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. 2025 May 21:16:1564327.
doi: 10.3389/fneur.2025.1564327. eCollection 2025.

CONFIDENCE treatment success: long-term real-world effectiveness and safety of ocrelizumab in Germany

Mathias Buttmann  1 , Martin S Weber  2   3 , Sven G Meuth  4 , Sandra Blümich  5 , Stefanie Hieke-Schulz  5 , Petra Dirks  6 , Julius C Eggebrecht  5 , Tjalf Ziemssen  7
Affiliations

CONFIDENCE treatment success: long-term real-world effectiveness and safety of ocrelizumab in Germany

Mathias Buttmann et al. Front Neurol. .

Abstract

Background: Early high-efficacy treatment for people with relapsing multiple sclerosis (pwRMS) may provide better long-term outcomes compared with the escalation strategy. In this study, we present an analysis of treatment success and safety from the CONFIDENCE study in a real-world cohort of pwRMS treated with ocrelizumab in different treatment lines for up to 5.5 years.

Methods: The ongoing German non-interventional post-authorization safety study, CONFIDENCE (ML39632, EUPAS22951), evaluates the long-term safety and effectiveness of therapy in pwMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. This analysis presents CONFIDENCE treatment success (proportion of people with no clinical disease activity measured by relapse or disease progression and no treatment discontinuation due to adverse event [AE] or lack of therapeutic effectiveness), confirmed disability progression (CDP), annualized relapse rates, and safety in pwRMS stratified by the number of previous MS therapies (PMSTs).

Results: At the data cutoff (11 October 2023), the full analysis set included 2,261 pwRMS treated with ≥1 dose of ocrelizumab. At baseline, the mean age (SD) of the participants was 41.16 (11.39) years (treatment-naïve, 39.19 [12.95] years; ≥3 PMSTs, 42.80 [10.08] years), and the mean Expanded Disability Status Scale (EDSS) score was 3.08 (1.86) (treatment-naïve, 2.37 [1.54]; ≥3 PMSTs, 3.57 [1.90]). Overall, 58.4% of pwRMS with continuous treatment achieved CONFIDENCE treatment success from baseline until year 5 (74.0 and 50.3% of pwRMS with 0 and ≥3 PMSTs). The main reasons for not achieving CONFIDENCE treatment success were relapse and CDP, while treatment discontinuation due to AEs or lack of effectiveness played a minor role. The proportion of pwRMS with AEs did not increase with longer treatment duration and tended to be higher with more PMSTs. The spectrum of AEs was similar across treatment lines, and no new or unexpected AEs were observed.

Conclusion: CONFIDENCE treatment success remained high over 5 years of ocrelizumab treatment, even among people with RMS (pwRMS) with a higher number of PMSTs. Only a small proportion of pwRMS discontinued treatment due to AEs. These results support early intervention with high-efficacy ocrelizumab treatment to optimize long-term outcomes for pwRMS.

Trial registration: https://catalogues.ema.europa.eu/node/3142/administrative-details, identifiers ML39632 and EUPAS22951.

Keywords: Relapsing multiple sclerosis; effectiveness; humanized monoclonal anti-CD20 antibody; neurodegenerative diseases; non-interventional study (NIS); ocrelizumab; real-world cohort; treatment success.

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Conflict of interest statement

MB received honoraria for lecturing, consulting and/or travel expenses for attending meetings from Biogen, Bristol Myers Squibb, Das Fortbildungskolleg, Merck, Novartis, RG Ärztefortbildung, Roche, Sandoz, Sanofi, Teva and Viatris. MW receives research support from the Deutsche Forschungsgemeinschaft (DFG; WE 3547/5-1, WE3547/7-1; in association with SFB TRR 274), from Novartis, TEVA, Biogen Idec, Roche, Merck and the ProFutura Programm of the Universitätsmedizin Göttingen. MW is serving as an editor for PLoS One. He received travel funding and/or speaker honoraria from Biogen Idec, Merck Serono, Novartis, Roche, TEVA, Bayer and Genzyme. SM receives honoraria for lecturing, travel expenses and for attending meetings from Academy 2, Argenx, Alexion, Almirall, Amicus Therapeutics Germany, AstraZeneca, Bayer Health Care, Biogen, BioNtech, BMS, Celgene, Datamed, Demecan, Desitin, Diamed, Diaplan, DIU Dresden, DPmed, Gen Medicine and Healthcare products, Genzyme, Hexal AG, IGES, Impulze GmbH, Janssen Cilag, KW Medipoint, MedDay Pharmaceuticals, Medmile, Merck Serono, MICE, Mylan, Neuraxpharm, Neuropoint, Novartis, Novo Nordisk, ONO Pharma, Oxford PharmaGenesis, QuintilesIMS, Roche, Sanofi, Springer Medizin Verlag, STADA, Chugai Pharma, Teva, UCB, Viatris, Wings for Life international and Xcenda. His research is funded by the German Ministry for Education and Research (BMBF), German Federal Institute for Risk Assessment (BfR), German Research Foundation (DFG), Else Kröner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology, Ministry of Culture and Science of the State of North Rhine-Westphalia, The Daimler and Benz Foundation, Multiple Sclerosis Society North Rhine-Westphalia Regional Association (dmsg), Peek & Cloppenburg Düsseldorf Foundation, Hempel Foundation for Science, Art and Welfare, German Alzheimer Society e.V. Dementia self-help and Alexion, Almirall, Amicus Therapeutics Germany, Argenx, Bayer Vital GmbH, BGP Products Operations (Viatris Company), Biogen, BMS, Demecan, Diamed, DGM e.v., Fresenius Medical Care, Genzyme, Gesellschaft von Freunden und Förderern der Heinrich-Heine-Universität Düsseldorf e.V., HERZ Burgdorf, Hexal, Janssen, Merck Serono, Novartis, Novo Nordisk Pharma, ONO Pharma, Roche and Teva. SB is an employee of Roche Pharma AG and shareholder of F. Hoffmann La Roche AG. SH-S is an employee of Roche Pharma AG. PD is an employee of F. Hoffmann La Roche AG and shareholder of F. Hoffmann La Roche AG. JE is an employee of Roche Pharma AG and shareholder of F. Hoffmann La Roche AG. TZ reports personal fees from Biogen, Roche, Merck, TEVA, NovoNordisk, Neuraxpharm, BMS, Novartis, Sanofi, Sandoz, Viatris; research support from Genzyme, Novartis, Roche, Sanofi, Teva, Novartis, Neuraxpharm. The authors declare that this study received funding from Roche Pharma AG (Grenzach-Wyhlen, Germany). Financial support for medical writing services from Ashfield MedComms GmbH (Mannheim, Germany), an Inizio Company, was provided by Roche Pharma AG (Grenzach-Wyhlen, Germany). The funder had the following involvement in the study: study management, study design, data collection, data analysis and interpretation, writing of this article, and decision to submit it for publication.

