Comparison of Efficacy and Safety in Patients Switching From MabThera® to Rixathon® in Relapsing-Remitting Multiple Sclerosis

NCT ID: NCT07235644

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 184 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2025-12-30

Brief Summary

This observational study investigates if switching from MabThera® to Rixathon® is associated with changes in disease activity and/or safety in people with multiple sclerosis (MS).

The main questions it aims to answer are:

• Does switching to Rixathon® affect tissue damage, measured by blood levels of neurofilament light (pNfL)?
• Does switching to Rixathon® affect the number of new MRI lesions, relapses, or disability progression?

Researchers will look at health information already collected from participants before and after the medication switch. Participants include people with MS treated at Uppsala University Hospital who switched from MabThera® to Rixathon® starting in January 2023. Researchers will use data from regular clinical visits, blood tests, brain MRI scans, and disability scores (EDSS) recorded in the Swedish MS Registry.

Detailed Description

This is a retrospective observational study conducted at Uppsala University Hospital. The study aims to evaluate the efficacy and safety of switching from MabThera® (rituximab originator) to Rixathon® (rituximab biosimilar) in people with multiple sclerosis (MS), specifically those diagnosed with relapsing-remitting MS (RRMS) and progressive MS.

Starting in January 2023, the Department of Neurology at Uppsala University Hospital made an administrative decision to move from using rituximab (MabThera®) to rituximab (Rixathon®) in the treatment of MS, primarily for cost-saving reasons. This study will retrospectively analyze clinical and radiological outcomes collected before and after the switch. Data will be extracted from the Swedish MS Registry (SMSreg), a national database containing clinical information on people with MS across Sweden. Only patients treated at Uppsala University Hospital are included.

The primary objective of the study is to determine whether switching to Rixathon® affects disease activity, as measured by changes in plasma neurofilament light (pNfL) concentrations. pNfL is a biomarker of neuroaxonal damage, and elevated levels are associated with ongoing inflammation and neurodegeneration in MS.

Secondary objectives include comparing:

• The number of new T2 lesions on brain MRI scans before and after the switch
• The annualized relapse rate before and after the switch
• Changes in disability progression, measured by the Expanded Disability Status Scale (EDSS)
• Proportion of participants maintaining "No Evidence of Disease Activity" (NEDA) status
• Occurrence of serious adverse events (Grade 3-5 according to CTCAE v5.0)

Exploratory analyses will incorporate quantitative MRI (qMRI) metrics, including brain parenchymal fraction (BPF), myelin correlated fraction (MyCPF), myelin correlated volume (MyC), cerebrospinal fluid (CSF) volume, brain parenchymal volume (BPV), and intracranial volume. These parameters are obtained from SyMRI sequences that have been part of standard clinical practice at Uppsala University Hospital since 2017.

Participants eligible for inclusion were already being treated with MabThera® at the end of 2022 and completed the switch to Rixathon®. These individuals have been followed through routine clinical care with yearly MRI scans, regular EDSS assessments, and quarterly pNfL blood testing.

Data Quality Assurance:

Data will be obtained directly from SMSreg, which ensures quality through national standard operating procedures, regular audits, and predefined data validation rules. The registry will be vetted against clinical source documentation in the electronic medical records. Variables such as MRI findings, pNfL levels, relapse events, and EDSS scores are standardized across Sweden. No additional site-specific audits are planned beyond the SMSreg's internal quality controls.

Handling Missing Data:

In case of missing or inconsistent data points, standard imputation methods will be used as outlined in the analysis plan. For missing values that cannot be resolved, sensitivity analyses will be performed to assess the impact on results.

Sample Size and Power Considerations:

At the time of the medication switch, 184 MS patients were being treated with rituximab at the Department of Neurology. Given this sample size and historical relapse rates in RRMS, the study is adequately powered to detect meaningful differences in clinical and biomarker outcomes pre- and post-switch.

Statistical Analysis Plan:

The primary analysis will use a mixed-model repeated measures ANOVA to compare pNfL levels before and after the switch. Secondary outcomes (MRI activity, relapse rates, EDSS scores, NEDA status, and adverse events) will be analyzed using appropriate methods, including paired t-tests, Wilcoxon signed-rank tests, or McNemar's test, depending on the data distribution. Subgroup analyses will be performed separately for participants with RRMS and progressive MS. All analyses will adjust for potential confounders such as age, sex, disease duration, and prior treatment history.

This study will provide critical real-world evidence on whether switching to a rituximab biosimilar affects clinical outcomes and disease progression in MS.

Conditions

MS (Multiple Sclerosis); Multiple Sclerosis (MS) - Relapsing-remitting; Multiple Sclerosis (Relapsing Remitting)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

MS patients switched from MabThera® to Rixathon®

This cohort includes people with multiple sclerosis (MS) who were treated with MabThera® at Uppsala University Hospital and switched to Rixathon® starting January 2023 as part of routine clinical care. Participants were followed through standard clinical visits, blood tests, and MRI scans. Health outcomes before and after the switch will be compared using retrospective data from the Swedish MS Registry (SMSreg).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Diagnosed with multiple sclerosis (MS) according to the 2017 McDonald criteria (or previous applicable versions at the time of diagnosis).
• Treated with MabThera® (rituximab originator) at the Department of Neurology, Uppsala University Hospital before January 1, 2023.
• Switched to Rixathon® (rituximab biosimilar) for MS treatment starting January 1, 2023.
• Registered in the Swedish MS Registry (SMSreg) with available clinical data.
• At least one clinical follow-up visit recorded before the switch and one after the switch.
• Available plasma neurofilament light chain (pNfL) measurement and/or brain MRI scan during the study period.

