Ellen S. Lathi

A review of disease-modifying therapies for MS: maximizing adherence and minimizing adverse events

ABSTRACT Background: In a chronic disabling disorder such as multiple sclerosis (MS), adherence to treatment is of critical importance in maximizing benefits of therapy over the long term. Adverse events (AEs) are often cited by patients who discontinue therapy. Methods: Databases including Medline, CINAHL, and International Pharmaceutical Abstracts were searched for literature pertaining to adherence and AEs in MS published between January 1970 and August 2008. Clinical studies and case reports of AEs were included, as were papers that outlined factors that influence adherence. An advisory board with extensive experience in managing patients with MS developed guidelines to assist healthcare providers in maximizing adherence to disease-modifying therapy. Discussion: Internally based factors such as self-image, and externally based factors such as AEs, may influence patients’ willingness and ability to adhere to therapy. Management of AEs associated with disease-modifying therapies and other therapies is reviewed, including intramuscular and subcutaneous interferon beta (IFNβ)-1a, IFNβ-1b, glatiramer acetate, natalizumab, methylprednisolone, mitoxantrone, cyclophosphamide, methotrexate, azathioprine, and intravenous immunoglobulin. Conclusions: Effective management of MS is an ongoing, dynamic process that can enhance patients’ adherence to therapy. Healthcare practitioners may address factors influencing adherence among patients with MS by managing treatment expectations, maintaining good communication with the patient, and managing AEs of treatment. Although the guidelines proposed herein originate from a single advisory board, it seems clear that by addressing patient concerns, healthcare practitioners can work with patients to enhance their ability to continue to adhere to their therapies and thereby gain the benefits of their treatment over the long term.

A Prospective Study of Radiofrequency Rhizotomy in the Treatment of Posttraumatic Spasticity

Posttraumatic spasticity severely impedes rehabilitation potential and nursing care. Treatment of severe spasticity has included medical therapy, spinal cord ablative procedures, anterior and posterior root lesions and peripheral denervations, and tendon releases. Open rhizotomy and percutaneous radiofrequency rhizotomy have achieved good results. We prospectively studied 25 patients with severe spasticity to assess the efficacy of percutaneous radiofrequency rhizotomy. All or most of the prospectively identified goals were accomplished in 24 of the 25 patients, with improvement persisting during an average follow-up period of 12 months. The improvement due to decreased tone was much greater than the improvement due to increased range of motion.

Cerebral embolism as the initial manifestation of peripartum cardiomyopathy

Peripartum cardiomyopathy is characterized by heart failure in the last trimester or puerperium without obvious cause. We studied a 30-year-old woman who had an embolic stroke as the result of an otherwise asymptomatic peripartum cardiomyopathy.

Radiation-induced malignant fibrous histiocytoma of the brachial plexus.

SummaryBrachial plexopathy is a common and disabling complication in cancer patients most often attributed to metastasis or radiation-induced fibrosis. Occasionally, other rare but potentially treatable causes are found. A 73 year old woman had a left radical mastectomy followed by radiation to the chest wall and axilla 24 years ago. She recently presented with left arm pain, chronic, nonprogressive lymphedema, profound distal arm sensory loss and progressive severe hand weakness. There was moderate atrophy of all intrinsic hand muscles, anesthesia of the hypothenar eminence and 4th and 5th digits, and no adenopathy or palpable mass in the axilla. EMG confirmed a brachial plexopathy. MRI showed loss of tissue planes consistent with radiation fibrosis, but CT showed a discrete mass in the brachial plexus. Open biopsy showed pleomorphic spindle shaped cells with immunoperoxidase stains consistent with malignant fibrous histiocytoma.Radiation-induced malignant fibrous histiocytoma may present with a brachial plexopathy in the absence of a palpable mass and should be considered in the differential diagnosis of brachial plexus lesions in cancer patients. CT scanning through the plexus may be useful when MRI is normal or equivocal.

Effectiveness of alternative dose fingolimod for multiple sclerosis

Background Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited. Methods We conducted a multicenter, retrospective, observational study at 14 sites and identified 170 patients with MS taking alternate doses of fingolimod for ≥1 month. Clinical and radiologic outcomes were collected and compared during daily and alternate fingolimod dosing. Results Profound lymphopenia (77%), liver function abnormalities (9%), and infections (7%) were the most common reasons for patients to switch to alternate fingolimod dosing. The median follow-up was 12 months on daily dose and 14 months on alternate dose. Most patients (64%) took fingolimod every other day during alternate dosing. Disease activity was similar on alternate dose compared to daily dose: annualized relapse rate was 0.1 on daily dose vs 0.2 on alternate dose (p = 0.25); proportion of patients with contrast-enhancing MRI lesions was 7.6% on daily vs 9.4% on alternate (p = 0.55); proportion of patients with cumulative MS activity (clinical and radiologic disease) was 13.5% on daily vs 18.2% on alternate (p = 0.337). Patients who developed contrast-enhancing lesions while on daily dose were at higher risk for breakthrough disease while on alternate dose fingolimod (odds ratio 11.4, p < 0.001). Conclusions These data support the clinical strategy of alternate dosing of fingolimod in patients with good disease control but profound lymphopenia or other adverse events while on daily dose. Classification of Evidence This study provides Class IV evidence that for patients with MS on daily dose fingolimod with adverse events, alternate dose fingolimod is associated with disease activity similar to daily dose fingolimod.

No evidence of disease activity in patients receiving fingolimod at private or academic centers in clinical practice: a retrospective analysis of the multiple sclerosis, clinical, and magnetic resonance imaging outcomes in the USA (MS-MRIUS) study

Abstract Objective: The impact of multiple sclerosis (MS) center type on outcomes has not been investigated. This study aimed to evaluate baseline characteristics and clinical and magnetic resonance imaging (MRI) outcomes in patients with MS receiving fingolimod over 16 months’ follow-up at private or academic centers in the USA. Methods: Clinical and MRI data collected in clinical practice from patients initiating fingolimod were stratified by center type and retrospectively analyzed. No evidence of disease activity (NEDA-3) was defined as patients with no new/enlarged T2/gadolinium-enhancing lesions, no relapses, and no disability progression (Expanded Disability Status Scale scores). Results: Data were collected for 398 patients from 25 private centers and 192 patients from eight academic centers. Patients were older (median age = 43 vs 41 years; p = .0047) and had a numerically shorter median disease duration (7.0 vs 8.5 years; p = .0985) at private vs academic centers. Annualized relapse rate (ARR) was higher in patients at private than academic centers in the pre-index (0.40 vs 0.29; p = .0127) and post-index (0.16 vs 0.08; p = .0334) periods. The opposite was true for T2 lesion volume in the pre-index (2.86 vs 5.23 mL; p = .0002) and post-index (2.86 vs 5.11 mL; p = .0016) periods; other MRI outcomes were similar between center types. After initiating fingolimod, ARRs were reduced, disability and most MRI outcomes remained stable, and a similar proportion of patients achieved NEDA-3 at private and academic centers (64.1% vs 56.1%; p = .0659). Conclusion: Patient characteristics differ between private and academic centers. Over 55% of patients achieved NEDA-3 during fingolimod treatment at both center types.