Use of Long-Term Intrathecal Methotrexate in Progressive Forms of MS (P04.139)

Abstract

Objective: To establish the safety and tolerability of long-term therapy with intrathecal methotrexate (ITMTX) in patients with treatment-resistant progressive forms of multiple sclerosis (MS). Background Currently there are no treatment options that successfully treat progressive MS, especially in the most severely disabled patients (EDSS > 6.0). We previosuly reported results of IT administration of MTX in the treatment of 121 patients with severe MS for up to 8 treatments. However, long-term safety has not been reported. This study is a IRB-approved retrospective chart analysis of patients who have had 18 or more treatments (3-6 years) to further examine the long-term safety and tolerability of ITMTX in this select cohort of advanced MS patients. Design/Methods: Thirty three patients, 27 secondary progressive (SPMS) and 6 primary progressive (PPMS) were clinically assessed every two months while receiving ITMTX at a dose of 12.5mgs every 8-11 weeks for a period of 3-6 years (range of 18 to 38 treatments). Assessments included EDSS, documentation of infections, other adverse events and hospitalizations. Results: There were no deaths or hospitalizations related to ITMTX and no serious adverse effects occurred. Headaches occurred at least once in 12% of patients, possibly minimized by the use of 25-gauge spinal needles and transient fatigue was reported in 6%. No cases of MTX associated leukoencephalopathy were seen. Almost all patients with SPMS had stable EDSS scores over the study period wheres the 6 PPMS patients had a mean decline on EDSS of 0.7. Conclusions: ITMTX was remarkably well tolerated over a period of 3-6 years in progressive MS patients with no serious adverse effects noted. Although this study was not controlled there was evidence of disease stabilization given the poor natural history of severe progressive MS. These findings support the use of ITMTX treatment as an inexpensive and relatively safe treatment for progressive MS. Supported by: MSRCNY funding. Disclosure: Dr. Stark has nothing to disclose. Dr. Dulak has nothing to disclose. Dr. Sadiq has nothing to disclose.