Rituximab in Combination with Corticosteroids for the Treatment of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of rituximab (Roche Products) to submit evidence of the clinical and cost effectiveness of rituximab in combination with corticosteroids for treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the manufacturer’s submission to NICE. The evidence was derived mainly from a double-blind, phase III, placebo-controlled trial of rituximab in patients with new or relapsed ‘severe’ AAV, which compared a rituximab treatment regimen with an oral cyclophosphamide treatment regimen. Intravenous cyclophosphamide is also commonly used but was not included in the pivotal trial. The evidence showed that rituximab is noninferior to oral cyclophosphamide in terms of induction of remission in adults with AAV and de novo disease, and is superior to oral cyclophosphamide in terms of remission in adults who have relapsed once on cyclophosphamide. The ERG concluded that the results of the manufacturer’s economic evaluation could not be considered robust, because of errors and because the full range of relevant treatment sequences were not modelled. The ERG amended the manufacturer’s model and demonstrated that rituximab was likely to represent a cost-effective addition to the treatment sequence if given after cyclophosphamide treatment

Effect of small-vessel disease on cognitive trajectory after atrial fibrillation-related ischaemic stroke or TIA

Post-stroke dementia is common but has heterogenous mechanisms that are not fully understood, particularly in patients with atrial fibrillation (AF)-related ischaemic stroke or TIA. We investigated the relationship between MRI small-vessel disease markers (including a composite cerebral amyloid angiopathy, CAA, score) and cognitive trajectory over 12 months. We included patients from the CROMIS-2 AF study without pre-existing cognitive impairment and with Montreal Cognitive Assessment (MoCA) data. Cognitive impairment was defined as MoCA < 26. We defined “reverters” as patients with an “acute” MoCA (immediately after the index event) score < 26, who then improved by ≥ 2 points at 12 months. In our cohort (n = 114), 12-month MoCA improved overall relative to acute performance (mean difference 1.69 points, 95% CI 1.03–2.36, p < 0.00001). 12-month cognitive impairment was associated with increasing CAA score (per-point increase, adjusted OR 4.09, 95% CI 1.36–12.33, p = 0.012). Of those with abnormal acute MoCA score (n = 66), 59.1% (n = 39) were “reverters”. Non-reversion was associated with centrum semi-ovale perivascular spaces (per-grade increase, unadjusted OR 1.83, 95% CI 1.06–3.15, p = 0.03), cerebral microbleeds (unadjusted OR 10.86, 95% CI 1.22–96.34, p = 0.03), and (negatively) with multiple ischaemic lesions at baseline (unadjusted OR 0.11, 95% CI 0.02–0.90, p = 0.04), as well as composite small-vessel disease (per-point increase, unadjusted OR 2.91, 95% CI 1.23–6.88, p = 0.015) and CAA (per-point increase, unadjusted OR 6.71, 95% CI 2.10–21.50, p = 0.001) scores. In AF-related acute ischaemic stroke or TIA, cerebral small-vessel disease is associated both with cognitive performance at 12 months and failure to improve over this period

Patient behavior immediately after transient ischemic attack according to clinical characteristics, perception of the event, and predicted risk of stroke.

BACKGROUND AND PURPOSE: Little research has been done on patients' behavior after transient ischemic attack (TIA). Recent data on the high early risk of stroke after TIA mean that emergency action after TIA is essential for effective secondary prevention. We therefore studied patients' behavior immediately after TIA according to their perceptions, clinical characteristics, and predicted stroke risk. METHODS: Consecutive patients with TIA participating in the Oxford Vascular Study or attending dedicated hospital clinics in Oxfordshire, UK, were interviewed. Predicted stroke risk was calculated using 2 validated scores. RESULTS: Of 241 patients, 107 (44.4%) sought medical attention within hours of the event, although only 24 of these attended the emergency department. A total of 107 (44.4%) delayed seeking medical attention for &gt; or =1 day. Correct recognition of symptoms (42.2% of patients) was not associated with less delay. However, patients with motor symptoms or duration of symptoms &gt; or =1 hour were more likely to seek emergency attention (hazard ratio, 2.1; 95% CI, 1.4 to 3.2; P=0.00005), as were those at higher predicted stroke risk (P=0.001). The other main correlate with delay was the day of the week on which the TIA occurred (P&lt;0.001), with greater delays at the weekend. Delay was unrelated to age, sex, or other vascular risk factors. CONCLUSIONS: Many patients delay seeking medical attention after a TIA irrespective of correct recognition of symptoms, although patients at higher predicted risk of stroke do act more quickly. Public education about both the urgency and nature of TIA is required