Patients with relapsing forms of multiple sclerosis (MS) who are older than age 45 have less radiologic disease compared with younger patients after first-line disease-modifying therapy (DMT) discontinuation. These are the findings of a study published in the journal Multiple Sclerosis and Related Disorders.
Patients increasingly receive DMT for relapsing-remitting multiple sclerosis (RRMS) relatively early after diagnosis. Therefore, it is important to understand the consequences of first-line DMT discontinuation. Previous studies have indicated a lower risk for clinical relapse in older patients, those with longer history of stable disease, and those with less radiologically evident disease. However, such research has focused largely on clinical relapse outcomes; by contrast, the relative importance of radiographic disease evidence after DMT discontinuation, and its strength of association with clinical relapse, are uncertain.
For the study, researchers from the Netherlands recruited 130 patients (age >18 years) at MS Center Amsterdam and at Rijnstate Hospital Arnhem who had received first-line DMT (including any interferon medication, glatiramer acetate, teriflunomide, and dimethyl fumarate) for at least 6 months, had discontinued that medication without a plan to resume it or switch medications, and had follow-up magnetic resonance imaging (MRI) data for at least 3 months after DMT discontinuation. Approximately 88% of these participants had RRMS; the remainder had secondary progressive MS.
In addition to patient baseline and follow-up clinical data, and reason for DMT discontinuation, the researchers examined MRI studies for T2- and contrast-enhancing lesions.
The researchers found that 43 patients most frequently discontinued DMT because of side effects.
A total of 78 patients had disease activity after DMT discontinuation. Of these patients, 63 had radiological evidence of T2- or contrast-enhancing lesions, in a median time of 24 months post discontinuation. However, 38 of these patients with MRI-evident disease had not had a clinical relapse.
Conversely, after a median 30.5 months, 40 patients had clinical relapses; 25 of these patients had radiologic activity in a follow-up MRI.
The researchers noted that patient age at DMT discontinuation had the strongest association with renewed disease activity. In patients younger than age 45, MRI demonstrated disease activity in 68.6%, and 45.1% had a clinical relapse. However, in those age 45 and older, lesions on MRI were present in 35.3%, and 5.9% relapsed clinically.
Logistic regression analysis confirmed the protective effect of age in patients between ages 45 and 55 compared with those younger than age 45 (OR, .301; P =.007) and in patients older than age 55 compared with those younger than age 45 (OR, .296; P =.044). Following DMT discontinuation, a lower risk for relapse(s) was seen in patients between ages 45 and 55 compared with those younger than age 45 (OR, 0.495, P =.106) and in patients older than age 55 compared with those younger than age 45 (OR, 0.081; P =.020).
A total of 29 patients (approximately 22% of the cohort) resumed DMT after a median 17 months. Only 11 patients restarted with the DMT they had discontinued previously.
Older patients were not significantly more likely to resume DMT, have clinically stable disease prior to discontinuation, or have prior abolition of radiographic disease.
The researchers suggested that, given the clear protective effect of age, remaining on DMT might offer lower benefit relative to cost for older patients.
Study limitations included potential selection bias, as the study participants had all self-discontinued DMT; differing follow-up frequencies among patients; and inclusion only of patients discontinuing first-line drugs.
“[T]he occurrence of inflammatory disease activity is relatively infrequent in patients aged >55 years that discontinued DMT, and, when present, mostly radiological with a low number of T2-lesion,” the researchers concluded.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Coerver EME, Bourass A, Wessels MHJ, et al. Discontinuation of first-line disease-modifying therapy in relapse onset multiple sclerosis. Mult Scler Relat Disord. Published online April 3, 2023. doi:10.1016/j.msard.2023.104706