Author Of 5 Presentations
LB1185 - Real-world experience with Ocrelizumab in the German NeuroTransData Registry (ID 1978)
Ocrelizumab (OCR) is approved for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS).
In a real-world setting, to describe 1) baseline characteristics of patients with MS treated with OCR, 2) treatment pathway across lines of therapy up to initiation of OCR, and 3) initial clinical experience.
This analysis included adult patients with MS from the German NeuroTransData (NTD) Registry, a network of 66 neurology outpatient services across Germany. Patients were treated with OCR between January 2018 and January 2020. Descriptive statistics were used to analyze baseline patient characteristics recorded within 3 months prior to or at time of OCR initiation. Occurrence of relapse was analyzed in relapse-remitting MS (RRMS) patients with ≥3 months follow-up data from OCR initiation.
As of January 2020, the NTD registry included 439 patients treated with OCR, including 352 patients with RRMS, 35 with relapsing secondary progressive MS (rSPMS), and 52 with primary progressive MS (PPMS). Median age at OCR initiation varied from 41.7 years, 54.5 years, to 52.5 years in patients with RRMS, rSPMS, and PPMS, respectively. Most RRMS and rSPMS patients were female (64.8% and 54.3%) compared to PPMS patients (46.2%). Median disease duration from symptom onset up to OCR initiation was longer in rSPMS patients (14.9 years) than in RRMS (10.8 years) and PPMS (5.7 years). Median EDSS at OCR start was 2.5, 6.0, and 4.0 in the RRMS, rSPMS, and PPMS cohorts, respectively. OCR was initiated as first disease modifying therapy (DMT) therapy in 12.2%, 11.4%, and 71.2% of RRMS, rSPMS, and PPMS patients, respectively. 258 RRMS patients directly switched from another DMT, primarily from fingolimod (23.3%) and natalizumab (19.8%). 319 patients with RRMS had ≥3 months follow-up during OCR exposure; of these, 283 remained relapse free (88.7%; 95% CI 84.9, 91.8) within a median follow-up time of 1 year (Q1-Q3, 0.6-1.3 years). Annualized relapse rate was 0.13 (95 % CI 0.09, 0.16).
In this German outpatient real world cohort, RRMS and rSPMS patients treated with OCR, on average had a disease duration ≥10 years and already reached a moderate to severe disability status. Most patients received previous DMT and OCR was initiated most frequently as second line treatment. Although PPMS patients showed a shorter disease duration, the disability status was relatively severe. Only about one third of patients received previous DMT.
P0837 - Assessing the real-world effectiveness of ocrelizumab in patients with multiple sclerosis – CONFIDENCE one-year interim analysis (ID 1133)
Multiple sclerosis (MS) is a chronic inflammatory neurological disease that requires life-long treatment, and new therapies must be safe and effective over a long treatment duration. Ocrelizumab is a humanized antibody that selectively targets CD20+ B cells and has been shown to be efficacious for the treatment of both relapsing MS (RMS) and primary progressive MS (PPMS). Effectiveness data in large, real-world populations are needed for better informed clinical treatment.
CONFIDENCE (ML39632, EUPAS22951) evaluates the safety and effectiveness of ocrelizumab in patients with RMS & PPMS in a real-world setting. Here, we present the first analysis of one-year effectiveness data from patients newly treated with ocrelizumab.
CONFIDENCE is a non-interventional study in patients with RMS or PPMS newly treated (up to 30 days prior or 60 days after enrolment) with ocrelizumab or other selected disease modifying therapies (DMTs) during the course of their disease. Data will be collected for 3000 ocrelizumab-treated patients and 1500 patients treated with other DMTs according to label at ~250 centers in Germany for up to 10 years. Here, we analyze effectiveness outcomes for patients treated with ocrelizumab for the first year, including treatment success (the proportion of patients with no relapse, progression or treatment discontinuation due to an adverse event) and change in Expanded Disability Status Scale (EDSS) from baseline. In addition, we will present patient-reported outcomes. Safety assessments are presented separately.
As of 30 June 2020, 2,129 patients have been recruited for ocrelizumab treatment. The interim analysis is expected to include data from approximately 559 patients newly treated with ocrelizumab that had one year of follow up. Of these patients, ~82% had RMS and ~18% had PPMS. Mean (standard deviation [SD]) baseline EDSS was 3.3 (1.9) for patients with RMS and 4.5 (1.7) for patients with PPMS. Preliminary data show that 64% of patients were female (66% female RMS; 55% female PPMS). Over an observational period of one year, 83.6% of RMS and 93.2% of PPMS patients experienced treatment success. About 85.3% of patients with RMS experienced no relapses. The mean (SD) change in EDSS from baseline after one year of treatment was 0.0 [0.6] for patients with RMS and 0.1 [0.6] for patients with PPMS.
