OBJECTIVES: To systematically review the impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and severe adverse events (SAEs) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity (LDA) state. MATERIALS AND METHODS: A meta-analysis based on a systematic review of PubMed, Embase, Cochrane, until August 2019, as well as relevant databases of international conferences, was used to evaluate the risk difference (RD) at 95% confidence interval (95% CI) of incidence density of serious infections, SAEs, malignancies, cardiovascular adverse events (CV AEs), or deaths after tapering (dose reduction or spacing) compared to continuation of targeted therapies. RESULTS: Of the 1957 studies initially identified, 13 controlled trials (9 RA and 4 SpA trials) were included in the meta-analysis. 1174 patient-years were studied in the tapering group (TG) versus 1086 in the usual care group (UC). There were 1.7/100 patient-year (p-y) serious infections in TG versus 2.6/100 p-y in UC (RD (95% CI) 0.01 (0.00 to 0.02), p = 0.13) and 7.4/100 p-y SAEs in TG versus 6.7/100 p-y in UC (RD 0.00 (- 0.02 to 0.02), p = 0.82). The risk of malignancies, CV AEs, or deaths did not differ between the tapering and the usual care groups. Subgroup analysis (RA and SpA) detected no significant differences between the two groups. CONCLUSION: We could not show significant impact of tapering bDMARD or JAKi over continuation concerning the risk of serious infections, SAEs, malignancies, CV AEs, or deaths in RA and SpA patients in remission or LDA state.

1st Faculty of Medicine Institute of Rheumatology and Department of Rheumatology Charles University Na Slupi 4 Prague Czech Republic

Centre for Rheumatic Diseases Department of Inflammation Biology Faculty of Life Sciences and Medicine School of Immunology and Microbial Sciences King's College London Cutcombe Road London SE5 9RJ UK

Department of Pharmacology Therapeutics and Toxicology Unitat docent Parc Taulí Medical School Universitat Autònoma de Barcelona Sabadell Barcelona Spain

Department of Rheumatology Sint Maartenskliniek 6500 GM Nijmegen The Netherlands

INSERM U1043 CPTP Toulouse France

Rheumatology Department CHU Sainte Marguerite 270 Boulevard de Sainte Marguerite 13009 Marseille France

Rheumatology Department Hôpital Purpan Toulouse France

Rheumatology Department Pellegrin Hospital Bordeaux France

Skeletal Biology and Engineering Research Center Department of Development and Regeneration Rheumatology University Hospitals Leuven KULeuven Leuven Belgium

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