EFFECTIVENESS ( EFFECTIVE DOSAGE - IN RELATION TO VARIOUS SOURCE OF EVIDENCES )
ALSO CALLED EBM ( EVIDENCE BASED MEDICINE )
1 0.5 to 1.25 mg / day according to double blind , placebo controlled study termed FREEDOMS ( FTY 720 RESEARCH EVALUATING EFFECTS OF DAILY ORAL THERAPY IN MS )
2 Fingolimod at daily doses ( 0.5 to 1.25 mg / day ) significantly reduced the risk of disability progression as measured using EXPANDED DISABILITY STATUS SCALE ( EDSS ) over a 24 month period - 54 % and 56 % reduction in ARR ( ANNUAL RELAPSE RATE )
3 A 12 month double dummy phase III study involving patients with RRMS TRANSFORMS ( TRIAL ASSESSING INJECTABLE INTERFERON VS FTY 720 ORAL IN RRMS ) compared fingolimod at a dosages of 0.5 to 1.25 mg with intramuscular IFN B 1 a at a weekly dose of 30 microgram
THE ANNUAL RELAPSE RATES WERE LOWER AS COMPARED TO INTERFERON
COMPLICATIONS / SIDE EFFECTS
1 Transient dose dependent bradycardia - occurs more significantly in patients who are taking beta blockers and calcium channel blockers ( 3 % ) higher risk
2 Atrioventricular conduction block ( AVB )
3 Hypertension
4 Macular edema
5 Elevated liver enzymes
6 Lymphocytopenia
7 Skin cancers
RARE - DISSIMINATED PRIMARY VARICELLA ZOSTER and HERPES SIMPLEX ENCEPHALITIS
2 TERIFLUONOMIDE
or AUBAGIO is an active metabolite of lefunomide an immunosuppresant drug used for rheumatoid arthritis
MECHANISM OF ACTION
1 Acts by reversibly inhibiting the enzyme dihydroorotate dehydrogenase , the rate limiting mitochondrial enzyme of denovo pyrimidine synthesis by -
A ) non competitively inhibiting the binding of its substrate , dihydroorotate
B ) By acting as a competitive inhibitor of ubiquinone binding
2 Exerts cytostatic effects on activated and rapidly proliferating T and B cells responding to autoantigens
3 The pyrimidine salvage pathway is spared , allowing maintenance of protective immunity throughout treatment
A ) This is important since seasonal influenza vaccine can be given easily
EFFECTIVENESS ( EFFECTIVE DOSAGE - IN RELATION TO VARIOUS SOURCE OF EVIDENCES )
ALSO CALLED EBM ( EVIDENCE BASED MEDICINE )
1 A randomised double blind phase II study involving patients with RRMS and Secondary Progressive MS with Relapses revealed that treatment with terifluonomide ( 7 to 14 mg / day ) significantly reduce the combined number of active lesions evident over brain MRI in 36 weeks
2 TEMSO ( Terifluonomide Multiple sclerosis Oral ) Study was the 1st Phase III Clinical trial to demonstrate efficacy , patients recieving 7 to 14 mg / day demonstrated Significant ARR - a decrease of 31 % , slower progression of disability
3 According to TOPIC ( Terifluonomide vs Placebo In Patients experiencing their 1st symptom - the drug was associated with 43 % risk reductions
4 The TENERE study ( TERIFLUONOMIDE VS REFIB ) compared efficacy with subcutaneous IFN B 1 a - was not favourable and since it was recommended as 2nd line agent * ( v imp )
COMPLICATIONS / SIDE EFFECTS
1 Elevated Alanine Transferase activity
2 Diarrhea
3 Nausea
4 Influenza
5 Thinning of hairs or decreased hair density
6 Peripheral neuropathy
THESE ABOVE 6 ARE DOSE DEPENDENT
Increased blood pressure , A reduction in neutrophil and lymphocyte counts And Development of Skin Disorders were frequent in these patients
THESE DRUG IS AVOIDED IN PREGNANT MOTHERS , FATHERS - TO BE AVOIDED DURING CONCEIVING AS IT IS A TERATOGENIC AGENT
3 DIMETHYLFURATE
A ) Also kn as BG - 12 or FUMADERM
B ) Contains 4 different fumaric ester
C ) Serves a 2nd line agent in Severe Psoriasis
MECHANISM OF ACTION
1 Since , it is antiinflammatory drug it reduces the lymphocytes - decreases the activity of TH 1 helper cells and increases the activity of TH 2 helper cells
2 Causes Apoptosis of Active T cells
3 Increases the cellular content of glutathione to prevent cellular damage
EFFECTIVENESS ( EFFECTIVE DOSAGE - IN RELATION TO VARIOUS SOURCE OF EVIDENCES )
ALSO CALLED EBM ( EVIDENCE BASED MEDICINE )
1 In 2006 , the finding of a 18 week , open label prospective study indicated that it reduces the number of gadolinium enhanced lesions in the dosages of 240 mg TID by 69 %
2 The DEFINE trial ( DETERMINING EFFICACY AND SAFETY OF ORAL FUMARATE IN RRMS , a 2 yr phase III study , there was 56 % relative reduction of ARR - There was 94 % reduction in Gadolinium Enhanced MRI
3 Another Phase III trial CONFIRM ( COMPARATOR AN AND ORAL FUMARATE IN RRMS ) confirms the same as mentioned above
SO , ITS AN ALTERNATIVE TO CURRENT THERAPIES
4 AND 5 - IN CLINICAL TRIALS
4 CLADRIBINE
A ) is an Adenosine Deaminase resistant purine nucleoside
B ) is initially launched for the treatment of hairy cell leukemia
MECHANISM OF ACTION
1 It Enters the cell via purine nucleoside transporter and is phoslhorylated by deoxycytidine kinase
2 Thus , it causes cell death
EFFECTIVENESS ( EFFECTIVE DOSAGE - IN RELATION TO VARIOUS SOURCE OF EVIDENCES )
ALSO CALLED EBM ( EVIDENCE BASED MEDICINE )
A ) According to Phase III ORACLE study ( ORAL CLADRIBINE FOR EARLY MS TRIAL ) - in the dosages of 3.5 -5.5 mg / day it reduces the conversion according to MACDONALD CRITERIA OR reduces the progression into MACDONALD CRITERIA IF STARTED EARLY
B ) According to Phase III CLARITY STUDY ( ORAL CLADRIBINE FOR TREATING MS ) SHOWED a decrease of 55 - 56 % of ARR
C ) But its use is DISCARDED owing to a lot of side effects and serious effects such as activation of latentTB , more no of opportunistic infections IN CLARITY STUDY
5 LAQUINIMOD
A ) Is an orally administered quinoline 3 carboxyamide derived from limomide
B ) is recommended in a dose of 2.5 mg
C ) causes a 23 % reduction in ARR according to BRAVO STUDY ( AVONEX VS LAQUINIMMODE
D ) Is not to be recommended since its use is associated with venous thrombosis and BUDD CHIARI SYNDROME And cardiopulmonary toxicity and Pancreatitis in Phase 3 study