COVID-19 Cases

Ocrelizumab and COVID-19 Data

  • While it is too early to draw definitive conclusions, our data suggest that COVID-19 follows a similar course in patients with MS who are treated with ocrelizumab, with risk factors for severe COVID-19 similar to those observed in the general population1-10
    • These risk factors for severe COVID-19 include old age and presence of comorbidities, such as hypertension, diabetes, obesity, smoking, and cardiovascular and lung disease1-3,7,8
  • Patients receiving ocrelizumab who are either exposed to SARS-CoV-2 or confirmed to have COVID-19 should contact their neurologist or other medical professional right away. Patients should consult their neurologist or other medical professional before discontinuing their medication
  • Ocrelizumab administration must be delayed in patients with an active infection until the infection is resolved11

Ongoing Clinical Trials: Rates of COVID-19 in Ocrelizumab-Treated Patients10

  • Fifty-one suspected or confirmed cases of COVID-19 (1.3% of the trial population), including 26 later classified as confirmed, were identified in the 4000 patients enrolled in 9 ongoing OCR clinical trials as of 31 July 2020
  • Rates of COVID-19 relative to the duration of exposure to ocrelizumab by 3-year periods were calculated using the reference populationa (Figure 1)
  • No association was observed between duration of exposure to ocrelizumab and risk for COVID-19

Figure 1: Rates of COVID-19 in ocrelizumab-treated patients in ongoing clinical trials10a

Figure 1: Rates of COVID-19 in ocrelizumab-treated patients in ongoing clinical trials 10a

Post-Marketing Reports: COVID-19 Cases in Ocrelizumab-Treated Patients10

  • As of 31 July 2020, 307 cases of COVID-19 in ocrelizumab-treated patients were identified in pharmacovigilance reports
    • Overall, 263 cases were classified as confirmed COVID-19 cases, and 44 as suspected COVID-19 cases
    • More than 170,000 people with MS have been treated with ocrelizumab globally, in clinical trial and real-world, post-marketing settings

Post-Marketing Reports: Severity and Outcomes of COVID-19 in Ocrelizumab-Treated Patients10

  • A total of 100 (33%) of the 307 cases required hospitalizationb (Table 1/Figure 2)
    • Among patients <50 years old (46.3%; n=142), the majority (59.2%; n=84) experienced asymptomatic, mild, or moderate disease. 23.9% (n=34) experienced  severe, critical, or fatal disease
    • Among patients ≥50 years old (28.3%; n=87), a lesser proportion of patients (34.5%; n=30) experienced asymptomatic, mild, or moderate disease. A greater proportion (43.7%; n=38) experienced severe, critical, or fatal disease compared with the <50-year group
  • Outcomes were reported in >80% of cases. In the majority of all cases (211/307; 68.7%), patients were either recovered or were recovering

Table 1: Severity and outcomes of COVID-19 in ocrelizumab-treated patients10

Severity All cases, n (%) Cases requiring hospitalisation,a n (%)
 
COVID-19 cases 307 (100) 100 (100)
  Asymptomatic, mild, or moderate 143 (46.6) 6 (6)
  Severe 52 (16.9) 44 (44)
  Critical 15 (4.9) 15 (15)
  Fatal 17 (5.5) 11 (11)
  Severity not reported 80 (26.1) 24 (24)
 

aAll but 1 case requiring hospitalisation was confirmed; the remaining case had radiographic evidence of COVID-19 and was reported as "suspected COVID, resolved."

Figure 2: Severity of COVID-19 according to age in ocrelizumab-treated patients10c

Figure 2: Severity of COVID-19 according to age in ocrelizumab-treated patients 10c

Post-Marketing Reports: Details of 20 Cases With a Fatal Outcome12

  •  Patient demographics for these cases, including 3 patients from clinical trials, were as follows: Sex: male (n=10), female (n=9), unspecified (n=1); age range: 21-74 years (n=19), unspecified (n=1)
    •  The majority (n=14) of the 20 cases with fatal outcomes had risk factors known to be associated with severe COVID-19 outcomes in the general population (ie, hypertension, malignancy, respiratory disease, diabetes mellitus)
    •  Most (n=8) of the total reported EDSS scores (n=10) were within the 6.0-9.0 range, indicating a more severe course; MS registries identified MS severity as a risk factor for severe COVID-19 outcomes

Table 2: Number of cases and deaths in the general population

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General population (region)17 France Italy USA Global
Confirmed COVID-19 cases,17 n 383,292 281,583 6,361,265 28,191,178
COVID-19 deaths,17 n 30,805 35,577 190,859 909,927
Case Fatality Rate, % 8.0 12.6 3.0 3.2

 

Table 3: Number of cases and deaths in MS data sets, including reported ocrelizumab cases  

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MS datasets
All cases (ocrelizumab cases)10
COVISEP Franced MuSC-19 Italye OPTUM®️ databasef COViMS North Americag
Confirmed COVID-19 cases h 347 (38) 844 (89) 357 (48) 312 (94)
COVID-19 deaths 12 (0) 13 (1) 13 (1) 17 (3)
Case Fatality Rate, % 3.5 (0) 1.5 (1.1) 3.6 (2.1) 5.4 (3.2)

Data presented as of 26 June 2020. N/% in brackets indicate ocrelizumab cases. 

