Background Cladribine tablets 3.5 mg/kg (CT3.5) demonstrated efficacy in patients with early (ORACLE-MS) and relapsing MS (CLARITY/CLARITY-Extension).

Objective Evaluate B, T lymphocyte and natural killer (NK) cell profiles after CT administration in ORACLE-MS, CLARITY and CLARITY-Extension.

Methods Longitudinal evaluation of peripheral blood lymphocytes was conducted for patients receiving the CT (either part of the initial 3.5 mg/kg active treatment groups or placebo switched to active treatment). Absolute lymphocyte counts (ALC) and subtype dispositions were evaluated at baseline, and Weeks 5, 13, 24, 48.

Results Baseline distributions of ALC and temporal profiles of CD19+ B and CD4+ and CD8+ T lymphocytes were generally consistent across studies. Rapid reductions were observed for CD19+ B cells (~75% reduction; Week 5), with nadirs at Week 13 (~80% reduction). Reconstitution of CD19+ B cells towards baseline occurred from Week 24–48. Lesser, discontinuous reductions also occurred for CD4+ and CD8+ T cells that had not fully returned to baseline by Week 48. CD16+/CD56+ NK cells were transiently reduced with CT, with recovery evident at Weeks 24 (29%) and 48 (23%).

Conclusions CT3.5 achieved early, discontinuous reduction of peripheral blood B cells, with rapid reconstitution towards baseline; a moderate, discontinuous reduction of T cells; and early, transient NK cell reductions.

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