L15 - systemic therapies Flashcards
Steroid complications
obesity, acid reflux problems, increased infection risk, diabetes, induces apoptosis, osteoporosis
Cyclosporine
used in asthma, associated with reduction ins steroid treatment and exacerbation frequency
Cyclosporine side effects
increased blood pressure, creatinine and LFTs
Cyclosporine mechanism
inhibition of T cell proliferation in cyclophilin and calcineurin
Biologics in eosinophilic asthma
can target specific components of inflammatory response with causing marked immunosuppression
Eosinophilic treatments
mepolizumab, reslizumab and benralizumab
Atopic treatments
Omalizumab
Omalizumab
humanised murine anti-IgE antibody binding in IgE FC region
binds IgE without cross-linking it
reduces allergic responses to allergies that appear to be central in inflammation in atopic asthma
Omalizumab half-life
approx 26 days with 7-8 day absorption from subcutaneous site
Omalizumab benefits
specific targeting of allergy without steroids side effects
reduces exacerbations by approx 75%, less effect on background lung function
doesn’t replace inhaled therapies but can replace oral steroids
Omalizumab disadvantages
mostly hospital administration, subcutaneous injections every 2-4 weeks
uncertain use in pregnancy
very expensive per patient per uear
Omalizumab side effects
increased risk of vascular episodes and low risk of anaphylaxis
Omalizumab NICe criteria
continuous oral steroids or 4+ courses per year, optimised treatment, confirmed adherence, impaired lung function with reduced FEV1
Targeting IL-5
IL-5 required for eosinophils to be made in bone marrow, eosinophil depletion slower in tissue than the blood
Mepolizumab
4 weekly subcutaneous dosing
relatively few side effects
Mepolizumab NICE criteria
blood eosinophil count 300+ in past year, continuous oral steroids over previous 6 months of 4+ courses a year
at 12 months stop if no adequate response
Reslizumab
4 weekly dosing IV, minimal side effects, reduces exacerbation frequency and decreases oral steroids
Relizumab NICE criteria
continuous oral steroids with blood eosinophil count 400+, 3+ exacerbations requiring oral steroids in last 12 months
12 months stop if no adequate response
Benralizumab
4 weekly subcutaneous doses for 3 doses then every 8 weeks, reduces exacerbation frequency, no significant side effects
Benealizumab NICE criteria
blood eosinophil 400+ plus 3+ exacerbations requiring oral steroids in last 12 months
or blood eosinophil count 300+ with 4+ exacerbations
12 months stop if no response
Dupilumab
reduction in severe exacerbations and oral steroids
improvement in lung function FEV1
currently only licensed for eczema, undergoing NICE evaluation
Dupilumab mechanism
inhibits IL-4 and IL-13 signal transduction
Anti-IL-13 asthma studies
multiple studies, reduces exacerbations and not yet used
Other immuno-modulators
range of drugs employed with variable effects and uncertain mechanisms of action
may also have benefits with respect to chronic airways infection
AMAZEs study
400 participants with placebo control
using Azithromycin 3x a week
minimal side effects
60% reduction in exacerbations regardless of asthma phenotype
AMAZES study before
macrolides showed little evidence of benefit, theoretical environmental cost so try to us rarely, considered in some conditions already
AMAZES study after
biologic costs 5-20k a year whereas azithromycin costs 100-200 a year
biologics change lives when they work and favour eosinophilic disease, options are currently limited for neutrophilic asthma
