ProfG has argued that if hand-function was the major endpoint of clinical trials then you would have had an approved treatment for progressive MS over a decade ago. In this study they look at the influence of intrathecal methotrexate. Methotrexate is an anti-proliferative agent
Safety of long-term intrathecal methotrexate in progressive forms of MS. Stark JW, Josephs L, Dulak D, Clague M, Sadiq SA. Ther Adv Neurol Disord. 2019 Dec 3;12:1756286419892360. doi: 10.1177/1756286419892360. eCollection 2019
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: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: 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: 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.