Bayer AG

Author Of 3 Presentations

COVID-19 Late Breaking Abstracts

LB1226 - Use and safety of interferon beta-1b during the COVID-19 outbreak: current data from a pharmacovigilance safety database (ID 2105)

Speakers
Presentation Number
LB1226
Presentation Topic
COVID-19

Abstract

Background

Since the first report of coronavirus disease (COVID-19) in late 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease quickly became a pandemic with a variety of clinical presentations, including death.

The risk of COVID-19 for patients with multiple sclerosis (MS) receiving interferon beta-1b (IFN β-1b) has been unclear.

In the absence of specific antiviral agents, IFN β has been suggested as a potential therapeutic option for COVID-19 based on its immunomodulatory and antiviral properties. In preclinical studies, IFN β has shown antiviral activities against coronavirus in Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome, but currently there is no clinical data supporting its therapeutic use in COVID-19 patients.

Objectives

The objective of our study is to review the current safety data on IFN β-1b in MS and non-MS patients impacted by COVID-19.

Methods

Retrospective data on IFN β-1b case reports with mention of COVID-19 were extracted from Bayer’s pharmacovigilance (PV) database through July 29, 2020.

Results

A total of 109 cases mentioned COVID-19, which included 75 MS patients (68.8%) and 34 non-MS patients (31.2%) who received IFN β-1b.

Of the 75 MS patients, 23 (30.7%) were diagnosed with COVID-19 (median 49 years; range 27-65 years). No relevant drug-related adverse events (AE) were reported. Two patients (2.7% of 75, 8.7% of 23; ages 42 and 49 years) died due to COVID-19. The 52 patients (69.3%) with no evidence of COVID-19 reported being negatively impacted with depression, anxiety, and difficulty accessing medical care for MS exacerbations and other health conditions.

Of the 34 non-MS patients who received IFN β-1b for experimental COVID-19 treatment, AEs were reported in 19 (55.8%). The most frequently reported AEs were associated with hepatic impairment such as hepatitis, mixed liver injury, hyperbilirubinemia, and increased hepatic enzyme. These events are appropriately reflected in the reference safety information. In almost all cases, IFN β-1b was concomitantly used with other antiviral drugs. Seven patients (20.6%) died due to COVID-19 (median 71 years; range 64-79 years) but IFN β-1b use was not implicated. Five patients (14.7%) reported non-approved route of administration (sublingual), however no AEs were associated with this method.

Conclusions

Our study revealed a small portion of MS patients using IFN β-1b who became infected with SARS-CoV-2 or developed COVID-19.

Although underreporting is a known limitation of PV data, our findings are in accordance with the published low incidence of COVID-19 in IFN β-treated MS population. Future serum anti-SARS-CoV-2 antibody tests may determine the number of asymptomatic COVID-19 IFN-b-1b-treated MS patients.

AEs reported in IFN β-1b-treated COVID-19 patients are consistent with the established safety profile. No new safety concerns were observed in MS or non-MS COVID-19 patients treated with IFN β-1b.

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Biomarkers and Bioinformatics Poster Presentation

P0132 - Prediction of 15-year MS outcomes in BENEFIT trial patients using serum neurofilament light chain concentrations (ID 1726)

Speakers
Presentation Number
P0132
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Serum neurofilament light chain (sNfL) levels are a promising biomarker for quantifying neuro-axonal injury in multiple sclerosis (MS). Recent studies showed sNfL levels relate to disease activity and treatment response.

Objectives

To analyze the predictive capacity of baseline (BL) sNfL levels for disease outcomes in the 15-year BENEFIT study long-term follow-up

Methods

Monofactorial regression analyses were conducted on outcomes at Year 15, including sNfL age-adjusted percentiles (80th, 90th, 95th, 97.5th and 99th; Disanto et al., 2017).

Further BL covariates included sex; age; lowest EDSS up to Month 6; mono/multifocal onset; presence of optic nerve, brainstem, or spinal cord lesions; Paced Auditory Serial Addition Test 3 (PASAT-3), Timed 25 Foot Walk (T25W), and 9 Hole PEG test (9HPT) scores; number/volume of hypointense T1, gadolinium-enhancing T1, and T2 lesions; cerebral volume; and initial treatment assignment. On-study covariates at Years 1, 2, and 5 were annualized relapse rate; EDSS change; PASAT-3, T25W, and 9HPT scores; annualized rate of new lesions; lesion number/volume; brain volume change; and relative duration of treatment. Covariates with p≤0.1 (at ≥2 time points for on-study covariates) were entered into multifactorial models.

