Ocrelizumab 920mg/23ml solution for injection vials

BackgroundMultiple sclerosis is an immune-mediated inflammatory disease, causing long-term disability in young adults. Most cases begin as relapsing-remitting multiple sclerosis. Some people have a form of relapsing-remitting multiple sclerosis known as highly active relapsing-remitting multiple sclerosis, defined as multiple sclerosis with unchanged or increased disease activity despite prior treatment with at least one disease-modifying therapy.ObjectivesTo appraise the clinical and cost-effectiveness of natalizumab [Tysabri® (Biogen, Cambridge, MA, USA)] and natalizumab biosimilar [Tyruko® (Sandoz)] for treating highly active relapsing-remitting multiple sclerosis compared to other disease-modifying therapy.DesignSystematic review with network meta-analysis and economic model. Searches last updated in April 2024.ResultsWe included 42 studies (22,409 participants): 40 in people with relapsing-remitting multiple sclerosis and 2 in highly active relapsing-remitting multiple sclerosis. Six studies also reported data separately for highly active relapsing-remitting multiple sclerosis. Only four studies evaluated natalizumab or natalizumab biosimilar; none provided data on those with highly active relapsing-remitting multiple sclerosis. Follow-up ranged from 4 to 36 (median 24) months. Most interventions reduced relapses (39 studies, 17 interventions) and magnetic resonance imaging lesions (19 studies, 11 interventions for gadolinium enhancing lesions and 17 studies, 12 interventions for T2-weighted lesions) compared to placebo. Alemtuzumab, ocrelizumab, cladribine, natalizumab, fingolimod and peginterferon beta-1a reduced disease progression compared to placebo (15 studies, 12 interventions). There were no differences in any adverse events (24 studies, 16 interventions), serious adverse events (31 studies, 15 interventions) or treatment-related adverse events (8 studies, no network meta-analysis) for any intervention compared to placebo. Fingolimod, glatiramer acetate, interferon beta-1a, interferon beta-1b and peginterferon beta-1a were associated with an increased treatment discontinuation (29 studies, 13 interventions). There was little evidence for a difference in quality of life. There was no evidence of a difference between natalizumab and natalizumab biosimilar for relapse rates [rate ratio 0.65 (95% credible interval 0.33 to 1.23], gadolinium enhancing lesions [hazard ratio 1.29 (0.69 to 2.37)], T2-weighted lesions [hazard ratio 1.07 (0.73 to 1.57)], any adverse events [hazard ratio 1.06 (0.77 to 1.46)] or treatment discontinuation [hazard ratio 0.48 (0.13 to 1.76)]. Data in highly active relapsing-remitting multiple sclerosis were available for fingolimod, ocrelizumab, alemtuzumab, cladribine, interferon beta, autologous haematopoietic stem cell treatment and placebo. We also included one study on natalizumab conducted in a population that was close to our definition of highly active relapsing-remitting multiple sclerosis. All interventions except interferon beta-1a were associated with reduced relapse risk compared to placebo (six studies; seven interventions). Compared with natalizumab-intravenous, natalizumab biosimilar-intravenous and natalizumab subcutaneous, all treatments had greater net benefit at £20,000-30,000/quality-adjusted life-year, with the only exception being ocrelizumab, which had lower net benefits. Costs were generally higher on natalizumab than other treatments, though there was no difference in quality-adjusted life-years with 95% credible interval completely overlapping. The results and conclusions were unchanged under all sensitivities. VOI analysis found that the greatest contributor to decision uncertainty was the effectiveness of treatments.ConclusionsThere is no direct evidence on the effectiveness of natalizumab or its biosimilar in patients with highly active relapsing-remitting multiple sclerosis. Limited data suggest similar effectiveness in patients with relapsing-remitting multiple sclerosis. The economic model found that natalizumab and natalizumab biosimilar were not cost-effective compared to any of the included comparators in highly active relapsing-remitting multiple sclerosis, with similar quality-adjusted life-years but higher costs, with the only exception being ocrelizumab.Future workThere is need for studies of natalizumab and natalizumab biosimilar in people with highly active relapsing-remitting multiple sclerosis.Study registrationThe study is registered as PROSPERO CRD42024556838.FundingThis award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR165943) and is published in full in Health Technology Assessment; Vol. 30, No. 60. See the NIHR Funding and Awards website for further award information.

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Multiple sclerosis (MS) predominantly affects women of childbearing age, and decision-making regarding disease-modifying therapies during pregnancy and lactation, particularly for highly effective anti-CD20 therapies such as rituximab and ocrelizumab, remains challenging. This review aims to synthesize available evidence on the course of MS, pregnancy, and neonatal outcomes, complications, and safety considerations in pregnant and breastfeeding women with MS exposed to rituximab or ocrelizumab. This structured narrative review was conducted in accordance with the PRISMA reporting framework. A systematic search of major scientific databases was performed for studies published between 2000 and 2026. Included study designs comprised cohorts, registries, case series, case reports, and systematic reviews. Data were extracted based on exposure type (preconception, during pregnancy, postpartum, and during breastfeeding) and key outcomes (relapse and disease activity, live birth, miscarriage, preterm delivery, congenital anomalies, infections, and neonatal immune parameters) and were narratively synthesized. The body of evidence indicates that exposure to rituximab or ocrelizumab, particularly when treatment was administered prior to pregnancy and conception occurred at an interval from the last dose, is often associated with better disease stability during pregnancy and a reduced risk of postpartum relapse. Most reports have not identified a consistent pattern of increased major congenital anomalies, and pregnancy outcomes have generally fallen within expected ranges. The most important neonatal consideration is transient B-cell lymphopenia in some exposures occurring close to late pregnancy; this finding has usually been reported as reversible and requires attention to the timing of live vaccinations. During breastfeeding, existing evidence supports minimal drug transfer into breast milk and the absence of clinically meaningful adverse outcomes in infants. Current evidence suggests that rituximab and ocrelizumab may be considered as strategies for disease control around pregnancy and in the postpartum period in women with active MS. However, decision-making should be individualized, based on disease severity, timing of exposure, maternal benefit, and neonatal monitoring considerations. Prospective studies and expanded pregnancy registries are needed to better evaluate long-term maternal and infant outcomes.

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