Safety of long-term intrathecal methotrexate in progressive forms of MS.
PPMS
SPMS
intrathecal methotrexate
progressive multiple sclerosis
Journal
Therapeutic advances in neurological disorders
ISSN: 1756-2856
Titre abrégé: Ther Adv Neurol Disord
Pays: England
ID NLM: 101480242
Informations de publication
Date de publication:
2019
2019
Historique:
received:
22
03
2019
accepted:
05
11
2019
entrez:
14
12
2019
pubmed:
14
12
2019
medline:
14
12
2019
Statut:
epublish
Résumé
There are few treatment options for multiple sclerosis (MS) patients with advanced disability [expanded disability status scale (EDSS) ⩾ 6.0]. In 2010, we reported initial results of using intrathecal methotrexate (ITMTX) in patients with progressive MS. We now report on long-term use of ITMTX. We performed a retrospective chart analysis of patients who have had 18 or more treatments to establish the ongoing safety and tolerability of ITMTX. Thus, the objective of this study was to establish the safety and tolerability of long-term therapy with (ITMTX) in patients with treatment-resistant, progressive forms of MS. We studied 83 patients (67 secondary and 16 primary progressive) who received ITMTX 12.5 mg every 8-11 weeks for 3-10 years (range: 18-57 treatments). All patients were evaluated neurologically, and their EDSS was assessed at every treatment. In addition, all adverse events, frequency of infections, and any hospitalizations, were noted. There were no deaths, hospitalizations, or other serious adverse effects related to ITMTX. Headaches occurred at least once in 12% of patients, and transient fatigue occurred in 53% of patients. As determined by EDSS, there was no significant change from baseline status to post-treatment scores in both primary progressive MS (PPMS) and secondary progressive (SPMS) patients. Pulsed ITMTX was well tolerated for up to 10 years in PPMS patients with no serious adverse effects. Although this was an open-label, retrospective analysis, and efficacy could not be studied, there was evidence of disease stabilization in many patients receiving ITMTX. It appears that long-term ITMTX is a safe therapeutic option in advanced progressive MS.
Sections du résumé
BACKGROUND
BACKGROUND
There are few treatment options for multiple sclerosis (MS) patients with advanced disability [expanded disability status scale (EDSS) ⩾ 6.0]. In 2010, we reported initial results of using intrathecal methotrexate (ITMTX) in patients with progressive MS. We now report on long-term use of ITMTX. We performed a retrospective chart analysis of patients who have had 18 or more treatments to establish the ongoing safety and tolerability of ITMTX. Thus, the objective of this study was to establish the safety and tolerability of long-term therapy with (ITMTX) in patients with treatment-resistant, progressive forms of MS.
METHODS
METHODS
We studied 83 patients (67 secondary and 16 primary progressive) who received ITMTX 12.5 mg every 8-11 weeks for 3-10 years (range: 18-57 treatments). All patients were evaluated neurologically, and their EDSS was assessed at every treatment. In addition, all adverse events, frequency of infections, and any hospitalizations, were noted.
RESULTS
RESULTS
There were no deaths, hospitalizations, or other serious adverse effects related to ITMTX. Headaches occurred at least once in 12% of patients, and transient fatigue occurred in 53% of patients. As determined by EDSS, there was no significant change from baseline status to post-treatment scores in both primary progressive MS (PPMS) and secondary progressive (SPMS) patients.
CONCLUSIONS
CONCLUSIONS
Pulsed ITMTX was well tolerated for up to 10 years in PPMS patients with no serious adverse effects. Although this was an open-label, retrospective analysis, and efficacy could not be studied, there was evidence of disease stabilization in many patients receiving ITMTX. It appears that long-term ITMTX is a safe therapeutic option in advanced progressive MS.
Identifiants
pubmed: 31832101
doi: 10.1177/1756286419892360
pii: 10.1177_1756286419892360
pmc: PMC6891004
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1756286419892360Informations de copyright
© The Author(s), 2019.
Déclaration de conflit d'intérêts
Conflict of interest statement: The authors declare that there is no conflict of interest.
Références
Curr Treat Options Neurol. 2013 Jun;15(3):241-58
pubmed: 23609781
Value Health. 2005 Nov-Dec;8 Suppl 1:S9-S24
pubmed: 16336491
Brain. 2006 Mar;129(Pt 3):606-16
pubmed: 16415308
Neurology. 2002 Jan 22;58(2):314-7
pubmed: 11805267
Semin Oncol. 1985 Jun;12(2):131-48
pubmed: 3892694
J Neurol. 2010 Nov;257(11):1806-11
pubmed: 20532907
Health Qual Life Outcomes. 2004 Feb 26;2:12
pubmed: 14987333
N Engl J Med. 2000 Nov 16;343(20):1430-8
pubmed: 11078767
Neurology. 1996 Nov;47(5):1153-7
pubmed: 8909421
Pharmacol Rev. 2005 Jun;57(2):163-72
pubmed: 15914465
Neurology. 2001 Jun 12;56(11):1496-504
pubmed: 11402106
Neurol Sci. 2001 Apr;22(2):209-10
pubmed: 11603629
Neurology. 1983 Nov;33(11):1444-52
pubmed: 6685237
Brain. 1989 Feb;112 ( Pt 1):133-46
pubmed: 2917275
J Rheumatol Suppl. 1985 Dec;12 Suppl 12:3-6
pubmed: 3913774
Neurology. 1991 Apr;41(4):533-9
pubmed: 2011253
Ann Neurol. 1996 May;39(5):684
pubmed: 8619559
Front Mol Neurosci. 2013 Oct 16;6:34
pubmed: 24137109
Drugs. 2013 May;73(7):625-50
pubmed: 23609782
Mult Scler. 2008 Mar;14(2):272-3
pubmed: 17986509
Lancet. 2002 Dec 21-28;360(9350):2018-25
pubmed: 12504397
Lancet. 2016 Mar 12;387(10023):1075-1084
pubmed: 26827074
Ann Neurol. 1995 Jan;37(1):30-40
pubmed: 7818255
N Engl J Med. 2017 Jan 19;376(3):209-220
pubmed: 28002688
Neurology. 2010 May 4;74(18):1463-70
pubmed: 20439849
Neurology. 2004 Nov 23;63(10):1779-87
pubmed: 15557490
Neurology. 2004 Dec 28;63(12 Suppl 6):S41-6
pubmed: 15623670
Ann Neurol. 2007 Jan;61(1):14-24
pubmed: 17262850
Ann Neurol. 2009 Oct;66(4):460-71
pubmed: 19847908
J Neuroimmunol. 1999 Jul 1;98(1):29-36
pubmed: 10426359