5698
Progressive Multifocal Leukoencephalopathy (PML) Occurring with Extended Interval Dosing (EID) of Natalizumab: Analysis of Cases in the Touch Database

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
John Foley, MD , Rocky Mountain MS Clinic, Salt Lake City, UT
Lana Zhovtis-Ryerson, MD , Department of Neurology, NYU Langone Health, New York University, New York, NY
Ih Chang, PhD , Biogen, Cambridge, MA
Ilya Kister, MD , Department of Neurology, NYU Langone Health, New York University, New York, NY
Gary Cutter, PhD , University of Alabama School of Public Health, Birmingham, AL
Ryan Metzger, PhD , Rocky Mountain MS Clinic, Salt Lake City, UT
Judith D Golberg, PhD , New York University School of Medicine, New York, NY
Xiaochun Li, PhD , New York University School of Medicine, New York, NY
Evan Riddle, PhD , Biogen, Cambridge, MA
Rachna Kasliwal, MPH , Biogen, Cambridge, MA
Zheng Ren, PhD , Biogen, Cambridge, MA
Christophe Hotermans, MD, PhD , Biogen, Cambridge, MA
Pei-Ran Ho, MD , Biogen, Cambridge, MA
Nolan Campbell, PhD , Biogen, Cambridge, MA
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Background: A recent analysis of multiple sclerosis (MS) patient data in the TOUCH® registry and the TYSABRI® Global Safety Database demonstrated that natalizumab EID is associated with a clinically and statistically significant lower risk of PML than standard interval dosing (SID) in anti–JC virus (JCV) antibody positive patients.

Objectives: To characterize the PML risk factors of the patients who were on EID as defined in the recent TOUCH analysis and who later developed PML.

Methods: The recent TOUCH analysis assessed 3 defined EID dosing patterns. In 2 of the EID definition cohorts, 13 PML cases were observed. Demographics, treatment history, and other PML risk factors of the EID PML cases were assessed and compared to EID patients under the same definition. All patients in these analyses were anti-JCV antibody positive.

Results: Overall, 1988 patients met the primary EID definition (with 3 PML cases) and 3331 met the secondary definition (with 12 PML cases). Two of the primary EID definition cases also met the secondary EID definition. Anti-JCV antibody index data from the 6–12 months prior to PML diagnosis were available for 6 cases; 5 had index values ≥2.5. Compared to the overall secondary definition EID cohort, the EID PML cases generally had shorter average dosing intervals (ADIs) (mean (SD) 31.7 (1.10) vs 35.0 (4.93) days), longer natalizumab duration (median [quartile 1 (Q1), quartile 3 (Q3)]: 74.5 [59.5, 85.0] vs 56.0 [36.0, 81.0] months), more total natalizumab infusions (median [Q1, Q3]: 68 [58, 83] vs 51 [31, 75]), and more natalizumab infusions before starting EID (median [Q1, Q3]: 40.5 [19.0, 56.5] vs 25.0 [13.0, 44.0]). Prior immunosuppressant (IS) use was more common in the EID PML cases than in the overall EID cohort (17% vs 5%). At the time of diagnosis, 8/12 PML cases were on SID. Of the 13 PML cases, 5 resulted in death. Similar results were observed for the 3 primary definition EID cases except that none of these patients had returned to SID prior to PML diagnosis.

Conclusions: EID is associated with a lower PML risk, but risk is not completely eliminated. EID patients diagnosed with PML had elevated known risk factors for PML, including longer natalizumab treatment duration and a higher proportion of prior IS use than the overall EID cohort. Our conclusions are limited by missing anti-JCV antibody index values.

Support: Biogen

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