This analysis of one-year interim data in the CONFIDENCE study shows the effectiveness of ocrelizumab in a real-world setting.
P0909 - Real-world experience with Ocrelizumab in the MSBase Registry (ID 1559)
- H. Butzkueven
- T. Spelman
- S. Ozakbas
- T. Kalincik
- C. Boz
- K. Buzzard
- O. Skibina
- R. Alroughani
- R. Karabudak
- A. Van Der Walt
- J. Lechner-Scott
- S. Hodgkinson
- G. Laureys
- L. Van Hijfte
- M. Terzi
- E. Butler
- R. Macdonell
- F. Patti
- V. Van Pesch
- M. Slee
- M. Barnett
- P. Grammond
- J. Prevost
- F. Grand-Maison
- B. Taylor
- A. Kermode
- P. McCombe
- P. Duquette
- A. Prat
- M. Girard
- S. Eichau Madueño
- G. Izquierdo
- A. Soysal
- J. Sánchez-Menoyo
- J. Sotoca
- E. Muros-Le Rouzic
- P. Dirks
Ocrelizumab (OCR) is a humanised anti-CD20+ monoclonal antibody approved for the treatment of primary progressive multiple sclerosis (PPMS), and relapsing forms of MS, including both relapsing-remitting (RRMS) and secondary progressive MS (SPMS) with relapses.
In a real-world setting, to describe 1) baseline characteristics of patients with MS treated with OCR, 2) treatment pathway across lines of therapy up to initiation of OCR, and 3) initial clinical experience in patients with ≥6 months follow-up data from OCR initiation.
Secondary data analysis using MSBase Registry data including patients with a confirmed diagnosis of MS and started OCR therapy within 3 months prior to or at time of MSBase eligible/initial visit. Descriptive statistics were used to analyze baseline patient characteristics' recorded within 3 months of OCR initiation, including demographics, disease course and duration, prior disease modifying therapies (DMT), and EDSS. Occurrence of relapse was analyzed in patients with ≥6 months follow-up data from OCR initiation.
As of 4th June 2020, MSBase included 2531 patients newly treated with OCR, of whom 1679 had an EDSS evaluation within 3 months of OCR start. There were 1185 patients with RRMS, 236 with SPMS, and 183 with PPMS. Median age at OCR initiation was 41.9 years, 49.5 years, to 50.1 years in RRMS, SPMS, and PPMS, respectively. Mean disease duration from symptom onset up to OCR initiation was longer in SPMS (19.7 years) than in RRMS (10.6 years) and PPMS (9.7 years). OCR was initiated as first line therapy in 17.5%, 5.5%, and 54.2% of RRMS, SPMS, and PPMS patients respectively. Most frequent previous DMT’s in RRMS were fingolimod (25.7%) and natalizumab (23.5%). 693 patients with RRMS had ≥6 months follow-up during OCR exposure. Of these, 643 remained relapse free (93%; 95% CI 86.0, 100.0) over a mean OCR exposure of 1.23 years. The annualized relapse rate (ARR) was 0.08 (95% CI 0.06-0.10), compared to an ARR of 0.85 in the 24 months pre-OCR start. In the overall cohort, treatment persistence at 12 and 24 months was 98.4% (95% CI: 97.3-9.1%) and 92.5% (95%CI 89-95%), respectively.
This study characterizes an international population of patients with RRMS, PPMS, and SPMS newly treated with OCR in a real-world clinical setting. First-line use was uncommon in RRMS and SPMS. During OCR treatment, ARR was below 0.1, and OCR discontinuations were very rare.
P0916 - Safety and tolerability in patients with multiple sclerosis receiving ocrelizumab in a real-world setting – CONFIDENCE one-year interim analysis (ID 1136)
As of April 2020, >160,000 patients with relapsing forms of multiple sclerosis (RMS) or primary progressive MS (PPMS) worldwide had started treatment with ocrelizumab (OCR), a humanized monoclonal antibody selectively targeting CD20+ B-cells.
Pivotal studies established the risk-benefit profile of OCR under controlled trial conditions.
Real-world data are needed to further characterise the safety of OCR in clinical practice. Here we present 1-year, real-world safety data for patients receiving OCR.
