COVID-19 Cases

Ocrelizumab and COVID-19 Pharmacovigilance Data

Download PDF

Main takeaways

  • While it is too early to draw definitive conclusions, based on the limited information that is available from pharmacovigilance data, the risk factors for severe COVID-19 outcomes do not indicate a difference between ocrelizumab-treated patients1 and the general population2–10, and may suggest that COVID-19 follows a similar course in ocrelizumab-treated MS patients as 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, cardiovascular, and lung disease1–4,8,9
  • The known benefit/risk profile of ocrelizumab remains unchanged

Incidence of COVID-19 cases in ocrelizumab-treated patients1

  • As of 31 May 2020, 201 cases of COVID-19 in ocrelizumab-treated patients were identified in pharmacovigilance reports; all cases were conservatively considered as having confirmed COVID-19 (including the cases with missing information on diagnosis confirmation, e.g. by PCR)
  • More than 160,000 people with MS have been treated with ocrelizumab globally, in clinical trial and real-world settings; data continue to show a consistent and favourable benefit/risk profile
  • Patients receiving ocrelizumab that are either exposed to SARS-CoV-2 or confirmed to have COVID-19, should contact their neurologist or other medical professional right away, and patients should consult their neurologist or other medical professional before discontinuing their medication

Seriousness and outcomes of COVID-19 in ocrelizumab-treated patients1

  • Of the 201 cases, 61% (n=122/201) were reported as not serious, and 39% (n=79/201) were reported as serious
    • Included in the serious cases were:
      • 2.0% (n=4/201) reported as life-threatening and 5.5% (n=11/201) reported a fatal outcome
      • 65% (n=51/79) of cases were classified as serious on the basis of hospitalisation
      • Reasons for hospitalisation were variable and included (but were not limited to) the following: treatment of pneumonia and for ICU treatment
      • At the time of reporting, 32% (n=25/79) of the serious cases were reported as recovered/recovering, and 33% (n=26/79) cases had an unknown outcome

Table 1: Reported outcomes by most serious seriousness criteriona for all serious cases (n=79)1

Reported Outome
    Fatal Recovered Recovering Not recovered Missing information Total
Most serious
seriousness 
criterion		 All serious cases 11 15 10 17 26 79
Medically significant 0 3 2 2 5 12
Hospitalisation 0 11 8 14 18 51
Disability 0 0 0 0 1 1
Life-threatening 0 1 0 1 2 4
Death 11 0 0 0 0 11

 

 

Details of 11 cases with a fatal outcome1

  • For the 11 cases with fatal outcomes the reported causes of death were: COVID-19 (n=8); COVID-19 pneumonia (n=1); coronavirus infection (n=1); and respiratory failure (n=1)
    • None of the 11 cases had an available autopsy report
  • Patient demographics for these cases were as follows: Sex: male (n=7), female (n=3), unspecified (n=1); Age range 43–66 years (n=10), unspecified (n=1)
  • The majority (n=7) of the 11 cases with fatal outcomes had risk factors known to be associated with severe COVID-19 outcomes in the general population
    • Reported previous DMTs (n=2); of note, as indicative of a more advanced MS
    • Reported EDSS 6.0–9.0 (n=5), indicating a more severe course; MS registries identified MS severity as risk factor for severe COVID-19 outcomes
    • Risk factors were identified for all patients with COVID-19 confirmed by RT-PCR (n=4), and all patients who received mechanical ventilation (n=5)
    • Two patients were not assessable; follow-up for missing information is ongoing
  • Time from starting ocrelizumab to outcome ranged from 1.5 to 3 years, but was unknown in 2 cases

