A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial

Background: Palmoplantar pustulosis is a rare but painful and debilitating disease. It consistently ranks the highest of all psoriasis phenotypic variants in terms of symptoms and functional impairment. Management of plaque-type psoriasis has been revolutionised in the last 10 years with the advent of biologic therapies, but treatment options for pustular psoriasis remain profoundly limited. On the basis of mechanistic findings which suggest a key pathogenic role for interleukin (IL)-1 in pustular psoriasis, we hypothesise that anakinra (IL-1 blockade) will be an efficacious treatment for pustular psoriasis.

Methods/design: We will conduct a two-stage, adaptive, double-blind, randomised, placebo-controlled trial to test the hypothesis that anakinra, self-administered daily by subcutaneous injection over 8 weeks, will deliver therapeutic benefit in palmoplantar pustular psoriasis, a localised form of pustular psoriasis typically involving the palms and/or soles. Safety outcomes will be collected for 20 weeks. A total of 64 participants will be randomised to anakinra or placebo in a 1:1 ratio. At the end of stage 1, a decision to progress to stage 2 will be made. This decision will take place after 24 participants have been randomised and followed for 8 weeks and will be based on the ordering of the observed mean outcome values in both treatment arms. At the end of stage 1, the reliability of outcome measurements and method to collect the data will also be assessed, and the primary outcome will be confirmed for stage 2.

Discussion: We have undertaken an adaptive approach in which we will gain proof-of-concept data prior to completing a powered efficacy trial because pustular psoriasis is a rare disease, no validated outcome measures to detect change exist, and limited safety data for anakinra exist in this population. To our knowledge, this will be the first randomised controlled trial that will provide valuable evidence for the efficacy and safety of IL-1 blockade for treatment in pustular psoriasis.

Trial registration: ISRCTN13127147 . Registered on 1st August 2016. EudraCT, 2015-003600-23 . Registered on 1st April 2016.