Author Of 3 Presentations
P0141 - Real-world data on the use of Ocrelizumab, among MS patients: B-cell suppression and clinical outcomes. (ID 934)
Abstract
Background
Ocrelizumab (OCR) is an anti-CD20 B-cell-depleting agent, recently approved for treating relapsing-remitting (RR) MS.
Objectives
In a real-world population of RRMS patients, we described baseline characteristics and clinical outcomes in correlation with the level of OCR-induced B-cell suppression.
Methods
Data were retrospectively collected from 170 RRMS patients, who received 6-monthly 600mg OCR infusions at Imperial College Healthcare NHS Trust from August 2018 to March 2020. Disability progression was defined as ≥1.0 or ≥0.5 Expanded Disability Status Scale (EDSS) increase from baseline EDSS of ≤5.5 or ≥6 respectively. Patients were grouped by level of B-cell depletion after 6 months from the first OCR infusion relative to their baseline B-cell count, into categories of “depleted” (>90%) and “not depleted” (≤90%).
Results
The whole cohort (females 67%, males 33%) was followed up for 5.6 mean months (0-15 months) from OCR initiation. At baseline, the mean age was 45.5 years, the mean disease duration was 13.1 years and the mean EDSS was 4.3. While 15% of patients were treatment naïve, most patients (85%) were escalated to OCR from other disease-modifying therapies: Dimethyl Fumarate (30%), Fingolimod (16%), Alemtuzumab (15%) and Natalizumab (10%). Majority received at least 2 OCR infusions (36%, 51% and 13% with 1, 2 and 3 infusions respectively). The mean B-cell count at baseline was 272/mm3; after OCR initiation, 89% were “depleted” and 11% were “not depleted”. During the follow-up, 7% (n = 12) experienced a relapse and 20% (n = 27) showed disability progression at 4.8 and 6.5 mean months after OCR initiation, respectively. Those who relapsed had in larger proportion new MRI lesions 1 year before OCR initiation (58% vs 20%; p = 0.039) and those experiencing disability progression had longer disease duration (16.8 vs 12.1 mean years; p = 0.039). Although not statistically significant, compared to “depleted” patients, the group without adequate B-cell depletion had a worse clinical outcome, with a larger proportion experiencing a relapse (14% vs 7%; 4.5 vs 4.8 mean months to relapse; p = 0.297).
Conclusions
This study characterizes the use of OCR in a real-world population of RRMS patients. Data suggests that the level of B-cell suppression could be a potential marker of treatment response. This should be validated in further studies with longer follow-up.
P0191 - Autologous Stem Cell Transplantation versus Alemtuzumab or Ocrelizumab in Relapsing Remitting Multiple Sclerosis (StarMS) (ID 359)
Abstract
Background
In recent years, autologous haematopoietic stem cell transplantation (aHSCT) has been increasingly used to treat patients with highly-active relapsing remitting multiple sclerosis (RRMS) who failed disease modifying therapies (DMTs). Observational and limited clinical trial data suggest that aHSCT reduces relapse rates, improves disability and enhances quality of life to a greater degree than most DMTs. There is now a need to compare aHSCT with the two most efficacious DMTs: Alemtuzumab and Ocrelizumab.
Objectives
StarMS aims to determine whether aHSCT has superior clinical efficacy to Alemtuzumab and Ocrelizumab with an acceptable safety profile. Mechanistic studies will assess immune re-constitution which will enhance understanding of the biological mechanisms of these treatments. Other sub-studies will assess their effect on cognitive recovery, neurofilament light and retinal nerve fibre layer measurements as markers of neuronal damage, and the safety of re-vaccination post-aHSCT.
Methods
This National Institute for Health Research (NIHR) funded parallel-group rater-blinded RCT will randomise 198 patients (1:1) to aHSCT versus DMT (Alemtuzumab or Ocrelizumab) from 19 centres across the UK. The primary endpoint, no evidence of disease activity (NEDA) rate, will be assessed throughout the 2-year follow-up period.
Results
Results are expected to be available in approximately 4 years’ time. Results will be published in peer-reviewed academic journals, presented at relevant conferences, and disseminated via patient groups as applicable.
Conclusions
The StarMS trial has the potential to provide definitive data on the comparative efficacy of aHSCT vs highly efficacious DMTs, help improve patient outcomes, and impact national and international guidelines.
P0902 - Real world evidence of progression independent of relapsing activity among MS patients treated with Alemtuzumab. (ID 1165)
Abstract
Background
Background:Disability accumulation can result from progression independent of relapsing activity (PIRA) even during the RR phase.
Objectives
Aims: We assessed the contribution of PIRA to the development of permanent disability, among RRMS treated with Alemtuzumab(ATZ).
Methods
Methods: retrospective data from 147 RRMS patients, who received ATZ at Imperial College Healthcare Trust, followed up for 3 mean years. PIRA was defined as 1.5point increase of EDSS if baseline EDSS was 0, 1point increase if baseline EDSS was <5.5, or 0.5point increase if baseline EDSS was >= 5.5,90days from the previous relapse. The logistic regression analysis was used to assess factors affecting the risk of PIRA.
Results
Results In the whole group female predominated (60%), 19% were treatment naïve and 81% were escalated to ATZ from previous DMTs; 15% (n = 23) received one course of ATZ only. At first ATZ infusion, the mean age was 42 years, the mean disease duration was 8 years and the mean EDSS score was 4. During the observation period, the EDSS remained stable in 58% (n=84) or improved in 11% (n = 17), while it worsened by 1.5 mean point (min 0.5 max 4.5) in 31% (n = 46). Among patients who experienced EDSS worsening, disability accumulation was related to PIRA in 76% (n = 35), while in only a minority (n = 11) it resulted from relapse-associated worsening. Compared to the whole group, patients with PIRA had at first ATZ infusion same mean EDSS score (4, p =0.8), but they had longer disease duration (11 versus 7 mean years, p=0.007), were significantly older both at disease onset (36 vs 32 mean years, p=0.046) and at commencement of the therapy (47 vs 40 mean years, p=0.001). In addition, in the PIRA group vast majority (94%) of patients were escalated to ATZ after lack of response to previous DMTs. The logistic regression analysis confirmed that older age at first ATZ course (OR 6.7, p=0.037) and being escalated to ATZ from previous DMTs (OR 1.1, p= 0.002) are factors significantly associated with higher risk of PIRA.
Conclusions
Conclusions We confirmed in the real-world setting that in a large proportion of patients the disability accumulation can occur despite effective therapeutic relapse suppression. Older patients receiving ATZ as escalation therapy are more likely to experience PIRA.