Will NHS England ever endorse off-label prescribing in MS? #ResearchSpeak #OffLabel #MSBlog #MSResearch
"The relatively small study below shows that when PwMS who are stable on natalizumab stop treatment that pulsed monthly steroids can prevent rebound activity compared to pwMS not receiving this treatment. This observation has not been seen by others. In the RESTORE study (study 2 below); in this study methylprednisolone was not effective at preventing rebound. The following slide set makes the case for using either fingolimod or rituximab post- natalizumab. Unfortunately, in the NHS we are not allowed to use rituximab to treat MS. We have however made a case to NHS England's Neuroscience CRG (Clinical Reference Group) to consider the case for us using rituximab in this situation. We have provided them with the Swedish data. However, preliminary feedback from NHS England is that we are unlikely to get the greenlight as rituximab is not a licensed MS therapy. In other words NHS England are not in a position to condone off-label prescribing. Interesting; I wonder if we can challenge them on this position?"
PURPOSE: Interruption of natalizumab (NTM) treatment in multiple sclerosis (MS) patients may be followed by disease reactivation. On the other hand, patients with positive John Cunningham virus (JCV) antibodies treated with NTM over 24 months demonstrate a higher risk for developing progressive multifocal encephalopathy (PML). No established therapeutic approach is available for treating these patients to prevent disease reactivation.
MATERIALS AND METHODS: Of the MS patients treated with NTM at the authors' institution, 30 were found positive for JCV abs. NTM was interrupted followed by a washout period of 6 months. During this period, 20/30 patients received monthly intravenous (i.v.) methylprednisolone (MPD) 1000 mg infusion and regular clinical assessment. On months 3 and 6, brain MRI was performed and 1000 mg MPD was administered for 5 days.
RESULTS: All patients were clinically and radiologically stable at the time of NTM break. No clinical relapse was observed during the six-month washout period for the MS patients under monthly MPD treatment, while one patient had a relapse and active lesions in the MRI on month 6. Of the other patients not receiving i.v. MPD regularly after NTM withdrawal, one showed several active lesions in brain MRI and the other had a severe relapse.
CONCLUSIONS: Despite the limited size of this patients' cohort, the results of this study support that monthly MPD treatment for 6 months may result in a clinically stable disease status, thus ensuring safe transition to another second-line therapy such as fingolimod, following NTM withdrawal.
Study 2: Fox et al. MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study. Neurology. 2014 Apr 29;82(17):1491-8.
OBJECTIVE: RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab.
METHODS: Eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon β-1a [IM IFN-β-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks.
RESULTS: Patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-β-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-β-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%-29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4-8 weeks (n = 2 in weeks 4-8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity.
CONCLUSIONS: MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab.