Tofacitinib Plus Imatinib in Moderate-to-Severe Palmoplantar Pustulosis

Prior treatment

• Any active infection within 14 days prior to the baseline visit.
• Severe infection requiring hospitalization or intravenous anti-infective treatment within 8 weeks prior to the baseline visit.
• Major surgery (including joint surgery) within 8 weeks prior to the screening visit, or planned surgery during the study period.
• History of chronic alcohol or drug abuse within 6 months prior to the screening visit, as determined by the investigator based on medical history, interview, and examination findings.
• Current or prior use of IL-17A, IL-17A/F, or IL-23 inhibitors.
• Receipt of any live vaccine (including attenuated vaccines) within 8 weeks prior to the baseline visit.

Other illness

• Presence of any of the following conditions: guttate psoriasis, erythrodermic psoriasis, generalized pustular psoriasis, acrodermatitis continua of Hallopeau, atopic dermatitis, dyshidrotic eczema, chronic hand eczema, or folliculitis.
• Active infection or history of infection, as follows:
• History of opportunistic infections, recurrent infections, or chronic infections that, in the investigator's opinion, would make participation in this study harmful to the participant.
• Positive test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Exclusion is defined as:
• HBV positive: 1) hepatitis B surface antigen positive, or 2) anti-hepatitis B core antibody positive.
• HCV positive: 1) hepatitis C antibody positive, and 2) confirmed by a confirmatory HCV test (e.g., HCV polymerase chain reaction).
• Any of the following tuberculosis (TB)-related conditions:
• Known active TB disease.
• History of active TB involving any organ system, unless adequately treated per WHO/CDC treatment guidelines and confirmed as fully recovered by consultation with a relevant specialist.
• History of lymphoproliferative disorders (e.g., lymphoma) or current symptoms suggestive of lymphoproliferative disorders.
• Current active malignancy or history of malignancy within 5 years prior to the screening visit, except for squamous cell carcinoma or basal cell carcinoma of the skin, or treated and considered cured in situ cervical cancer.
• Presence of other inflammatory diseases, including but not limited to rheumatoid arthritis, hidradenitis suppurativa, inflammatory bowel disease, or systemic lupus erythematosus.
• Any systemic disease (e.g., cardiovascular, neurological, renal, hepatic, metabolic, gastrointestinal, hematological, coagulation disorders, immune system disease) that, in the investigator's opinion, is uncontrolled, unstable, or likely to progress to a clinically significant degree during the study.
• Any medical or psychiatric condition (including ongoing major depression or active suicidal ideation) that, in the investigator's opinion, may impair the participant's ability to participate in the study.

Lab values

• Drug-induced psoriasis (e.g., first onset or current flare triggered by beta-blockers, calcium channel inhibitors, lithium preparations, or TNF inhibitors) or drug-induced pustular psoriasis (e.g., acute generalized exanthematous pustulosis, acute localized exanthematous pustulosis).
• Latent TB infection (LTBI): Participants with LTBI may be rescreened once after receiving at least 4 weeks of appropriate LTBI treatment, provided that no treatment-related hepatotoxicity is evident prior to the first dose of investigational medicinal product (ALT/AST still ≤ 3×ULN).
• Laboratory abnormalities at the screening visit, including any of the following:
• ALT, AST, or ALP ≥ 3×ULN.
• Bilirubin \> 1.5×ULN (unconjugated bilirubin \> 1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin/total bilirubin ratio is \< 35%).
• White blood cell count \< 3.0×10³/μL.
• Absolute neutrophil count \< 1.5×10³/μL.
• Lymphocyte count \< 500 cells/μL.
• Hemoglobin \< 8.5 g/dL.
• Any other laboratory abnormality that, in the investigator's opinion, may interfere with the participant's ability to complete the study or confound the interpretation of study results.

Other

• Significant improvement in PPP symptoms between the screening and baseline visits, defined as a reduction in PPPASI score of ≥ 5 units.
• Vaccination not permitted during the study and within 17 weeks after the last dose of study treatment.

• Age ≥ 18 years at the time of screening.
• Diagnosis of palmoplantar pustulosis (PPP) for at least 12 weeks prior to the screening visit.
• May have a history of or concurrent plaque psoriasis.
• PPPASI score ≥ 12 at both the screening and baseline visits.
• PPP-IGA score ≥ 3 at both the screening and baseline visits.
• Presence of pustules on the palms and/or soles at both the screening and baseline visits, defined as pustule severity ≥ 2 in at least one region (one palm or one sole) based on the PPPASI.
• Must have a confirmed diagnosis of PPP by photographic adjudication.
• Male and/or female participants.
• Female participants must not be pregnant, not be lactating (including feeding an infant by breast pump).