The TY-STOP study is a spontaneous, observational, prospective multicenter trial.
A total of 130 patients 18 years or older with clinically definite relapsing-remitting multiple sclerosis (RR-MS) who received 24 doses of natalizumab had clinical and magnetic resonance (MR) imaging MS stability, and had at least one MR image within 10 days after 24 doses of natalizumab, were recruited from eight Italian MS centers and were followed up for one year.
No significant differences in demographic or baseline clinical characteristics were found among the study participants. The aim of the study was to evaluate the effect of therapeutic choices on the mean annualized relapse rate and on magnetic resonance imaging MS activity after 24 doses of natalizumab.
After 24 doses of natalizumab, treatment was rediscussed with individual patients in accord with EMA recommendations. The treatment options offered to patients were:
(1) continuing intravenous natalizumab every 28 days
(2) switching to another disease-modifying therapy (DMT)
(3) discontinuing all treatment
(4) beginning intravenous mitoxantrone hydrochloride.
Alternative DMTs were:
(1) interferon beta-1a or subcutaneous interferon beta-1b
(2) glatiramer acetate
(3) oral fingolimod.
Patients were examined after 24 doses of natalizumab and every three months thereafter. Assessments included a physical examination and a neurological examination with the evaluation of the EDSS. Proton density T2-weighted and pre-post gadolinium-enhanced T1-weighted MR images were obtained at months 0, 3, 6, and 12 after 24 doses of natalizumab.
The MR imaging was scheduled at three-month intervals to detect possible disease reactivation in patients discontinuing natalizumab and to monitor for the occurrence of progressive multifocal leukoencephalopathy (PML) in patients continuing treatment with the monoclonal antibody. In the intent-to-treat group (n = 124), clinical and radiologic MS activity was significantly lower in patients continuing natalizumab (n = 43) than in patients interrupting natalizumab (n = 81), with a protective effect of natalizumab continuation on both outcomes year. In the as-treated group (n = 124), clinical and radiologic MS activity was significantly lower in natalizumab continuers than in natalizumab switchers or quitters, confirming a protective effect of natalizumab on the risk of relapse in natalizumab continuers compared with natalizumab quitters and natalizumab switchers.
No disease rebound was observed in natalizumab quitters. After natalizumab discontinuation, one patient developed progressive multifocal leukoencephalopathy during the observation period, with complete recovery. This study provides class III evidence of an increased risk of MS activity resumption after natalizumab discontinuation. Therapy discontinuation after 24 doses in natalizumab-responding patients should be considered only if the risk of PML is high and outweighs the benefits of continuing the drug. According to these results, continuing natalizumab seems to be the most efficacious therapeutic strategy in patients who have already received 24 doses of the drug, although it may be associated with a risk of developing PML in patients previously exposed to JCV.
: Clerico M, Schiavetti I
: JAMA Neurol. 2014 Jun 30. doi: 10.1001/jamaneurol.2014.1200. [Epub ahead of print]
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