Fludarabine add-on therapy in interferon-beta-treated patients with multiple sclerosis experiencing breakthrough disease.

BACKGROUND: Patients with relapsing-remitting multiple sclerosis (RRMS) may experience breakthrough disease despite effective interferon beta (IFNß) therapy. Fludarabine (FLU) is a chemotherapeutic agent used in lymphoproliferative disorders that may be synergistic when combined with immunomodulatory therapy to control active multiple sclerosis (MS). OBJECTIVE: The objective of this study was to explore the safety and tolerability of FLU versus monthly methylprednisolone (MP) in IFNß-treated RRMS patients with breakthrough disease. Clinical and MRI effects of IFNß-1a plus FLU were evaluated. METHODS: Eighteen patients with breakthrough disease [⩾2 relapses over the prior year and ⩾1.0-point increase in Expanded Disability Status Scale (EDSS) score sustained for ⩾3 months] after >1 year of IFNß therapy were enrolled in this prospective, open-label, randomized, proof-of-concept, pilot study. Patients received intravenous (IV) MP 1 g daily for 3 days and then were randomized to receive 3 monthly IV infusions of FLU 25 mg/m(2) daily for 5 consecutive days (n = 10) or MP 1 g (n = 8). All patients maintained their intramuscular IFNß-1a treatment throughout the study. Analyses explored safety signals and directional trends; this preliminary study was not powered to detect clinically meaningful differences. RESULTS: Both combination treatments were safe and well tolerated, with all adverse events mild. Patients treated with IFNß-1a plus FLU had similar relapse rates, EDSS scores, and MS Functional Composite scores, but significantly less acute corticosteroid use for on-study relapses and better responses on some MRI outcomes, versus patients treated with IFNß-1a plus MP. CONCLUSIONS: Further study of FLU for breakthrough disease in patients with RRMS is warranted.

Emerging oral therapies for multiple sclerosis.

Despite notable advances in the understanding of multiple sclerosis (MS) and the availability of several treatment options, there is a need for therapies that are more effective, safe, convenient, and well tolerated. Several new oral MS therapies are being investigated. Because data on these new therapies continue to emerge, nurses will play a pivotal role in educating patients regarding the benefits and risks of potential treatments and in monitoring patients for response, safety, tolerability, and adherence. This article reviews the oral MS therapies recently approved as well as those currently in development or submitted for Food and Drug Administration approval.