IMMUNO SUPPRESSIVES

Question 1

Ciclosporin for AD indications

Answer 1

Despite the lack of formal FDA approval for this use, the AAD Guidelines of Care committee recommends ciclosporin as being effective for the treatment of atopic dermatitis refractory to conventional treatment with no statement as to the recommended dosage .

Question 2

Ciclosporin for AD Dosing aims

Answer 2

•lowest effective dose
 shortest treatment period - toxicity related
 Short courses (up to 3 months) with periods of rest can be administered to limit total exposure to the drug.

Question 3

Ciclosporin for AD Dosing

Answer 3

Start at a higher initial dose (4-5 mg/kg/d) for a rapid initial response and then taper to a lower-maintenance dose
OR
Start at a lower dose (2.5 mg/ kg/d) and gradually increase if clinical response is inadequate

Question 4

Azathioprine efficacy AD

Answer 4

retrospective study

• 35 patients with AD treated average of 100 mg/d median 7 mo 69% subjective improvement .
• 38 patients with severe AD, efficacy in 80% decreased serum IgE levels .

Question 5

Azathioprine Dosing

.

Answer 5

1 to 3 mg/kg daily- studies 2.5mg/kg/day
children-full dose 2.5 mg/kg/day,
one-third dose 3–4 w, two-thirds dose 3–4 w

Question 6

Methotrexate efficacy AD

adults

Answer 6

-open-label prospective 12 patients
incremental dosing regimen start 10mg/w
moderate-severe AD 52% within 24 weeks. improvement 12 weeks after cessation
-RCT 45 adults, methotrexate comparable to azathioprine disease severity QOL

Question 7

Methotrexate efficacy AD

children -

Answer 7

children - 
5mg/10mg p/w  effective, safe and well-moderate to severe discoid eczema 
failed conventional topical therapy 
increased15 mg weekly 
Folic acid supplement

Question 8

methotrexate is significantly ___

Compared with ciclosporin and azathioprine,

Answer 8

less immunosuppressive with a preferable longer-term safety profile.

Question 9

Mycophenolate mofetil efficacy

A 12-week pilot study found a 68% improvement in disease severity in 10 patients with severe AD with an initial dose of 1 g daily for 1 week followed by 2 g daily for a further 11 weeks . Improvement in the SCORAD was correlated with a decrease in serum IgE, the number of activated human leukocyte antigen-DR+, CD3+ T lymphocytes, and serum levels of interleukin-10 and interferon-g. There was no evidence of tachyphylaxis observed within 3 years. Alternatively in another study, 1 g twice daily for 4 weeks, followed by a reduction to 500 mg twice daily for a further 4 weeks also resulted in reduction in SCORAD by 74% at the end of 20 weeks .

A recent RCT showed that enteric-coated mycophenolate sodium is as effective as ciclosporin as maintenance therapy in patients with AD, but with a delay in clinical improvement compared with ciclosporin; SCORAD was higher in the enteric-coated mycophenolate sodium arm for the first 10 weeks, but comparable to the ciclosporin arm subsequenty. However, clinical remission after stopping enteric-coated mycophenolate sodium lasts longer compared with ciclosporin .

Mycophenolate mofetil is useful for patients in whom other available systemic therapies are contraindicated or not tolerated.It is generally well tolerated; the most common adverse effect is gastrointestinal upset. This can usually be reduced by dividing the total daily dose into 2 or 3 equal doses per day. For side effects and monitoring in MMF use, refer to “Immunobullous diseases”guidelines. There have been cases of central nervous system lymphoma in patients treated with mycophenolate for lupus and myasthenia gravis . In 2008, an alert from the FDA has suggested a possible link between immunosuppression with mycophenolate and the development of progressive multifocal leukoencephalopathy .

Answer 9

Short-term oral mycophenolate mofetil 2 g daily monotherapy clearing adults resistant AD

Question 10

methotrexate Short-term side-effects

Answer 10

haematological toxicity and gastrointestinal upset.