A Randomized Controlled Trial Comparing Proactive Therapeutic Drug Monitoring with Routine Care Using Secukinumab, Ixekizumab, or Guselkumab in Moderate-to-Severe Psoriasis

The primary objective of this study is to assess whether **proactive therapeutic drug monitoring (TDM)** is non-inferior to the standard of care in achieving sustained disease control in patients with moderate-to-severe **psoriasis**. Sustained disease control is defined as an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 or a delta PASI from baseline ≥ 50% during at least 80% of all 3-monthly study visits over an 18-month period. This is clinically relevant as it aims to optimize treatment outcomes and improve long-term management of psoriasis using novel biologics such as secukinumab, ixekizumab, or guselkumab.

Secondary objectives include comparing proactive TDM to standard care in terms of:

• Disease activity
• Quality of life
• Treatment satisfaction
• Cost of treatment
• Safety
• Identifying baseline predictors for sustained disease control

The clinical trial focuses on individuals diagnosed with **moderate-to-severe psoriasis**, specifically targeting adults aged 18 years or older. Both male and female participants are included, and the study acknowledges the involvement of a vulnerable population. Participants must have a documented diagnosis of psoriasis, predominantly type vulgaris, confirmed by an accredited dermatologist. They are required to have been undergoing treatment with the biologics secukinumab, ixekizumab, or guselkumab for at least six months following the standard dosing regimen. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on these criteria, ensuring that all participants have given informed consent. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of proactive therapeutic drug monitoring (TDM) compared to routine care in patients with **moderate-to-severe psoriasis**. This study is a pragmatic, multicentric, randomized, controlled trial involving the use of novel biologics, specifically **secukinumab**, **ixekizumab**, and **guselkumab**. The trial is structured as a double-blind study to ensure unbiased results. The total duration of the trial is estimated to be 18 months, with the recruitment phase expected to commence on September 1, 2024, and conclude by September 1, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, documented diagnosis of psoriasis, and current treatment with the specified biologics for at least six months. Following the screening, participants will attend study visits every three months to monitor disease control, defined as achieving a Psoriasis Area and Severity Index (PASI) score of ≤ 2 or a reduction of ≥ 50% from baseline in at least 80% of these visits. The primary endpoint is sustained disease control over the 18-month period.

Secondary endpoints include changes from baseline in PASI, Dermatology Life Quality Index (DLQI_R), and SF-36 scores at 18 months, as well as the occurrence of new or flaring arthritis, drug discontinuation, serious adverse events, and adverse events of special interest. Additionally, the study will assess treatment costs, healthcare consumption, and treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM) and Visual Analogue Scale (VAS).

Participants are expected to be involved in the study for the full 18-month duration unless conditions arise that necessitate early termination, such as significant adverse events or withdrawal of consent. The trial is categorized as a low-intervention study, with minimal additional risk or burden compared to standard clinical practice. Blood samples will be collected every three months, and participants will complete questionnaires to assess various health and quality of life metrics.

The clinical trial involves the administration of **Taltz** (ixekizumab), a solution for injection available in pre-filled pens and syringes. Each pre-filled pen contains 80 mg of ixekizumab, a protein-based active substance. The pharmaceutical form is a solution for injection, and the route of administration is subcutaneous. The maximum daily dose is 80 mg, with a total maximum dose of 5760 mg over the treatment period. The treatment period is set for 18 months, with the frequency of administration determined by the study protocol. Participant compliance is monitored through regular study visits.

Another experimental medication used in the trial is **Cosentyx** (secukinumab), which is also a solution for injection provided in pre-filled pens. The active substance, secukinumab, is a recombinant human monoclonal antibody targeting interleukin (IL)-17A. The medication is available in two dosages: 150 mg and 300 mg per pen. The maximum daily dose is 300 mg, with a total maximum dose of 21600 mg over the 18-month treatment period. Administration is subcutaneous, and dosing schedules are aligned with the study's requirements, with compliance monitored at scheduled intervals.

**Tremfya** (guselkumab) is the third experimental medication in the trial, available as a solution for injection in pre-filled syringes and pens. Each unit contains 100 mg of guselkumab, a protein-based active substance. The maximum daily dose is 100 mg, with a total maximum dose of 7200 mg over the course of the study. The route of administration is subcutaneous, and the dosing schedule is determined by the study protocol. Participant adherence to the treatment regimen is assessed during regular study visits.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. The focus is on evaluating the efficacy and safety of the experimental medications in patients with moderate-to-severe psoriasis. The trial aims to assess proactive therapeutic drug monitoring compared to routine care, with the objective of achieving sustained disease control.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is defined as sustained disease control in patients with moderate-to-severe **psoriasis**. This is measured by achieving an absolute Psoriasis Area and Severity Index (PASI) score of ≤ 2 or a reduction in PASI score from baseline by ≥ 50% during at least 80% of all 3-monthly study visits over an 18-month period. The PASI score is a widely used tool to measure the severity and extent of psoriasis, with scores ranging from 0 (indicating no skin lesions) to 72 (indicating severe disease).

Secondary endpoints include various measures of quality of life and treatment satisfaction. These include changes from baseline at 18 months in the Dermatology Life Quality Index (DLQI_R), the Short Form Health Survey (SF-36), and the Treatment Satisfaction Questionnaire for Medication (TSQM). The DLQI_R score ranges from 0 (no impact on quality of life) to 30 (greatest impact), while the SF-36 score ranges from 0 (maximum disability) to 100 (no disability). The TSQM is a 9-point questionnaire with scores ranging from 0 to 100, where higher scores indicate greater satisfaction. Additionally, the Visual Analogue Scale (VAS) will be used to measure treatment satisfaction, with scores ranging from 0 (no satisfaction) to 10 (extreme satisfaction).

Other secondary endpoints include the occurrence of new onset or flare of arthritis, drug discontinuation and reasons, serious adverse events (SAE), adverse events of special interest (AEoSI) such as infusion reactions and infections, cost of treatment, healthcare consumption, number of dose modifications, and cost-effectiveness measured by the iMCQ and EQ-5D-5L. The EQ-5D-5L is noted for its correlation with clinical endpoints and responsiveness, with a minimal clinically important difference (MCID) of 6 units.