Annals of the Rheumatic Diseases 2020;79:760-770This SLR informed the 2019 EULAR taskforce updating recommendations for RA management. Overall, no new safety signals were reported. The known safety profile of bDMARDs was confirmed and extended to tsDMARDS. IL-6i associated lower intestinal perforation has been further confirmed, while VTE and PE concerns in JAKi treatment need further evaluation.Previous updates for the EULAR recommendations on RA pharmacological management were conducted in 2016. In this SLR safety of csDMARDs, tsDMARDs, and bDMARDs was considered. Medline, Embase, and Cochrane searches provided a total of 8297 reports. Of these, 99 were considered in the final study.TNFi and non-TNFi therapies demonstrated an increased risk for serious infection compared to csDMARDs. In tofacitinib treatment, no significant increase was noted compared to abatacept. Increased herpes zoster risks were reported with tofacitinib use compared to abatacept, whilst low and comparable risks were shown between tofacitinib, baricitinib, and adalimumab.Excluding NMSC, bDMARDs showed no increased risk of malignancy compared to the general population. No difference was noted between csDMARD and bDMARD patients. However, safety signals indicated increased NMSC risks in methotrexate and bDMARDs compared to the general population, and in abatacept compared to csDMARDs and TNFi.MACE risk was considered reduced in abatacept treatment compared to TNFi. However, concerns are still prevalent in JAKi treatments, with 3 placebo-controlled and 2 head-to-head trials reporting VTE and PE concerns.Finally, increased risk of lower intestinal perforation (LIP) was noted for tocilizumab in a study comparing risks between various bDMARD and csDMARD, while 2 other studies indicated similar increased risk in comparison of non-TNFi and TNFi. In RCTs reporting LIP (without observational data) LIP was also reported in IL-6i patients. Of 9 RCTs/LTEs investigating tsDMARDs, none reported any LIP.