Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis

Abstract

Objective To develop recommendations for disease-modifying therapy (DMT) for multiple sclerosis (MS).Methods A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine-compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus-based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsingremitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination. Recommendations were supported by structured rationales, integrating evidence from one or more sources: systematic review, related evidence (evidence not from the systematic review), principles of care, and inference from evidence. ResultsThirty recommendations were developed: 17 on starting DMTs, including recommendations on who should start them; 10 on switching DMTs if breakthrough disease develops; and 3 on stopping DMTs. Recommendations encompassed patient engagement strategies and individualization of treatment, including adherence monitoring and disease comorbidity assessment. The panel also discussed DMT risks, including counseling about progressive multifocal leukoencephalopathy risk in people with MS using natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate; and made suggestions for future research to evaluate relative merits of early treatment with higher potency DMTs vs standard stepped-care protocols, DMT comparative effectiveness, optimal switching strategies, long-term effects of DMT use, definitions of highly active MS, and effects of treatment on patient-specified priority outcomes. This guideline reflects the complexity of decisionmaking for starting, switching, or stopping MS DMTs. The field of MS treatment is rapidly changing; the Academy of Neurology development process includes planning for future updates.

Disease-modifying therapies for multiple sclerosis

“…This is the first episode of neurological symptoms suggestive of multiple sclerosis with brain MRI abnormalities (indicating a high risk of multiple sclerosis). The aim of treatment is to delay a second attack 89…”

“…International guidelines recommend offering DMTs to patients with active relapsing multiple sclerosis (table 1). 789…”

Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective

“…MS-based medications would either attempt at depleting entire subset of immune cells (selective B-cell or both B and T-cell depletetors like ocrelizumab and alemtuzumab, respectively), sequester the pathological immune cells away from the CNS (natalizumab and sphingosine-phosphate receptor modulators), or inhibit the expansion of stimulated lymphocytes (teriflunomide and cladribine). [9,10]. However, none of these interventions target the underlying pathophysiology that still remains largely unknown.…”

The Potential of Computational Modeling to Predict Disease Course and Treatment Response in Patients with Relapsing Multiple Sclerosis

“…The most common treatment strategy so far has been that of escalating from a moderate to a high-efficacy drug, if disease activity was still persistent or resurgent. However, for patients with highly active disease at the presentation, the use of high-efficacy therapies from the onset is recommended to prevent the accumulation of disability [10]. Furthermore, some of the high-efficacy DMDs such as alemtuzumab and cladribine have profound depleting effects on T and B lymphocytes.…”