CONFIDENCE (ML39632, EUPAS22951), a non-interventional, post-authorization safety study, aims to enrol 3,000 patients with RMS or PPMS newly treated (up to 30 days prior or 60 days after enrolment) with OCR and 1,500 patients newly treated with other selected DMTs according to label at ~250 German neurological practices. Each patient is followed for 7.5–10 years. Study visits, documented circa every 6 months, follow routine clinical practice. The primary outcome is the incidence and type of uncommon adverse events (AEs) (incidence of 0.1% to 1% [1 to 10 out of 1000 patients] or less). Statistical analyses are mainly descriptive and exploratory. Assessments of effectiveness (secondary objectives) are presented separately.
As of 30 June 2020, 2,129 patients treated with OCR had been recruited. The interim analysis is expected to include approximately 559 OCR-treated patients, ~82% with RMS and ~18% with PPMS, with 1-year follow-up data (mean baseline age [SD], 45.5 [11.4] years; 64.4% female; mean baseline EDSS [SD] RMS 3.3 [1.9], PPMS 4.5 [1.7]). Preliminary data showed that ~63.0% of patients had ≥1 AE during OCR treatment; ~26.8% had treatment-related AEs (TRAEs). The most common AEs were infections and infestations (~31.5%), nervous system disorders (~14.7%), and general disorders and administration site conditions (~12.3%). The incidence of serious AEs was ~14.0%, most frequently infections and infestations (~3.6%; RMS, ~3.9% [n=18]; PPMS, ~1.9% [n=2]), nervous system disorders (~3.2%), and injury, poisoning and procedural complications (~2.1). The most frequent serious infections were urinary tract infections (~1.3% [n=7]) and pneumonia (~0.5% [n=3]). Seven patients overall (1.3%) had treatment-related serious infections.
The safety profile of OCR in this first interim analysis of the CONFIDENCE study, representing a real-world population currently treated with OCR in Germany, was consistent with controlled clinical trials.
P1063 - Treatment persistence and adherence to Ocrelizumab in the real-world setting- an ad-hoc analysis of the CONFIDENCE study (ID 1731)
Ocrelizumab (OCR) is a humanised anti-CD20+ monoclonal antibody approved for the treatment of relapsing and primary progressive forms of multiple sclerosis (RMS and PPMS). Real-world evidence on adherence and persistence with OCR is limited.
To examine the persistence and adherence to OCR in a real-world setting.
CONFIDENCE (ML39632, EUPAS22951) is an ongoing non-interventional, post-authorization safety study, aiming to enroll 3,000 patients newly treated with OCR and 1,500 patients newly treated with other DMTs at ~250 centers in Germany. Follow up regardless of discontinuation of treatment will be for up to 10 years. In this ad-hoc analysis of CONFIDENCE, persistence and adherence were measured exclusively for patients treated with OCR with at least one post-initiation (i.e., first two 300mg doses IVs') assessment visit. Persistence was examined as a survival function of event-free time from discontinuation. Patients were considered at-risk until the last assessment visit recorded prior to data cut-off (31 March 2020) or censored at time of OCR discontinuation, whichever occurred first. Adherence was assessed using median time intervals between infusions.
Overall, 1614 patients treated with OCR were included in this analysis; 1296 patients with RMS and 318 with PPMS. Median [IQR] age at OCR initiation was 42 [44, 57] years and 52 [33, 51] years in patients with RMS and PPMS, respectively. Most RMS patients were females (66.7%) while gender distribution in PPMS patients was approximately equal (51.6% females). Median [IQR] disease duration from diagnosis up to OCR initiation was longer in RMS (7.9 [3.0, 14.7] years) than in PPMS patients (3.4 [0.8, 9.7] years). Median [IQR] EDSS at OCR start was 3.0 [2.0, 4.5] and 4.5 [3.5, 6.0] in the RMS and PPMS population, respectively. At data cut-off, the median [IQR] OCR exposure duration was 7.85 [5.5, 13.1] months for RMS and 6.87 [0.5, 12.5] months for PPMS patients. Overall, the median time between infusions ranged from 5.9 and 6.0 months and did not differ between RMS and PPMS cohorts. Treatment persistence at 18 months was 96.6% (95% CI: 95.3-97.8%) and very consistent between RMS and PPMS patients.
Adherence to disease-modifying therapy (DMT) is critical for achieving therapeutic goals in MS. This analysis shows high treatment persistence for OCR patients at 18 months and strong adherence to recommendations to administer OCR infusions every 24 weeks.