Antibody Levels, Age Linked to Infection Risk in Ocrevus-treated MS

Lower antibody levels in the bloodstream and younger age are associated with a greater likelihood of infection in people with multiple sclerosis (MS) receiving Ocrevus (ocrelizumab) therapy, a study has found.

“Our work adds to the body of literature detailing real-world outcomes in MS patients treated with [Ocrevus] and safety outcomes,” the study’s researchers wrote. “Our results highlight the need to monitor patients’ immunoglobulin profiles prior to commencing [treatment] and during the maintenance course.”

The study, “Predicting Infection Risk in Multiple Sclerosis Patients Treated with Ocrelizumab: A Retrospective Cohort Study,” was published in the journal CNS Drugs.

In MS, immune cells known as B-cells produce antibodies that mistakenly attack myelin, the fatty molecule surrounding nerve fibers that is key for proper nerve cell communication. Without myelin, nerve impulses are interrupted or poorly transmitted, leading to MS symptoms.

Ocrevus is a disease-modifying therapy (DMT) that binds to the CD20 protein on the surface of mature B-cells, decreasing their numbers and leading to the suppression of the immune attack on myelin. As it suppresses the immune system, people taking this medication are at a higher risk of infection.

While safety outcomes have been evaluated in clinical trials and open-label extension studies, risk factors for infection in people with MS receiving Ocrevus have not been thoroughly examined in a real-world setting.

“Identifying patients who may be at higher risk of infection when treated with [Ocrevus] and other B-cell depleting DMTs is, therefore, an important consideration,” the investigators wrote.

To this end, researchers based at the Royal Melbourne Hospital in Australia analyzed the medical records of 185 MS patients who received Ocrevus from April to October 2020 in a local tertiary health center.

While in hospital for Ocrevus treatment or via a phone survey, participants completed surveys reporting the number of infections since their last infusion. They were asked if their infection rates had remained stable, increased, or decreased since starting Ocrevus, and if antimicrobial therapy was prescribed for a given infection.

The mean age of surveyed participants was 43.4 years, with a mean disease duration of 10.7 years. A majority (72.4%) were female, and the mean number of Ocrevus doses was 4.6. Among the 135 patients who had received treatment before Ocrevus, Tysabri (natalizumab) was the most commonly prescribed DMT.

Nearly all had relapsing-remitting MS (90.3%), followed by secondary progressive MS (3.8%), primary progressive MS (3.8%), and MS overlapped with myelin oligodendrocyte glycoprotein antibody disorder, a similar condition with inflammation mainly in the optic nerve (2.2%).

The team measured the blood levels of antibodies immunoglobin A (IgA), IgM, and IgG as they are produced by B-cells and affected by B-cell depleting therapies such as Ocrevus.

A total of 176 infections were reported in 89 (48.1%) participants, of which 78 (27.6%) were upper respiratory tract infections (nose and throat), followed by 33 (11.9%) urinary tract infections. No patients reported a SARS-CoV-2 infection.

The incidence rate of infections was 169.4 per 100 patients-years (about 1.7 per year per patient). Of those reporting infection, 47 were prescribed antimicrobial medication, and 27 had confirmed infection-related healthcare visits. Five (2.7%) patients were hospitalized, with viral infections concomitant with bacterial infections of the bone, urinary tract, and bladder.

Most (72%) reported no change in infection frequency since first starting Ocrevus, with an increase reported in 16% of participants and a decrease in 12%.

A simple statistical model — which compared the likelihood of infections to single factors including age, gender, disease duration, Ocrevus doses, disability status (measured with the Expanded Disability Status Scale), and antibody levels — found that only lower IgA showed a statistically significant association with increased odds of infection.

A complex statistical model was then calculated, in which all factors were included, in addition to IgG, IgM, or IgA levels separately. In the IgA model, lower IgA levels were associated with higher odds of infection. Adding IgG levels to the calculation found that those who were younger and had lower IgG levels were more likely to have an infection. In the IgM model, only younger age was associated with higher risk.

The analysis also found that younger age was the only factor significantly associated with more antimicrobial use. When assessing IgG, IgM, and IgA levels separately, in all cases, younger age and longer disease duration were associated with an increased use of antimicrobial therapy. Additionally, in the IgA model, more disability and lower IgA levels led to more antimicrobial use. No associations between IgG or IgM levels and antimicrobial medication use were found.

“The association of younger age with risk of infection and antimicrobial use was an unexpected finding,” the team wrote. “The association of antimicrobial use with increasing disease duration seen in our study represents a novel finding. Greater cumulative exposure to DMTs with longer disease duration, and greater likelihood of having medical comorbidities [co-existing conditions] may underpin this relationship.”

“Further studies are required to delineate the relationship of immunoglobulin levels and infection risk, and more broadly, assess long-term risks factors for infection in patients receiving [Ocrevus],” the researchers added.