L15 - systemic therapies Flashcards

1
Q

Steroid complications

A

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

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2
Q

Cyclosporine

A

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

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3
Q

Cyclosporine side effects

A

increased blood pressure, creatinine and LFTs

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4
Q

Cyclosporine mechanism

A

inhibition of T cell proliferation in cyclophilin and calcineurin

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5
Q

Biologics in eosinophilic asthma

A

can target specific components of inflammatory response with causing marked immunosuppression

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6
Q

Eosinophilic treatments

A

mepolizumab, reslizumab and benralizumab

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7
Q

Atopic treatments

A

Omalizumab

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8
Q

Omalizumab

A

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

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9
Q

Omalizumab half-life

A

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

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10
Q

Omalizumab benefits

A

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

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11
Q

Omalizumab disadvantages

A

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

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12
Q

Omalizumab side effects

A

increased risk of vascular episodes and low risk of anaphylaxis

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13
Q

Omalizumab NICe criteria

A

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

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14
Q

Targeting IL-5

A

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

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15
Q

Mepolizumab

A

4 weekly subcutaneous dosing

relatively few side effects

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16
Q

Mepolizumab NICE criteria

A

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

17
Q

Reslizumab

A

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

18
Q

Relizumab NICE criteria

A

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

19
Q

Benralizumab

A

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

20
Q

Benealizumab NICE criteria

A

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

21
Q

Dupilumab

A

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

22
Q

Dupilumab mechanism

A

inhibits IL-4 and IL-13 signal transduction

23
Q

Anti-IL-13 asthma studies

A

multiple studies, reduces exacerbations and not yet used

24
Q

Other immuno-modulators

A

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

25
AMAZEs study
400 participants with placebo control using Azithromycin 3x a week minimal side effects 60% reduction in exacerbations regardless of asthma phenotype
26
AMAZES study before
macrolides showed little evidence of benefit, theoretical environmental cost so try to us rarely, considered in some conditions already
27
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