Russian registry of Infliximab.Impact of therapy on the functional status of patients with rheumatoid arthritis

Objective. To evaluate the functional state of rheumatoid arthritis (RA) patients receiving Infliximab therapy (IF) in real clinical practice and its efficiency. Subjects and methods. The analysis covered 225 patients receiving IF therapy, the follow-up duration in whom was 54 weeks. Disease activity was estimated by the DAS 28 index; functional status was assessed according to the Health Assessment Questionnaire (HAQ). The authors made an analysis of a Per-Protocol (PP) population (n = 154) at 54 weeks of treatment and an analysis that could consider the results of treatment (by the ACR and EULAR criteria) in patients who had been withdrawn before the control time - a LOCF (Last Observation Carried Forward analysis) population. Results. The mean age of the patients was 47.6±11.4 years; the duration of the disease was 7.8±6.4 years; DAS 28 activity scores were 6.6±1.1; the majority of patients had significant functional impairments (HAQ scores of 2.0±0.7), 86.7% of the patients had extraarticular manifestations; 79.6% were found to have rheumatoid factor (RF); the patients received an average of > 2 disease-modifying antirheumatic drugs (DMARDs). After 2 week-therapy, there was a reduction in RA activity by DAS 28 index in both the PP (from 6.7±1.1 to 4.0±1.4) and LOCF (6.6±1.1 and 4.2±1.4; p < 106) populations. Drug-induced remission (DAS 28 < 2.6) at 54 weeks was observed in 16.9 and 15.1% of the patients, respectively. Functional improvement was noted in the PP population: HAQ decreased from 2.0±0.7 to 1.7±0.7 scores by week 2; its reduction continued until week 14 (p < 0.05), by remaining stable later on. HAQ dropped from 2.0±0.7 to 1.2±0.7 scores in the LOCF population. At 54 weeks, normal population values of functional activity were achieved in 16.4%. Log regression analysis in the LOCF population indicated that the previous use of DMARDs and a short history of the disease were predictors of an ACR70 response to IF therapy [OR=1.61 (1.13-2.30), p = 0.008 and OR = 0.91 (0.84-0.98), p = 0.018, respectively]. RF seronegativity was a predictor for achievement of low RA activity [OR = 0.44 (0.23-0.84)]. The previous use of glucocorticoids failed to increase the probability of a good response to IF therapy and achievement of clinical remission [OR = 0.26 (0.11-0.60), p = 0.001]. Conclusion. Therapy with IF in combination with methotrexate or other DMARDs reduces RA activity and improves the functional capacities of patients with RA in real clinical practice

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen