PMC:7102591 / 10152-17809 JSONTXT 13 Projects

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Id Subject Object Predicate Lexical cue
T53 0-83 Sentence denotes 4 The impact of drugs for rheumatic diseases on viral infections: what do we know?
T54 85-116 Sentence denotes 4.1 Corticosteroids and NSAIDs
T55 117-395 Sentence denotes It has now been more than 70 years that corticosteroids (CS) are pivotal for RA management and their role as remission inducer and bridging therapy for the management of disease flare has recently been renewed by the latest update of EULAR recommendations for RA treatment [36].
T56 396-695 Sentence denotes Even though CS efficacy in rapidly suppressing inflammation during RA initial course or flares is well recognized [37], their downside is the broad spectrum of adverse events, including severe infections and the high risk of developing comorbidities further increasing the risk of infection [27,38].
T57 696-965 Sentence denotes Although RCTs conducted in the past with CS showed no higher risk of infections in RA patients [[39], [40], [41]], cohort and case-control studies reported increased rates of overall infections in RA patients treated with CS, according to a dose-dependent fashion [42].
T58 966-1121 Sentence denotes The majority of these infectious events are of bacterial etiology, but RA patients receiving CS exhibit a greater risk of developing even viral infections.
T59 1122-1320 Sentence denotes As an example, a 2012 retrospective cohort-study demonstrated an increased risk of Herpes Zoster infections with an incidence rate of 8.54 cases per 1000 patient-years in CS treated population [29].
T60 1321-1617 Sentence denotes Thus, CS on the one hand inhibit the immune response and delay the clearance of the pathogen, while on the other hand they suppress the host inflammatory response, which in the case of viral infections of the respiratory tract is the major responsible for lung damage and occurrence of ARDS [43].
T61 1618-1867 Sentence denotes The latter represented the rational for the widely use of CS for the management of Middle East respiratory syndrome (MERS)-CoV [44] and SARS-CoV [45] outbreaks, both histologically characterized by lung inflammation and diffuse alveolar damage [46].
T62 1868-1998 Sentence denotes However, evidence from the literature points to a predominantly negative effect of CS in the management of this type of infection.
T63 1999-2191 Sentence denotes A 2019 systematic review and meta-analysis including ten observational studies (n = 6548) conducted in influenza reported increased mortality (risk ratio [RR] 1.75, 95% CI 1.3–2.4; p = .0002),
T64 2192-2406 Sentence denotes increased rate of secondary bacterial or fungal infection (RR 2·0, 95% CI 1·0–3·8; p = .04), and longer stay in an intensive care unit (mean difference 2.1, 95% CI 1.2–3.1; p < .0001) in patients receiving CS [47].
T65 2407-2584 Sentence denotes Moreover, a review exploring treatments for ARDS, including six studies with a total of 574 patients, concluded that insufficient evidence exists to recommend CS treatment [48].
T66 2585-2753 Sentence denotes Overall, no clear reason exists to expect that patients with COVID-19 infection will benefit from CS, and they might be more likely to be harmed with such therapy [49].
T67 2754-2913 Sentence denotes In fact, current interim guidance from WHO on clinical management of COVID-19 infection advises against the use of CS unless indicated for another reason [10].
T68 2914-2990 Sentence denotes The role of NSAIDs in the course of viral infections is still controversial.
T69 2991-3233 Sentence denotes Ibuprofen has been demonstrated to induce an overexpression of ACE2 when used in diabetic rats [50] and this effect might theoretically increase the susceptibility and worsen the clinical course of COVID-19 infection in treated patients [15].
T70 3234-3431 Sentence denotes In addition, the use of both NSAIDs and acetaminophen could be associated with a masking of the fever rise during COVID-19, resulting in a delay in diagnosis and proper management of the infection.
T71 3433-3446 Sentence denotes 4.2 csDMARDs
T72 3447-3737 Sentence denotes The most comprehensive analysis of infectious risk in patients treated with csDMARDs is a retrospective, longitudinal study of a population-based RA cohort using an administrative database including a total of 27,710 individuals with RA and providing 162,710 person-years of follow-up [51].
