Home > Key safety topics > COVID-19
In the ALITHIOS open-label extension trial1
- As of 29 Jan 2021, 139 of 1703 patients (8.2%) in the ALITHIOS trial reported COVID-19 (confirmed: 115 [82.7%]; suspected: 24 [17.3%])
- Mean age at baseline was 37.7 ± 8.7 years and majority (64%) were female
- All 139 COVID-19 cases (100%) had IgG levels above lower limit of normal (5.65 g/L) either before or during the period effected by COVID-19
- At the data cut-off, majority of patients recovered, recovered with sequelae or were recovering (96.4%)
- A total of 10 patients were hospitalized; one patient with confirmed COVID-19 and pneumonia had a fatal outcome (48 years old at COVID-19 onset; BMI, 28.3 kg/m2; recent MS relapse)
COVID-19 outcomes by severity
Grading by CTCAE v5.0. Values expressed as mean (SD) unless specified.
aIncludes 1 asymptomatic patient; bConfirmation of positive SARS-CoV-2 laboratory test was not available by data cut-off date for one COVID-19 pneumonia suspected case
In the post-marketing setting
- As of 31 Jan 2021, Novartis has received 28 confirmed or suspected COVID-19 cases in ofatumumab-treated patients in the post-marketing setting
- Mean age at baseline was 44 (20-65) years for COVID-19 confirmed cases
- 26 cases were confirmed (SARS-CoV-2 test positive, or noted to be diagnosed with COVID-19)
- There were no fatal cases
- Outcome was not reported in 10 cases; the majority of patients recovered (n=13); condition was unchanged in 3 cases
Summary of Confirmed Cases: N=262
‡ascertained based on the most serious criteria; ¶no information regarding comorbidities provided; ¶¶Important medical event that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other serious outcomes
††all 3 cases received from non HCPs
*Published literature case from France.
$based on 20 cases where age was reported
HCP, healthcare professional.
COVID-19 outcomes by severity : Confirmed cases1
Severity was assessed using WHO and FDA. COVID-19 severity scales by an independent adjudication committee comprising experts in MS and infectious diseases and where data were available, categorization was done as follows: asymptomatic (infection without symptoms); mild (not requiring hospitalization, symptoms did not include dyspnea); moderate (hospitalization with pneumonia not reported to be severe and/or with respiratory rate [RR] >20 and/or oxygen saturation [SpO2] >90%, shortness of breath or dyspnea, hospitalization less than 7 days without further details); severe (pneumonia reported as severe – RR ≥30, SpO2 ≤93%, hospitalization 7 days or more without further details); or critical (respiratory failure and/or intubation).
Percentages are calculated based on available information for severity (N = 17) and not reported for 9 patients
This section provides a summary of cases of ofatumumab treated patients either suspected as having or reported to have COVID-19 as reported in the Novartis safety database, including spontaneous reports submitted voluntarily and cases identified in the scientific literature. There is typically underreporting in this setting, therefore the true numerator is unknown. The denominator is also unknown, as the actual number of patients on therapy with ofatumumab is not readily available. Many of the cases contain very limited information and includes cases that are lost to follow up. Therefore, due to these limitations, it is not possible to draw any meaningful conclusions concerning the incidence of COVID-19 or course of illness in patients receiving ofatumumab.
Additional information
Impact of COVID-19 in MS in the real-world setting
- MS is an autoimmune, chronic inflammatory, neurodegenerative disorder of CNS where patients are generally treated with immunosuppressants or immunomodulators.3 The current COVID-19 pandemic has raised concerns regarding the immune response to viral infections and post vaccination in MS patients treated with disease modifying therapies4
- Comprehensive data sharing and analyses regarding the effect of COVID-19 in people with MS have been conducted by the COVID-19 in MS - GDSI.5 The GDSI initiative is a joint initiative of the MS International Federation and the MS Data Alliance, acting under the umbrella of the European Charcot Foundation and in collaboration with many (data) partners across the globe
- In people with MS, the incidence of COVID-19 varies from 0.5% to 1.13%.6The mortality due to COVID-19 has been reported from 1.6% to 4.2%7,8
- Prosperini L, et al. reported crude death rate of 1.97% and estimated indirectly-adjusted age-standardized lethality ratio to be 1.24, suggesting 24% increased risk of death from COVID-19 in patients with MS9
Ofatumumab and COVID-19 – Guidance to HCPs
- Novartis is committed to patient's health and safety. In these unprecedented times, we are striving to keep patients, care partners, and healthcare providers up to date and provide the latest information to help inform decisions related to the use of our products. Novartis continues to collect data about COVID-19 infection in patients treated with ofatumumab.
- In general, patients and prescribers should act in accordance with local government and health authority guidance concerning the COVID-19 pandemic (including guidance on social distancing and self-isolation, as applicable). HCPs may also consult advice specific to patients with MS provided by international or local HCPs and patient organizations10-12
- Ofatumumab has the potential for an increased risk of infections.3,13 Administration should be delayed in patients with an active infection until the infection is resolved.3,13 Novartis believes that treatment decisions should be made between a patient and their treating healthcare professional based on a benefit-risk assessment specific to the individual patient.
