The past several years have shown promising research in the development of agents that may be used in the treatment of psoriasis. This is an exciting and action packed area, as there have been very few changes in the management of psoriasis for several years. Findings from these studies demonstrate benefits for both inflammation and psoriasis and may provide unprecedented treatment and management for patients suffering from the disease.
Robert Bissonnette from Innovaderm Research Inc. in Montreal, Quebec, Canada, presented findings regarding vascular inflammation in patients with psoriasis when treated with a tumor necrosis factor (TNF)-α inhibitor. Research has shown that patients suffering from psoriasis have an increased risk of occlusive cardiovascular events such as myocardial infarctions (MIs). In addition, the use of drugs that treat inflammation, in patients with psoriasis, such as methotrexate or TNF-α antagonist, have demonstrated a decreased risk of cardiovascular events in psoriasis patients. As there were no studies that looked at this direct correlation, this study was undertaken to determine if and what type of relationship was present.
TNF-α is known to play a role in atherosclerosis in coronary artery disease. Inflammation is central to this disease with the main cell involvement from macrophages. To gain a better understanding of the role of cardiovascular inflammation on psoriasis, a study was developed to evaluate the effect of blocking TNF-α with adalimumab on vascular inflammation in patients with psoriasis.
Using PET/CT technology and radio-labeled glucose dyes (preferential higher uptake in metabolically active cells), cellular uptake could be quantified providing a direct correlation with inflammation. Scans were taken at baseline, and at 16 and 52 weeks. All 107 patients included in the study had moderate-to-severe psoriasis with a minim body surface area (BSA) of 5% or more, inflammation in the ascending aorta, and no history of MI or recent cardiovascular intervention within 12 weeks of the study initiation. Average BSA and PASI (Psoriasis Area Severity Index) scoring was 10% in both the adalimumab and placebo groups.
While there was no statistical difference in vascular inflammation in either group at week 16, there was a modest increase in vascular inflammation in carotid arteries at 52 weeks when treated with adalimumab. These negative responses were an unexpected finding as previous literature suggests there is a stronger correlation. Bissonnette theorized that adalimumab may not have an effect on inflammation or that the low levels of IL-6 may have been a limiting factor.
Another well awaited set of clinical trial results was certolizumab pegol, an anti-TNF monoclonal antibody fragment. It is composed of the Fab region only and does not have a constant region. Pegylation is used to increase the half-life of the drug. Certolizumab is not a new drug and in fact is already approved in a number of other inflammatory conditions such as psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis, and Crohn’s disease.
Alice Gottlieb, professor of Dermatology, New York Medical College, Valhalla, New York, USA presented the results from two phase 3 clinical trials, named CIMPASI-1 and CIMPASI-2, which focused on the outcomes for the first 16 weeks. The study is scheduled to continue for a total duration of 144 weeks. Patients were either treated with certolizumab 200 mg, 400 mg, or placebo.
There were two co-primary endpoints for the CIMPASI studies which included patients achieving a PASI 75 and the number of patients achieving the Physicians’ Global Assessment (PGA) of 0 or 1 and at least a 2 point drop of PGA.
The studies themselves were undertaken in North America and parts of Europe, with relative equal distribution in CIMPASI-1 and a slightly higher distribution favoring North America in CIMPASI-2. PASI scores were roughly 20% across the board along with BSA scores of approximately 20-25% across the two studies.
The response rate for certolizumab showed statistically significant results for PASI 75 with the 400 mg dose demonstrating a 76% response rate and the 200 mg dose demonstrating a 67% response rate compared to less than 7% in the placebo. The CIMPASI-2 trial also demonstrated similar PASI 75 findings with both the 400 mg and 200 mg doses having greater than an 80% response rate in both arms compared to 12% in the placebo arm.
The second co-primary endpoint of PGA 0/1 also demonstrated statistically significant results with certolizumab 400 mg and 200 mg with a 58% response rate and a 47% response rate respectively at 16 weeks in CIMPASI-1. The CIMPASI-2 trial demonstrated similar responder rate results with 72% for certolizumab 400 mg and 67% for certolizumab 200 mg.
While not a primary endpoint, the Dermatology Life Quality Index (DLQI) was utilized to gain a better perspective on patient satisfaction with treatment. Both the CIMPASI-1 and CIMPASI-2 studies demonstrated clinically significant findings in both certolizumab groups compared with placebo.
While it is too early to determine an accurate adverse event profile, certolizumab did not appear to have any significant adverse events during the 16-week study, albeit longer and more robust data will be needed to ascertain a more accurate adverse event profile.