Frequent treatment switching linked to worse outcomes in study

Findings highlight 'importance of timely and equitable access' to next DMT

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with neuromyelitis optica spectrum disorder (NMOSD) who switch between treatments more than once because of side effects or non-medical reasons have an increased risk of disease activity, a study shows.

While each additional switch for either reason increased the risk of NMOSD activity, no such association was seen when switching because of medical reasons. Switches associated with side effects or non-medical causes also took markedly longer than those for medical reasons.

These findings “highlight additional factors that may be equatable to the efficacy of prescribed treatments in the prevention of acute neurological events,” and “may assist in transforming the way healthcare providers bridge the gap between therapies and the approach to the timing of a switch,” researchers wrote.

The study, “Treatment transitions in neuromyelitis optica spectrum disorder increase risk for disease advancement,” was published in Multiple Sclerosis and Related Disorders.

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Experts publish recommendations for modern NMOSD treatment

3 disease-modifying therapies approved in US for NMOSD patients

Three disease-modifying therapies are approved in the U.S. for NMOSD patients who are positive for antibodies against AQP4, which is the most common target protein of the self-reactive antibodies driving the rare autoimmune disease.

However, many patients are still taking immunosuppressants, such as mycophenolate mofetil, azathioprine, rituximab, and methotrexate, that were used prior to DMTs being available.

While people diagnosed with NMOSD may switch treatment over the course of their disease, the impact of these switches on clinical outcomes hasn’t been thoroughly investigated.

“The impact of treatment transitions whether due to lack of effective disease control, adverse reactions, insufficient medical coverage, or tolerability related issues, in the context of disease evolution is not well understood,” the researchers wrote.

To gain more insight, researchers at the University of Texas Southwestern Medical Center reviewed data from 164 AQP4-related NMOSD patients treated at their center from 2008 to 2022.

A total of 89 patients (54.3%) had switched between treatments at least once over a median disease duration of 10.1 years, and most of them were women (88%). More than half of these patients (52.8%) had switched between treatments at least twice.

The researchers divided each documented change in treatment into three categories, based on the reason for the switch: medical reasons (such as NMOSD clinical relapse, MRI activity, or abnormal lab test results), tolerability or side effects, and non-medical reasons (including cost of treatment, wanting a newer therapy or a different route of administration, and pregnancy).

The team created statistical models to investigate whether and how each of these types of switches significantly affected clinical outcomes.

Results showed patients who switched from a first to a second treatment due to non-medical reasons or tolerability issues were 40.3% less likely to be hospitalized, 53.1% less likely to have a NMOSD relapse, and 65.9% less likely to have new or enlarging lesions on MRI scans.

The picture changed, however, for patients who switched after their second therapy due to non-medical or tolerability reasons. In these cases, each additional switch was significantly associated with a 25.2% increased risk of hospitalization, 24.4% higher risk of relapse, and 41.9% higher risk of MRI activity.

Among patients who switched treatments due to medical reasons, the risk of relapse decreased by 20.9% and the risk of MRI activity increased by 32.2% upon the first treatment switch, but subsequent transitions were not significantly linked to altered clinical risk.

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Treatment Changes More Common in NMOSD Patients with Relapses

Switching treatments for non-medical reasons raises risk after 2nd therapy

“For treatment transitions resulting from non-medical/tolerability related reasons, the risk of acute relapse, MRI worsening, and hospital admission was higher when switching from the second to the third disease modifying therapy and with each subsequent treatment transition,” the researchers wrote. “The same pattern of risk was not observed when treatment transitions were the result of medical-related reasons.”

When switches occurred due to tolerability or non-medical reasons, there was usually a longer gap before starting the next treatment compared with switches due to medical reasons. In addition, patients who’d previously switched due to medical reasons tended to have faster future switches even if they were for other reasons.

“We identified that treatment history was relevant as individuals who had switched due to a medical reason in the past were more urgent about transitioning to the next treatment, even if the most recent discontinuation was due to a non-medical/tolerability reason,” the scientists wrote.

Given that repeated non-medical and tolerability switches were associated with worse clinical outcomes, these data “highlight the importance of timely and equitable access to a next disease-modifying therapy, even in the absence of acute disease activity,” the researchers wrote.

Among the study’s limitations, the researchers noted the lack of access to insurance coverage, which plays a major role in influencing treatment decisions, and the fact that the period studied was mostly before availability of NMOSD DMTs. Therefore, it’s unclear how well these findings translate for patients on more recent medications.