An integrated analysis of the DMF Phase 2b, Phase 3 (DEFINE/CONFIRM) and extension (ENDORSE) studies assessed data from 1^st DMF exposure as of September 2017. ALCs were assessed at weeks 4, 8, 12, and every 12 weeks thereafter.

The analysis included 2513 patients (10454 patient-years). In patients followed for up to 11 years, severe, prolonged lymphopenia was not associated with increased incidence of serious infection (0.016 vs. 0.010 for patients with ALC ≥lower limit of normal [LLN]) or serious herpes zoster (0 vs. 0.006 for patients with ALC ≥LLN). Aside from 1 fatal case of PML, no opportunistic infections were observed in DEFINE/CONFIRM and ENDORSE. In patients with mild or moderate lymphopenia while on DMF, and an ALC <0.91x10⁹/L at DMF discontinuation (n=138), median time to ALC ≥0.91x10⁹/L was 7 weeks after discontinuation. Most of these patients (62%, 86/138) achieved this milestone during follow-up, or prior to study discontinuation.

These data did not demonstrate an increased incidence of serious or opportunistic infections in DMF-associated lymphopenia aside from very rare cases of PML. ALCs increased following DMF discontinuation for the majority of patients; ALCs generally reconstitute 6-8 weeks following DMF discontinuation.  Reconstitution rate after DMF discontinuation due to lymphopenia was similar for all patients, regardless of ALC at time of discontinuation.

Study Supported by: Biogen