Response to oral supplementation in copper deficiency myeloneuropathy

Neurological manifestations due to copper deficiency include ataxic myeloneuropathy that resembles subacute combined degeneration due to B12 deficiency. We report our experience in the treatment of 10 patients with copper deficiency myeloneuropathy and conclude that copper supplementation leads to stabilization rather than improvement in the neurological deficits. © 2008 by Lippincott Williams & Wilkins

Treatment of chronic inflammatory demyelinating polyneuropathy with pulsed oral steroids

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy that responds to various immunosuppressive treatments. Oral daily prednisone therapy is effective and inexpensive, but the long-term treatment that is usually necessary leads to serious adverse effects. Consequently, intravenous immunoglobulin and plasma exchange have been widely used to treat CIDP, making treatment expensive and inconvenient. A steroid regimen that reduces adverse effects but preserves efficacy would simplify treatment. Pulsed steroids have nongenomic actions not seen with low-dose steroids, including rapid inhibition of arachidonic acid release and of calcium and sodium cycling across plasma membranes of immune cells. Objective: To study the efficacy, safety, and tolerability of pulsed oral methylprednisolone therapy in patients with CIDP. Design: Open-label prospective study. Setting: University of Minnesota Neuropathy Center, Minneapolis. Patients: Ten patients (3 women and 7 men) with CIDP followed up for at least 22 months. Main Outcome Measures: Neuromuscular score and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score were used as outcome measures for efficacy; weight, blood pressure, changes in bone density, and steroid-related adverse effect questionnaire were used as outcome measures for safety. Results: This steroid regimen leads to significant improvement in weakness and disability in all patients treated and to off-treatment remission in 60% of patients. Treatment was fairly well tolerated, and only 1 patient discontinued treatment because of adverse effects. Steroid-induced osteoporosis remained a problem, especially in older patients. Conclusions: Pulsed oral methylprednisolone may be efficacious in the long-term treatment of CIDP and is relatively well tolerated. Remission can be induced in most patients, especially those with a shorter duration of disease. ©2008 American Medical Association. All rights reserved

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)