Therapeutic inertia in relapsing-remitting multiple sclerosis.

Background: Therapeutic inertia (TI) is defined as a failure to initiate or intensify treatments despite evidence of disease activity. Its prevalence and determining factors in Relapsing-Remitting Multiple Sclerosis (RRMS) patients in Portugal are not known. The main objective of this work was to ascertain the prevalence of TI in RRMS and its determining factors.

Methods: We conducted a multicentre retrospective observational study of RRMS patients followed in MS Clinics of six Portuguese hospitals with at least one medical appointment in 2018. TI was defined as the absence of treatment initiation or intensification when therapeutic goals were unmet, that is when there was evidence of disease activity based on the definition of "no evidence of disease activity" (NEDA) which refers to absence of clinical relapses, absence of disease progression measured by expanded disability status scale (EDSS) and absence of new disease activity (new T2 lesions/enhancing lesion) on magnetic resonance imaging (MRI) over the period of observation.

Results: We included 427 patients with RRMS meeting inclusion criteria, 69.6% females, with a mean age of 41.66 years old. The mean age at diagnosis was 33.17 years old and the average number of years since diagnosis was 8.72. MS relapses were reported on 54 patients. Moderate to severe relapses were reported in 59.3%. Median EDSS score was 1.5. Intention to get pregnant was explicit in 39 patients, representing 18.8% of the women at childbearing age. Among the 365 patients who had an MRI, 23.8% had new T2 lesions and 7.4% had enhancing lesions. Regarding DMT, 72.8% were treated with interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate, 20.6% were under fingolimod, natalizumab, rituximab, and cladribine, and the remaining 6.6% were without treatment. Adverse events were reported in 12.9% of patients, and 10.1% mentioned preferences regarding the treatment. TI was present in 80 (18.7%) patients, representing 54.8% of those with potential to inertia. Patients with a radiologically less active disease, who were already on a DMT and who had no adverse events from their current treatment were more likely to have TI (p<0,05). Also, patients followed in centers classified as higher level of care (level 1) had more TI compared with patients followed in centers of levels 2 and 3.

Conclusion: TI was present in 1 in 5 patients, exceeding half of the sample with the potential to inertia, corroborating the high prevalence of TI in other studies. The determining factors of TI were the absence of relapses or the occurrence of mild relapses, being already on DMT, absence of adverse events, and follow-up in higher care level centers. TI is a topic rarely addressed in MS and this work highlights the importance of therapeutic optimization in these patients. Further studies should be held to explore the factors that influence TI once they have a great impact on therapeutic decisions.