APRICOT - Anakinra for pustular psoriasis

INTERVENTION: Participants will be randomised at baseline to either active or placebo treatment arms, 1:1. Both treatments are in prefilled syringes and given by daily subcutaneous injection for eight weeks (treatment period). Active group: Participants receive anakinra (Kineret®) 100mg/0.67ml Placebo group: Participants receive a matched 0.67ml vehicle solution Participants will attend clinic visits at the following time points: screening, baseline (treatment initiation ‐ up to 3 months after screening), week 1, week 2, week 4, week 6, week 8, and follow up at week 12 and at 90 days post last treatment dose. Baseline to week 8 is the “treatment period” and at each visit clinical assessments of disease severity will be made to collect data for the outcome measures. Any adverse events and changes to other medication will also be recorded. The two follow up visits are for safety, and at both visits the participant will be asked about their health over the intervening weeks and any adverse events noted. CONDITION: Specialty: Dermatology, Primary sub‐specialty: Dermatology; UKCRC code/ Disease: Inflammatory and Immune System/ Certain disorders involving the immune mechanism, Skin/ Other disorders of the skin and subcutaneous tissue ; Skin and Connective Tissue Diseases ; Palmo‐plantar pustulosis (PPP) PRIMARY OUTCOME: Disease severity as measured by fresh pustule count (i.e. number of macroscopically visible, sterile, white/yellow pustules present on the palms and soles) and/or palmoplantar pustulosis psoriasis area severity index (PP‐PASI) score at baseline, 2, 4, 6 and 8 weeks. INCLUSION CRITERIA: 1. Adults (18 years and over) with diagnosis of Palmo‐Plantar Pustulosis (PPP) made by a trained dermatologist with disease of sufficient impact and severity to require systemic therapy 2. Disease duration of >6 months, not responding to an adequate trial of topical therapy including very potent corticosteroids 3. Evidence of active pustulation on palms and /or soles to ensure sufficient baseline disease activity to detect efficacy 4. At least moderate disease on the PPP Investigator’s Global Assessment (PPP‐IGA) 5. Women of child bearing potential who are on adequate contraception, who are not pregnant or breast feeding 6. Who have given written, informed consent to participate SECONDARY OUTCOME: Investigator assessed:; 1. Disease severity as measured by total pustule count on palms and soles (i.e. number of macroscopically visible, sterile, brown/white/yellow pustules present) at baseline, 2, 4, 6 and 8 weeks; 2. Global disease severity as measured using the Investigator's Global Assessment (PPP‐IGA) (i.e. clinical opinion of disease severity as defined by the validated scale; clear, nearly clear, mild, moderate, severe, very severe, by the investigating physician) at baseline, 2, 4 and 8 weeks; 3. Time to response of PPP (defined as a 75% reduction in fresh pustule count) and relapse rate (defined as a return to baseline fresh pustule count) as measured by clinical examination and fresh pustule count at baseline, 2, 4, 6 and 8 weeks ; 4. Achievement of ‘clear‘ on PPP‐IGA by 8 weeks as measured by the investigating physician at 8 weeks; 5. Development of a disease flare (i.e. >50% deterioration in PP‐PASI compared to baseline) as measured by clinical examination and PP‐PASI score at baseline, 2, 4, 6 and 8 weeks ; 6. Pustular psoriasis at non acral sites as measured by change in percentage area of involvement at baseline and 8 weeks; 7. Plaque type psoriasis (if present) measured using Psoriasis Area and Severity Index (PASI) at baseline and 8 weeks; 8. Serious infection rate, defined by any infection leading to death, hospital admission or requiring IV antibiotics, as measured by adverse event reports at week 1, 2, 4, 6, 8, and 12 weeks. ; 9. Neutropenia (i.e. neutrophil count of 1.0x10‐9/l on at least one occasion) as measured by blood tests at baseline, 1, 2, 4, 6, and 8 weeks. ; ; Patient reported outcomes:; 1. Patient reported disease severity as measured using the Patient's Global Assessment (measured on the scale: clear, nearly clear, mild, moderate, severe, very severe) at baseline, 2, 4, 6 and 8 weeks; 2. Patient reported opinion of palmo‐plantar specific quality of life as measured using the Palmoplantar Quality of Life Instrument (validated questionnaire) score at baseline and 8 weeks; 3. Patient reported opinion of general quality of life as measured using the Dermatology Life Quality Index (validated questionnaire) at baseline and 8 weeks; 4. Patient reported opinion of general health as measured using the EQ5D‐3L (a European, validated questionnaire) score at baseline and 8 weeks; 5. Treatment acceptability as evaluated using a brief questionnaire with a response scale of 1‐5 at study end; 6. Adherence to treatment measured by responses to daily text message over 8 weeks of treatment; ; Exploratory:; 1. Expression levels of IL‐1 related gene transcripts in blood, skin and keratinocytes derived from hair plucks as measured by RNA levels detected in collected samples by study end; 2. Identification of disease‐associated mutations as measured by whole‐exome/whole‐genome sequencing or by targeted screening of candidate genes in collected samples by study end; 3. Identification of patient immune phenotypes as measured by functional assays on collected samples by study end; 4. Curation of complete clinical, DNA, RNA, serum datasets (with optional tissue samples [skin and hair pluck]) on recruited study participants as measured by number of samples collected and subsequent storage of samples per participant by study end