Anticoagulant treatment for venous thromboembolism: A pooled analysis and additional results of the XALIA and XALIA-LEA noninterventional studies.

BACKGROUND: The XALIA and XALIA-LEA prospective, noninterventional studies investigated the safety and effectiveness of rivaroxaban versus standard anticoagulation for venous thromboembolism (VTE) treatment in routine clinical practice across global regions. OBJECTIVES: This pooled analysis combined their data to determine the incidence of thromboembolic and bleeding events in both treatment groups and addressed specific bleeding patterns in a broad range of patients. METHODS: Patients with objectively confirmed VTE and an indication for ≥3 months' anticoagulation treatment received rivaroxaban or standard anticoagulation (eg, initial treatment with heparin/fondaparinux, followed by a vitamin K antagonist [VKA]). Treatment choice, dose, management, and duration were at the physician's discretion. Primary outcomes (major bleeding, recurrent VTE, and all-cause mortality) were compared between the two treatment groups. Propensity score stratification, and matching were used to reduce bias due to confounding variables. RESULTS: Overall, 7129 patients were enrolled from 36 countries; 6445 and 2714 patients were included in the propensity score-stratified and -matched analyses, respectively. Major bleeding and incidences of recurrent VTE were similar between treatment groups; all-cause mortality was lower with rivaroxaban than with standard anticoagulation. The incidences of genitourinary bleeding were higher with rivaroxaban than with standard anticoagulation therapy (46 and 23 events in the matched analysis, respectively). VKA management in real-world practice was suboptimal. CONCLUSION: XALIA and XALIA-LEA show similar safety and effectiveness profiles of rivaroxaban and standard anticoagulation for VTE treatment in routine practice in many parts of the world. The observations are consistent with results from the phase III EINSTEIN randomized controlled trials.

Patient Management Strategies and Long-Term Outcomes in Isolated Distal Deep-Vein Thrombosis versus Proximal Deep-Vein Thrombosis: Findings from XALIA.

Background Overall, 30 to 50% of lower-limb deep-vein thrombosis (DVT) cases are isolated distal DVT (IDDVT). The recurrent venous thromboembolism (VTE) risk is unclear, leaving uncertainty over optimal IDDVT treatment. We present data on patients with IDDVT and proximal DVT (PDVT) from the prospective, noninterventional XALIA study of rivaroxaban for acute and extended VTE treatment. Methods Patients aged ≥18 years scheduled to receive ≥3 months' anticoagulation with rivaroxaban or standard anticoagulation were eligible, with follow-up for ≥12 months. We describe baseline characteristics, management strategies, and incidence proportions of VTE recurrence, major bleeding, and all-cause mortality in patients with IDDVT or PDVT, with or without distal vein involvement. Findings Overall, 1,004 patients with IDDVT and 3,098 with PDVT were enrolled; 641 (63.8%) and 1,683 (54.3%) received rivaroxaban, respectively. Patients with IDDVT were younger and had lower incidences of renal impairment, cancer, and unprovoked VTE than those with PDVT. On-treatment recurrence incidences for IDDVT versus PDVT were 1.0 versus 2.4% (adjusted hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.29-1.08), and incidences posttreatment cessation were 1.1 versus 2.1% (adjusted HR: 0.65; 95% CI: 0.32-1.35), respectively. On-treatment major bleeding incidences were 0.9 versus 1.4% and mortality was 0.8 versus 2.2%, respectively. Median treatment duration in patients with IDDVT was shorter than in those with PDVT (102 vs. 192 days, respectively). Interpretation Patients with IDDVT had fewer comorbidities and were more frequently treated with rivaroxaban than those with PDVT. On-treatment and posttreatment recurrences were less frequent in patients with IDDVT. Trial registration number: NCT01619007.

XALIA-LEA: An observational study of venous thromboembolism treatment with rivaroxaban and standard anticoagulation in the Asia-Pacific, Eastern Europe, the Middle East, Africa and Latin America.

