COVID-19 Frequently Asked Questions

  • Patient safety is Roche’s highest priority and we are closely monitoring the evolving COVID-19 (coronavirus disease 2019) situation. We are committed to working closely with the community to better understand the impact of COVID-19 on people who are treated with ocrelizumab, and will continue to share new findings with the MS community as they emerge.
  • COVID-19 is caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2, and although new findings and case studies around the impact of this virus continue to emerge, knowledge of the effect of SARS-CoV-2 on the general population and for the multiple sclerosis (MS) community remains limited.
  • Like many other disease-modifying therapies for MS, ocrelizumab works by making changes to the immune system. In clinical trials, those receiving ocrelizumab had a slightly increased risk of contracting certain infections, including upper respiratory tract infections, but these infections were predominantly mild to moderate (classified as non-serious)3,4.
    •  Respiratory tract infections5:
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RMS

 Upper respiratory tract infection Lower respiratory tract infection   

PPMS

 Upper respiratory tract infection Lower respiratory tract infection
Ocrelizumab 39.9% 7.5% Ocrelizumab 48.8% 9.9%
Interferon-beta 1a 33.2% 5.2% Placebo 42.7% 9.2%

 

  • Based on results from pivotal clinical studies, ocrelizumab was not associated with an overall increased risk of serious infections in MS. 
    • Serious infections5:
---

RMS:

  

PPMS:
Ocrelizumab 1.3% Ocrelizumab 6.2%
Interferon-beta 1a 2.9% Placebo 6.7%

 

  • In patients with an active infection, treatment with ocrelizumab should be delayed until the infection is resolved5.*
  • Patients receiving ocrelizumab that are either exposed to the coronavirus or confirmed to have COVID-19 should contact their neurologist or other medical professional right away.*
  • Patients should speak with their neurologist or other medical professional before discontinuing their medication.

*Physicians and patients should consult their local ocrelizumab label for relevant information regarding the safety of ocrelizumab.
For additional information and context surrounding the risk of infections with ocrelizumab, see the Ocrelizumab and Infections page here

 

Frequently asked questions

  • We are closely assessing emerging data, both our own pharmacovigilance data and RWD. 
    • Our pharmacovigilance data suggests that COVID-19 follows a similar course in ocrelizumab-treated MS patients as in the general population6–17, with risk factors for severe COVID-19 reflecting those seen in the general population.6,12 Risk factors for severe COVID-19 in the general population include: old age and presence of comorbidities including hypertension, diabetes, obesity, smoking, cardiovascular and lung disease.
    • The known benefit/risk of ocrelizumab remains unchanged.
    • We are aware that emerging data from real-world registries show varying findings on the impact of ocrelizumab treatment on the severity of COVID-19 in people with MS. The differences in these findings are to be expected due to the challenges of collecting, analysing, and interpreting real-world data and due to how healthcare systems in different counties are being impacted by the pandemic.
    • There has been no association between ocrelizumab and fatal COVID-19 outcomes reported to date9–15.
    • From the limited RWD available globally, the MS population does not seem to be at higher risk from contracting
      SARS-CoV-2.
    • Major risk factors identified for fatal COVID-19 in the MS population are advanced age (>55 years old), high levels of disability, a progressive form of MS and comorbidities (e.g., cardiovascular)14,16.
    • The emerging real-world data have not changed our position and assessment of the known benefit/risk of ocrelizumab in patients with MS.
    • We believe we need to continue to gather as much data as we can to help address limitations in real-world data and get a clearer understanding of the impact of COVID-19 on patients treated with ocrelizumab in the absence of randomized, controlled trials in order to inform future recommendations. We base our benefit/risk assessment on the totality of data available from all sources.
  • We believe that treatment decisions should be made between a patient and their treating neurologist or other medical professional based on a benefit/risk assessment specific to the individual patient.
  • *Physicians and patients should consult their local ocrelizumab label for relevant information regarding the safety of ocrelizumab. For additional information and context surrounding the risk of infections with ocrelizumab, see the Ocrelizumab and Infections page here

