The main purpose of this study is to demonstrate that when participants with moderate to severe plaque psoriasis and obesity or overweight in the presence of at least 1 weight-related comorbid condition receive ixekizumab and tirzepatide concomitantly administered, participants see improvement in their psoriasis and achieve weight reduction compared to when receiving ixekizumab.

Participation in this study includes up to 12 visits and could last up to 61 weeks including screening, open label treatment period, and post-treatment follow-up period.

Inclusion Criteria:

• Have a diagnosis of moderate-to-severe plaque psoriasis (PsO) for at least 6 months.
• Have both a Static Physician's Global Assessment (sPGA) score of ≥3 and a Psoriasis Area and Severity Index (PASI) ≥12.
• Have ≥10% body surface area (BSA) involvement.
• Have obesity, body mass index of ≥30 kilograms per meter squared (BMI ≥30 kg/m²) or overweight (BMI ≥27 to <30 kg/m²) in the presence of at least 1 of these weight-related comorbid conditions (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, or T2DM).

Exclusion Criteria:

Medical Conditions

• Have Type 1 Diabetes Mellitus (T1DM).

• Have insulin-treated Type 2 Diabetes Mellitus (T2DM).

• Have a prior or planned surgical treatment for obesity.

• Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia (MEN) syndrome type 2.

• Have active, or a history of inflammatory bowel disease (Crohn's or ulcerative colitis).

• Have a diagnosis or history of malignant disease within the 5 years prior to randomization, with the following exceptions:

  • basal cell or squamous epithelial carcinomas of the skin that have been resected, with no evidence of metastatic disease for 3 years.
  • cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to randomization.

• Have serious disorder or illness other than PsO.

• Have a history of chronic or acute pancreatitis.

• Have any prior use of ixekizumab or tirzepatide.

• Have a previous failure or intolerance to an interleukin 17 inhibitor (IL-17i) or glucagon-like peptide 1 (GLP-1) receptor agonists.

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.