T73 3738-4011 Sentence denotes Use of csDMARDs without corticosteroids was associated with a small decrease in mild infection risk (adjusted rate ratio [RR] 0.90, 95% confidence interval [95% CI] 0.88–0.93) and was not associated with increased serious infection risk (adjusted RR 0.92, 95% CI 0.85–1.0).
T74 4012-4285 Sentence denotes Similarly, another retrospective analysis conducted on 1993 patients from a claim database demonstrated a slightly reduced risk of hospitalized infection for methotrexate (adjusted RR 0.81, 95% CI 0.70–0.93) and hydroxychloroquine (adjusted RR 0.74, 95% CI 0.62–0.89) [52].
T75 4286-4432 Sentence denotes A recent systematic review and meta-analysis of the literature confirmed the lack of an increased risk of infection in patients receiving MTX (RR:
T76 4433-4463 Sentence denotes 1.14; 95% CI, 0.98–1.34) [53].
T77 4464-4556 Sentence denotes However, all these reports provided no data on the risk of stratified infection by pathogen.
T78 4558-4570 Sentence denotes 4.3 bDMARDs
T79 4571-4734 Sentence denotes The risk of infection observed in RA patients treated with bDMARDs is generally considered slightly higher (from 1.5- up to 2-fold) compared with csDMARDs [27,54].
T80 4735-5004 Sentence denotes This evidence recurred in most RCTs [55] and observational registry studies [[56], [57], [58]] and was confirmed by a recent meta-analysis which showed that this risk is progressively increasing in relation to the use of bDMARDs at higher than recommended dosages [59].
T81 5005-5156 Sentence denotes Following the results of comparative metanalyses and real-life studies, abatacept is accepted as the safest bDMARD in terms of infectious risk [60,61].
T82 5157-5242 Sentence denotes Data focused on viral respiratory infections in bDMARD cohort are still very limited.
T83 5243-5567 Sentence denotes The incidence of influenza-like infections observed in a cohort of 159 Italian patients treated with bDMARDs during the influenza season 2009–2010 was higher than the value reported in a wide sample of Italian population in the same period, even though no important complications or hospitalizations have been reported [62].
T84 5568-5815 Sentence denotes Overall, post-marketing experience is relatively reassuring that anti-TNF treated patients may not be at any specifically increased risk of influenza and that severe adverse outcomes, including death, do not appear to be exceedingly frequent [63].
T85 5817-5830 Sentence denotes 4.4 tsDMARDs
T86 5831-6141 Sentence denotes The overall risk of serious and opportunistic infections observed with Janus Kinase (JAK) inhibitors in RA patients is roughly comparable with bDMARDs [64,65], although these early years of tofacitinib and baricitinib use have raised the issue of an increased risk of Herpes Zoster virus (HZV) infections [66].
T87 6142-6386 Sentence denotes Data from tofacitinib pooled population enrolled in RCTs showed an HZV incidence rate of 4.0 per 100 patient-years (with greater incidence in geographic area with high HZV endemicity), doubling the rates of RA patients not receiving JAKis [67].
T88 6387-6538 Sentence denotes A similar picture has also been observed in the overall development program of baricitinib, with an incidence rate of 3.2 cases per patient-years [68].
T89 6539-6843 Sentence denotes The subsequent real-life experience from US claim databases revealed that the risk of HZV was higher in patients receiving tofacitinib compared to those treated with abatacept (aHR 2.01 (95% CI 1.40; 2.88) [69], and the risk of serious hospitalized HZV infection is 2-fold higher versus all bDMARDs [70].
T90 6844-7046 Sentence denotes Older age, female sex, prednisone >7.5 mg/day, prior infection, and greater number of hospitalizations were associated with increased HZV risk, whereas vaccination was associated with a lower risk [71].
T91 7047-7294 Sentence denotes More recent reports from RCTs conducted with novel JAK-1 selective inhibitors upadacitinib and filgotinib have basically confirmed the same trend, suggesting that the increase in HZV infections can be considered as a class effect of JAKis [72,73].
T92 7295-7553 Sentence denotes Although the exact mechanism by which HZV reactivation occurs in the context of JAK inhibition is unclear, the downregulation of both cell-mediated immunity and innate antiviral signaling through type I and II interferons (IFN) is likely to be involved [74].
T93 7554-7657 Sentence denotes Currently, no data are available on the risk of respiratory virus infections carried by JAK inhibitors.