Novel approaches in the treatment of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, which usually affects young adults. The most common clinical course of the disease is the relapsing-remitting form of multiple sclerosis (RRMS). Although there is no causative therapy, treatment outcomes in patients with RRMS have been significantly improved with the introduction of disease modifying therapy (DMT), which decreases disease activity and delays progression of disability. Drugs used as DMT are immune modulator and immunosuppressive drugs. The conventional immunomodulatory drugs, interferons (IFN-β 1b and IFN-β 1a) and glatiramer acetate, applied parenterally, have been the first line therapy for many years in patients with RRMS. IFN-β and GA are generally safe and well-tolerated. However, due to the heterogeneity of the pathophysiology and clinical presentation of MS, their efficacy is modest, which requires substitution of IFN-β with GA or the use of certain novel immunomodulatory therapies: monoclonal antibodies, alemtuzumab and natalizumab, (parenteral administration) or teriflunomide, dimethyl-fumarate and fingolimod (peroral administration). The antineoplastic agent, mitoxantrone, is used for the treatment of aggressive forms of MS. The overall benefit/risk ratio for novel approaches in the treatment of MS has yet to be determined.

Multipla skleroza (MS) je hronično autoimunsko oboljenje centralnog nervnog sistema koje uglavnom pogađa mlade odrasle osobe. Najčešća klinička forma bolesti je relapsno- remitentna multipla skleroza (RRMS). Iako ne postoji kauzalna terapija, ishod lečenja pacijenata sa RRMS značajno je poboljšan uvođenjem terapije koja modifikuje prirodni tok bolesti (disease modifying therapy, DMT), u smislu smanjenja aktivnosti bolesti i odlaganja razvoja progresivne onesposobljenosti pacijenata. Lekovi koji se koriste u DMT su imunomodulatori i imunosupresivi. Standardni imunomodulatorni lekovi, interferoni (IFN-β 1b i IFN-β 1a) i glatiramer acetat (GA), koji se primenjuju parenteralno, prva su terapijska linija dugi niz godina kod pacijenata sa RRMS. Bezbednosni profil IFN-β i GA je generalno dobar. Međutim, zbog heterogenosti patogeneze i kliničke prezentacije MS, njihova efikasnost je delimična, što nameće potrebu za međusobnom zamenom IFN-β i GA ili za ustupanjem mesta nekoj od novih odobrenih imunomodulatornih terapija: alemtuzumab i natalizumab (parenteralna primena) ili teriflunomid, dimetil-fumarat i fingolimod (peroralna primena). Citostatik, mitoksantron, primenjuje se kod agresivne forme MS. Odnos korist/rizik novih terapijskih opcija u MS tek treba da se proceni/potvrdi.