Table 3.

Comparison of IR therapies.

	Autologous hematopoietic stem cell transplantation (AHSCT)	Alemtuzumab	Cladribine
Mechanism of action	Lympho/myeloablative chemotherapeutic conditioning followed by autologous stem cell rescue	IgG3 mediated cell lysis of CD52 lymphocytes. Dosed at 0 and 12 months	Purine anti-proliferative oral therapy mediating selective lymphocyte apoptosis. Dosed at 0, 1, 12, and 13 months
Clinical efficacy (for RRMS)	Phase 1/2 trials and observational studies estimate MRI and clinical disease-free survival 78–83% at 2 years	Phase 3 treatment-controlled trials report MRI and clinical disease-free survival 39% at 2 years	Phase 3 placebo-controlled trials report 57.6% reduction in relapse rate, 74.4% relative reduction in combined unique lesions on MRI
CD4 repopulation	Memory cell counts approach baseline by 18–24 months	70–80% baseline at 12 and 24 months	Fall by 40–60%. Naïve cells fall to greater degree than memory cells
CD8 repopulation	Early reconstitution 3–6 months dominated by CD8 memory cells	Fall by 80–90% post-dosing, reach 50% baseline at 12 and 24 months	Fall by 20–40% from baseline after dosing
B cell repopulation	Approach baseline levels at 6–9 months	CD19+ cells return to baseline at 3–6 months, reach 120–130% prior to re-dosing	Fall by 90% after dosing, close to baseline prior to re-dosing at 12 months
Effect on thymic output	Multiple publications demonstrating increased CD4+CD31+ (RTE) and increased T cell receptor excision circle (TREC) post-AHSCT	Single study showing decrease in TREC post-alemtuzumab treatment	Unclear
Secondary AID	14/273 (5%) cases in largest longitudinal observational study	Estimated up to 50% at 7 years post treatment	None reported in Phase 3 trials