Progressive MS, Degree of Disability Increase Infection Risk

People with progressive forms of multiple sclerosis (MS) and those with greater MS-related disability have a significantly greater risk of serious infections relative to people without the disease, according to a population-based study in Sweden.

Notably, these associations were observed regardless of the use of disease-modifying therapies, many of which work by suppressing the immune system and thereby increase the risk of infections.

The findings suggest that these disease-specific markers, particularly disability —readily assessed with the Expanded Disability Status Scale (EDSS) — may be used to identify at-risk patients who might benefit from mitigation strategies to prevent serious infections, the researchers noted.

The study, “Risk of serious infections in multiple sclerosis patients by disease course and disability status: Results from a Swedish register-based study,” was published in the journal Brain, Behavior, and Immunity – Health.

Increasing evidence shows that people with MS are “at increased risk of serious infections, reflected by infection-related hospital admissions and cause-specific mortality,” the researchers wrote.

While the use of some DMTs known to suppress the immune system are considered a potential risk factor of serious infections in this patient population, “the extent to which MS disease features influence infectious susceptibility is poorly characterized,” the researchers wrote.

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With this in mind, a team of researchers in Sweden evaluated whether MS disease course and disability status influenced the risk of serious infections in a well-characterized group of MS patients and matched individuals from the general population.

A total of 8,660 people diagnosed with MS from 1996 to 2012 were individually matched on age, sex, and region of residence with 86,600 people without MS from the general population (10 for each patient) using national registers in Sweden. Follow-up data were analyzed until Dec. 31, 2014.

The researchers analyzed the rates of serious infections, including those associated with hospital admission and those causing death. Patients were divided based on disease course — relapsing-remitting MS (RRMS) or progressive MS — and on EDSS score: below six, indicating mild-to-moderate disability, and six and higher indicating severe disability.

Potentially influencing factors, such as demographic information for all participants and DMT use for MS patients, also were collected and analyzed.

Only DMTs known to have a general impact on the immune system were collected and categorized as ever or never used. These included rituximab (sold as Rituxan, among others), Tysabri (natalizumab), Lemtrada (alemtuzumab), dimethyl fumarate (sold as Tecfidera and others), and Gilenya (fingolimod).

The median age at MS diagnosis was 39 years, and 70.6% of patients were female. Nearly two-thirds of patients (65.4%) had RRMS and did not develop progressive disease during follow-up. EDSS scores were recorded for 87.6% of patients, with 25.2% of them showing severe disability. Information on DMT use was available for 85.2% of patients.

Results showed that during a median follow-up of 9.6 years, 1,337 MS patients experienced a serious infection, including 1,331 infection-related hospital admissions and 93 infection-related deaths.

Compared with individually matched people without MS, patients with progressive MS had a nearly fourfold higher risk of serious infections, while the risk of those with RRMS was increased by nearly two times.

Severe disability also was associated with a higher risk of serious infections, as patients with an EDSS score of six or above had a 4.3 times higher risk relative to matched non-affected people, and those with milder disability showed a 1.3 times greater risk.

These significant associations between progressive MS/severe disability and increased risk of serious infections were observed regardless of whether patients were treated with immunosuppressive DMTs, emphasizing the independent impact of these disease-specific features in this risk.

Interestingly, among RRMS patients, use of these DMTs was associated with a higher risk of serious infections than no use (2.2 vs. 1.5 increased risk).

Further analyses showed that this pattern of increased infection susceptibility with disease severity was more pronounced for urinary tract infections and more among male than female patients.

Also, the relative risk of serious infection linked to progressive disease and greater disability was reduced with increasing age, which may be due to the naturally increasing frequency of infections with advancing age, “especially when age-related consequences occur more frequently among the general population,” the researchers wrote.

These findings highlight that “susceptibility to serious infections is determined by disease-specific markers that are readily available in clinical practice,” the team wrote.

The data support the use of disease course or EDSS score — which may be more readily available than MS course — “as disease specific predictors to identify at-risk patients who could potentially benefit from mitigation strategies to prevent serious infections,” they added.

“Proposed mitigation strategies range from DMT targeted strategies focusing on dose/frequency adjustment … to more general preventive measures including vaccination and behavioural modification strategies,” such as simple hygiene measures, the researchers wrote.

This study also adds to previous findings showing that higher EDSS scores are an independent risk factor for COVID-19 complications, extending this link to serious infections in general. This highlights “the importance of strengthening precautionary measures among patients with greater disability to limit the risk of infections,” the team wrote.