INTRODUCTION: The prospective, non-interventional XALIA study investigated the safety and effectiveness of rivaroxaban and standard anticoagulation for the treatment of deep vein thrombosis (DVT). XALIA-LEA was conducted in regions not included in XALIA (Latin America, Eastern Europe, the Middle East, Africa, and the Asia-Pacific), and enrolled patients with isolated pulmonary embolism (PE). MATERIALS AND METHODS: Adult patients with acute venous thromboembolism (VTE) indicated for ≥3 months' anticoagulant treatment were eligible; treatment strategies were at the physician's discretion. Patients receiving rivaroxaban or standard anticoagulation (unfractionated or low-molecular weight heparin/fondaparinux alone or overlapping with and followed by a vitamin K antagonist [VKA]) were included in the safety analysis. "Early switchers" to rivaroxaban (i.e. after receiving heparin/fondaparinux for >2-14 days and/or a VKA for 1-14 days) were not included in the safety analysis set. RESULTS: Of the 1972 eligible patients, 1285 received rivaroxaban, 402 received standard anticoagulation, and 285 were early switchers. Most patients who received rivaroxaban were appropriately selected, received the correct dosing schedule, reported few adverse effects. Outcomes were similar to previously published results, with rivaroxaban associated with a low rate of major bleeding (1.6%), recurrent VTE (1.4%) and all-cause mortality (2.3%). Including early switchers, relatively fewer patients with index isolated PE received rivaroxaban (14.4%) versus standard anticoagulation therapy (20.9%). Some regional variations and differences in outcomes by VTE subtype were apparent with standard anticoagulation treatment. CONCLUSION: XALIA-LEA reaffirms the safety and effectiveness of rivaroxaban for VTE treatment for countries not included in XALIA.

Interferon beta-1b in treatment-naïve paediatric patients with relapsing-remitting multiple sclerosis: Two-year results from the BETAPAEDIC study.

BACKGROUND AND OBJECTIVE: Study evaluating Betaferon(R)'s safety and tolerability in paediatric patients with multiple sclerosis (BETAPAEDIC) is a prospective, open-label observational multicentre study to assess the safety and effectiveness of interferon beta-1b in paediatric patients with relapsing-remitting multiple sclerosis. METHODS: Treatment-naïve patients (12-16 years) scheduled to start interferon beta-1b were enrolled with follow-up visits every six months for two years. Effectiveness was evaluated by annualised relapse rate, Expanded Disability Status Scale progression, cranial magnetic resonance imaging and cognitive testing. Fatigue was assessed by the Fatigue Severity Scale. RESULTS: Sixty-eight patients were screened and 67 enrolled, with mean (standard deviation) age 14.2 (1.3) years (n=65 in the effectiveness analysis). Mean disease duration was 11 months before study enrolment; at baseline, mean (standard deviation) Expanded Disability Status Scale was 0.6 (1.0); T2 lesion number 18.3 (15.1). Mean annualised relapse rate during the study was 0.7 (n=57), 28/57 patients (49.1%) had no relapses and for 40/52 (76.9%) no Expanded Disability Status Scale progression was observed; 23/56 (41.1%) were relapse- and progression-free to last follow-up. Neuropsychological test and fatigue scores were within normal ranges (baseline and last follow-up). Eighteen patients had fatigue at some point. New T2 and gadolinium-enhancing (Gd+) lesions were seen in 43/55 (66.2%) and 29/55 (52.7%) patients respectively. Most frequent adverse events were influenza-like illness, headache, injection-site reactions and elevated liver enzymes. CONCLUSION: Interferon beta-1b is an effective treatment with a favourable safety profile for paediatric patients.

Quality of life and depression in multiple sclerosis patients: longitudinal results of the BetaPlus study.

Enhancing quality of life (QoL) is an important objective of disease-modifying therapies in multiple sclerosis (MS). Strategies to substantiate the effect on QoL and depression have been suggested, including injection devices and nursing support. This study assesses QoL and depression in MS patients treated with interferon beta-1b (IFNB-1b) and evaluates the impact of different elements of a patient support programme and of coping strategies on QoL and depression. A prospective, observational, 2-year cohort study was conducted. MS patients were eligible if they had previously switched to IFNB-1b. Data were collected every 6 months. For the measurement of QoL the Functional Assessment of MS (FAMS) was used. Depression symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D); coping strategies were assessed using the 66-item version of Ways of Coping Questionnaire. A total of 1,077 patients were recruited into the study. Seven hundred (65 %) patients completed the study. Within the subgroup completing questionnaires on QoL (N = 472) and depression (N = 363), QoL increased (110.4 vs. 115.8, p < 0.001), and the proportion of depressed patients decreased from 53.7 to 43.3 % (p < 0.001). Modelling QoL and depressions, the use of the autoinjector Betaject(®) over time showed a positive association with QoL (p = 0.049). The support from a nurse was positively associated with lower depressive symptoms (p = 0.039). The coping strategies 'planful problem-solving' and 'positive reappraisal' were associated with higher QoL and lower depressive symptoms. Patients on IFNB-1b treatment who were included in the patient support programme and completed the study showed an improvement in QoL. Moreover, compared to baseline the proportion of depressive patients decreased. Coping strategies as well as supportive elements such as autoinjectors and nurses had a significant impact on QoL and depression. However, the study had the general limitations of a non-controlled design.