Contraindications: active bacterial infections (urinary tract, lung, hepatitis), systemic mycosis in the past 6 months; viral infections: herpes zoster or herpes simplex infections with acute reactivations in the past 3 months; HIV-infection and subsequent opportunistic infections in the past 3 months; other chronic or recurrent viral selleck kinase inhibitor or bacterial infections, malignant tumours,

organ transplantation with ongoing immunosuppression, pregnancy and lactation. Fingolimod (FTY 720) has a unique immunoregulatory mechanism of action. Following its in-vivo phosphorylation, FTY720 becomes FTY720-phosphate(p), a non-selective, high-affinity antagonist of sphingosine 1-phosphate receptors (S1P-R). FTY720-p binds directly to S1P-Rs on lymphocytes, selleck compound precipitating internalization and degradation of the receptor. This functional antagonism impairs the egress of autoreactive lymphocytes from lymph nodes along an endogenous chemotactic S1P-gradient. FTY720-p also binds to S1P-Rs on endothelial cells of the lymph node, which impairs the transmigration of lymphocytes from the medullary parenchyma to draining regions of lymph nodes. Hence, fingolimod retains T cells and B cells in secondary lymphatic organs, causes a pronounced lymphopenia in the blood and thus

impairs invasion of lymphocytes into the inflamed CNS parenchyma. Fingolimod may also exert direct protective effects on parenchymal cells (neurones, oligodendrocytes) in the CNS. Preparations and administration: in the United States, fingolimod [63, 64] is approved for basic therapy, whereas in Europe fingolimod is approved for the escalation therapy of patients with RRMS. Fingolimod is administered orally at a dose of 0·5 mg once daily. Clinical trials: a Phase III clinical trial is currently being initiated ADAMTS5 to compare oral fingolimod (0·5 mg/day) to placebo in patients with CIDP (‘Evaluate efficacy and safety of fingolimod 0·5 mg orally once daily versus placebo in chronic

inflammatory demyelinating polyradiculoneuropathy patients’). Adverse effects, frequent: infections, headache, gastrointestinal disturbances, bradycardia, elevation of liver enzymes; infrequent: sinuatrial block and/or atrioventricular block I–II°, increased arterial blood pressure, macula oedema. Contraindications: immunodeficency, severe active infections, chronic active infections (hepatitis, tuberculosis), active malignancies, severe liver dysfunction, pregnancy and lactation. Alemtuzumab is a humanized monoclonal antibody binding specifically to the CD52 antigen on the surface of B, T and natural killer (NK) cells, as well as monocytes and macrophages. It depletes these immune cell types by inducing complement-mediated cell lysis. Currently, alemtuzumab is approved for the treatment of patients with chronic lymphatic leukaemia of the B cell type (B-CLL).