We assessed the predictive capacity of BL sNfL levels for the following outcomes: EDSS ≥4, clinically silent disease, T2 lesion volume, and cerebral volume.

Results

Patients with sNfL values at screening (N=258) above the 90th (n=176), 95th (n=157), 97.5th (n=149), and 99th (n=129) percentiles (adjusted for other relevant covariates) had a significantly higher risk of EDSS≥4 at Year 15 for BL model (odds ratio 2.45 [95% CI: 1.05,5.68] p=0.0376; 2.60 [1.18,5.75] p=0.0181; 2.61 [1.20,5.66] p=0.0154; 2.47 [1.19,5.13] p=0.0150, for the 90th, 95th, 97.5th and 99th percentiles, respectively), and for on-study models at Year 1 (3.86 [1.16,12.78] p=0.0272; 3.38 [1.13,10.14] p=0.0296; 2.92 [1.02,8.35] p=0.0461; 2.98 [1.11,8.00] p=0.0305, respectively) and Year 2 (5.36 [1.26,22.85] p=0.0231; 4.88 [1.34,17.77] p=0.0163; 3.86 [1.18,12.66] p=0.0259; 3.34 [1.17,9.48] p=0.0237, respectively). Covariates that remained statistically significant with EDSS≥4 as the endpoint in most percentile models were lowest EDSS value up to Month 6 for BL and Year 1, and change in brain volume at Year 1, 2, and 5.

Conclusions

Findings in this unique long-term BENEFIT study suggest that higher sNfL values in early MS disease stages are independent predictors of long-term disability.

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Observational Studies Poster Presentation

P0854 - Clinical characteristics of middle-aged and older patients with MS treated with interferon beta-1b in the BEACON study (ID 1139)

Speakers
Presentation Number
P0854
Presentation Topic
Observational Studies

Abstract

Background

Multiple sclerosis (MS) peak prevalence has shifted towards older age groups owing to declining premature mortality rates, yet the disease course of MS in older patients is poorly understood in terms of modern clinical practice. Thus, we re-analysed data from BEACON (BEtaferon prospective study on Adherence, COping and Nurse support), an international, non-interventional, prospective study of patients with MS and initiating interferon beta-1b (Betaferon) treatment within 6 months before study entry.

Objectives

To assess patient characteristics and treatment response in the age ranges of 41–50 and >50 years, to better define MS disease course and treatment outcomes in older patients.

Methods

The BEACON study observational period lasted 2 years, with visits/assessments every 6 months. Assessments included disease history and course, annualized relapse rate (ARR), Expanded Disability Scale Score (EDSS), treatment adherence, Hospital Anxiety and Depression Scale (HADS), and adverse events.

Results

Intention-to-treat (ITT) patients (any post-baseline visit) aged 41–50 (n=327) and >50 years (n=154), had mean (SD) ages at baseline of 45.1 (2.8) and 56.2 (4.2) years, respectively, and duration of MS since onset of symptoms of 3.9 (5.2) and 5.9 (7.1) years, respectively. The proportion of patients with confirmed relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) diagnoses at baseline was similar for those aged 41–50 years (96.3 and 3.7%) and >50 years (94.9 and 5.1%), respectively. The ARR during the 2 years before study start was 0.93 (0.48) vs 0.86 (0.54) for the 41–50 and >50 years groups, respectively, and during the study period the ARR was 0.20 (1.09) vs 0.07 (0.37), respectively. At last visit, mean (SD) HADS anxiety scores were 8.0 (4.5) and 7.5 (4.2) in the 41–50 and >50 years age groups, respectively, and likewise HADS depression scores were 6.4 (4.0) and 7.0 (4.1), respectively. The proportion with any adverse events and any serious adverse events was 15.0 and 4.2% in the 41–50 years group and 19.6 and 1.3% in the >50 years group, respectively.

Conclusions

MS disease activity was similar at baseline in the two age groups. Decreases in ARR for both age groups during the study compared favorably with ARR in the 2 prior years. Interferon beta-1b appears to be effective and well tolerated in middle age and older patients with MS above 40 and above 50 years.

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