  • Data shared in our recent publication is of validated reports of ocrelizumab-treated patients with a confirmed or suspected SARS-Cov-2 infection and / or COVID-19 as of April 30, 202012. 
  • As of 31 May 2020, we have received 201 validated reports as per standard pharmacovigilance activities relating to ocrelizumab-treated patients with a confirmed or suspected SARS-Cov-2 infection and/or COVID-196. 
  • Our pharmacovigilance data suggests that COVID-19 follows a similar course in ocrelizumab-treated MS patients as in the general population6–17, with risk factors for severe COVID-19 reflecting those seen in the general population6,12. Risk factors for severe COVID-19 in the general population include: old age and presence of comorbidities including hypertension, diabetes, obesity, smoking, cardiovascular and lung disease. The known benefit/risk of ocrelizumab remains unchanged.
  • Out of those 201 reports, 122 (61%) were classified as non-serious and 79/201 (39%) as serious; the serious cases included 11/201 (5.5%) fatal and 4/201 (2.0%) life-threatening cases6.
    • Hospitalisation was the most frequent seriousness criterion with 51/79 of the serious cases being categorised as serious due to hospitalisation. Reasons for hospitalisation were variable and included (but were not limited to) the following: treatment of pneumonia and for ICU treatment.
    • Outcome at the time of reporting of the serious cases; was unknown for ~1/3, recovered/recovering for ~1/3, and ~1/3 had not recovered of which 11 cases were fatal.
  • For additional information and context surrounding ocrelizumab and COVID-19 pharmacovigilance data, see the COVID-19 Cases page here

  • We are actively discussing with the neurology community insights and perspectives relating to MS and COVID-19. Currently there are only limited data available to inform specific recommendations or changes to treatment protocols for people treated with ocrelizumab. 
  • From our pharmacovigilance data, the risk factors for severe/fatal COVID-19 outcomes do not indicate a difference between ocrelizumab treated patients and the general population. The known benefit/risk of ocrelizumab remains unchanged.
  • We appreciate how difficult it may be for physicians and people with MS to make treatment decisions at this time and we understand that some neurological and patient societies recommend the delay of treatment initiation or re-treatment, we believe patients should speak with their neurologist or other medical professional before discontinuing or delaying treatment, so that decisions can be made based on a benefit/risk assessment specific to the individual patient. 

  • We are aware of reported cases and, as per our safety reporting processes, we will follow up to validate the information and report to health authorities in accordance with standard pharmacovigilance processes.
  • The overall number of COVID-19 cases reported in ocrelizumab-treated MS patients continues to be low6.
    • As of 31 May 2020, we have received 201 validated reports as per standard pharmacovigilance activities relating to ocrelizumab-treated patients with a confirmed or suspected SARS-Cov-2 infection and/or COVID-19.
    • Out of those 201 cases, 11 were reported as fatal cases (5.5%). From our pharmacovigilance data the risk factors for severe COVID-19 outcomes do not indicate a difference between ocrelizumab treated patients and the general population3.
  • 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 profile6.
  • We actively support transparent safety communications (e.g., congresses, publications, www.ocrelizumabinfo.global) and we are working with the MS community and independent external advisors to assess the most appropriate way to continue sharing our safety data related to COVID-19 with the community regularly in the coming months. 
  • With the evolving worldwide situation in relation to COVID-19, it is anticipated that the number of COVID-19 cases will increase and, as a result, it is likely that the number of COVID-19 cases in people with MS will also rise12. 
  • For additional information and context surrounding ocrelizumab and COVID-19 pharmacovigilance data, see the COVID-19 Cases page here

