Rituximab Linked to Greater Risk of Infections in MS Patients in Real-world Swedish Study

Rituximab Linked to Greater Risk of Infections in MS Patients in Real-world Swedish Study

Newer disease-modifying treatments for multiple sclerosis (MS) are effective but also known to carry a greater risk of infections in a patient group already more likely to be troubled by infections — and this higher risk is particularly evident in treatment with rituximab, a DMT often used off-label in Sweden, a nationwide study into its use reports.

The study “Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies” was published in the journal Jama Neurology.

Compared to the public at large, MS patients are thought to be at an increased risk of infections, because disease-modifying therapies used to lower relapse rates act by dampening the immune system. Although helpful, such therapies can raise a risk of subsequent infections.

Evidence suggests that treatment with first-generation DMTs, such as beta-interferon (sold as Avonex and Rebif, among others) or glatiramer acetate (Copaxone and its generic, Glatopa), do not raise this infection risk further. In contrast, newer, second-generation DMTs are linked to a greater infection risk. These DMTs include Tysabri (natalizumab) and Gilenya (fingolimod).

However, “the magnitude of potential risk increase is not well established in real-world populations,” the researchers wrote, as this evidence has largely been gathered in clinical trials.

Moreover, few data are available regarding the risk of infection with rituximab, an engineered antibody developed by Roche to specifically target the cell surface protein CD20 often found in immune B-cells. Rituximab is sold under the brand name Rituxan in the U.S. and MabThera in Europe, among others, approved largely to treat certain blood cancers. It is used off-label in MS, meaning it is not approved specifically for this disease.

Researchers in Sweden performed a nationwide observational study to better determine actual infection rates among Swedish MS patients being treated with rituximab, Tysabri, Gilenya, Copaxone, and interferon beta.

They analyzed data from relapsing-remitting MS (RRMS) patients registered in the Swedish MS register (SMSreg), treated between 2011 and 2017.  SMSreg covers approximately 80% of all MS patients in Sweden. As controls, researchers evaluated five people without MS for each patient they studied, all matched for age, sex, and region.

In total, data from 6,421 RRMS patients (mean age of 39 at treatment start) were analyzed. During the period, they registered a total of 8,600 treatments — 2,217 initiations of interferon beta and Copaxone, 1,535 starts with Gilenya, 1,588 initiations of Tysabri, and 3,260 of rituximab. The control group consisted of 42 ,645 individuals.

Results showed that, compared to controls, RRMS patients were more often to require a sick leave (28.1% vs 11.0%), use antidepressants (26.8% vs 15.7%), and have more infections (4.1% vs 2.3%) in the five years before treatment start.

Researchers then assessed the impact of each DMT on the risk of serious infections, defined as those requiring hospitalization. They also looked at outpatient treatment with antibiotics or herpes antiviral medications.

The infection incident rate was found to be 5.2 per 1000 person-years (the sum of follow-up years of all included patients in a specific study) in the general population, with RRMS patients in general showing a higher risk of infection in all treatments analyzed. That is, an incidence rate of 8.9 in patients treated with interferon beta and Copaxone, 11.4 in those taking Tysabri, and an incidence rate of 14.3 with Gilenya that rose to 19.7 with use of rituximab.

After adjusting for patients characteristics, like age and disability level, the rate of infections remained significantly higher for rituximab (hazard ratio of 1.70, meaning a 1.7 times higher risk of infection), and higher — but not significantly so — for Gilenya (hazard ratio of 1.30) and Tysabri (hazard ratio 1.12) when compared to use of interferon beta and Copaxone (first-generation DMTs).

Antibiotic use was also found to be greater among patients treated with rituximab and Tysabri. In contrast, use of herpes antivirals was similar among patients given rituximab, interferon beta and Copaxone, but in general their use was lower than that seen with Tysabri (a hazard ratio 1.61) and Gilenya (a hazard ratio 1.70), again after adjusting for characteristics.

“This nationwide cohort study found that patients with multiple sclerosis are at a generally increased risk of infections, and this risk is partly dependent on the choice of treatment,” the researchers wrote. “Among newer treatments, off-label use of rituximab was associated with the highest rate of serious infections.”

These findings call attention to the need for physicians and patients to be “aware of infection risks associated with newer multiple sclerosis treatments, and perhaps particularly anti-CD20 therapies” like rituximab, the team suggested.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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3 comments

  1. anon says:

    Pointing out the obvious, but safer, more tolerable medications are needed across the board. Patients should be not be using horrid injectables for life only because other treatments are even more risky. MS research does seem stalled out (and unreliable).

  2. tricia says:

    I am newly diagnosed with MS and I’m having a hard time choosing a treatment that’s right for me. Its terrifying to be diagnosed and even more scary to take medications that may be even worse for me.I am tired of hearing the risk is worth the reward. Is it? really? I have never been the type of patient that just takes a pill because my doctor tells me too, I always do my research first.For many years I worked in the medical field and i know first hand that SOME(not all)doctors don’t do any research on what they are prescribing, a pharmaceutical rep for the drug shows up with lunch or lattes for the whole office and they go over the information for approx 10-25 min or less time if the doctor is really busy and that’s it! I think having been on the other side of the spectrum makes me even more careful and most definitely not the ideal patient for a doctor who just wants me to fall in line and trust that they have all the answers. I try to choose doctors that are okay with me being involved with MY
    medical care. Believe me some have not been very enthusiastic about it. But..It is my body, and I will always trust my own instincts over anyone elses.

    I am hoping there will be more approved treatments with less side effects in the future.

  3. Marissa H says:

    I’ve done injections which were horrible and Rituxan chemotherapy. I have RRMS and to say the least, they both have seemed to cause me more harm than help. Granted who knows if I wouldn’t be worse off without them, but the way they have made me feel, the side effects I have dealt with, and the amount of time I’ve had to take off work alone, makes me not even want to take medicine and just leave it in God’s hands. What makes it worse is my Neurologist doesn’t hear me when I talk and none of my Dr.’s seem to acknowledge that these issues can be from the medicine I have taken/ exasperating my MS and try to blame it on saying I have a possible severe anxiety disorder. I’ve already had an assessment with a therapist who doesn’t agree with my neurologist’s anxiety diagnosis either, so it’s like who do I go to for help? I’m so frustrated and confused by this. It’s like they don’t hear that the things I have issues with are things a lot of MS patients deal with, especially who had these treatments.

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