Psoriasis treatment with "small molecules"

Available “small molecules”:

• Apremilast (Otezla)
  • inhibits phosphodiesterase 4 (PDE4)
  • exhibits anti-inflammatory properties
  • apart from PDE4 action, its complete effects are not fully known but it is known (at the time of writing) that it modulates inflammation by reducing TNF-alpha, Il-2, IFN-gamma, leukotrienes and NO synthases. The effect appears to act through increased intracellular cAMP accumulation which in turn decreases production of these cytokines.
  • ESTEEM Study
    • At 16 weeks:
      • 33% achieved PASI 75 (vs 5.3% in the placebo group. It also included a group of patients who had priorly received biologics and predictively they responded less well than the biologic “naive” patient group
      • also reduction in Pruritus (seen as soon as week 2), scalp disease, nail disease (NAPSI) as well as improved DLQI.
    • It is comparatively slower and less effective for joint treatment than Humira or Etanercept. In the latter the improvement is around 50% whereas for apremilast in is around 30%. This is balanced by the mode of administration (oral intake of apremilast vs injection for the biologics)
    • The depression rate was low. It was probably studied because of another PDE4 inhibitor called roflumilast (Daliresp) shows a high incidence of strong depression.

• There is another small molecule called tofacitinib (Xeljanz):
  • acts as a Janus Kinase 3 (JAK3) enzyme inhibitor
  • is approved for the treatment of rheumatoid arthritis – but not for plaque psoriasis
  • is administered orally at a dosage of 5mg but can be increased to 10mg
  • carries a black box warning because of the risk of infection, lymphoma and other malignancies

Contributors

Dr Christophe Hsu – dermatologist. Geneva, Switzerland

S002 – Leonardi C et al. Systemic Therapies for Dermatologists: a Comprehensive Review and Update. AAD 2015 Annual Meeting, San Francisco CA – United States