Contributions
Abstract: EP1528
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Natalizumab has demonstrated efficacy at reducing relapse rates, disability worsening, and inflammatory disease activity measured by MRI in multiple sclerosis (MS) patients. However, natalizumab use is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). Our previously published analysis of 372 natalizumab-associated PML patients as of June 2013 demonstrated that asymptomatic patients had improved survival and less functional disability than those who were symptomatic at diagnosis.
Objective: To provide an updated analysis evaluating the outcomes of 566 natalizumab-associated PML cases in MS patients who were asymptomatic at diagnosis compared with those who presented with clinical symptoms.
Methods: Confirmed PML cases identified from long-term observational clinical trials and postmarketing surveillance as of June 4, 2015 were analyzed. Survival over 12 months, Expanded Disability Status Scale (EDSS) and Karnofsky Performance Scale (KPS) scores, PML lesion patterns on MRI, demographics, and MS disease characteristics were compared between patients with and without PML symptoms at PML diagnosis.
Results: A total of 566 natalizumab-associated PML cases were analyzed as of June 4, 2015; 62 (11.0%) were asymptomatic and 504 (89.0%) were symptomatic at diagnosis. The survival rate was significantly higher among asymptomatic patients (95.2%) than symptomatic patients (74.2%; P< 0.0001). At PML diagnosis and 6 and 12 months post-diagnosis, asymptomatic patients had less functional disability than symptomatic patients. However, symptomatic patients had greater pre-PML disability than asymptomatic patients. Characteristics of asymptomatic and symptomatic patients were generally similar, though asymptomatic patients were younger (P=0.04) and had less disability (P=0.01) at PML diagnosis. The time from PML suspicion to PML diagnosis in asymptomatic patients was significantly shorter than in symptomatic patients (median, 11 vs 30 days; P=0.002). PML lesions were more localized (unilobar) in asymptomatic than symptomatic patients (60.0% vs 36.7%; P=0.0005).
Conclusions: These analyses confirm and extend our previous findings that diagnosis of PML prior to symptom appearance is associated with better functional and survival outcomes compared with PML diagnosis after the symptom onset. However, confounders such as PML disease progression variability and lead-time bias may have influenced the observed outcomes.
Disclosure: Supported by Biogen.
All authors are employees of and may hold stock and/or stock options in Biogen.
Abstract: EP1528
Type: ePoster
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Natalizumab has demonstrated efficacy at reducing relapse rates, disability worsening, and inflammatory disease activity measured by MRI in multiple sclerosis (MS) patients. However, natalizumab use is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). Our previously published analysis of 372 natalizumab-associated PML patients as of June 2013 demonstrated that asymptomatic patients had improved survival and less functional disability than those who were symptomatic at diagnosis.
Objective: To provide an updated analysis evaluating the outcomes of 566 natalizumab-associated PML cases in MS patients who were asymptomatic at diagnosis compared with those who presented with clinical symptoms.
Methods: Confirmed PML cases identified from long-term observational clinical trials and postmarketing surveillance as of June 4, 2015 were analyzed. Survival over 12 months, Expanded Disability Status Scale (EDSS) and Karnofsky Performance Scale (KPS) scores, PML lesion patterns on MRI, demographics, and MS disease characteristics were compared between patients with and without PML symptoms at PML diagnosis.
Results: A total of 566 natalizumab-associated PML cases were analyzed as of June 4, 2015; 62 (11.0%) were asymptomatic and 504 (89.0%) were symptomatic at diagnosis. The survival rate was significantly higher among asymptomatic patients (95.2%) than symptomatic patients (74.2%; P< 0.0001). At PML diagnosis and 6 and 12 months post-diagnosis, asymptomatic patients had less functional disability than symptomatic patients. However, symptomatic patients had greater pre-PML disability than asymptomatic patients. Characteristics of asymptomatic and symptomatic patients were generally similar, though asymptomatic patients were younger (P=0.04) and had less disability (P=0.01) at PML diagnosis. The time from PML suspicion to PML diagnosis in asymptomatic patients was significantly shorter than in symptomatic patients (median, 11 vs 30 days; P=0.002). PML lesions were more localized (unilobar) in asymptomatic than symptomatic patients (60.0% vs 36.7%; P=0.0005).
Conclusions: These analyses confirm and extend our previous findings that diagnosis of PML prior to symptom appearance is associated with better functional and survival outcomes compared with PML diagnosis after the symptom onset. However, confounders such as PML disease progression variability and lead-time bias may have influenced the observed outcomes.
Disclosure: Supported by Biogen.
All authors are employees of and may hold stock and/or stock options in Biogen.