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Published on: December 9, 2015
Effectiveness of Ocrelizumab in Primary Progressive Multiple Sclerosis: a Multicenter, Retrospective, Real-world
Clara G Chisari1, Assunta Bianco2, Vincenzo Brescia Morra3
1Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia, " University of Catania, Via S. Sofia 78, 95100, Catania, Italy.
Abstract:
Ocrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospective study collected data about the effectiveness of ocrelizumab in PPMS patients who received treatment between May 2017 and June 2022 in the Italian MS centers contributing to the Italian MS Registry who adhered to the Compassionate Use Program. The confirmed EDSS worsening (CEW) (defined as either a ≥ 1-point or ≥ 2-point increase in EDSS score from baseline that was confirmed at T12 and T24) was calculated. At the date of data extraction, out of 887 PPMS patients who had received ocrelizumab, 589 (mean age 49.7 ± 10.7 years, 242 (41.1%) females) were enrolled. The mean follow-up period was 41.3 ± 12.3 months. A total of 149 (25.3%) received ocrelizumab according to the ORATORIO criteria (ORATORIO group) and 440 (74.7%) outside the ORATORIO criteria (non-ORATORIO group). No differences in terms of cumulative probabilities of 12 and 24 months of CEW of ≤ 1 point were found between ORATORIO and non-ORATORIO groups. Cox regression analyses showed that age older than 65 years (HR 2.51, 25% CI 1.07-3.65; p = 0.01) was associated with higher risk of CEW at 24 months. Patients not responding to ORATORIO criteria for reimbursability may benefit from ocrelizumab treatment, as disease activity, disease duration, and EDSS seem to not impact the disability outcome. Our results may suggest to extend the possible use of this powerful agent in selected patients under the age of 65 years.
Insights
Ocrelizumab effectively treats primary progressive multiple sclerosis (PPMS) in patients outside standard trial criteria. Older patients over 65 showed a higher risk of confirmed disability worsening.
Area of Science:
- Neurology
- Immunology
- Pharmacology
Background:
- Ocrelizumab is a CD20-targeting monoclonal antibody approved for primary progressive multiple sclerosis (PPMS).
- Phase 3 trials evaluated ocrelizumab in PPMS patients under 55 years with Expanded Disability Status Scale (EDSS) ≤ 6.5.
- Effectiveness in older, more disabled patients, or those with longer disease duration remains less understood.
Purpose of the Study:
- To assess the clinical effectiveness of ocrelizumab in PPMS patients who fall outside the eligibility criteria of the ORATORIO trial.
- To evaluate if patients not meeting ORATORIO criteria benefit from ocrelizumab treatment.
Main Methods:
- A multicenter retrospective study analyzed data from Italian MS centers (May 2017-June 2022).
- Included 589 PPMS patients treated with ocrelizumab, comparing those within (n=149) and outside (n=440) ORATORIO criteria.
- Confirmed EDSS worsening (CEW) at 12 and 24 months was the primary outcome measure.
Main Results:
- No significant differences in 12- and 24-month probabilities of CEW (≤ 1 point) were observed between ORATORIO and non-ORATORIO groups.
- Age over 65 years was associated with a significantly higher risk of CEW at 24 months (HR 2.51).
- Disease activity, duration, and EDSS at baseline did not significantly impact disability outcomes in the non-ORATORIO group.
Conclusions:
- Ocrelizumab treatment appears beneficial for PPMS patients outside the ORATORIO trial criteria.
- Age over 65 is a risk factor for disability worsening despite treatment.
- Consideration should be given to extending ocrelizumab use to selected PPMS patients under 65 not meeting current reimbursement criteria.
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