What happens after fingolimod discontinuation? A multicentre real-life experience

Therapy Switches in Fingolimod-Treated Patients with Multiple Sclerosis: Long-Term Experience from the German MS Registry

“…A similar finding was recorded in a longitudinal study examining patients with relapsing MS treated with fingolimod: over a 36-month period, relapses were detected in 41.8% of the 1571 patients [ 44 ]. In a study on cessation of fingolimod treatment, 55.8% of the 230 MS patients included in the analysis reported insufficient efficacy of fingolimod as a reason for discontinuation [ 45 ]. In a cross-sectional study that examined the reasons for switching in 595 patients with RRMS taking mildly or moderately effective DMDs, the most common reason was failure of the current therapy (53.9%) [ 46 ].…”

“…In a U.S. study that assessed 535 patients on fingolimod for treatment switches, the proportion of such patients was 7.5% [ 48 ], similar to our study. In a sociodemographically and clinically comparable population of 230 Italian patients with RRMS, the proportion of patients without reinitiation of therapy after fingolimod discontinuation was higher at 12.6% [ 45 ]. In general, the proportion of patients without new therapy initiation is relatively low.…”

“…Moreover, the proportion of fingolimod patients is expected to decrease in the coming years due to the approval of the more selective binding S1PR modulators siponimod, ozanimod, and ponesimod. Our study is distinguished from previously published studies on therapy changes in fingolimod patients [ 45 , 49 ] by including > 2500 MS patients who were studied for sociodemographic and clinical changes over the largest and most recent observation period, identifying both prior and subsequent fingolimod therapies in a representative cohort of MS patients, breaking down the reasons for switching, and additionally identifying patient characteristics associated with switches and relapses.…”

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

“…Among first-line pharmacotherapies in MS is glatiramer acetate; however, the response rate is not greater than 55% due to variability in genetic polymorphisms [72]. Recent studies have demonstrated that long-term disability outcomes tend to be better in MS patients who are treated early with "high-efficacy" medicines including the anti-CD20 monoclonal antibodies rituximab (Rituxan) and ocrelizumab (Ocrevus) targeting B cells, the anti-α4β1 integrin monoclonal natalizumab (Tysabri), the type II topoisomerase inhibitor mitoxantrone (Novantrone), the sphingosine-1-phosphate receptor modulator fingolimod (Gilenya) [73], the monoclonal anti-CD52 alemtuzumab (Campath, Lemtrada) targeting mature lymphocytes, and the purine analogue cladribine (Mavenclad) that delivers "intensive" immune intervention, as compared to patients who are treated with "moderate-efficacy" medications for one or more years prior to "escalation" to the high-potency agents [74,75]. Adverse effects are more complex for the "high-efficacy" treatment strategies and include increased risks of serious infections and cancers associated with immunosuppression, autoimmune diseases associated with immunomodulation, cardiotoxicity, hepatotoxicity, and gastrointestinal and neuropsychiatric disorders [76,77].…”

Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis

“…In recent years, an increasing number of case reports 1 – 7 as well as retrospective cohort studies reported the occurrence of recurring disease activity (RDA) after FGL discontinuation. 8 – 15 On the contrary, a post hoc analysis of pooled data from FGL phase III studies did not find an increased individual risk of unexpectedly high clinical or radiological RDA after FGL discontinuation compared with placebo. 16 A recently published ‘FDA drug safety communication’, however, informed about the potential risk of severe worsening after stopping FGL.…”