COVID-19 Real-World Data: General Population and MS Data Sets

  • The data that are emerging on COVID-19 in people with MS are mainly derived from real-world data and it is important to recognise the limitations (and biases) inherent in these data sources13,14
    • Real-world evidence is complex and challenging to interpret because there are many limitations and biases in the data sets, including significant unknown and/or unreported data, differences in data collection and reporting (patient reported vs healthcare professional reported), suspected vs confirmed COVID-19 cases, identification of other comorbidities, and generally a reporting bias toward more severe cases
    • Due to limitations of real-world data and countries being affected differently by the pandemic, there may be differences in emerging data and interpretations
    • Publication of the real-world evidence in peer-reviewed journals will provide a robust assessment of the data quality and analytical methods, especially accounting for potential confounders and biases, which is essential to understand the impact of COVID-19 in patients with MS
  • While it is too early to draw definitive conclusions, case-fatality rates from COVID-19 in pwMS receiving ocrelizumab appear to be in line with those in pwMS and the general population15-17
    • The risk factors associated with a more severe COVID-19 disease course in the general population (eg, age >50 years, male sex, hypertension, obesity, diabetes, coronary heart disease, and chronic lung disease) also appear to be associated with a more severe outcome in pwMS    

Prescribing Information

Indications vary in different countries. The local prescribing information from your country is the primary source of information on the known and potential risks associated with ocrelizumab.

 aReference population: All patients ongoing in the trials in January 2020, except for ORATORIO HAND (June 2020) and OCARINA (July 2020). ORATORIO HAND is an ongoing double-blind study; all patients were assumed to be on ocrelizumab. There were 86 patients who received ocrelizumab for more than 9 years, with one unconfirmed report of COVID-19. bAll but 1 case requiring hospitalisation was confirmed, with the remaining case having radiographic evidence of COVID-19 and reported as “suspected COVID, resolved.” cAge was unknown in 78 (25.4%) patients. There were 2 (0.65%) patients under 19 years of age. One 16-year-old patient (off-label use) experienced mild COVID-19, and one 18-year-old patient experienced severe COVID-19; both recovered. dAs of 21 May 2020. Louapre C, et al. JAMA Neurol 2020;26:e202581. eSormani MP, et al. Disease modifying therapies and Covid-19 severity in Multiple Sclerosis. Ann Neurol. Published online ahead of print January 21, 2021. doi:10.1002/ana.26028. fDillon P, et al. Americas Committee for Treatment and Research in Multiple Sclerosis-European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS) 2020; Poster LB1254. gAs of 14 July 2020, available at https://www.covims.org/current-data. hClinically suspected + laboratory confirmed.

COVID-19=coronavirus disease 2019; COViMS=COVID-19 Infections in MS & Related Diseases; COVISEP=Epidemiological Characteristics of COVID-19 in Patients With MS or neuromyelitis optica; DMT=disease-modifying therapy; EDSS=Expanded Disability Status Scale; ISARIC=International Severe Acute Respiratory and emerging Infection Consortium; MS=multiple sclerosis; MuSC-19=Multiple Sclerosis and COVID-19; pwMS=persons with multiple sclerosis; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; WHO=World Health Organisation.

 

References
 
  1. Hughes R, et al. Mult Scler Relat Disord. 2020;42:102192;
  2. Richardson S, et al. JAMA. 2020;323:2052-2059;
  3. Sormani MP, et al. Lancet Neurol. 2020 Jun; 19(6):481-482;
  4. Montero-Escribano P, et al. Mult Scler Relat Disord. 2020;42:102185;
  5. Safavi F, et al. Mult Scler Relat Disord. 2020;43:102195;
  6. Barzegar M, et al. Mult Scler Relat Disord. 2020;45:102276;
  7. Sormani MP, et al. Lancet. Preprint - not yet peer reviewed. 363124413;
  8. Louapre C, et al. JAMA Neurol. 2020;e20258114;
  9. Dalla Costa G, et al. Neurol Sci. 2020;doi:10.1007/s10072-020-04519-x;
  10. Hughes R, et al. Mult Scler Relat Disord. Published online ahead of print December 30, 2020. doi: https://doi.org/10.1016/j.msard.2020.102725;
  11. Summary of product characteristics (OCREVUS [ocrelizumab]). https://www.ema.europa.eu/en/documents/product-information/ocrevus-epar-product-information_en.pdf. Last updated 5 June 2020. Accessed 8 December 2020;
  12. Roche data on file;
  13. Cohen JA, et al. Mult Scler. 2020;26:23-37;
  14. Evans K. Drugs Real World Outcomes. 2019;6:43-45;
  15. Louapre C, et al. JAMA Neurol. 2020;e20258114;
  16. MS International Federation. COVID-19 & MS data sharing: for healthcare professionals. www.msif.org/covid-19-ms-data-sharing-for-healthcare-professionals. Accessed 14 July 2020;
  17. Johns Hopkins University of Medicine Coronavirus Resource Center. Mortality analyses. https://coronavirus.jhu.edu/data/mortality. Accessed 11 September 2020.