KESIMPTA® (ofatumumab) Coffee Breaks: Exploring Patient Concerns With KESIMPTA Safety and COVID-19 Infection Data

Dr Jeffery

How do you navigate the risk of COVID-19 infection in patients taking disease-modifying therapies, or DMTs? How do you address concerns about vaccine efficacy before and during therapy? The risk of COVID-19 is particularly acute in patients taking immunosuppressive therapy. Although the data are rapidly evolving, there is still uncertainty in how to manage these risks in patients with relapsing multiple sclerosis, or RMS.

Stephanie

* Dr Jeffery, at the beginning of the pandemic there were significant concerns in the MS community about increased COVID-19 infection risk in patients taking DMTs, especially for B-cell–targeting therapies like KESIMPTA. Can you explain how COVID-19 impacted the way you thought about initiating or modifying treatment in your patients with RMS?

Dr Jeffery

That's a great question. During this pandemic, we've had to balance the risk of COVID-19 with that of relapsing MS disease progression. However, COVID-19 has not made me modify my practice; my primary focus is treating their relapsing MS. My first line of therapy was, and still is, B-cell–targeting therapies, such as KESIMPTA, for appropriate patients because of the efficacy and the safety profile.

Dr Jeffery

* However, there was considerable debate at the beginning of the pandemic over how to manage relapsing MS patients on B-cell–targeting therapies. Stephanie, now that we know more about COVID-19, has your approach to relapsing MS treatment changed?

Stephanie

* My practice has indeed changed over time. Initially, I was hesitant to give someone KESIMPTA because the response to vaccination could be impaired when B cells are depleted.

* KESIMPTA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

You can see the Important Safety Information on KESIMPTA within this video and on the adjacent panel. The full Prescribing Information, including Medication Guide is also linked in the adjacent panel.

Stephanie

* Over time, we had emerging data on COVID-19 infection outcomes in patients taking KESIMPTA. As of [September 2021], 245 of the 1703 patients enrolled in the ALITHIOS open-label extension study who received KESIMPTA reported that they had contracted COVID-19.

* COVID-19 cases with severity, seriousness, outcomes, vaccination status, and breakthrough infections were all included in this analysis

* The open-label extension study is not blinded and not controlled so no statistical or clinical conclusion can be made.

* The majority of COVID-19 cases were mild or moderate in severity, while over 98% of patients who were treated with KESIMPTA and contracted COVID-19 either recovered, recovered with sequelae, or were recovering. And 2 patients had yet to recover.

* 2 cases had a fatal outcome. Both patients were unvaccinated and had underlying comorbidities of diabetes and hypertension, and one of the two patients was slightly overweight.

* 84% of patients who have been infected with COVID-19 while on KESIMPTA remained on KESIMPTA without drug interruption.

Stephanie

* Post-marketing data on COVID-19 outcomes are also available.

* As of [September 25, 2021], 90 patients reported confirmed COVID-19 infections, and 3 suspected cases of COVID-19 were reported to the Novartis safety database for patients with RMS taking KESIMPTA.

* Of the 90 confirmed cases, 10 were serious in nature, including 1 medically significant case and 9 hospitalizations. There were no fatalities or life-threatening COVID-19 cases reported.

Stephanie

* Fortunately, we now have better tools, such as vaccination, to reduce the risk of COVID-19 infection in the first place. Dr Jeffery, how do you advise patients considering COVID-19 vaccination before KESIMPTA initiation?

Dr Jeffery

* I have a discussion with all my patients before they start KESIMPTA about getting vaccinated to lower the risk of COVID-19 infection.

* According to the Prescribing Information, vaccination with non-live vaccines is recommended at least 2 weeks prior to initiation of KESIMPTA. For the COVID-19 mRNA vaccines, I recommend getting the second dose of vaccine at least 1 month but ideally 6 weeks before starting KESIMPTA. I understand there's a risk of relapse in the meantime. If there is a relapse, we will treat it accordingly.

Stephanie

* I had a patient in the military who was considering KESIMPTA as a first-line therapy after an RMS diagnosis and who had risk factors for progression. We were both concerned about an increased risk of COVID-19 infection while taking KESIMPTA and had to decide whether to start KESIMPTA right away due to her disease activity or complete her mRNA COVID-19 vaccinations before starting KESIMPTA.

* We knew that vaccinations decrease the risk of serious disease and that taking a B-cell–targeting therapy may decrease the antibody response to vaccination. She already took one vaccine dose, so we decided to finish her vaccination course before starting KESIMPTA to maximize her protection against COVID-19 infection. This is a recommendation we've carried forward to other patients considering KESIMPTA as well, to get vaccinated before starting.

In addition to vaccination, I also recommend that my patients take basic precautions such as wearing a mask, avoiding crowded places and other areas of high risk of spread, staying away from people that they know have COVID-19, and other basic health measures.

Dr Jeffery

* And for my patients already taking KESIMPTA, I tell them, according to the Prescribing Information, inactivated vaccines may be administered, as indicated, prior to recovery of B-cell depletion. In the pivotal trials, concomitant treatment with non-live vaccines was permitted.

However, my patients using KESIMPTA are understandably concerned about their immune system being suppressed, so I usually give a short immunology primer describing the role of B cells, antibodies, and T cells. I tell them that T cells are an important part of a response to viral infections, including COVID-19, and T cells remained largely unaffected in KESIMPTA patients.

Stephanie

* Those are all important things I cover with my patients.

In the pivotal trials, concomitant treatment with non-live vaccines was permitted, though KESIMPTA may interfere with the effectiveness of inactivated vaccines.

Stephanie

* A major concern is that targeting B cells may lead to a decrease in immunoglobulin levels, leading to an increased risk of infection.

* Dr Jeffery, how frequently do you monitor immunoglobulin levels in patients who are taking KESIMPTA?

Dr Jeffery

I make sure to check their immunoglobulin levels before and during therapy, every 3-6 months. If their levels are decreased and they're not having frequent infections, then I feel we don't need to do anything about it. If they start having frequent infections and their immunoglobulin levels drop, we reevaluate and consider intravenous immunoglobulins.

Stephanie

* That's about the same frequency we check our patients, as well. Occasionally, if I see a patient with low immunoglobulins, we typically try to repeat the tests a couple weeks later and observe if the immunoglobulins come back up. I let the patient know that there could be transient decreases in immunoglobulins.

However, I don't give KESIMPTA to patients if they're sick with an infection. I usually postpone the next KESIMPTA dose until they feel better and then start the medication back up again once the infection is cleared.

Dr Jeffery

* I just want to close by saying, in my clinical experience, KESIMPTA demonstrated powerful efficacy in terms of significantly reducing lesions, relapses, and disability progression compared to the oral therapy teriflunomide. The safety of KESIMPTA was similar to that of teriflunomide. If you see your patients achieve similar results to the clinical trials in your clinical experience, that influences your clinical decision-making.

Stephanie

* I agree. I just think the flexibility of KESIMPTA really helps with buy-in. As a result, my patients feel more independent when it comes to their health care.

Dr Jeffery

Thank you, Stephanie. This has been an informative discussion.

IMPORTANT SAFETY INFORMATION

Infections

* Delay KESIMPTA administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with KESIMPTA and after discontinuation, until B-cell repletion.

Injection-Related Reactions

* Management for injection-related reactions depends on the type and severity of the reaction.

Reduction in Immunoglobulins

* Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with KESIMPTA until B-cell repletion. Consider discontinuing KESIMPTA if a patient develops a serious opportunistic infection or recurrent infections if immunoglobulin levels indicate immune compromise.

Fetal Risk

May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for at least 6 months after the last dose.