Absolute lymphocyte count recovery in patients with relapsing-remitting multiple sclerosis (RRMS) treated with cladribine tablets 3.5 mg/kg in CLARITY and CLARITY Extension (P5.379)

Objective: To investigate the absolute lymphocyte count (ALC) in patients with RRMS receiving 2 years of treatment with CT 3.5 mg/kg (CT3.5). Background: In CLARITY, cladribine tablets (CT) significantly reduced relapse rates, disability progression and MRI measures of disease activity over 2 years. The most commonly reported adverse event was lymphopenia, consistent with the mechanism of action for CT. Design/Methods: Data from patients randomized to CT3.5 for 2 years in CLARITY or CLARITY Extension including time spent in the PREMIERE registry (N=685) were pooled to provide long-term follow-up data. Data from patients randomized to placebo in CLARITY and followed up in CLARITY Extension and PREMIERE are also reported (PBO; N=435). Results: At baseline (start of CLARITY or CLARITY Extension), median (Q1–Q3) ALC was 1.86×109/L (1.50–2.29) for CT3.5 and 1.91×109/L (1.54–2.32) for PBO. During Year 1, ALC in CT3.5 reached a nadir at 9 weeks post-treatment [1.00×109/L (0.80–1.30)]. At the end of Year 1 (48 weeks), median ALC had increased to 1.21×109/L (0.95–1.50). During Year 2, ALC in CT3.5 reached a nadir 7 weeks after re-treatment [0.81×109/L (0.60–1.04)], increasing to 1.03×109/L (0.80–1.30) at the end of Year 2 (96 weeks). At the end of Years 3 and 4 (144 and 192 weeks), ALC in the CT3.5 group (with no further treatment) increased to 1.36×109/L (1.02–1.65) and 1.40×109/L (1.10–1.81), respectively, reaching a final median ALC of 1.76×109/L (1.17–2.65) after 6.5 years (312 weeks). In PBO patients, median ALC values were between 1.69×109/L (1.45–2.05) and 1.95×109/L (1.59–2.38). Conclusions: Rapid reductions in ALC after CT3.5 treatment in Years 1 and 2 were followed by gradual returns toward baseline. Median lymphocyte counts were within normal range beyond Year 2 (96 weeks) in all patients for whom follow-up data are available. Disclosure: Dr. Soelberg-Sorensen has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Genmab, TEVA, Elan, and GlaxoSmithKline, and Bayer. Dr. Soelberg-Sorensen has received personal compensation in an editorial capacity for European Journal of Neurology, Multiple Sclerosis Journal, European Journal of Neurology, and Therapeutic Advances in Neurological Disorders. Dr. Soelberg-Sorensen has received research support from Biogen Idec, Bayer Schering, Merck Serono, TEVA, Baxter, Sanofi-Aventis, BioMS, Novartis, Bayer, RoFAR, Roche, Genzyme, the Danish Multiple Sclerosis Society, and the Danish Medical Research Council. Dr. Dangond has received personal compensation for activities with EMD Serono, Inc. as an employee. Dr. Hicking has received personal compensation for activities with Merck KGaA, Darmstadt, Germany as an employee. Dr. Giovannoni has received personal compensation for activities with AbbVie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex for honoraria. Dr. Giovannoni has received personal compensation from Elsevier in a co-chief editor capacity of MS and Related Disorders. Dr. Giovannoni has received research support from Biogen, Ironwood, Merck Serono, Merz, and Novartis.