Safety of biologic DMARDs in RA patients in real life: A systematic literature review and meta-analyses of biologic registers.

Objectives: In daily practice, safety in rheumatoid arthritis (RA) patients receiving biological treatment is an important issue. Unlike randomized controlled trials, biologic registers provide long-term real life safety data. To identify all biologic registers worldwide, to extract and analyze data regarding safety in RA patients under biologics.

Method: Systematic review was performed independently by 2 rheumatologists using PUBMED, COCHRANE Library and EMBASE databases, up to December 2014. Worldwide biologic registers and related publications were identified. Data on safety issues in RA patients were extracted for meta-analyses. Random-effect meta-analyses were performed to estimate risk ratios (RRs) of mortality, cardiovascular events, cancer, including lymphoma and melanoma and serious infections between (1) biological and non-biological DMARD (cDMARD), (2) between biologics when data were available.

Results: Forty-three biological registers were identified worldwide and 27 publications were included for safety meta-analyses on anti-TNFs. Compared to cDMARD, mortality and cardiovascular events were significantly decreased in patients treated with anti-TNFs: RR=0.60 [95% CI 0.38-0.94] and RR=0.62 [0.44-0.88], respectively. Anti-TNFs did not increase the risk of solid cancer in patients without or with prior malignancy (RR=0.84 [0.60-1.18] and RR=0.77 [0.29-2.03], respectively), lymphoma (RR=0.90 [0.62-1.31]) and melanoma (RR=1.17 [0.86-1.59]). As expected, serious infections were significantly increased during anti-TNF treatment (RR=1.48 [1.18-1.85]) compared to cDMARD. No significant difference was found between soluble receptor to TNF and monoclonal antibodies (RR=0.55 [0.22-1.35]).

Conclusions: By reducing dramatically chronic inflammation in RA patients, anti-TNFs decrease mortality, cardiovascular events without increase significantly the risk of cancer, compared to cDMARDs.