ABSTRACT

BACKGROUND: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI).

RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time.

CONCLUSION: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy.

PMID:37763071 | PMC:PMC10532886 | DOI:10.3390/jpm13091303

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PubMed articles on: Cancer & VTE/PE

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios

J Clin Med. 2023 Sep 13;12(18):5955. doi: 10.3390/jcm12185955.

ABSTRACT

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

PMID:37762897 | PMC:PMC10531873 | DOI:10.3390/jcm12185955

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prophylaxis practices for patients with sickle cell disease prior to and during the COVID-19 pandemic

Blood Coagul Fibrinolysis. 2023 Sep 21. doi: 10.1097/MBC.0000000000001250. Online ahead of print.

ABSTRACT

Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state due to alterations in the coagulation system. Despite concern for the development of venous thromboembolism (VTE) in this population, there are no standardized guidelines for routine thromboprophylaxis. The objective of this study was to assess thromboprophylaxis practices of adult and pediatric treaters of SCD before and during the coronavirus disease of 2019 (COVID-19) pandemic. A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through seven SCD-specific interest groups between May 29, 2020, and July 13, 2020. Of 93 total responses, 14% (N = 13) reported they only treat patients more than 21 years old; 38.7% (N = 36) only treat patients 0-21 years old and 47.3% (N = 44) reported they treat both. Our study showed that before the COVID-19 pandemic, 96% of adult practitioners would recommend pharmacologic thromboprophylaxis, mechanical thromboprophylaxis or both for hospitalized adults with thromboprophylaxis, but only 76% of pediatric treaters would recommend any thromboprophylaxis in hospitalized children (P < 0.0001), with 24% of pediatric treaters choosing no thromboprophylaxis at all. During the COVID-19 pandemic, pharmacologic thromboprophylaxis specifically was recommended for adults by 94% of treaters and for pediatric patients by 76% of treaters. These findings suggest that despite the lack of evidence-based thromboprophylaxis guidelines in adults and children with thromboprophylaxis, subspecialty treaters routinely provide pharmacologic thromboprophylaxis in their adult patients and will modify their practice in pediatric patients who are considered at a high risk for VTE.

PMID:37756203 | DOI:10.1097/MBC.0000000000001250

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PubMed articles on: Cancer & VTE/PE

Correction to: Epidemiological Study Regarding the Incidence of Venous Thromboembolism in Patients After Cancer Remission

Cardiol Ther. 2023 Sep 27. doi: 10.1007/s40119-023-00330-9. Online ahead of print.

NO ABSTRACT

PMID:37755611 | DOI:10.1007/s40119-023-00330-9

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PubMed articles on: Cancer & VTE/PE

Long-term risk of venous thromboembolism among patients with gastrointestinal non-neoplastic and neoplastic diseases: A prospective cohort study of 484 211 individuals

Am J Hematol. 2023 Sep 27. doi: 10.1002/ajh.27106. Online ahead of print.

ABSTRACT

We conducted a prospective cohort study to examine the associations of 21 gastrointestinal diseases with the risk of incident venous thromboembolism (VTE). The study included 485 936 UK Biobank participants free of baseline VTE. The gastrointestinal diseases were defined by the International Classification of Disease (ICD)-9 and 10 codes with data from the nationwide inpatient data set, the primary care data set, and the cancer registries. Incident VTE cases were defined by ICD-9 and 10 codes with data from the nationwide inpatient data set. Cox proportional hazards regression was used to estimate the associations of baseline gastrointestinal diseases with incident VTE risk. During a median follow-up of 12.0 years, 13 646 incident VTE cases were diagnosed. Eleven gastrointestinal diseases (nine non-neoplastic and two neoplastic) were associated with an increased risk of incident VTE after Bonferroni corrections. The risk of VTE was >50% higher among patients with gallbladder and biliary tract cancer (hazard ratio [HR] 3.15, 95% confidence interval [CI] 95% CI 1.74-5.70), pancreatic cancer (HR 2.84, 95% CI 1.65-4.91), cirrhosis (HR 2.34, 95% CI 1.96-2.79), Crohn's disease (HR 1.61, 95% CI 1.33-1.95), or pancreatitis (HR 1.57, 95% CI 1.31-1.88) compared with individuals without each of these diseases. We observed multiplicative interactions of age, sex, and body mass index with some gastrointestinal diseases (p < .05). A more pronounced, increased risk of VTE was found among younger, female, or obese patients. The study suggests a 50% higher risk of developing VTE among patients with gallbladder and biliary tract cancer, pancreatic cancer, cirrhosis, Crohn's disease, or pancreatitis.

