Stable versus tapered and withdrawn treatment with - PowerPoint Presentation

1. Stable versus tapered and withdrawn treatment withtumor necrosis factor inhibitor in rheumatoid arthritis remission: a randomized, open-label, phase 4, non-inferiority trialSiri Lillegraven, MD, PhDDiakonhjemmet HospitalOslo, Norway

2. Key messageRemission is the desirable target of RA management, and biologic treatment is often needed to achieve this goal.There is some debate over whether TNF inhibitors should be tapered or withdrawn once remission is achieved.ARCTIC REWIND demonstrated that continued treatment should be the preferred choice in RA patients achieving sustained remission on TNF inhibitors.

3. Background (1)What do we already know about this topic?Remission is the preferred treatment target in rheumatoid arthritis (RA), and many patients require biologics to reach this state.Some recommendations suggest that tapering of tumor necrosis factor inhibitor (TNFi) – even to the stage of discontinuation – should be considered in RA patients achieving sustained remission.1

4. Background (2)How was this study conducted?ARCTIC REWIND was a phase 4, randomized, controlled, open-label, parallel non-inferiority trial.99 RA patients in remission for at least 12 months on stable TNFi were randomized to continue or taper TNFi (half-dose for 4 months, and thereafter withdraw), with visits every 4 months.csDMARD co-medication was kept stable in both arms.Patients had to be in DAS remission at inclusion with 0 swollen joints of 44 assessed.The primary study objective was to assess the effect of TNFi tapering and withdrawal on the risk of disease flare over 12 months.

5. FindingsWhat does this study add?The most common TNFi was etanercept (44%), followed by certolizumab pegol, and the majority of patients were taking their TNFi in combination with csDMARD.In the primary analysis, 5% of patients in the stable TNFi arm experienced a flare during 12 months, compared to 63% in the tapering arm.There was no evidence of radiographic progression in 90% of patients in the stable, and 81% in the tapering arm.At 12 months, DAS score, DAS remission, and function were similar between groups.At the time of flare, CRP and ESR were increased, compared to the visit immediately before and after.Overall, safety was similar between the two groups, with numbers of adverse events in the stable and tapering arms were 57 and 50, respectively; although there were more infections with stable versus tapered TNFi (26 versus 15).

6. PerspectivesHow does this study impact clinical practice?In ARCTIC REWIND there was a large increase in flare rate in patients who tapered and discontinued TNFi.Overall, the study indicated that continued treatment should be the preferred choice in RA patients achieving sustained remission on TNFi.These data should be used to inform shared decision making.

7. ReferencesSmolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79(6):685–99.

8. Related contentIbrahim F, Lorente-Cánovas B, Doré CJ, et al. Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders? Rheumatology (Oxford) 2017;56(11):2004–14. Schett G, Emery P, Tanaka Y, et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis 2016;75(8):1428–37. Alperi-López M, Alonso-Castro S, Morante-Bolado I, et al. Biological Dose Tapering in Daily Clinical Practice: A 10 Year Follow-up Study. Reumatol Clin 2020;16(5 Pt 1):319–23. Lillegraven S, Sundlisæter NP, Aga A-B, et al. Stable versus Tapered and Withdrawn Treatment with Tumor Necrosis Factor Inhibitor in Rheumatoid Arthritis Remission: A Randomized, Open-Label, Phase 4, Non-Inferiority Trial. Presented at ACR Convergence 2020; abstract 2010.