SARS-CoV-2 vaccination considerations
- To date all of the SARS-CoV-2 vaccines currently approved and available or in development belong to several categories/platforms, namely : (1) mRNA-based vaccines, (2) nonreplicating viral-vector vaccines, (3) inactivated vaccines, (4) protein vaccines and (5) live attenuated vaccines
- As with inactivated vaccines, the use of nonreplicating viral-vector vaccines or mRNA based SARS-CoV-2 vaccines in patients receiving immunomodulant/immunosuppressant therapies such as ofatumumab may have a diminished immune response
- Novartis is conducting in Germany an open label, multicenter, clinical trial, to evaluate the humoral and cellular immune response post-vaccination (mRNA based vaccines) in people living with RMS receiving treatment with ofatumumab according to the regular clinical practice.
- To date the available data of the occurrence and severity of breakthrough infections after a full course of vaccination in people living with MS (plwMS) is very scarce. Its incidence varies from 0.04% to 1.1% and its course has been reported as mild to moderate in most of the cases. 14-16
- Breakthrough infections also happen in the fully vaccinated general population. Its rate varies from 1 in 100 to 1 in 5,000 in fully vaccinated people.17 Majority of the cases were mild or moderate, although some deaths have also been described (from 0.001% to 6.3%). 18-20
- There is presently no contraindication for the use of inactivated, nonreplicating viral-vector, or mRNA-based SARS-CoV-2 vaccines while on treatment with ofatumumab, even if vaccinations may be less effective3,13
- Vaccination against SARS-CoV-2 should be considered on a case-by-case basis at the discretion of the treating physician and should be in adherence to immunization guidelines in the local vaccine label21
- Please review local prescribing information for any specific SARS-CoV-2 vaccine and comply with local prescribing information requirements for specific contraindications and special warnings and precautions for use
- People with MS who are considered to be immunocompromised could be adviced to receive an additional dose of COVID-19 vaccine depending on local recommendations of their countries22
- All immunizations should be administered according to local immunization guidelines, at least 4 weeks prior to initiation of ofatumumab for live or live-attenuated vaccines and, whenever possible, at least 2 weeks prior to initiation of ofatumumab for inactivated vaccines3,13
- The safety of immunization with live or live-attenuated vaccines following ofatumumab therapy has not been studied. Vaccination with live or live-attenuated vaccines is not recommended during treatment and after discontinuation until B-cell repletion3,13
- The guidance provided by National Multiple Sclerosis Society (NMSS) suggests that people with MS who are fully vaccinated with an mRNA vaccine and using S1PR modulators, alemtuzumab, and anti-CD20 therapies may benefit from an additional dose of mRNA vaccine23
- Some other countries and regions are also recommended to go for additional dose of vaccine after being fully vaccinated in people with immunosuppressive conditions (due to their disease or their treatment)24-26
FAQs
1. Where do I find safety information related to COVID-19 infections with ofatumumab treatment?
- Novartis is committed to proactive and transparent safety communications of data related to COVID-19 infections with the MS community regularly in the coming months (e.g., local label, publications and website)
- Please refer to the ofatumumab Prescribing Information for relevant information regarding the risk of infections.
2. Should RMS patients initiate treatment with ofatumumab ?
- Prior to initiating therapy, follow local guidelines on testing for SARS CoV-2. Patients can initiate therapy with ofatumumab in accordance with Prescribing Information approved by your national regulatory authorities.
3. Are patients on therapy with ofatumumab at a higher risk for COVID-19 infection?
- Based on its mode of action of depleting B cells, ofatumumab has the potential for an increased risk of infections, including COVID-19. Patients should consult with their physicians and treatment decisions should be made based on the individual patient benefit-risk assessment. Please refer to the Prescribing Information for information regarding the safety of ofatumumab
4. Does treatment with ofatumumab cause a more severe course of SARS CoV-2 infection?
- There is no consistent evidence that MS patients treated with B-cell targeting therapies are at a higher risk for a more severe course of infections. Although, most of the registries currently on going reported a higher risk of having a more severe course of COVID-19 in plwMS exposed to RTX or OCR (including hospitalization but not death), the available information for ofatumumab in these registries is nearly zero. Among plwMS, risk factors for a more severe course of infection seem to be higher EDSS score, recent use of corticoids, progressive MS phenotype, obesity, age, and comorbidities. 5-9,27-31
- Our clinical data suggest that COVID-19 follows a similar course of SARS CoV-2 infection in ofatumumab-treated patients as in the general population1
- There has been a report of one COVID-19 pneumonia fatality in clinical trial. The investigator considered the event as not related to treatment with ofatumumab1
- The known benefit-risk of ofatumumab remains unchanged. Patients should consult with their physicians and treatment decisions should be made based on individual patient benefit-risk assessment. Please refer to the Prescribing Information for information regarding the safety of ofatumumab
5. Should patients interrupt or discontinue therapy with ofatumumab if they are diagnosed with COVID-19?
- Limited data are available for providing any specific recommendations for people treated with ofatumumab
- Therapy with ofatumumab may need to be temporarily interrupted if a patient has a confirmed or suspected diagnosis of COVID-19 and/or severe symptoms; treatment can be restarted after COVID-19 resolution. Though the known benefit-risk of ofatumumab remains unchanged, physicians should make decisions based on individual patient benefit-risk assessment
- From the limited clinical study data, COVID-19 outcomes do not indicate a difference between ofatumumab-treated patients and the general population1
6. What is the guidance for ofatumumab treatment following a delay of a scheduled dose?
- Any delay in the scheduled ofatumumab administration is considered a ‘missed dose’. Please refer to your country’s national regulatory authority approved ofatumumab Prescribing Information for guidance on missed dose
- Per the country’s national regulatory authority approved ofatumumab Prescribing Information, if an injection of ofatumumab is missed, it should be administered as soon as possible without waiting until the next scheduled dose. Subsequent doses should be administered at the recommended intervals