Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis

Abstract

ObjectiveThis observational cohort study investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on the outcomes of serious infections (SIs) in patients with rheumatoid arthritis.MethodsWe investigated outcomes of SIs observed in 947 patients enrolled in the German biologics register RABBIT(Rheumatoid arthritis: observation of biologic therapy). Outcomes were (1) recovery without complication, (2) sepsis following SI (≤30 days), and (3) death after SI without known sepsis (≤90 days). We applied a multinomial generalised estimating equation model for longitudinal data to evaluate the risks of sepsis and death simultaneously.ResultsSepsis within 30 days after SI was reported in 135 out of 947 patients, 85 of these had a fatal outcome. Fifty-three patients died within 90 days after SI without known sepsis. The adjusted risk of developing sepsis increased with age and was higher in patients with chronic renal disease. Compared with conventional synthetic (cs)DMARDs, the risk was significantly lower when patients were exposed to bDMARDs at the time of SI (OR: 0.56, 95% CI 0.38 to 0.81). Risk factors of fatal SI were higher age, use of glucocorticoids at higher doses and heart failure. Patients treated with bDMARDs and those with better physical function had a significantly lower mortality risk.ConclusionsThese results suggest a beneficial effect of bDMARDs on the risk of sepsis after SI and the risk of a fatal outcome. Successful immunosuppression may prevent an unregulated host response to SI, that is, the escalation to sepsis. Further investigation is needed to validate these results.

Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

“…It was interesting to observe that a lower rate of sepsis was seen with the anti-TNF drugs compared with rituximab. Previous work from the German RABBIT register found that the risk of developing sepsis among individuals with SI and mortality from sepsis was lower with anti-TNF therapy compared with non-biologic DMARDs 16. This is perhaps not surprising as TNF is thought to be an important cytokine in the development of sepsis and clinical trials have been carried out to evaluate the use of TNF blockade in treating patients with severe sepsis 17 18.…”

Acute Respiratory Events in Connective Tissue Disorders

“…Compared to the general population, the increased susceptibility of CTD patients to infections is related to three main parameters: (a) intrinsic immunological abnormalities associated with the mater CTD; (b) chronic specific CTD-related lung involvement such as bronchiectasis and fibrotic ILDs, both constituting hosts to an altered human microbiome, and (c) clinically significant immunological dysfunction induced by the use of synthetic and biological disease-modifying drugs [4,29,54,55,56]. Increased age and digestive tract involvement, predisposing to aspiration as in DM-PM and scleroderma, further aggravate the risk [25].…”

“…In addition, acute respiratory events may precipitate disease-specific extrapulmonary organ involvement such as aspiration pneumonia as well as the far less frequently occurring Mendelson syndrome with digestive tract involvement, mainly in scleroderma and DM-PM [17,18,19] as well as in acute heart-related respiratory events in myocarditis or pericarditis with tamponade [20]. Last but not least, acute antirheumatic drug-related respiratory toxicity as well as acute lung infections related to the ‘mater' disease, specific manifestations of rheumatic disease in the lung, and/or immunosuppressive treatment (including the widespread use of biological factors) complete the spectrum of acute respiratory events in CTDs (table 1) [4,21,22,23,24]. …”

“…Subacute-acute, hyperacute, or even catastrophic and fulminant respiratory events occur in the ambit of almost all classic connective tissue disorders (CTDs); they may share systemic life-threatening manifestations, may precipitously lead to respiratory failure - in most cases requiring ventilatory support - as well as a combination of specific therapeutic measures, and in most affected patients constitute the devastating end-of-life event [1,2,3,4,5,6,7,8,9,10]. …”

Digestive comorbidity in patients with rheumatic diseases: Not only NSAID-induced gastropathy

“…Почти каждый десятый из них (n=1017) имел хотя бы один эпи-зод серьезных инфекций. Суммарно было отмечено 135 случаев сепсиса, ставшего причиной гибели 85 (65%) больных [24].…”