All interferons are approved for the treatment of RRMS, moreover Betaferon and Avonex are also approved for the treatment of clinical isolated syndrome (CIS) and Betaferon for the treatment of active secondary progressive MS (SPMS) as well (EMA website). Long-term data regarding safety and efficacy show.
IFN-β was first approved for MS in the in 1993.
There are three different products available:
IFN-β-1b preparations (Betaseron®, Extavia®) that are administered s.c. every other day
IFN-β-1a preparations that are either administered s.c. (Rebif®) three times weekly
intramuscularly (i.m.) (Avonex®) once a week.
The mechanism of action by which interferon be mediates its beneficial effects in multiple sclerosis
(MS) treatment is only partly resolved, and likely multifactorial and complex:
1-shift expression of cytokines from a pro-inflammatory cytokine profile towards an anti-inflammatory
2-reduce inflammatory cell populations in the central nervous system (CNS) by preventing cellmigration across the blood brain barrier.
3- may stimulate neuronal growth.
1-injection site reactions and necrosis
3-flu like symptoms
4-transient deterioration of neurologic symptoms
5-mood disorder and depression.
8-thyroid autoimmunity and hypothyroidism
9-Menstrual disorders:Menstrual disorders, such as breakthrough bleeding or spotting
10-Other rare potential side effects. Capillary leak syndrome, TTP–like syndrome, anaphylactic shock, psoriasis
liver enzymes measurement at 1, 3, and 6 months and then every 6 months after initiating therapy. The dose needs to be reduced if the liver enzymes are found tobe five times greater than baseline.
Interferon b needs to be discontinued if liver enzymes do not normalize with dose reduction, but a full dose can be re-implemented if enzymes normalize.
Blood cell count should be done 1,3,6 months after iniatiation of treatment and then every 6 months.
Thyroid testing should be performed initially and afterwards only in the case of abnormalities every 6 months and when clinical signs of hypo- or hyperthyroidism are obvious.
Glatiramer acetate is one of the first generation DMTs approved by the FDA for management of
There are two doses that are currently approved by the FDA:
20mg subcutaneously (s.c.) daily
40mg s.c. 3 times a week.
Mechanism of action : is still not fully understood.Although glatiramer acetate itself does not cross the blood brain barrier, it shifts the pro-inflammatory T helper type 1 (interleukin-2, interleukin-12, IFNg, tumor necrosis factor) cytokine profile to anti-inflammatory T helper type 2 (interleukin-4,interleukin-5, interleukin-10, transforming growth factor-b) cytokine profile, leading to down re some neuro-protective action by increasing the production of brain derived neurotrophic factor (BDNF)
The most common side effect reported is injection site reaction.
Only 5% of patients discontinued glatiramer acetate because of injection site reaction, urticaria, flushing, chest pain, palpitation, anxiety, and throat constriction
Reports of liver injury by GA has been documented.
Most of the side effects from glatiramer acetate were self-limited.
Rare side effects:
Drug-induced liver injury by glatiramer acetate leading to liver transplant: A case report
Normocomplementemic urticarial vasculitis.
central retinal vein occlusion
Calcinosis Cutis Associated With Subcutaneous Glatiramer Acetate
Monitoring: No laboratory monitoring is required during GA therapy.