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Practice Guideline
. 2024 Jun;31(6):e16264.
doi: 10.1111/ene.16264. Epub 2024 Mar 12.

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD)

Philip Van Damme  1 , Ammar Al-Chalabi  2 , Peter M Andersen  3 , Adriano Chiò  4   5 , Philippe Couratier  6 , Mamede De Carvalho  7 , Orla Hardiman  8 , Magdalena Kuźma-Kozakiewicz  9 , Albert Ludolph  10 , Christopher J McDermott  11 , Jesus S Mora  12 , Susanne Petri  13 , Katrin Probyn  14 , Evy Reviers  15 , François Salachas  16 , Vincenzo Silani  17   18 , Ole-Bjørn Tysnes  19 , Leonard H van den Berg  20 , Gemma Villanueva  14 , Markus Weber  21
Affiliations
Practice Guideline

European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD)

Philip Van Damme et al. Eur J Neurol. 2024 Jun.

Abstract

Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).

Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.

Results: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management.

Conclusions: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

Keywords: disease‐modifying treatment; gastrostomy; guideline; multidisciplinary care; non‐invasive ventilation.

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Conflict of interest statement

P.V.D. has served in advisory boards for Biogen, CSL Behring, Alexion Pharmaceuticals, Ferrer, QurAlis, Cytokinetics, Argenx, UCB, Muna Therapeutics, Alector, Augustine Therapeutics, VectorY, Zambon, and Amylyx (paid to institution). P.V.D. has received speaker fees from Biogen and Amylyx (paid to institution). P.V.D. has participated as investigator to clinical trials on amyotrophic lateral sclerosis (ALS) sponsored by Biogen, Cytokinetics, Ferrer, Amylyx, Wave Life Sciences, Corcept Therapeutics, Transposon Therapeutics, Sanofi, AB Science, IONIS Pharmaceuticals, Apellis Pharmaceuticals, Alexion Pharmaceuticals, Orphazyme, Orion Pharma, and AL‐S Pharma. P.V.D. is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders (from CSL Behring, paid to institution).

A.A.C. reports consultancies or advisory boards for Amylyx, Apellis, Biogen, Brainstorm, Cytokinetics, GenieUs, GSK, Lilly, Mitsubishi Tanabe Pharma, Novartis, OrionPharma, Quralis, Sano, and Sanofi; the following patent: ‘Use of CSF‐neurofilament determinations and CSF‐neurofilament thresholds of prognostic and stratification value with regards to response to therapy in neuromuscular and neurodegenerative diseases’; and is a member of the Cochrane Collaboration for a systematic review of ‘Disease‐modifying pharmacological treatments for amyotrophic lateral sclerosis/motor neuron disease’, some of which has contributed to this article.

P.M.A. has served on advisory boards for Arrowhead, Avrion, Biogen Idec, Orphazyme, Hoffman La Roche, Regeneron, uniQure, and VectorY. P.M.A. participates/has participated as an investigator in clinical drug trials on ALS sponsored by AB Science, AL‐S Pharma and Lilly, Amylyx, Alexion Pharmaceuticals, Biogen Idec, IONIS Pharmaceuticals, Orion Pharma, PTC, Rhône‐Poulenc, and Sanofi.

A.C. has served on scientific advisory boards for Mitsubishi Tanabe, Biogen, Roche, Denali Pharma, Ferrer, Cytokinetics, Lilly, VectorX, Zambon, and Amylyx Pharmaceuticals, and has received a research grant from Biogen. A.C. serves on data safety monitoring boards (DSMB) for AL‐S Pharma and AB Science. A.C. has participated as investigator to clinical trials on ALS sponsored by Biogen, Cytokinetics, Ferrer, Amylyx, Corcept Therapeutics, Sanofi, AB Science, IONIS Pharmaceuticals, Apellis Pharmaceuticals, Alexion Pharmaceuticals, Orion Pharma, and NeuroSense.

PC has served in scientific advisory boards for Mitsubishi Tanabe, Biogen, Cytokinetics, Zambon and Amylyx Pharmaceuticals. PC serves on DSMB for AB Science. PC has participated as investigator to clinical trials on ALS sponsored by Biogen, Cytokinetics, Ferrer, Amylyx, AB Science, IONIS Pharmaceuticals, Apellis Pharmaceuticals, Alexion Pharmaceuticals, and Orion Pharma.

M.D.C. has served on advisory boards for Cytokinetics. MdC has participated as investigator to clinical trials on ALS sponsored by Cytokinetics, Ferrer, Amylyx, and AB Science. M.D.C. has received research grants from Cytokinetics and Biogen.

O.H. has served on advisory boards for Biogen, Orion Pharma, Novartis, Amylyx, Cytokinetics, Accelsior, Sanfofi, Neuroscense, and Sanofi. She has received speaker fees from Biogen, Novartis, Lundbeck, Cytokinetics, and Apellis. She is an investigator on clinical trials sponsored by Biogen, Cytokinetics, Ferrer, Amylyx, Corcept Therapeutics, IONIS Pharmaceuticals, Apellis Pharmaceuticals, Alexion Pharmaceuticals, and Orion Pharma. She is lead investigator on an academic/industry partnership PRECISION ALS. She is Editor‐in‐Chief of the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.

