Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: a retrospective study.
BACKGROUND
Natalizumab disease-modifying therapy for relapsing-remitting multiple sclerosis (MS) is efficacious in randomized controlled trials. Few studies have estimated the association between real-world natalizumab persistence behavior and relapse-related outcomes.


OBJECTIVE
To (a) examine the impact of using natalizumab consistently (i.e., persistent) on relapse-related outcomes as compared with transitioning to inconsistent natalizumab use (i.e., nonpersistent) and (b) examine the impact of other treatment patterns on relapse-related outcomes for those who initiated natalizumab.


METHODS
Using the IMS PharMetrics Plus claims database (years 2006-2012), we identified MS subjects who initiated natalizumab (no natalizumab claims in year prior) and had at least 2 years of follow-up. Persistence in annual follow-up periods was defined as no 90-day or greater gap in natalizumab therapy. Relapse was an MS-related hospitalization or outpatient visit with intravenous or oral steroid burst claim within 7 days. Analyses compared observations based on changes in natalizumab persistence and natalizumab nonpersistence status from 1 year to the next (e.g., transitioning from persistent to nonpersistent), estimating differences in mean annual relapses and mean annual relapse-related costs.


RESULTS
A total of 2,407 natalizumab initiators had at least 2 years of follow-up, yielding 4,770 year-to-year natalizumab treatment patterns where each subject contributed 1, 2, or 3 year-to-year treatment patterns. In the year prior, 3,187 treatment patterns were persistent; 731 (22.9%) of these transitioned to nonpersistence. The remaining 1,583 treatment patterns were nonpersistent in the year prior; 132 (8.3%) of these transitioned to persistence. Persistent to nonpersistent treatment patterns were associated with a mean relapse-rate increase of 0.23 (95% CI = 0.12, 0.35), and a mean increase in relapse-related costs of $1,346 (95% CI = $97, $2,595). Nonpersistent to persistent treatment patterns were associated with a mean relapse-rate decrease of -0.15 (95% CI = -0.32, 0.017) and a mean decrease in relapse-related costs of -$1,369 (95% CI = -$2,761, $23).


CONCLUSIONS
Findings suggest that real-world persistent natalizumab users who become nonpersistent have statistically significant increases in annual relapses and relapse-related costs. Those who transition from nonpersistent to persistent have nonsignificant reductions in relapses and their associated costs.
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Anschutz Medical Campus, Mail Stop C238, 12850 E. Montview Blvd., Aurora, CO 80045. Tel.: 303.709.9264; FAX: 303.724.0979. Robert.mcqueen@ucdenver.edu.
R Brett
RB
McQueen
Terrie
T
Livingston
Timothy
T
Vollmer
John
J
Corboy
Brieana
B
Buckley
Richard Read
RR
Allen
Kavita
K
Nair
Jonathan D
JD
Campbell
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D007223:Infant; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000503:physiopathology; D000069442:Natalizumab / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D055815:Young Adult
D007155:Immunologic Factors; D000069442:Natalizumab