Interpreting COVID-19 real-world data

  • COVID-19 is caused by a new strain of coronavirus called SARS-CoV-2, so knowledge about how it may affect people with MS remains limited11,12
    • The limited data that are emerging on COVID-19 in people with MS are mainly derived from real world data sources and it is important to recognise the limitations (and biases) inherent in these data sources13,14
  • From the limited real world evidence available globally, the MS population in general does not seem to be at higher risk from COVID-19 and no association between any DMTs and fatal COVID-19 outcomes has been reported9,15,16
    • Major risk factors identified for severe/fatal COVID-19 in the MS population are advanced age (>50 years old), high levels of disability, progressive form of MS and presence of comorbidities such as hypertension, diabetes, obesity, smoking, cardiovascular, and lung disease9,15,16
    • Treatment decisions,  should therefore be made between a patient and their treating neurologist or other medical professional based on a benefit/risk assessment specific to the individual patient
  • We are aware of many efforts to collect real world evidence to inform the community’s understanding of COVID-19 and the impact on patients with MS including the CoviSEP (French) and MuSC-19 (Italian) registries4,9,15
  • Real-world evidence is complex and challenging to interpret as 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 co-morbidities and generally a reporting bias towards more severe cases

Table 2: Number of cases and deaths in the general population, as of 14 July 202016

---
Country France Italy USA Global
Confirmed COVID-19 cases, nb 209,640 243,230 3,363,056 13,127,030
COVID-19 deaths, nb 30,032 34,967 135,605 573,663
Case–fatality rate , % 14.3 14.4 4.0 4.4

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

---
MS datasets CoViSEP France9
(as of 21 May 2020)		 MuSC-19 Italy17
 (as of 31 May 2020)		 CoViMS North America18
 (as of 14 July 2020)		 MSDA/MSIF 
Globalc,16,19
(as of 10 June 2020)
COVID-19 cases (OCR cases), nb 347 (38) 789 (83) 362 (110) 457d (85)
COVID-19 deaths (OCR cases), n 12 (0) 13 (1) 24 (4) 18 (3)
Case–fatality rate (OCR cases), % 3.5 (0.0) 1.6 (1.2) 6.6 (3.6) 3.9 (3.5)

NB: numbers and percentages in brackets indicate ocrelizumab 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 in peer-reviewed journals of the real world evidence 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 MS

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.

a, serious event is defined as one that requires in-patient hospitalisation, prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, is life-threatening or fatal; b, includes both clinically suspected and laboratory confirmed cases; c, Includes data from Germany, Sweden, Denmark, Brazil, North America; d, Overall dataset includes 527 cases, with alive/death status available for 457 patients

COVID-19, coronavirus disease 2019; DMTs, disease-modifying therapies; EDSS, Expanded Disability Status Scale; ICU, intensive care unit; MS, multiple sclerosis; PPMS, primary progressive MS; RMS, relapsing forms of MS; RT-PCR, reverse transcription polymerase chain reaction; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2
References
 
  1. Roche data on file; 
  2. Hughes R et al. Mult Scler Relat Disord 2020;42:102192; 
  3. Richadson S et al. JAMA., 2020;323:2052–2059; 
  4. Sormani MP et al. Lancet Neurology. 2020;19:481-482; 
  5. Montero-Escribano P et al., Mult Scler Relat Disord 2020;42:102185; 
  6. Safavi F et al.. Mult Scler Relat Disord 2020;43:102195; 
  7. Barzegar M et al. Mult Scler Relat Disord 2020;45:102276; 
  8. Sormani MP et al. SSRN. Preprint – not yet peer reviewed. 363124413; 
  9. Louapre C et al. JAMA Neurol 2020;e20258114; 
  10. Dalla Costa G et al. Neurol Sci 2020;41:1647-1650;
  11. Zhou P et al. Nature 2020;579:270-273; 
  12. del Rio C, and Preeti NM, JAMA. 2020;doi: 10.1001/jama.2020.3072; 
  13. Cohen JA et al. Mult Scler. 2020;26:23-37; 
  14. Evans K. Drugs Real World Outcomes 2019;6:43-45; 
  15. 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; 
  16. Johns Hopkins, Coronavirus Resource Center. Mortality analyses. https://coronavirus.jhu.edu/data/mortality Accessed 14 July 2020; 
  17. Unpublished MuSC-19 Italian Registry data, as of 31 May 2020; 
  18. CoViMS North American Registry data, as of 14 July 2020; 
  19. Unpublished MSDA/MSIF Global Sharing Initiative Data, as of 10 June 2020.