medwireNews: A prematurely halted trial provides support for a relatively short washout period when transitioning patients with relapsing–remitting multiple sclerosis (MS) from natalizumab to fingolimod.
The randomised trial, assessing washout periods of 8, 12 and 16 weeks, was designed to enrol 600 patients, but after experiencing funding issues it eventually included just 142, of whom 112 completed the study.
Among these patients, there was significantly less magnetic resonance imaging (MRI) and clinical evidence of disease reactivation if the washout period was 8 or 12 weeks, rather than 16 weeks, report Ludwig Kappos (University of Basel, Switzerland) and co-researchers in Neurology.
During washout plus the first 8 weeks of fingolimod treatment, patients who had 8- and 12-week washout periods had a median of 2.1 and 1.7 active lesions, respectively, on MRI, whereas the 16-week group had a median of 8.2. The proportions of patients with no active lesions were a corresponding 68.3%, 69.0% and 35.9%.
During the washout period itself, the median number of active lesions was 0.4 in the 8-week group, 2.1 in the 12-week group and 3.6 in the 16-week group, with the differences between all three groups being significant.
Clinical relapse occurred in two patients from each of the 8- and 12-week groups during washout plus the first 8 weeks of fingolimod therapy, compared with 10 patients in the 16-week group.
No patient in any group developed progressive multifocal leukoencephalopathy; a putative increased risk of this, caused by the overlapping effects of natalizumab and the new drug, is the reason a washout period is recommended. There were no systemic opportunistic infections, although there was an increased rate of mild nasopharyngitis and urinary tract infections in the 8-week washout group.
The team concludes that an 8- to 12-week washout is preferable to a longer period. However, in an accompanying editorial, Olaf Stüve (University of Texas Southwestern Medical Center, Dallas, USA) and Dennis Bourdette (Oregon Health & Science University, Portland, USA) ask if a washout period is needed at all.
They note that the “biological rationale for a washout has been unclear to many clinical neuroimmunologists, and it is not evidence-based”, and cite evidence that the immunological effects of natalizumab may last 6 months or more after stopping treatment, making the benefits of an 8- to 12-week washout “questionable”.
Stüve and Bourdette call for “accurate information” about individual MS treatments and transitions, concluding: “It is not good enough to rely on guessing and expert opinion.”
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