M.K.‐K. has served on advisory board for Ferrer and Amylyx. She has received speaker fees from Biogen and Ferrer. She is an investigator on clinical trials sponsored by Amylyx, Apellis, Alexion, Corcept, Cytokinetics, Ferrer International, IONIS, and PTC therapeuticals.

A.L. is a member of advisory boards of Roche Pharma AG, Biogen, Alector, and Amylyx. He has received compensation for talks from Biologix, the German Society of Neurology, Biogen, Springer Medicine, Amylyx, and the company Streamed Up! GmbH. AL is involved in trials which are sponsored by Amylyx, Ferrer International, Novartis Research and Development, Mitsubishi Tanabe, Apellis Pharmaceuticals, Alexion, Orion Pharma, the European Union, BMBF, Biogen, and Orphazyme.

C.J.M. has served on advisory boards for Biogen, Amylyx, Ferrer, Orion Pharma, Orphazyme, and Novartis. C.J.M. has participated as an investigator on clinical trials on ALS sponsored by Biogen, Cytokinetics, Ferrer, Amylyx, Orphazyme, and Orion Pharma.

J.S.M. has served on advisory boards for AB Science, Biogen Idec, Cytokinetics, Ferrer, and Trophos/Roche. J.S.M. has participated as an investigator on clinical trials on ALS sponsored by AB Science, Alexion Pharmaceuticals, Amylyx, Biogen Idec, Cytokinetics, ONO, Orion Pharma, Rhône‐Poulenc‐Rorer, Sanofi, and Trophos/Roche.

S.P. has received speaker fees from Amylyx, Biogen, ITF‐Pharma, Roche, and Zambon, and served on advisory boards for Amylyx, Biogen, Roche, Zambon, and ITF Pharma. S.P. has participated as an investigator on clinical trials on ALS sponsored by Alexion Pharmaceuticals, AL‐S Pharma, Amylyx, Apellis Pharmaceuticals, Biogen, Cytokinetics, Corcept Therapeutics, Ferrer, Sanofi, Orion Pharma, and Orphazyme. S.P. has received research support from NDR.

K.P. is employed by Cochrane Response, an evidence services unit operated by the Cochrane Collaboration. Cochrane Response was commissioned by EAN to perform a suite of systematic reviews that contributed to this publication.

E.R. is chairwomen of EUpALS, the European Organization for Professionals and Patients with ALS. EUpALS interacts with companies active in the clinical development of potential new ALS therapies. At the time of writing of the article, the EUpALS Industry Partners were (in alphabetical order): Amylyx, Apellis, Biogen, Brainstorm, Corcept Therapeutics, Cytokinetics, Ferrer, Italfarmaco, Julius Clinical, Novartis, Regeneron, Sanofi, Tranquis Therapeutics, UCB, Wave Life Sciences, Worldwide Clinical Trials, and Zambon Biotech. F.S. has served on advisory boards for Biogen.

F.S. has participated as an investigator on clinical trials on ALS sponsored by Biogen, Cytokinetics, Ferrer, Amylyx, Alexion Pharmaceuticals, and Corcept therapeutics.

V.S. received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., Novartis Pharma AG, Amylyx Pharmaceuticals, and Zambon Biotech SA, and receives or has received research support from the Italian Ministry of Health, AriSLA, and E‐Rare Joint Transnational Call. V.S. has participated as an investigator on clinical trials on ALS sponsored by Cytokinetics, Ferrer International SA, Mitsubishi Tanabe, Amylyx, AB Science, Sanofi, PTC Therapeutics, and PPD. He is a member of the Editorial Boards of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology, and Exploration of Neuroprotective Therapy. V.S. was appointed Chair and Co‐Chair of the ERN EURO‐NMD expert working group on motor neuron diseases.

O.‐B.T. has given invited lectures on ALS at the invitation of Novartis Pharma A.G.

L.H.v.d.B. has served on advisory boards for Biogen, Amylyx, Ferrer, Corcept, QurAlis, Cytokinetics, Argenx, VectorY, and Zambon. L.H.v.d.B. has participated as principal investigator on clinical trials on ALS sponsored by Biogen, Cytokinetics, Ferrer, Amylyx, Wave Life Sciences, Corcept Therapeutics, Sanofi, AB Science, IONIS Pharmaceuticals, Apellis Pharmaceuticals, Alexion Pharmaceuticals, Orphazyme, and Orion Pharma.

G.V. is employed by Cochrane Response, an evidence services unit operated by the Cochrane Collaboration. Cochrane Response was commissioned by EAN to perform a suite of systematic reviews that contributed to this publication.

M.W. has served on advisory boards for Biogen Idec, Mitsubishi Tanabe, Merz Switzerland, Amylyx, Neuraxpharm, Biologix, and Allmiral. M.W. participates/has participated as an investigator on clinical drug trials on ALS sponsored by Alexion Pharmaceuticals, Biogen Idec, IONIS Pharmaceuticals, and Mitsubishi Tanabe.

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