Exclusion Criteria

• No recorded clinical follow-up visit after switching to Rixathon®.
• Switched to Rixathon® but later discontinued treatment within 3 months for reasons unrelated to disease activity (e.g., administrative, insurance, or non-medical reasons).
• Participation in another interventional clinical trial affecting MS outcomes during the study period.
• Diagnosis of other major neurological diseases that could confound MS outcomes (e.g., stroke, CNS infection, or primary CNS tumors).
• Lack of consent for research use of data in the Swedish MS Registry.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Uppsala University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joachim Burman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

Uppsala University Hospital

Uppsala, , Sweden

Countries

Sweden

References

Simren J, Andreasson U, Gobom J, Suarez Calvet M, Borroni B, Gillberg C, Nyberg L, Ghidoni R, Fernell E, Johnson M, Depypere H, Hansson C, Jonsdottir IH, Zetterberg H, Blennow K. Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years. Brain Commun. 2022 Jul 4;4(4):fcac174. doi: 10.1093/braincomms/fcac174. eCollection 2022.

Reference Type: BACKGROUND

PMID: 35865350 (View on PubMed)

McCamish M, Woollett G. The state of the art in the development of biosimilars. Clin Pharmacol Ther. 2012 Mar;91(3):405-17. doi: 10.1038/clpt.2011.343. Epub 2012 Feb 8.

Reference Type: BACKGROUND

PMID: 22318617 (View on PubMed)

Ventola CL. Biosimilars: part 1: proposed regulatory criteria for FDA approval. P T. 2013 May;38(5):270-87.

Reference Type: BACKGROUND

PMID: 23946620 (View on PubMed)

Calo-Fernandez B, Martinez-Hurtado JL. Biosimilars: company strategies to capture value from the biologics market. Pharmaceuticals (Basel). 2012 Dec 12;5(12):1393-408. doi: 10.3390/ph5121393.

Reference Type: BACKGROUND

PMID: 24281342 (View on PubMed)

Simoens S, Verbeken G, Huys I. Biosimilars and market access: a question of comparability and costs? Target Oncol. 2012 Dec;7(4):227-31. doi: 10.1007/s11523-011-0192-7. Epub 2012 Jan 17.

Reference Type: BACKGROUND

PMID: 22249657 (View on PubMed)

Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008 Feb 14;358(7):676-88. doi: 10.1056/NEJMoa0706383.

Reference Type: BACKGROUND

PMID: 18272891 (View on PubMed)

Svenningsson A, Frisell T, Burman J, Salzer J, Fink K, Hallberg S, Hambraeus J, Axelsson M, Nimer FA, Sundstrom P, Gunnarsson M, Johansson R, Mellergard J, Rosenstein I, Ayad A, Sjoblom I, Risedal A, de Flon P, Gilland E, Lindeberg J, Shawket F, Piehl F, Lycke J. Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial. Lancet Neurol. 2022 Aug;21(8):693-703. doi: 10.1016/S1474-4422(22)00209-5.

Reference Type: BACKGROUND

PMID: 35841908 (View on PubMed)

Brown JWL, Coles A, Horakova D, Havrdova E, Izquierdo G, Prat A, Girard M, Duquette P, Trojano M, Lugaresi A, Bergamaschi R, Grammond P, Alroughani R, Hupperts R, McCombe P, Van Pesch V, Sola P, Ferraro D, Grand'Maison F, Terzi M, Lechner-Scott J, Flechter S, Slee M, Shaygannejad V, Pucci E, Granella F, Jokubaitis V, Willis M, Rice C, Scolding N, Wilkins A, Pearson OR, Ziemssen T, Hutchinson M, Harding K, Jones J, McGuigan C, Butzkueven H, Kalincik T, Robertson N; MSBase Study Group. Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis. JAMA. 2019 Jan 15;321(2):175-187. doi: 10.1001/jama.2018.20588.

Reference Type: BACKGROUND

PMID: 30644981 (View on PubMed)

Lizak N, Lugaresi A, Alroughani R, Lechner-Scott J, Slee M, Havrdova E, Horakova D, Trojano M, Izquierdo G, Duquette P, Girard M, Prat A, Grammond P, Hupperts R, Grand'Maison F, Sola P, Pucci E, Bergamaschi R, Oreja-Guevara C, Van Pesch V, Ramo C, Spitaleri D, Iuliano G, Boz C, Granella F, Olascoaga J, Verheul F, Rozsa C, Cristiano E, Flechter S, Hodgkinson S, Amato MP, Deri N, Jokubaitis V, Spelman T, Butzkueven H, Kalincik T; MSBase Study Group. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Mar;88(3):196-203. doi: 10.1136/jnnp-2016-313976. Epub 2016 Sep 28.

Reference Type: BACKGROUND

PMID: 27683916 (View on PubMed)

Capra R, Cordioli C, Rasia S, Gallo F, Signori A, Sormani MP. Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS. Mult Scler. 2017 Nov;23(13):1757-1761. doi: 10.1177/1352458516687402. Epub 2017 Jan 12.

Reference Type: BACKGROUND

PMID: 28080255 (View on PubMed)

Other Identifiers

2024-08358-01

Identifier Type: -

Identifier Source: org_study_id