Author Of 1 Presentation
SS02.05 - COVID-19 in persons with multiple sclerosis treated with ocrelizumab: pharmacovigilance update
Limited evidence-based data exist on potential risks of COVID-19 infection in persons with multiple sclerosis (pwMS) receiving immunotherapy. More than 160,000 pwMS have been treated with ocrelizumab (OCR), in clinical trial and real-world settings; data continue to show a consistent and favorable benefit/risk profile.
To present a summary of postmarketing pharmacovigilance data (as of May 31, 2020) from pwMS treated with OCR, who have either confirmed or suspected COVID-19.
Pharmacovigilance-reported adverse event (AE) COVID-19 cases, identified in a search of the Roche Global Safety Database using MedDRA preferred terms and string searches, were defined as valid when at least an identifiable reporter, a single identifiable patient, a medicinal product and a suspected AE were provided. Cases were designated as serious if described by the reporter as serious according to their judgment or if adjudicated as serious by the company when regulatory definitions were met. Patient characteristics and details of OCR treatment were usually provided. All cases were conservatively considered as having confirmed COVID-19. Outcome was classified as recovered, recovering, not recovered, fatal, or not reported.
Of 201 cases, 61% (n=122/201) were reported as non-serious, and 39% (n=79/201) were reported as serious, mostly due to hospitalization (n=51/79). Where known, reasons for hospitalization included, among others, treatment of pneumonia and treatment in ICU. Serious cases were reported as recovered/recovering in 32% (n=25/79) of patients, whilst the outcome was not reported in 33% (n=26/79) of serious cases. A fatal outcome was reported in 5.5% (n=11/201) of patients; risk factors included hypertension, diabetes mellitus, respiratory disease, and malignancy. Updated assessment of the pharmacovigilance cases will be presented.
Taking into account the known limitations of postmarketing safety data, this analysis appears to be in line with published larger case series of non-MS and MS COVID-19 patients. Risk factors in fatal cases were similar to known risk factors reported in the general population.
Author Of 4 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.
LB1254 - A real-world data study of Coronavirus-2019 disease severity in patients with multiple sclerosis treated with ocrelizumab (ID 2150)
Ocrelizumab (OCR) is a B-cell depleting monoclonal antibody approved for the treatment of multiple sclerosis (MS), including relapsing and primary progressive forms of MS. The Coronavirus-2019 disease (COVID-19) pandemic raises concerns about clinical course and outcomes of COVID-19 in MS patients undergoing immunosuppressive treatment.
To describe the clinical course and outcomes of COVID-19 in multiple sclerosis (MS) patients treated with ocrelizumab (OCR).
A retrospective cohort study of OCR treated MS patients with COVID-19 diagnosis who received treatment for COVID-19 in the Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset. Inclusion criteria: confirmed COVID-19 diagnosis (ICD10 diagnosis, or positive diagnostic lab test since Feb 20th 2020), and OCR treatment ≤6 months prior to COVID-19 diagnosis. Patients with less than 28 days of follow-up were excluded. COVID-19 severity was categorized according to a 4 level ordinal scale based on worst status experienced during COVID-19 clinical course: 1) not hospitalized, 2) hospitalized, 3) hospitalized requiring invasive mechanical ventilation, 4) death. Secondary outcomes included the proportion of hospitalized patients diagnosed with respiratory failure, bacterial pneumonia, and sepsis on admission.
As of 13 July 2020, there were EHRs for almost 128,000 patients with laboratory or clinically confirmed diagnosis of COVID-19. Forty-seven OCR treated patients were identified (32% male, median age 47 years, median Charlson comorbidity index 1.0, mean BMI 29.4 kg/m2, mean time since OCR initiation 1.3 years). Per COVID-19 severity scale, 75% (n=35) were not admitted to hospital, 21% (n=10) were hospitalized, 2% (n=1) required invasive ventilation and 2% (n=1) died. Compared to OCR cohort, Hospitalized patients (n=12) were older (median age 57.0 years) and consisted of proportionally more males (50%). On hospital admission, of patients not requiring ventilation, 40% (n=4) had respiratory failure, 10% (n=1) bacterial pneumonia and 0% sepsis, while both patients requiring ventilation, one of whom subsequently died, had respiratory failure and sepsis on admission.
In this large US cohort of confirmed/clinically COVID-19, a few treated with OCR were identified with majority experiencing mild disease not requiring hospitalization, and two patients suffering critical illness. This study provides initial real-world insights on the impact of COVID-19 in MS patients treated with OCR.
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.
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.