  •  Rates of serious infections in all patients exposed to ocrelizumab in clinical trials remain low and consistent with rates of infection-related hospitalisations in real-world MS cohorts18.
    • Ocrelizumab was not associated with an increased risk of serious infections in MS patients, as shown in our Phase III clinical studies vs comparators (interferon beta-1a or placebo). Of those serious infections, which occurred, the vast majority were bacterial, and the patients responded to standard of care treatment. Longer-term data through continued observation in our open-label extension studies has revealed no new or particular pattern of serious infections in MS patients treated with ocrelizumab.
  • Ocrelizumab-treated patients have been shown to have an increased risk of contracting certain infections, including upper respiratory tract infections that were predominantly mild to moderate (classified as non-serious)3–5.*
    • In pivotal clinical trials a higher proportion of ocrelizumab-treated patients experienced non-serious infections compared to patients taking Rebif (interferon beta-1a) (58.5% vs. 53.4%) or placebo (71.4% vs. 69.9%). These infections were predominantly mild to moderate, were equally likely to be bacterial or viral, and resolved with standard of care treatment and in most cases patients remained on treatment with ocrelizumab.
  • *Physicians and patients should consult their local ocrelizumab label for relevant information regarding the safety of ocrelizumab. For additional information and context surrounding the risk of infections with ocrelizumab, see the Ocrelizumab and Infections page here

  • Research suggests that two different immune responses may be crucial for eliminating SARS-CoV-2 from the body. B cells are not involved in the first immune response, but the second immune response leads to a production of antibodies under normal conditions and following vaccination.
  • Data from our Phase III studies show that pre-existing adaptive immunity is not affected by ocrelizumab treatment. Although reduced in comparison to placebo-treated patients, vaccination study results show that patients treated with ocrelizumab were able to mount an attenuated immune responses to vaccines and new antigens at week 12 after ocrelizumab infusion5,19.*
  • As ocrelizumab is a twice-yearly (six-monthly) infusion, it is expected that vaccination in a later phase of the infusion free interval (e.g. five months after the last ocrelizumab infusion) may lead to a more pronounced immune response.
  • Roche is continually collecting evidence from clinical and biological sources to better understand these mechanisms to ensure any
    SARS-CoV-2 vaccine is as efficacious and safe as possible for ocrelizumab-treated patients.
  • *Physicians and patients should consult their local ocrelizumab label for relevant information regarding the safety of ocrelizumab. For additional information on vaccine responses with ocrelizumab, see the Updated safety analysis page here

  • The current clinical situation may make it necessary to delay a scheduled dose of ocrelizumab, due to logistical reasons or based on an individual benefit/risk decision.
  • As per ocrelizumab label: If an infusion of ocrelizumab is missed, it should be administered as soon as possible; do not wait until the next planned dose. The treatment interval of 6 months (with a minimum of 5 months) for ocrelizumab should be maintained between doses5.*
  • Based on limited data available from the ORCHESTRA studies, there is no evidence that a delay in ocrelizumab dosing will increase the Infusion-Related Reaction (IRR) rate with the next 600mg dose administered as a single infusion20,21.
  • *Physicians and patients should consult their local ocrelizumab label for relevant information regarding the safety of ocrelizumab.

  •  The European Medicines Agency (EMA) has approved a new, shorter two-hour ocrelizumab infusion time, dosed twice yearly, for relapsing or primary progressive multiple sclerosis5,20,21.*
  • The approval was based on data from the randomised, double-blind ENSEMBLE PLUS study, showing consistent safety to the conventional ocrelizumab dosing regimen.
    • Results showed comparable frequency and severity of IRRs for the two-hour ocrelizumab infusion time vs. the conventional 3.5-hour time in patients with relapsing-remitting MS. 
  • Roche hopes this approval will further improve the treatment experience for patients and increase capacity in healthcare systems. We believe it will assist both European patients and their healthcare providers to reach the ultimate goal of slowing disease progression in MS.
  • The U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application for a two-hour ocrelizumab infusion time, and is expected to make a decision by 14 December 202021.
  • *Physicians and patients should consult their local ocrelizumab label for relevant information regarding the safety of ocrelizumab.

