A wide range of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), which can be used in different sequences and/or combinations, is at the disposal of rheumatologists to offer to patients with rheumatoid arthritis (RA).  This also implies that choices are to be made when deciding on the best treatment for the individual patient. In order to inform the task force responsible for the 2019 update of the European League Against Rheumatism (EULAR) RA management recommendations, we performed a systematic literature review (SLR) to update the evidence for the safety of csDMARDs, tsDMARDs and bDMARDs in patients with RA.
The research questions were structured according to a PICO format (Patients, Intervention, Comparator and Outcomes) and eligible study types were defined.
All newly included studies were published from 2016 onwards.
Cohort-studies/registries were the main study type of interest; for treatments still without registry data, RCTs and LTEs were used to extract safety data.
Participants were adults (aged ≥18 years) with a clinical diagnosis of RA.
Studies including patients with other diagnoses were eligible only if the results from patients with RA were presented separately.
The intervention was any DMARD (csDMARD, bDMARD—including biosimilars—or tsDMARD).
The comparator was a(nother) bDMARD, sDMARD, glucocorticoid, combination therapy, or the general population.
Studies were only eligible if they included a comparator group, as a formal comparison is the only insightful manner to take any conclusions about safety.
All safety outcomes were considered, namely infections (including serious infections, opportunistic infections such as tuberculosis and herpes zoster (HZ)), malignancies, mortality, cardiovascular disease, change in lipid levels, impairment in renal function, elevation of liver enzymes, hematological abnormalities, gastrointestinal effects, demyelinating disease, induction of autoimmune disease, and teratogenicity.
Risk of bias (RoB) was assessed according to Hayden’s tool for observational studies and the Cochrane Collaboration’s tool for RCTs.
Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017 Jun;76(6):960-77.
Presenter disclosure: The presenter has reported that no relationships exist relevant to the contents of this presentation.