Rituximab and glatiramer acetate in secondary progressive multiple sclerosis: A randomized clinical trial

Abstract

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease characterized by demyelination of neurons in the central nervous system. 1,2 It is the most common cause of acquired disabling neurological disorder in young population worldwide and there is an ongoing increase in its prevalence and incidence in Europe, Mediterranean, and Middle East. 3,4 Relapsing remitting MS (RRMS) accounts for nearly 85% of MS cases and might evolve into the progressive form over time. 2,5 Around 25% of RRMS patients progress to secondary progressive MS (SPMS) by 10 years, and this rate grows as the duration of disease increases. 3,6 The progressive course is characterized by cumulative deterioration of neurological impairments, with or without relapses, with infrequent unstable minor improvements or plateau phases. 2

Rituximab in Multiple Sclerosis: Are We Ready for Regulatory Approval?

“…An interesting propensity score matching analysis performed on data retrospectively collected from three MS centers located in Switzerland and the Netherlands, showed, in contrast to what reported in the phase II/III trial in SPMS ( 68 ), a significantly lower EDSS score during a mean follow-up of 3.5 years (mean difference, −0.52; p<0.001) and a significantly delayed time to confirmed disability progression (p=0.03) for patients treated with rituximab compared with matched patients never treated with rituximab, suggesting a potential therapeutic benefit of rituximab also in SPMS ( 73 ). No major safety concerns were reported during the treatment period, although complications, mainly related to infections, were documented in five cases (9%).…”

“…Recently published results from another phase II/III, open-label, randomized clinical trial, in which 84 patients with SPMS were assigned to receive rituximab (1,000 mg every 6 months; n=37) or glatiramer acetate (40 mg subcutaneous 3 times/week; n = 40) for 12 months, documented an apparent lack of efficacy of both treatments in controlling EDSS progression ( 68 ). Indeed, the mean EDSS increased after 12 months from 3.05 ± 1.01 to 4.14 ± 0.91 in the rituximab group (p < 0.001), and from 3.22 ± 1.20 to 4.60 ± 0.67 in the glatiramer acetate group (p < 0.001).…”

Antibody-mediated cell depletion therapies in multiple sclerosis

“…In an open label phase II trial, switching to rituximab from first line injectable therapies in clinically stable RR-MS patients induced a reduction in the number of gadolinium-enhancing lesion and in mean levels of CSF neurofilament light chains compared to the 3-months the run-in period ( 130 ), whereas another open label study randomizing 73 SP-MS patients to rituximab or glatiramer-acetate showed no differences between groups in relapse activity, nor in EDSS worsening ( 131 ).…”

What Have Failed, Interrupted, and Withdrawn Antibody Therapies in Multiple Sclerosis Taught Us?

“…Induction therapy with rituximab followed by glatiramer acetate was more efficient in reaching NEDA, avoiding treatment failure defined as ≥ 2 new lesions, relapses, and/or sustained accumulation of disability, and reducing MRI activity than therapy with glatiramer acetate alone [ 183 ]. Another phase II/III trial (NCT03315923), in which 84 patients with SPMS and ARR ≥ 1 were randomly assigned to receive rituximab (1000 mg every 6 months; n = 37) or glatiramer acetate (40 mg subcutaneous 3 times/week; n = 40) for 12 months, documented an apparent lack of efficacy of both treatments in controlling EDSS progression (Table 1 ) [ 184 ]. Both treatments could decrease the ARR and the number of active lesions in brain and cervical spine, without significant difference between both groups [ 184 ].…”

“…Another phase II/III trial (NCT03315923), in which 84 patients with SPMS and ARR ≥ 1 were randomly assigned to receive rituximab (1000 mg every 6 months; n = 37) or glatiramer acetate (40 mg subcutaneous 3 times/week; n = 40) for 12 months, documented an apparent lack of efficacy of both treatments in controlling EDSS progression (Table 1 ) [ 184 ]. Both treatments could decrease the ARR and the number of active lesions in brain and cervical spine, without significant difference between both groups [ 184 ]. However, it has to be considered that the study had a short duration, and that patients randomized to glatiramer acetate had a longer disease and were older compared with those assigned to rituximab group.…”