| Participants |
Inclusion criteria of the trial
Adults (18 years and older) with diagnosis of palmoplantar pustulosis (PPP) made by a trained dermatologist with disease of sufficient impact and severity to require systemic therapy Disease duration > 6 months, not responding to an adequate trial of topical therapy including very potent corticosteroids Evidence of active pustulation on palms and/or soles to ensure sufficient baseline disease activity to detect efficacy At least moderate disease on the PPP Investigator’s Global Assessment (PPP‐IGA) Women of childbearing potential who are on adequate contraception, who are not pregnant or breastfeeding Who have given written, informed consent to participate
Exclusion criteria of the trial
Previous treatment with anakinra or other IL‐1 antagonists History of recurrent bacterial, fungal, or viral infection Evidence of active infection or latent TB or HIV, hepatitis B or C seropositive History of malignancy of any organ system (other than treated, localised non‐melanoma skin cancer), treated or untreated, within the past 5 years Use of therapies with potential or known efficacy in psoriasis during or within the following specified time frame before treatment initiation (week 0, visit 2): very potent topical corticosteroids within 2 weeks; topical treatment that is likely to impact signs and symptoms of psoriasis (e.g. corticosteroids, vitamin D analogues, calcineurin inhibitors, retinoids, keratolytics, tar, urea) within 2 weeks; methotrexate, ciclosporin, acitretin, or alitretinoin within 4 weeks; phototherapy or PUVA within 3 months; etanercept or adalimumab within 4 weeks; infliximab or ustekinumab or secukinumab within 3 months; other TNF antagonists within 3 months; other immunosuppressive or immunomodulatory therapy within 30 days or 5 half‐lives before treatment initiation, whichever is longer; any other investigational drug within 30 days (or 3 months for investigational monoclonal antibodies) or 5 half‐lives before treatment initiation, whichever is longer With moderate renal impairment (CrCl < 50 mL/min) With neutropenia (< 1.5 × 109/L) With known moderate hepatic disease and/or raised hepatic transaminases (ALT/AST) > 2 × ULN at baseline. Patients who fail this screening criterion may still be considered following review by a hepatologist and confirmed expert opinion that study entry is clinically appropriate Live vaccinations within 3 months before the start of study medication, during the trial, and up to 3 months following the last dose. Women who are pregnant, breastfeeding or of childbearing age not on adequate contraception or men planning conception Poorly controlled diabetes mellitus, cardiovascular disease, asthma, concomitant therapy that may interact with anakinra (e.g. phenytoin, warfarin), or any condition where, in the opinion of the investigator, anakinra would present risk to the patient Latex allergy (inner needle cover of pre‐filled syringe contains natural rubber) Unable to given written, informed consent Unable to comply with the study visit schedule
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| Outcomes |
Primary outcome of the trial
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 (PPPASI) score at baseline and at 2, 4, 6, and 8 weeks
Secondary outcome of the trial
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 and at 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 and at 2, 4, and 8 weeks; (3) time to response of PPP (defined as 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 and at 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 PPPASI compared to baseline) as measured by clinical examination and PPPASI score at baseline and at 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 at 8 weeks; (7) plaque‐type psoriasis (if present) measured using Psoriasis Area and Severity Index (PASI) at baseline and at 8 weeks; (8) serious infection rate, defined by any infection leading to death or hospital admission, or requiring IV antibiotics, as measured by adverse event reports at weeks 1, 2, 4, 6, and 8, and at 12 weeks; (9) neutropenia (i.e. neutrophil count of 1.0 × 10‐9/L on at least 1 occasion) as measured by blood tests at baseline and at 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 and at 2, 4, 6, and 8 weeks; (2) patient‐reported opinion of palmoplantar specific quality of life as measured using the Palmoplantar Quality of Life Instrument (validated questionnaire) score at baseline and at 8 weeks; (3) patient‐reported opinion of general quality of life as measured using the Dermatology Life Quality Index (validated questionnaire) at baseline and at 8 weeks; (4) patient‐reported opinion of general health as measured using the EQ‐5D‐3L (a European, validated questionnaire) score at baseline and at 8 weeks; (5) treatment acceptability as evaluated using a brief questionnaire with a response scale of 1 to 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
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