Dr Wallace Brownlee discusses reasons of and clinical impact of treatment discontinuation in multiple sclerosis.
Wallace Brownlee, MBChB, PhD, FRACP: As neurologists treating people with multiple sclerosis [MS], we spend most of our time discussing starting disease-modifying therapies and much less focus on stopping treatment. Observational studies—for example, the multicenter MS-based registry—have found that even among patients with stable MS, there are no relapses or changes in their MRI in recent years. People who opt to discontinue DMT [disease-modifying therapy] are at a higher risk of disability progression in the future, compared with people who remain on treatment. Younger patients and those with a lower level of disability as measured by EDSS [Expanded Disability Status Scale] scores are at the highest risk of experiencing a relapse. Older patients are at a higher risk of MS worsening in terms of disability progression.
Importantly, over follow-up periods of 5 years or so in patients who discontinue treatment, about half go on to restart their disease-modifying therapy. Accordingly, the American Academy of Neurology guidelines on the use of disease-modifying therapies in adults with MS, recommends that people who stopped their treatment should be counseled on the need for ongoing follow-up and periodic reevaluation regarding their decision to remain off treatment. We need to keep monitoring our patients for signs of a relapse, a change on their MRI, or disability worsening if treatment has stopped.
People discontinue treatment for a number of reasons, including a lack of efficacy, disease progression, adverse effects from the treatment, problems with tolerability, changes to insurance coverage, drug availability, and sometimes just because of a desire to discontinue treatment after a period of clinical stability. A particularly important reason to discontinue treatment is family planning, particularly for multiple sclerosis, a disease mainly affecting young women. The safety of many of the approved MS therapies during conception, pregnancy, and breastfeeding are unknown. Some therapies—for example, fingolimod, sphingosine-1-phosphate or S1P modulator—are known to be teratogenic in animal models and human studies and have been found to increase the risk of major congenital malformations. For that reason, women taking S1P modulators are recommended to stop treatment prior to conception.
Another DMT that’s frequently discontinued in different circumstances is natalizumab, an integrin inhibitor associated with an increased risk of progressive multifocal leukodystrophy, or PML. Patients may choose to discontinue that treatment because they become JCV [John Cunningham virus] positive, or if their risk of PML is increasing over time as a function of the duration of treatment. One of our big concerns when discontinuing patients on disease-modifying therapy, particularly fingolimod and natalizumab, is the risk of developing a relapse or new lesions on an MRI and more so a risk of the so-called rebound phenomenon. This is where patients can occasionally develop severe relapses or a marked increase in MRI activity, exceeding baseline levels prior to starting that therapy.
Transcript edited for clarity