Background/Purpose: Patients with multimorbid conditions are at high risk of developing serious infections (SI) and of premature mortality. TNF inhibitors increase the infection risk (1) in patients with rheumatoid arthritis (RA). However, they are likely to decrease all-cause mortality (2). We aimed to examine  a) the infection risk and b) the outcome of SI in a group of patients at high mortality risk: RA patients with congestive heart failure (CHF).   

Methods:  We used data from the German biologics register RABBIT with 10,671 RA patients included at start of a synthetic or biologic DMARD (bDMARD) after at least one DMARD failure. In 242 patients, CHF was reported as comorbid condition at enrollment (NYHA grade III: 16%, NYHA IV: none). We investigated the incidence of SI in CHF patients compared to a matched control sample and the rest of the cohort. Age, sex and co-morbidity (chronic lung disease, chronic kidney disease, hypertension) were used as matching criteria for the nested case control study. For 238 CHF patients exactly matching controls without CHF were found. Multiple logistic regression was applied to investigate the risk of fatal outcome of the first SI in CHF patients.

Results: Compared to the rest of the cohort (n=10,429), CHF patients were older (mean age 68 vs. 56), more frequently males (34% vs. 23%), at baseline they had a higher level of disease activity (DAS28: 5.9 vs. 5.2), considerably more comorbidities (e.g. chronic lung disease: 7% vs. 3%, kidney disease: 24% vs. 3%) and lower functional capacity (FFbH (mean % of full function): 44% vs. 63%). These patient characteristics predispose CHF patients to develop SI. Compared to the rest of the cohort, we observed a nearly five times higher incidence per 100 patient-years (PY) (16 [95%CI: 13, 19] vs. 3.4 [3.2, 3.6]). In addition we found a higher risk of fatal outcome of SI in CHF patients.

In the sample of 238 CHF patients with exact matched controls, the difference in incidence rates of SI in CHF patients vs. controls was considerably smaller: 13.0  [10.7;15.8] vs. 10.3 [8.2;13.0] per 100 PY.

In patients of the matched sample who developed SI we observed a significantly lower risk of fatal outcome in those who were treated with biologics at the time of the infection: The odds ratio for bDMARD treatment (adjusted for age, sex, CHF and physical function) was 0.4 [0.2, 0.96].

Conclusion: Patients with CHF are at increased risk of SI with a high lethality risk.  Our data suggest that SI occurring in RA patients on biologic therapy tend to have a lower risk of fatal outcome. 

(1)    Strangfeld et al., Ann Rheum Dis 2011;70(11):1914-20

(2)    Listing J et al. Ann Rheum Dis 2013 Nov 29 [Epub ahead of print]

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/do-patients-with-congestive-heart-failure-treated-with-biologics-for-ra-have-a-lower-risk-of-fatal-outcome-of-serious-infections/