#ECTRIMS2019 – Plasma Exchange Ineffective for Treating Tysabri-associated PML, Study Shows
Use of plasma exchange (PLEX) is not effective for treating progressive multifocal leukoencephalopathy (PML), a dangerous brain infection that has been associated with using the multiple sclerosis (MS) medicine Tysabri (natalizumab), a real-world study contends.
The findings highlight the importance of closely monitoring Tysabri users to detect PML as early as possible.
The data were presented by Chris McGuigan, MD, a neurologist at St Vincent’s University Hospital and professor at the School of Medicine and Medical Sciences, University College Dublin, in Ireland, at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which is being held Sept. 11–13 in Stockholm, Sweden.
The presentation was titled “Determinants of clinical outcomes for patients with Natalizumab-associated progressive multifocal leukoencephalopathy.”
Biogen‘s Tysabri — a medicine approved for relapsing-remitting multiple multiple sclerosis (RRMS) — is known to increase the risk of PML, a rare brain infection that can lead to serious disability and death.
PML is caused by John Cunningham (JC) virus, which is widespread in the population and normally rests inactive in healthy individuals. However, it can cause disease in people with weakened immune systems, such as those with HIV/AIDS or those who are taking immunosuppressant medications.
Various treatments have been adopted to treat PML associated with Tysabri, including PLEX, which is intended to rapidly clear the medicine from the blood.
Plasma exchange, or plasmapheresis, consists of removing the patient’s blood plasma and replacing it with a similar solution made of albumin and saline, supplemented with other factors.
“PLEX is associated with increased clearance of natalizumab [Tysabri]; however, the impact of PLEX on clinical outcomes has not been systematically evaluated,” McGuigan said.
To address that, researchers analyzed survival data of a group of 725 RRMS patients who had confirmed Tysabri-associated PML, and were listed on Biogen’s pharmacovigilance database. The team compared the survival of patients who had been treated with PLEX versus those who had not, and searched for patient characteristics that could predict recovery.
Of the 725 patients analyzed, most received PLEX (616 patients, 85%).
Compared to patients not treated with plasma exchange, a higher proportion of PLEX-treated patients had symptoms (87.8% vs 78.9%), and had greater viral loads (33.3% vs 17.4%) at the time they were diagnosed.
However, two years after PML detection, survival was no different between PLEX-treated and non-treated patients, irrespective of the viral burden of patients at diagnosis.
“PLEX was not associated with a beneficial effect on survival after PML,” McGuigan said.
But taking all data together, survival was better for those with lower numbers of viral copies. At two years, 88.2% (PLEX group) and 89.3% (no PLEX group) with fewer copies of JC virus were still alive, compared to 68.2% (PLEX) and 78.9% (no PLEX) of those with greater viral loads.
Other risk factors were detected in addition to viral levels. Older patients (50 and older), and those with widespread brain lesions on MRI, were less likely to survive.
In contrast, those who had no symptoms at the time of PML diagnosis had more chances of surviving.
Overall, the findings revealed that “PLEX treatment did not have a significant effect on 2-year survival rates,” McGuigan said. “It actually seems to be associated with worse outcomes,” he added.
McGuigan also emphasized that surviving PML is more likely in patients who are younger, present no symptoms at diagnosis, have localized brain lesions, and low viral loads.
“Taken together, these data support early, vigilant monitoring for PML as an important component of improving post-PML outcomes,” McGuigan concluded. “The use of PLEX in individual MS patients should be carefully considered given that there were no observed benefits of PLEX on natalizumab-associated PML outcomes at a population level.”