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.
References
 
  1. Zhou P, Yang, XL, Wang, XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin.
    Nature.2020;579:270–273. https://doi.org/10.1038/s41586-020-2012-7  
  2. del Rio C, Preeti NM. New insights on a rapidly changing epidemic. JAMA. 2020;323(14):1339–1340. https://doi.org/10.1001/jama.2020.3072
  3. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. https://doi.org/10.1056/NEJMoa1601277
  4. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209–220. https://doi.org/10.1056/NEJMoa1606468
  5. Summary of product characteristics (Ocrevus). https://www.ema.europa.eu/en/documents/product-information/ocrevus-epar-product-information_en.pdf. Last updated June 05, 2020. Accessed July 17, 2020.
  6. Roche, data on file, 2020
  7. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395:1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3
  8. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323:2052–2059. https://doi.org/10.1001/jama.2020.6775  
  9. Sormani MP, on behalf of the Italian Study Group on COVID-19 infection in multiple sclerosis. An Italian programme for COVID-19 infection in multiple sclerosis Lancet Neurol. 2020;19:481–482. https://doi.org/10.1016/S1474-4422(20)30147-2
  10. Montero-Escribano P, Gómez-Iglesias P, Porta-Etessam J, et al. Anti-CD20 and COVID-19 in multiple sclerosis and related disorders: A case series of 60 patients from Madrid, Spain. Mult Scler Relat Disord. 2020;42:102185. https://doi.org/10.1016/j.msard.2020.102185
  11. Safavi F, Nourbakhsh B, Azimi AR. B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. Mult Scler Relat Disord. 2020;43:102195.
  12. Hughes R, Pedotti R, Koengden H. COVID-19 in persons with multiple sclerosis treated with ocrelizumab – a pharmacovigilance case series. Mult Scler Relat Disord. 2020;42:102192. https://doi.org/10.1016/j.msard.2020.102192
  13. Barzegar M, Mirmosayyeba O, Ghajarzadeh M, et al. Characteristics of COVID-19 disease in multiple sclerosis patients. Mult Scler Relat Disord. 2020;42:102276. https://doi.org/10.1016/j.msard.2020.102276
  14. Chaudry F, Bulka H, Rathnam A, et al. COVID-19 in multiple sclerosis patients and risk factors for severe infection. medRxiv. 2020.05.27.20114827. https://www.medrxiv.org/content/10.1101/2020.05.27.20114827v1
  15. Sormani MP, De Ross N. Disease modifying therapies and COVID-19 severity in multiple sclerosis. SSRN. [epub ahead of print, July 8, 2020]. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3631244
  16. Louapre C, Collongues N, Stankoff B, et al. Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis. JAMA Neurol. [Epub ahead of print, June 26, 2020]. https://doi.org/doi:10.1001/jamaneurol.2020.2581
  17. Dalla Costa G et al. Real-time assessment of COVID-19 prevalence among multiple sclerosis patients: a multicenter European study. Neurol Sci. 2020;41:1647–1650. https://doi.org/10.1007/s10072-020-04519-x
  18. Hauser SL, Kappos L, Montalban X, et al Safety of ocrelizumab in multiple sclerosis: updated analysis in patients with relapsing and primary progressive multiple sclerosis. Presented at the 6th Congress of the European Academy of Neurology (EAN) VIRTUAL 2020; May 23–26, 2020. ePresentation number EPR2122.
  19. Stokmaier D, Winthrop K, Chognot C, et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis. Presented at the 4th Congress of the European Academy of Neurology; June 16–19, 2018; Lisbon, Portugal. Poster POD399.
  20. Roche. Press Release. Roche’s OCREVUS (ocrelizumab) shorter 2-hour infusion time approved in Europe. Posted online May 28, 2020. https://www.roche.com/media/releases/med-cor-2020-05-28b.htm. Accessed July 10, 2020
  21. Roche. Press Release. US FDA and EMA accept applications for Roche’s OCREVUS (ocrelizumab) shorter 2-hour infusion time. Posted online April 20, 2020. https://www.roche.com/media/releases/med-cor-2020-04-20.htm. Accessed July 10, 2020