Background Data on infections in patients exposed to biological therapies are mainly focused on rheumatoid arthritis (RA). Little is known about the safety profile in other chronic inflammatory immune-mediated diseases (CIID).
Objectives To describe and compare the risk of serious infections in RA and CIID patients on TNF antagonists or Rituximab (RTX) and to identify predictors of serious infections.
Methods Data from the Spanish registry BIOBADASER 2.0 (2000-2011) were analyzed. RA or CIID patients >16 years on TNF antagonists (infliximab, adalimumab, etanercept) or RTX were selected. Only first treatment was considered in the analysis. CIID included: systemic lupus erythematosus, mixed connective tissue disease, systemic sclerosis, poly/dermatomyositis, relapsing polychondritis, Sjögren’s syndrome, adult Still’s disease and vasculitis. For each group, incidence rate (IR) and mortality rate (MR) of serious infections with 95% confidence intervals were estimated. They were compared using incidence rate ratio (IRR) and mortality rate ratio (MRR).The standardized incidence ratio (SIR) and standardized mortality ratio (SMR) were estimated according to the Spanish general population. Risk factors for serious infectious were assessed using generalized linear models with Poisson distribution.
Results A total of 3,301 patients on TNF antagonists or RTX (95% RA patients and 5% CIID) were analyzed. RA patients were older, there were more women, reported more comorbidities and concomitant treatments compared with CIID patients. We found 331 and 39 serious infections in RA and CIID patients, respectively. The most frequent infections were located in the lower respiratory tract. IR of serious infections was higher in CIID patients, both with TNF antagonists or RTX, but it was only statistically significant in the TNF antagonists group (TABLE). A total of 23 patients on TNF antagonists (22 RA) and 2 with RTX (1 RA) died due to infections which was higher in CIID although it did not reach statistical significance [MRR-TNF antagonists ofCIID vs. RA patients1.6 (0.02, 11.91), MRR-RTX of CIID vs. RA 1.48 (0.09, 23.58)]. Both the SIR and the SMR were increased compared with Spanish general population. In a subanalysis of 292 RA and 16 CIID patients who switched from TNF antagonists to RTX, infections were more frequent in CIID [IRR 1.87 (0.48, 7.24) than in RA (IRR 1 (0.64, 1.59)] but without reaching statistical significance.Multivariate analysis showed that higher age, disease duration, COPD, interstitial lung disease, renal insufficiency, hypertension and concomitant corticosteroids were risk factors for serious infections. In the final multivariate model, adjusted for confounding variables, CIID were associated with a higher risk of infection [IRR 1.96 (1.06, 3.05)] compared with RA.
Conclusions Serious infections in patients on TNF antagonists or RTX are more frequent in CIID than in RA patients. This remark must be taken into account when a risk/benefit balance for off-label use is made.
Disclosure of Interest None Declared
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