L15 - systemic therapies

Question 1

Steroid complications

Answer 1

obesity, acid reflux problems, increased infection risk, diabetes, induces apoptosis, osteoporosis

Question 2

Cyclosporine

Answer 2

used in asthma, associated with reduction ins steroid treatment and exacerbation frequency

Question 3

Cyclosporine side effects

Answer 3

increased blood pressure, creatinine and LFTs

Question 4

Cyclosporine mechanism

Answer 4

inhibition of T cell proliferation in cyclophilin and calcineurin

Question 5

Biologics in eosinophilic asthma

Answer 5

can target specific components of inflammatory response with causing marked immunosuppression

Question 6

Eosinophilic treatments

Answer 6

mepolizumab, reslizumab and benralizumab

Question 7

Atopic treatments

Answer 7

Omalizumab

Question 8

Omalizumab

Answer 8

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

Question 9

Omalizumab half-life

Answer 9

approx 26 days with 7-8 day absorption from subcutaneous site

Question 10

Omalizumab benefits

Answer 10

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

Question 11

Omalizumab disadvantages

Answer 11

mostly hospital administration, subcutaneous injections every 2-4 weeks
uncertain use in pregnancy
very expensive per patient per uear

Question 12

Omalizumab side effects

Answer 12

increased risk of vascular episodes and low risk of anaphylaxis

Question 13

Omalizumab NICe criteria

Answer 13

continuous oral steroids or 4+ courses per year, optimised treatment, confirmed adherence, impaired lung function with reduced FEV1

Question 14

Targeting IL-5

Answer 14

IL-5 required for eosinophils to be made in bone marrow, eosinophil depletion slower in tissue than the blood

Question 15

Mepolizumab

Answer 15

4 weekly subcutaneous dosing

relatively few side effects

Question 16

Mepolizumab NICE criteria

Answer 16

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

Question 17

Reslizumab

Answer 17

4 weekly dosing IV, minimal side effects, reduces exacerbation frequency and decreases oral steroids

Question 18

Relizumab NICE criteria

Answer 18

continuous oral steroids with blood eosinophil count 400+, 3+ exacerbations requiring oral steroids in last 12 months
12 months stop if no adequate response

Question 19

Benralizumab

Answer 19

4 weekly subcutaneous doses for 3 doses then every 8 weeks, reduces exacerbation frequency, no significant side effects

Question 20

Benealizumab NICE criteria

Answer 20

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

Question 21

Dupilumab

Answer 21

reduction in severe exacerbations and oral steroids
improvement in lung function FEV1
currently only licensed for eczema, undergoing NICE evaluation

Question 22

Dupilumab mechanism

Answer 22

inhibits IL-4 and IL-13 signal transduction

Question 23

Anti-IL-13 asthma studies

Answer 23

multiple studies, reduces exacerbations and not yet used

Question 24

Other immuno-modulators

Answer 24

range of drugs employed with variable effects and uncertain mechanisms of action
may also have benefits with respect to chronic airways infection

Question 25

AMAZEs study

Answer 25

400 participants with placebo control using Azithromycin 3x a week minimal side effects 60% reduction in exacerbations regardless of asthma phenotype

Question 26

AMAZES study before

Answer 26

macrolides showed little evidence of benefit, theoretical environmental cost so try to us rarely, considered in some conditions already

Question 27

AMAZES study after

Answer 27

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