ABSTRACT
Background and aims: Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation (AC) dose in COVID-19. Methods: We conducted a living systematic review and meta-analysis on the effects of different low molecular weight heparin (LMWH) and/ or fondaparinux doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients. MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH or fondaparinux among confirmed COVID-19 cases. Results: Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between AC and mortality during the following comparisons: a) no AC versus any AC;b) prophylactic versus higher than prophylactic AC;c) prophylactic versus therapeutic AC;d) intermediate versus therapeutic AC;and e) lower than therapeutic versus therapeutic AC. However, the risk for all-cause mortality was higher in patients receiving prophylactic versus intermediate AC (OR=2.01;95%CI: 1.19-3.39). No associations were detected between the intensity of AC and the risk of thrombotic and hemorrhagic events, except the significantly lower risk for hemorrhage in patients on prophylactic compared to higher AC doses. Conclusions: The risk for all-cause mortality was significantly higher in patients receiving prophylactic AC compared to those on an intermediate dose of AC. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies.
ABSTRACT
Background/Aims Secukinumab has demonstrated long-lasting efficacy and a favorable safety profile in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). SERENA is an ongoing, longitudinal, observational study in>2900 patients with moderate to severe psoriasis, active PsA, and AS. We report interim data on impact of intermediate treatment interruption on secukinumab effectiveness in patients with active PsA or AS. Methods This analysis included data for 534 PsA and 470 AS patients enrolled in SERENA between Oct 2016 and Oct 2018 and followed-up for at least 2 years. Patients (≥18 years) with active PsA or AS were required to have received ≥16 weeks of secukinumab treatment before enrolment. Treatment interruption was defined as interruption of secukinumab therapy for at least 3 months between the last injection and re-initiation. Effectiveness assessments included swollen and tender joint count in PsA patients, and Patient Global Assessment (PtGA) and BASDAI score in AS patients before and during treatment interruption and post secukinumab re-initiation. Patients with assessments in≥2 of the time periods were included. Last assessment prior to intermediate treatment interruption was used as baseline. The assessment closest to 6 months after re-initiation was considered the post-secukinumab re-initiation assessment. Results A total of 31 (5.8%) PsA patients and 42 (8.9%) AS patients had an intermediate treatment interruption since initiation of secukinumab treatment. The mean (SD) duration of treatment interruption was 24.8 (16.4) and 26.4 (22.9) weeks for PsA and AS patients, respectively. The mean (SD) duration of secukinumab treatment before the treatment interruption was 86.8 (50.3) and 90.2 (46.9) weeks, and after the treatment interruption was 73.6 (44.4) and 63.2 (46.8) weeks. The most commonly reported reasons included adverse events (AEs;18 [58.1%] PsA, 19 [45.2%] AS), patient decision (3 [9.7%] PsA, 3 [7.1%] AS), and COVID-19 outbreak-related reasons (1 [3.2%] PsA, 6 [14.3%] AS patients). More than 80% of PsA patients and 76% of AS patients reinitiated secukinumab without a loading phase after the treatment interruption. The swollen and tender joint count increased in PsA patients from the last assessment prior to the treatment interruption (1.3 [1.0] and 7.2 [11.4];n=6) to the first assessment during the treatment interruption (4.0 [1.4] and 16.5 [19.1];n=2), and gradually decreased post secukinumab re-initiation (0.4 [0.5] and 2.0 [0.7];n=5). PtGA and BASDAI remained stable in AS patients from the last assessment prior to the treatment interruption to the first assessment during the treatment interruption and after secukinumab re-initiation. Conclusion Secukinumab intermediate treatment interruption occurred due to a variety of reasons in the real-world setting, mainly AEs and patient decision. Most patients re-initiated secukinumab treatment without a loading phase. No notable impact of the intermediate treatment interruption was observed on the effectiveness of secukinumab.
ABSTRACT
The immunopathogenesis of COVID-19 remains ill-defined. Through hyperstimulation of the immune system, SARS-CoV2 may cause a multi-facetted inflammatory disease and generate immune-mediated organ damage even leading to fatal consequences. However, it is still unclear, if a modified course of COVID-19 occurs in patients with autoimmune and/or autoinflammatory diseases.