Infections Nearly 4 Times as Likely for Patients With Progressive MS

Large study finds greater risk with progressive forms than RRMS

Patricia Valerio, PhD avatar

by Patricia Valerio, PhD |

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People with progressive forms of multiple sclerosis (MS) are nearly four times more likely to have serious infections — those leading to hospitalization — than those with relapsing-remitting MS (RRMS), according to a large study in Germany.

This higher infection risk was found despite the fact that, during the study period, most RRMS patients — but less than one-third of those with progressive MS forms — received disease-modifying therapies (DMTs), which typically suppress the immune system.

Older age and male sex also were associated with a significantly higher rate of infection-related hospitalizations among MS patients, the study found. Respiratory infections and those of the urinary tract and reproductive organs were most commonly reported serious infections.

The study, “Serious infections in patients with relapsing and progressive forms of multiple sclerosis: a German claims data study,” was published in Multiple Sclerosis and Related Disorders. The work was supported by Roche.

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In people with MS, infections are a common cause of comorbidity, or the presence of more than one disease or condition at the same time. Having co-existing diseases can negatively impact health outcomes.

Real-world studies have shown that MS patients are at a higher risk of developing serious infections, or those leading to hospitalization, than those without the autoimmune disease.

Disease type and infection risk

“The risk of intensive care unit admission is also higher in PwMS [people with MS] in association with infections,” the researchers wrote, adding that “infections, in particular those of respiratory and urinary origin, are a common cause of mortality in MS.”

The use of disease-modifying therapies or DMTs — the majority of which work by suppressing the immune system — is common in MS and has been linked to an increased risk of serious infections. Researchers have suggested, however, that other factors, such as age, sex, and MS type, also might contribute to a higher susceptibility to infections.

But “few real-world studies have explored the risk of serious infections (SIs) associated with these factors,” the researchers wrote.

Now, a team of researchers in Germany and Switzerland compared the occurrence of these infections among people with RRMS, primary progressive MS (PPMS), and secondary progressive MS (SPMS).

The researchers retrospectively analyzed administrative claims data from 4,250 adults diagnosed with MS in Germany from 2016 to 2018. All patients had available data one year before and after their diagnosis.

More than half of patients — 2,307 or 54.3% — had RRMS, while 282 (6.6%) were diagnosed with PPMS, and 558 (13.1%) had SPMS. The MS type was unspecified for 1,135 patients (26.7%).

All groups were composed mainly of women, with the percentages higher than 62% for each MS type. RRMS patients were generally younger than those with progressive forms of the disease, with a median age of 47 versus 63.

At the study’s start, PPMS and SPMS patients were more likely to have at least one comorbidity as compared with those in the RRMS group (87.23–87.46% vs. 61.86%). Urinary tract disorders were the most common co-existing condition, affecting 34.64%.

Patients were followed for a median of 3.87 years (range, about four days to four years), with no differences observed across groups.

DMTs were used by 82.1% of people with RRMS, 31.36% of SPMS patients, and 23.76% of PPMS patients during follow-up, reflecting a more common use in the RRMS group.

A total of 294 patients (6.92%) died, with a higher rate of deaths occurring in those with progressive MS (14.52–16.67% vs. 2.77% for RRMS).

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The team measured the incidence rate of serious infections, which corresponded to the number of new cases of serious infections per 100 patient-years.

Patient-years, or PY, is a measure of the number of people participating in the study and the amount of time they were followed. For example, 100 PY refers to data gathered from 100 patients who were followed for one year.

More infections for progressive MS patients

Results showed that a greater proportion of people with PPMS (14.54%) and SPMS (10.39%) experienced serious infections compared with RRMS patients (2.82%).

Similar results were obtained when looking at the incidence rate, which was nearly four times higher among PPMS and SPMS patients than in the RRMS group (13.52–13.58 vs. 3.36 serious infections per 100 PY).

Also, men showed a nearly twice as high rate of serious infections relative to women (10.4 vs. 5.69 infections per 100 PY).

When dividing patients into three age groups — 18–50 years, 51–65 years, and more than 65 years — the team found that serious infections were most common in the oldest group (16.47 per 100 PY) and less common in the youngest group (2.74 per 100 per PY).

Rates of serious infections generally remained stable over time and most infections were caused by bacteria.

The most commonly reported serious infections were of the respiratory (1.99 per 100 PY) and genitourinary (1.90 per 100 PY) tracts. These infections also were significantly more common among PPMS and SPMS patients, who showed at least a 70% higher incidence rate of each type of infection compared with the RRMS group.

In addition, while the team did not find differences in the incidence rate of respiratory infections between the progressive MS groups, SPMS patients were at a significantly higher risk  — by about 50% — of developing genitourinary tract infections than PPMS patients.

These findings highlight that MS patients with progressive forms of the disease, older age, and male sex have “an increased risk of infection-related hospitalizations,” the researchers wrote.

This study is the first “to examine the [incidence rate] of SIs across different MS [types] stratified by age and sex within a recent time window (2015-2019),” they added.

However, it was “geographically restricted to two administrative regions in Germany,” the team wrote. Thus, the findings may not be generalized to other parts of the country and other countries altogether.

Future studies are needed to “explore infection rates by disability status, comorbidity burden, DMT exposure, and other modulating factors, which may influence the risk of SIs,” the researchers concluded.

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