Pulsed steroids followed by glatiramer acetate to prevent inflammatory activity after cessation of natalizumab therapy: a prospective, 6-month observational study

Abstract

In this study, the tolerability and safety of treatment with pulsed steroids and glatiramer acetate and the occurrence of clinical and radiological activity after natalizumab (NTZ) cessation in multiple sclerosis (MS) patients were assessed. MS patients with NTZ were discontinued after 2 years of treatment, or if adverse events or disease progressed during NTZ. They were offered as alternative treatment 1 g methylprednisolone per month during 3 months followed by daily 20 mcg glatiramer acetate and were prospectively studied. Adverse events, occurrence of immune reconstitution inflammatory syndrome, clinical exacerbations, and gadolinium-enhancing lesions in MRI performed at 3 and 6 months after NTZ cessation were recorded. EDSS change during follow-up was also recorded. A total of 18 MS patients entered the study and were followed up for a mean of 10 months (range 6-18 months). There were no significant adverse events. At month 3, no patient had clinical or radiological disease activity. At month 6, 16.6% of patients had had a relapse and 55.5% of patients showed gadolinium-enhancing lesions in the MRI. After 6 months, 33.3% of patients had a further relapse. There was no IRIS, severe relapses, or significant difference between EDSS at NTZ discontinuation and after follow-up. The alternative treatment with monthly prednisolone followed by GA prevents the development of IRIS, but not the return to previous inflammatory activity, which occurs between 5 and 6 months after NTZ withdrawal.

Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE

“…The follow-up visit occurred at week 52. MRI scans were performed at the screening visit (week -4) and at weeks 0, 4,8,12,16,20,24,28, and 52 and were read by the Central MRI Reading Center (NeuroRx Research, Montreal, Canada).…”

“…In one trial, patients with MS naive to natalizumab were randomized to receive placebo or natalizumab infusions for 24 weeks; MRI scans (manual reads) were performed at weeks -4 (screening), 0, 4,8,12,16,20,24, and 36 and 52 (follow-up) [26]. In the other trial, patients with relapsing-remitting MS were randomized to receive placebo or dimethyl fumarate for 24 weeks.…”

“…In the other trial, patients with relapsing-remitting MS were randomized to receive placebo or dimethyl fumarate for 24 weeks. Brain MRI scans (automated reads) were performed at baseline and at weeks 4,8,12,16,20, and 24 [27]. Data were compared across common time points (weeks 4, 8, 12, 16, 20, and 24 Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated from a multivariate proportional odds model to identify the factors associated with high Gd?…”

“…Discontinuation of natalizumab is associated with return of MS disease activity [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Some reports suggest disease activity after natalizumab cessation exceeds baseline levels [11,13,16,18,19,[21][22][23], while other studies do not [12,14,17,24].…”

“…Some reports suggest disease activity after natalizumab cessation exceeds baseline levels [11,13,16,18,19,[21][22][23], while other studies do not [12,14,17,24].…”