DALLAS—Long-term data demonstrating the success of interferon titration suggests that a similar strategy could be effective for a select group of patients who struggle tolerating the initial recommended 0.5 mg daily fingolimod dose. Data presented at the 2014 Cooperative Meeting of CMSC and ACTRIMS suggest that there may be a role for fingolimod 0.25 mg/day, however the optimal recommended therapeutic dose of 0.5 mg/day is achievable for many patients if side effects and titration is efficiently and effectively managed.
A major Australian tertiary teaching hospital with a large multiple sclerosis (MS) clinic anticipated that patients starting on fingolimod and experiencing poor drug tolerability would request, or simply decide on their own, to cease their medication. Historical experience with inferferon prompted discussions with the neurologist and MS nursing staff. Through consultation in relation to dosing alternatives, it was identified that there was an opportunity to explore individualized oral drug titration. Select patients whose quality of life was being disrupted by unwanted side effects were offered a titration and monitoring opportunity. The goal of the “go slow” approach was to achieve the full recommended daily dose regime and establish confidence with a nonexistent or minimal acceptable side effect profile.
Susanne Baker and Meena Sharma from the MS Clinic at Liverpool Hospital in Sydney, Australia, in collaboration with neurologists, endeavored to manage side effects and titrate the fingolimod dose according to side effects experienced. Patient who chose to withdraw from fingolimod treatment were given the option of a personalized management plan. No clinical assessment tool was used to grade the severity of the adverse events and all supportive care was given based on the patients’ self-report of discomfort. The program offered regular monitoring and side effect management for lymphopenia, gastrointestinal disturbance, headache, and a feeling of being generally unwell. Ongoing consultation with the neurologist by the MS nursing staff was maintained along with fingolimod dose adjustments. Supportive medication included, but was not limited to, paracetamol, ibuprofen, ranitidine, metoclopramide, and loperamide.
In total, 209 patients were treated with fingolimod at the MS clinic at Liverpool Hospital and 51 (24.4%) significant adverse events (eg, lymphopenia, herpes zoster, malignancy, headache, ophthalmologic symptoms, gastrointestinal disturbance, and a feeling of being generally unwell) were reported. From this patient group, 24 (47%) were offered a side effect management and drug titration plan. Sixteen patients (66.7%) chose to participate in the proposed plan. Of these, 10 were able to achieve the full dose and remain on treatment, two (12.5%) discontinued treatment due to poor tolerance, and four (25%) continued to remain on drug titration. No relapses were observed or reported during the titration period.
—Glenn S. Williams