MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study.

OBJECTIVE: RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab. METHODS: Eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon ß-1a [IM IFN-ß-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks. RESULTS: Patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-ß-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-ß-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%-29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4-8 weeks (n = 2 in weeks 4-8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity. CONCLUSIONS: MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at increased surgical risk: results from the SAPPHIRE trial.

OBJECTIVES: To evaluate the cost-effectiveness of carotid stenting vs. carotid endarterectomy using data from the SAPPHIRE trial. BACKGROUND: Carotid stenting with embolic protection has been introduced as an alternative to carotid endarterectomy for prevention of cerebrovascular and cardiovascular events among patients at increased surgical risk. METHODS: Between August 2000 and July 2002, 310 patients with an accepted indication for carotid endarterectomy but at high risk of complications were randomized to and subsequently underwent either carotid stenting (n = 159) or endarterectomy (n = 151). Clinical outcomes, resource use, costs, and quality of life were assessed prospectively for all patients over a 1-year period. Life expectancy, quality-adjusted life expectancy, and health care costs beyond the follow-up period were estimated for patients alive at 1 year, based on observed clinical events during the first year of follow-up. RESULTS: Although initial procedural costs were significantly higher for stenting than for endarterectomy (mean difference: $4,081/patient; 95% CI, $3,849-$4,355), mean post-procedure length of stay was shorter for stenting (1.9 vs. 2.9 days; P < 0.001) with significant associated cost offsets. As a result, initial hospital costs were just $559/patient higher with stenting (95% CI, $3,470 less to $2,289 more). Neither follow-up costs after discharge nor total 1-year costs differed significantly. The incremental cost-effectiveness ratio for stenting compared with endarterectomy was $6,555 per quality-adjusted life year (QALY) gained, with over 98 percent of bootstrap estimates < $50,000/QALY gained. CONCLUSIONS: Although carotid stenting with embolic protection is more costly than carotid endarterectomy, by commonly accepted standards, stenting is an economically attractive alternative to endarterectomy for patients at high surgical risk.