PMID:37753710 | DOI:10.1002/ajh.27106

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PubMed articles on: Cancer & VTE/PE

An Updated Systematic Review and Meta-Analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients

Ann Surg. 2023 Sep 27. doi: 10.1097/SLA.0000000000006096. Online ahead of print.

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis compares the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCS) versus pharmacological thromboprophylaxis alone.

SUMMARY BACKGROUND DATA: Surgical inpatients have elevated VTE risk; recent studies cast doubt whether GCS confer additional protection against VTE, compared to pharmacological thromboprophylaxis alone.

METHODS: The review followed PRISMA guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched to November 2022. Randomised trials reporting VTE rate after surgical procedures, utilising pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism (PE), VTE-related mortality were pooled via fixed and random effects.

RESULTS: In head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms for GCS and pharmacological thromboprophylaxis was 0.54 (95% CI 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of PE for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-related mortality (27 trial arms, 3 events, 12,982 participants).

CONCLUSIONS: Evidence from head-to-head meta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTE-related mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients.

PMID:37753655 | DOI:10.1097/SLA.0000000000006096

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PubMed articles on: Cancer & VTE/PE

A case of metastatic breast cancer complicated by pulmonary tumor thrombotic microangiopathy

Zhonghua Jie He He Hu Xi Za Zhi. 2023 Oct 12;46(10):1014-1018. doi: 10.3760/cma.j.cn112147-20230521-00253.

ABSTRACT

Pulmonary tumor thrombotic microangiopathy is a malignancy-related complication with rapid progression and high mortality. To improve the understanding of the disease, early diagnosis and treatment are key to successful treatment. A 39-year-old patient with pulmonary hypertension transferred from another hospital was admitted to the First Affiliated Hospital of Guangzhou Medical University on September 26, 2021. The patient developed shortness of breath and progressive exacerbation over the past month. No pulmonary artery embolism was seen on computed tomography pulmonary angiography (CTPA) at the outside hospital where the breast cancer was diagnosed. Pulmonary tumor thrombotic microangiopathy was immediately considered on admission and oncological endocrine therapy was started. After treatment, the patient's dyspnoea improved, PET-CT showed significant tumor regression, and cardiac ultrasound showed a significant decrease in pulmonary artery pressure. The successful treatment experience of this case was summarized for reference.

PMID:37752045 | DOI:10.3760/cma.j.cn112147-20230521-00253

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PubMed articles on: Cancer & VTE/PE

Effect of factor XI inhibition on tumor cell-induced coagulation activation

J Thromb Haemost. 2023 Sep 24:S1538-7836(23)00717-1. doi: 10.1016/j.jtha.2023.09.015. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer-associated thrombosis (CAT) is a frequent complication in patients with malignancies. While FXI/FXIa inhibition is efficacious in preventing postoperative venous thromboembolism, its role in tumor cell-induced coagulation is less defined.

OBJECTIVES: We thus aimed to provide mechanistic insights into FXI/FXIa inhibition in tumor cell-induced coagulation activation.

METHODS: Procoagulant activity (PCA) of four different tissue factor (TF) expressing tumor cell lines was analyzed by single-stage clotting and thrombin generation assay in the presence of a FXIa inhibitor, BMS-262084 (BMS), an inhibitory FXI antibody (anti-FXI), or peak and trough concentrations of rivaroxaban or tinzaparin. Further, tumor cell-induced platelet aggregation was recorded. Recombinant human TF (rhTF) served as positive control.

RESULTS: Although BMS and anti-FXI potently inhibited FXIa amidolytic activity, both inhibitors efficiently mitigated rhTF- and tumor cell-induced fibrin clot formation and platelet aggregation only in the presence of low TF PCA. The anticoagulant effects showed an inverse correlation with the magnitude of cellular TF PCA expression. Similarly, BMS markedly interfered with tumor cell-induced thrombin generation, with the most prominent effects on peak and total thrombin. In addition, anticoagulant effects of FXIa inhibition by 10 μM BMS were in a similar range to those obtained by 600 nM rivaroxaban and 1.6 μM tinzaparin at low TF PCA levels. However, rivaroxaban and tinzaparin also exerted marked anticoagulant activity at high TF PCA levels.

CONCLUSIONS: Our findings indicate that FXI/FXIa inhibition interferes with tumor cell-induced coagulation activation only at low TF PCA expression levels, a finding with potential implications for future in-vivo studies.

PMID:37751848 | DOI:10.1016/j.jtha.2023.09.015

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PubMed articles on: Cancer & VTE/PE

ABO Blood Group and the Risk of Thrombosis in Cancer Patients: A Mini-Review

Semin Thromb Hemost. 2023 Sep 26. doi: 10.1055/s-0043-1775568. Online ahead of print.