Natalizumab discontinuation after PML risk stratification: outcome from a shared and informed decision

Abstract

Multifocal progressive leukoencephalopathy (PML) is associated with JC virus (JCV) seropositivity, past immunosuppression, and natalizumab treatment for two years or more. The aim of our study was to investigate the rate of treatment discontinuation after stratifying for the three risk factors in a group of 104 natalizumab-treated patients with relapsing-remitting multiple sclerosis. We investigated JCV serological status in our population. We then divided patients into groups according to their PML risk. Treatment indication was reassessed. Of the patients, 64 (61.5%) were JCV seropositive. Amongst seropositive patients on natalizumab for 2 years or more, 10 had received immunosuppression (group A), and 38 had not (group B). After an informed and shared decision-making process, 6/10 (60%) from group A compared with 9/38 (23.7%) from group B discontinued treatment (p=0.027). In groups A and B, discontinuation also depended upon doctors' views (p=0.019, group A; p=0.010, group B) and clinical outcomes (p=0.021, group A). No-one from low-intermediate risk groups discontinued. The decision to discontinue natalizumab treatment is complex, even when clear PML risk rates are described. Clinical outcomes and doctors' idiosyncrasies play a crucial part in patients' final choice.

Is the risk of progressive multifocal leukoencephalopathy the real reason for natalizumab discontinuation in patients with multiple sclerosis?

“…This result is supported by the significant relationship between physicians’ statements on continuation or discontinuation of therapy and the proportion of Patients stopped NTZ and Patients Cont. NTZ , and is in line with previous reports demonstrating that especially the views and idiosyncrasies of the treating physician play a prominent role in the decision-making process [8,25]. Interestingly, physicians’ judgments on continuation/discontinuation of therapy depended on the number of patients treated per year suggesting that physicians treating more NTZ-treated MS patients deal differently with PML risk, perhaps due to an increased acceptance and good experience with NTZ, the rarity of PML, and the low rates of AEs and SAEs in daily practice.…”

“…Thus, it was demonstrated that especially long-term NTZ-treated and JCV Ab + patients are more likely to discontinue NTZ [4,25,29,30]. Tur et al reported a treatment dropout rate of 23.7% in JCV Ab + patients on NTZ therapy longer than 2 years without prior history of immunosuppression (in contrast to 11% of patients of group C in our study) compared to the 0% in JCV Ab—patients and JCV Ab + patients on NTZ therapy less than 2 years (in contrast to 11% of patients of group A and 20% of patients of group B in our study) [25]. Of note, these treatment dropout rates were evaluated in a cross-sectional study situation where patients had to decide on NTZ continuation/discontinuation after being stratified for PML risk factors, and not within a longitudinal assessment, possibly explaining the discrepancies in our study.…”

Risk Acceptance in Multiple Sclerosis Patients on Natalizumab Treatment

“…In 2012, we reported that amongst the NTZ-treated patients who had the three PML risk factors, those with lower reductions in disability scores while on treatment were more likely to discontinue NTZ after a decision-making process[19]. We also found that the neurologist with whom treatment discontinuation had been discussed played a major role in the final decision.…”

Natalizumab is effective in controlling the inflammatory rebound after its discontinuation and failure of an alternative treatment

“…NAT discontinuation after PML risk stratification is a complex decision that can change the prognosis of MS in the event of a severe post-NAT withdrawal relapse (Tur et al, 2012). Our patient presented both with clinical and MRI exacerbations of the disease.…”