in the tapering group had a flare and 888 patients (67.3%) did not whereas 830 patients (55.3%) in the withdrawal group experienced a flare and 670 patients (44.7%) did not. Thus, even though an increased risk for flare was demonstrated in the meta-analyses it is noteworthy that the proportion of patients with no flare was larger in the tapering group (67.3%) compared to the withdrawal group (44.7%).

Conclusion: Patients with IA who taper or withdraw their b- or tsDMARDs compared to continuation of standard dosage have an increased risk of flare with no significant risk difference between patients with axSpA or RA. However, a complete withdrawal was associated with a substantially increased flare risk; thus, the most favorable approach to reduce b- or tsDMARDs dose seems to be tapering.

Figure 1: Flow diagram of study selection

Figure 2: Meta-analysis of risk ratio with 95% confidence interval (95%CI) for flare by diagnosis (i.e. RA or axSpA) who A) Taper or B) Withdraw b- or tsDMARDs compared to continuation of standard dosage.

Disclosures: L. Uhrenholt, None; R. Christensen, None; W. Dinesen, None; C. Liboriussen, None; S. Andersen, None; L. Dreyer, BMS, 5, Galderma, 6, Eli Lilly, 6, Janssen, 6; A. Schlemmer, None; E. Hauge, AbbVie, 6, Sanofi, 6, Sobi, 6, SynACT Pharma, 6, Novo Nordic Foundation, 5, Roche, 5, Novartis, 5; C. Skrubbeltrang, None; S. Kristensen, None.

To cite this abstract in AMA style:

Uhrenholt L, Christensen R, Dinesen W, Liboriussen C, Andersen S, Dreyer L, Schlemmer A, Hauge E, Skrubbeltrang C, Kristensen S. Tapering and Withdrawal of Biologics or Targeted Synthetic Disease-Modifying Antirheumatic Drugs in Patients with Inflammatory Arthritis: A Systematic Review and Meta-Analyses of Randomised Trials [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/tapering-and-withdrawal-of-biologics-or-targeted-synthetic-disease-modifying-antirheumatic-drugs-in-patients-with-inflammatory-arthritis-a-systematic-review-and-meta-analyses-of-randomised-trials/. Accessed .

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