TY - JOUR
T1 - Practice guideline recommendations summary
T2 - Disease-modifying therapies for adults with multiple sclerosis
AU - Rae-Grant, Alexander
AU - Day, Gregory S.
AU - Marrie, Ruth Ann
AU - Rabinstein, Alejandro
AU - Cree, Bruce A.C.
AU - Gronseth, Gary S.
AU - Haboubi, Michael
AU - Halper, June
AU - Hosey, Jonathan P.
AU - Jones, David E.
AU - Lisak, Robert
AU - Pelletier, Daniel
AU - Potrebic, Sonja
AU - Sitcov, Cynthia
AU - Sommers, Rick
AU - Stachowiak, Julie
AU - Getchius, Thomas S.D.
AU - Merillat, Shannon A.
AU - Pringsheim, Tamara
N1 - Funding Information:
The authors acknowledge the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry for its assistance in administering an outcomes survey, the results of which were included in this practice guideline. NARCOMS is supported in part by the Consortium of Multiple Sclerosis Centers (CMSC) and the Foundation of the CMSC.
Funding Information:
This practice guideline was developed with financial support from the American Academy of Neurology (AAN). Authors who serve as AAN subcommittee members or as methodologists (A.R.-G., G.S.D., A.R., G.S.G., M.H., S.P., T.P.), or who are or were AAN staff members (T.S.D.G., S.A.M.), were reimbursed by the AAN for expenses related to travel to subcommittee meetings where drafts of manuscripts were reviewed. All authors on the panel were reimbursed by the AAN for expenses related to travel to 2 in-person meetings.
Funding Information:
A. Rae-Grant receives royalties from 2 textbooks he has published, 1 on neurology and 1 on multiple sclerosis (MS); organizes and receives honoraria for grand rounds and neurology review courses; and is local primary investigator for a clinical trial with MedDay Pharmaceuticals, for which he receives no personal compensation. A. Rabinstein reports no disclosures relevant to the manuscript. B. Cree has received compensation for consulting from AbbVie, Biogen, EMD Serono, GeNeuro, MedImmune, Novartis, Shire, and Genzyme/Sanofi Aventis; has given expert testimony and prepared an affidavit for medical malpractice cases (1 or 2 per year) within his area of expertise; and has acted as consultant in a legal proceeding for Acorda and Biogen. G. Gronseth serves as associated editor (level of evidence review) for Neurology®; serves on the editorial advisory board for Neu- rology Now; and is compensated by the American Academy of Neurology (AAN) for methodologic activities. G. Day holds stock in ANI Pharmaceuticals. M. Haboubi has received travel reimbursement and honoraria for grand rounds presentations in Madisonville, KY. J. Halper and J. Hosey report no disclosures relevant to the manuscript. D. Jones has received personal compensation for consulting from Biogen and Genzyme; has received honoraria from the Consortium of Multiple Sclerosis Centers (CMSC), the Multiple Sclerosis Association of America (MSAA), and the Pharmacy Quality Alliance; has received institutional research support from Biogen and the National MS Society (NMSS); has received salary support from the CMSC; and has received travel reimbursement from Biogen and Genzyme and from the AAN, Can Do MS, the CMSC, and the MSAA. R. Lisak served as the President of the CMSC and serves as a member of the Board of the DMC Foundation; has served on scientific advisory boards for Mallinckrodt, Syntimmune, Celegene, and Alex-ion; serves as chair of the adjudication committee of a clinical trial (PAREXEL); has received funding for travel from the CMSC, the GBS/CIDP Foundation International, the NMSS, and Syntimmune for travel to consultants meetings; has served as a journal editor for Clinical and Experimental Neuroimmunology and Clinical Neuropharmacology; has received publishing royalties from Willey for International Neurology: A Clinical Approach; has received honoraria from Mallinckrodt, Syntimmune, and Teva Pharmaceuticals, and from the consulting agencies AlphaSights, ClearView Healthcare Partners, GLC, and Insights Consulting; has served on a speakers bureau for Teva Pharmaceuticals for talks unrelated to pharmaceuticals; has received research support from Mallinckrodt for investigator-initiated wet bench studies, and from Acorda, Avanir, Biogen, Chugai, Genentech, MedImmune, Novartis, and Teva Pharmaceuticals for serving as a site investigator in multicenter trials; has given expert testimony, prepared an affidavit, and acted as witness for Teva Pharmaceuticals; and has acted as an expert on a patent case for Acorda. Wayne State University has received financial compensation from the NMSS for his salary as principal investigator for a research grant. R.A. Marrie receives research grants from nonprofit organizations, including Canadian Institutes of Health Research (CIHR), the CMSC, Crohn’s and Colitis Canada, the NMSS, the Multiple Sclerosis Society of Canada, the Multiple Sclerosis Scientific Research Foundation, and Research Manitoba; and serves on the editorial board of Neurology. D. Pelletier has served on scientific advisory boards for Biogen, EMD Serono, Genzyme/Sanofi Aventis, Hoffman LaRoche, and Novartis; has received research support for Biogen, Genzyme, Hoffman LaRoche, and the National Institute of Neurologic Disorders and Stroke of the NIH; and has received honoraria for providing consulting services at scientific advisory board meetings from Biogen, EMD Serono, Genzyme/Sanofi Aventis, Hoffman LaRoche, and Novartis. S. Potrebic received an honorarium from CDI Quality Institute PLE for participation in a headache appropriate-use criteria panel for imaging; and receives travel reimbursement from the AAN for attending AAN Residency In-Service Training Examination Work Group meetings, AAN Axon Registry Committee meetings, AAN Guideline Development, Dissemination, and Implementation Subcommittee meetings, and the Guidelines International Network North America Evidence-based Guidelines Affecting Policy, Practice, and Stakeholders (E-GAPPS) conference. R. Sommers, C. Sitcov, and J. Stachowiak report no disclosures relevant to the manuscript. T. Getchius is a former AAN employee and reports no relevant disclosures. S. Merillat reports no disclosures relevant to the manuscript. T. Pringsheim has received research support from the CIHR and Shire Canada Inc. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
Copyright © 2018 American Academy of Neurology
PY - 2018
Y1 - 2018
N2 - 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 relapsing-remitting 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. Results Thirty 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 decision-making 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.
AB - 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 relapsing-remitting 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. Results Thirty 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 decision-making 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.
UR - http://www.scopus.com/inward/record.url?scp=85046794788&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000005347
DO - 10.1212/WNL.0000000000005347
M3 - Review article
C2 - 29686116
AN - SCOPUS:85046794788
SN - 0028-3878
VL - 90
SP - 777
EP - 788
JO - Neurology
JF - Neurology
IS - 17
ER -