Project: An independent prospective randomised controlled trial comparing the efficacy and cost effectiveness of infliximab and etanercept in 'high need' patients with moderate to severe chronic plaque type psoriasis

An independent prospective randomised controlled trial comparing the efficacy and cost effectiveness of infliximab and etanercept in 'high need' patients with moderate to severe chronic plaque type psoriasis

This is a summary of the request.

Research questions:

What is the clinical effectiveness, the effect on patient reported outcomes, safety and cost effectiveness of infliximab compared to etancercept?

Rationale:

2% of the populations suffers from psoriasis and 10% of these patients require photo(chemo)therapy orf systemic therapy. The health related quality of life (HRQOL) of psoriasis patients is strongly impaired. Many conventional treatments for psoriasis are available, but long term use is associated with risks and most patients are dissatisfied with these therapies. Recently, three biologics including etanercept and infliximab have been approved for severe and therapy resistant psoraisis. Due to the introduction of these expensive drugs, the drug costs associated with psoriasis care is expected to increase exponentially. Although etanercept is more commonly used, the optimal treatment paradigm for patients eligible for biological therapy is unclear. For an optimal positioning of the biologics, pharmaceutical industry independent comparative trials are necessary that assess effectiveness, patients' perspectives, safety and cost effectiveness.

Study design:

This trial is a multi-center, pharmaceutical independent, prospective randomised controlled trial comparing head-to-head infliximab and etanercept.

Study population:

Patients with moderate to severe chronic plaque type who failed or have contraindications and/or are intolerant to ultraviolet therapy, methotrexate and cyclosporin according to the Dutch reimbursement criteria are eligible. Consecutive patients of the Department of Dermatology of the AMC, Erasmus MC or Radboud hospital with chronic plaque type psoriasis will be screened and, if eligible, randomized in a 1:1 ratio to either infliximab or etanercept. The randomisation occurs in the coordinating center according to a computer-generated list.

Interventions:

Treatment will be given according to nowadays standard care with respect to dosage, frequency of follow up and monitoring.

Etanercept will be self administered by subcutaneous injection between week 0 and 12 at a doses of 50 mg twice weekly (BIW). At week 12, patients with a PASI75 or more will be switched to 25 mg BIW for another 12 weeks up to week 24, non-responders (< PASI50) will switch to infliximab.

Infliximab is an intravenous treatment with 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks thereafter. At week 12, responders (PASI75 or more) continue therapy with injections every other 8 weeks up to week 22, non-responders (< PASI50) switch to etanercept 50 mg BIW FOR 12 weeks.

Thereafter, patients will be followed every two months up to one year.

Outcome measures:

Clinical effectiveness and patient reported outcomes:

-PASI75 at week 12 and 26.

-PGA of clinical psoriasis severity of minimal or clear.

-Improvement of HRQOL: median changes in the three domain scores of the dermatology specific Skindex-17 and the scores physical and mental component scale of the generic SF-36.

-Treatment satisfaction will be measured with Median changes Treatment Medication Satisfaction Questionnaire (TMSQ) score

-In responders (PASI75), duration of remission (relapse of disease is defined as a 50% loss of the obtained PASI improvement and/or need to retreat with UV and/or systemic therapy includings biologicals) will be analysed

- In non-responders (PASI50), the clinical effectiveness and patients perspectives of the comparative drug will be analysed.

Economic evaluation:

-The difference between the cost effectiveness of the two treatment options will be assessed in anticipation of the new Dutch guidelines for expensive hospital medication and orphan drugs.

-The incremental cost effectiveness ratio (ICER) of infliximab will be calculated relative to etanercept. This incremental cost effectiveness ratio in terms of costs per QALY will be estimated using a probabilistic Markov model, to allow for a multivariate sensitivity analysis

-Utilities will be assessed by using the EQ-5D which is especially designed for the use in QALY analysis and is shown to be sensitive in psoriasis.

-The economoic evaluation will conducted from a societal perspective. Nonmedical costs (travel, productivity losses) and medical cost outside the hospital will be assess using the iMTA Labor and Health Questionnaire.

Sample size calculation:

In total, 60 patients will be included in each study arm (n=120).

Data-analysis:

The outcomes will be analyzed both on a per-protocol and intention-to-treat bases.

Time schedule:

Months 0-3: development of case record form and local ethical committees permission

Months 4-21: recruitement

Months 22-33: follow up

Months 34-36: data analysis and reporting