Search

Norman J KachuckUniversity of Southern California, Keck School of Medicine, Los Angeles, CA, USAAbstract: New more powerful therapies for the treatment of multiple sclerosis may also confer a potential for unprecedented life-endangering side effects. How does a physician respond to a patient's request for a treatment the benefit of which cannot be clearly established as worth its risk? The current challenge with prescription of natalizumab (Tysabri®, Biogen Idec) is used to illustrate how this conflict creates an opportunity to re-examine our goals as physicians and the nature of the physician-patient relationship. Understanding the physician's role in that partnership, and the ethical and psychological issues impacting on how reasonable risk is determined, can improve the neurologist's capacity to explicate such quandaries. Redefining what is required to mediate disagreement between doctors and patients about reasonable risk is at the heart of why many of us became physicians. However, such nuanced interpersonal dynamics of patient care can be neglected due to the time and resource pressures of our practices. These demands have increased the seductiveness of the efficiencies promoted by the trend toward the pseudoobjectification of evidence-based care, which has arguably monopolized the healing conversation often to the detriment of the shared narrative. We examine and attempt to reframe the fiduciary and biopsychosocial contretemps of the doctor and patient disagreeing on risk, emphasizing its humanistic, relational dimensions.Keywords: multiple sclerosis, natalizumab, medical ethics, medical decision-making, patient-physician relationship

Objective: To update the 2002 American Academy of Neurology (AAN) guideline regarding immunization and multiple sclerosis (MS)., Methods: The panel performed a systematic review and classified articles using the AAN system. Recommendations were based on evidence, related evidence, principles of care, and inferences according to the AAN 2011 process manual, as amended., Major Recommendations Level B Except Where Indicated: Clinicians should discuss the evidence regarding immunizations in MS with their patients and explore patients' opinions, preferences, and questions. Clinicians should recommend that patients with MS follow all local vaccine standards, unless there are specific contraindications and weigh local vaccine-preventable disease risks when counseling patients. Clinicians should recommend that patients with MS receive the influenza vaccination annually. Clinicians should counsel patients with MS about infection risks associated with specific immunosuppressive/immunomodulating (ISIM) medications and treatment-specific vaccination guidance according to prescribing information (PI) and vaccinate patients with MS as needed at least 4-6 weeks before initiating patients' ISIM therapy. Clinicians must screen for infections according to PI before initiating ISIM medications (Level A) and should treat patients testing positive for latent infections. In high-risk populations, clinicians must screen for latent infections before starting ISIM therapy even when not specifically mentioned in PI (Level A) and should consult specialists regarding treating patients who screen positive for latent infection. Clinicians should recommend against using live-attenuated vaccines in people with MS receiving ISIM therapies. Clinicians should delay vaccinating people with MS who are experiencing a relapse., (© 2019 American Academy of Neurology.)

Getting the facts about risk and benefit is a critical part of medical decision-making. But when doctors and patients disagree on what is reasonable risk, it takes more than a grasp of the data to establish the way forward. Our competence as physician-scientists relies on our ability to master the mechanics and information flow of our specialty. But we physicians, curious amalgams of scientists, scholars, researchers, and healers, should be aware of how we respond to the uniqueness of each of our physician-patient relationships, and be willing to explore ways in which the psychological and interpersonal dynamics influence the ethical, medically correct choices we pursue in them.

Interferon beta preparations are the most widely used initial therapies prescribed for patients with relapsing-remitting multiple sclerosis. Phase III studies have demonstrated comparable efficacy on clinical measures of disease activity, variable benefits on radiological measures, and good overall tolerability. Subsequent clinical studies have attempted to compare directly the three available interferon beta preparations, reporting both safety and efficacy data. We review the literature on studies evaluating interferon beta therapy for patients with relapsing-remitting multiple sclerosis, discuss reasons for discrepant findings, and assess the utility of interferon beta-based combination regimens as the focus of future studies in the increasingly complex multiple sclerosis therapy landscape.

Background: Fampridine-SR is under submission as the first drug to be FDA approved with an indication specifically for multiple sclerosis symptoms. Compounded forms of the active agent of Fampridine-SR (4-aminopyridine) have been used in clinical practice for many years. Clinical trials have now been completed that demonstrate a robust capacity of the drug to meet stringent statistical and clinically meaningful end points., Objective: To review the present understanding of multiple sclerosis, the proposed mechanism of action of Fampridine-SR in patients, the published data regarding its efficacy and safety in human clinical trials, and to discuss its potential clinical uses in MS., Results/conclusion: Fampridine-SR 10 mg twice a day has been shown to be safe and effective in improving the ambulation of patients with walking disability due to MS. It will probably find clinical application beyond this specific indication in a significant proportion of patients.

The approval of natalizumab for relapsing forms of multiple sclerosis, and the subsequent voluntary suspension of its use due to an unexpected viral infection, is a cautionary tale of how much we have to learn about how to prioritize and perform the necessary research and development of novel therapeutics for human diseases, the ethics of placebo-controlled trials and the relationships between researchers, regulatory authorities and the pharmaceutical industry.

Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS which is characterized by large mononuclear cell infiltration and significant demyelination. CXCL8 is a chemo-attractant for both neutrophils and monocytes and triggers their firm adhesion to endothelium. In this study, we demonstrate that serum CXCL8 and CXCL8 secretion from PBMCs are significantly higher in untreated MS patients compared to controls and are significantly reduced in MS patients receiving interferon-beta1a therapy. We suggest that CXCL8 may serve as a marker of monocyte activity in MS and may play a role in monocyte recruitment to the CNS., (Copyright 2004 Elsevier B.V.)