Figures

Figure 1
Figure 1
CONFIDENCE treatment success (A) by number of prior MS-specific therapies over a maximum of 5 years of ocrelizumab therapy and (B) for the overall cohort from baseline to year 5 who completed year 5 (landmark analysis; FAS). (A) Error bars represent 95% confidence intervals. (B) The outer hexagons describe the individual components of CONFIDENCE treatment success, which is illustrated in the inner hexagon. AE, adverse event; 24-w CDP, 24-week confirmed disability progression; FAS, full analysis set; MS, multiple sclerosis; PMST, prior MS-specific therapy; pwRMS, people with relapsing MS.
Figure 2
Figure 2
Multivariate logistic regression analysis of CONFIDENCE treatment success (FAS). pwRMS with available data were included (n = 1,907). EDSS, Expanded Disability Status Scale; CI, confidence interval; FAS, full analysis set; MS, multiple sclerosis; PMST, prior MS-specific therapy.
Figure 3
Figure 3
CONFIDENCE treatment success per year (landmark analysis; FAS). (A–E) CONFIDENCE treatment success and reasons for not reaching CONFIDENCE treatment success in the overall population up to (A) year 1, (B) year 2, (C) year 3, (D) year 4, and (E) year 5. Multiple answers were possible per pwRMS. (F–J) Percentages of pwRMS with no CONFIDENCE treatment success due to relapse only, 24-week CDP only, or both relapse and 24-week CDP in the overall population relative to the number of pwRMS analyzed for CONFIDENCE treatment success from (F) year 1, (G) year 2, (H) year 3, (I) year 4, and (J) year 5. AE, adverse event; 24-w CDP, 24-week confirmed disability progression; FAS, full analysis set; MS, multiple sclerosis; pwRMS, people with relapsing MS.
Figure 4
Figure 4
Reasons for not reaching CONFIDENCE treatment success stratified by the number of PMSTs (landmark analysis; FAS). (A) Percentage of pwRMS with no CONFIDENCE treatment success due to relapse up to the respective treatment year over a maximum of 5 years of ocrelizumab therapy. (B) Percentage of pwRMS with no CONFIDENCE treatment success due to 24-w CDP up to the respective treatment year over a maximum of 5 years of ocrelizumab therapy. Percentages of pwRMS with no CONFIDENCE treatment success are relative to the number of pwRMS analyzed for CONFIDENCE treatment success up to the respective year. Error bars represent 95% confidence intervals. 24-w CDP, 24-week confirmed disability progression; FAS, full analysis set; MS, multiple sclerosis; PMST, prior MS-specific therapy; pwRMS, people with relapsing MS.
Figure 5
Figure 5
Annualized relapse rate by the number of PMSTs over a maximum of 5 years of ocrelizumab therapy (FAS). Error bars represent the standard deviation. ARR, annualized relapse rate; FAS, full analysis set; MS, multiple sclerosis; PMST, prior MS-specific therapy.
Figure 6
Figure 6
Time to onset of 24-week CDP by the number of PMSTs over a maximum of 5 years of ocrelizumab therapy (FAS). Survival probability was determined using the Kaplan–Meier method. The y-axis only covers 60–100% for better readability. CDP, confirmed disability progression; FAS, full analysis set; MS, multiple sclerosis; PMST, prior MS-specific therapy; pwRMS, people with relapsing MS.
Figure 7
Figure 7
Safety outcomes by the number of PMSTs over a maximum of 5 years of ocrelizumab therapy (SAS). Percentages of pwRMS with (A) adverse events, (B) serious adverse events, (C) infections and infestations, and (D) serious infections and infestations by treatment year. Error bars represent 95% confidence intervals. AE, adverse event; MS, multiple sclerosis; SAS, safety analysis set; SAE, serious adverse event; pwRMS, people with relapsing MS; Y, year.
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