Understanding PASI scores, gauging the best biologic and more.
Is The PASI System Worthwhile and Does it Correlate With Real-Life Psoriasis Improvement?
Understanding the Value of the PASI System
By Robert E. Kalb, M.D.
Most clinical trials for psoriasis treatment use Psoriasis Area Severity Index (PASI) score improvement as a measurement of the success of treatment.
Initial PASI scores are composite measures that indicate severity of psoriasis for an individual patient. The scores are on a scale of 0 to 72. For clinical trials involving moderate to severe psoriasis, a typical PASI score at enrollment is about 20. To calculate a patient’s PASI score, the body is divided into four sections: legs, body (trunk area), arms and head. For each section, a score is given for the body surface area (BSA) affected and for the severity of the disease on that part of the body. These scores are entered into a weighted formula to calculate the PASI number.
PASI and Clinical Trials
Improvement in this score in clinical trials is presented as a percent improvement over the baseline score. Patients who experience a 75% improvement in their PASI scores after treatment (e.g from a score of 20 to 5) are said to have achieved PASI 75.
For most clinical trials, the number of patients on the study drug achieving PASI 75 is the primary efficacy measure. In terms of clinical improvement, a PASI 75 improvement correlates well with a physician global assessment (PGA) of clear to almost clear. There
is also an excellent correlation with statistically significant improvement in the patient’s quality of life.
Patients with degree of success are relieved of the daily burden of psoriasis. They can wear shorts in the summer and go swimming without embarrassment.
The PASI scoring system may not be practical in everyday practice, but it is the currently accepted objective measurement for clinical trials.
Setting the Bar Higher
Although many have argued that PASI 75 is a high bar to achieve it does correlate well with a PGA of clear or almost clear. This degree of improvement along with the improved quality of life is what our patients deserve.
Some trials are beginning to report PASI 90 or PASI 100 improvement as a benchmark for success. This raises the bar even further so that treatments with just average efficacy may not survive in the current
Dr. Kalb is a Clinical Associate Professor in the Department of Dermatology at the SUNY at Buffalo School of Medicine. He is in practice with the Buffalo Medical Group in Buffalo, NY.
The Problem with PASI Scores
By Jennifer Cather, M.D.
In everyday practice, the ultimate goal regarding psoriasis treatment outcome is patient quality of life not Psoriasis Area Severity Index (PASI) improvement. What one patient perceives as success another patient may consider an unacceptable amount of improvement.
PASI and QOL
Clinical trials in this country use PASI 75 and PASI 50 as benchmarks for improvement — some drugs have PASI 90 data, which is even more impressive. But, if you consider the myriad of different presentations psoriasis may have in any given patient or in the population as a whole, initial PASI scores cannot adequately capture the severity of the disease in all patients.
For example, patients with palmoplantar psoriasis, which affects approximately 4% body surface area (BSA), will have a low PASI score since PASI scores are weighted by the extent of area of involved as well as the severity of the erythema, induration and scaling in that area. Despite these low PASI scores, patients suffering from palmoplantar psoriasis typically have very low quality of life (QOL).
The low PASI scores do not correctly correspond to quality of life for these patients. These patients may not be able to walk, conduct business, or function in society due to the visible nature of their disease. Also, consider patients with psoriasis that happens to involve their inverse areas, such as their genitalia — here again you can see low PASI scores, but this type of psoriasis has a significant impact as far as the psychosocial implications of the disease.
Lack of Correlation
PASI scores have no place in the decision making process with respect to the appropriateness of systemic therapies — including the biologics.
There are no magical PASI scores that correlate to mild, moderate or severe psoriasis. PASI scores are simply a way for doctors to communicate levels of improvement on various therapies and, in general, have no practical place in daily dermatology clinics or in the decision for or against systemic therapy.
Patients are unique individuals and the impact of their disease on them and their daily lives cannot be translated into a score. Patients with low PASI scores are still candidates for first-line biologic therapies.
In the future, I believe degree of improvement for patients with psoriasis will incorporate the impact the therapy is having on the patient’s co-morbidities. Psoriasis has several co-morbidities associated with it, including arthritis, metabolic syndrome, cardiovascular disease and depression. We need to stop looking at PASI improvements and instead focus on “whole patient” improvement — the skin is the easiest disease burden marker to follow but may not be the most important measure of disease.
Dr. Cather is in private practice at Modern Dermatology – Aesthetics Center, which she co-founded, in Dallas.
Eye on Gene Therapy
Dr. James T. Elder, M.D., Ph.D.
While there have been significant advances in identification of genes involved in psoriasis, the genetics is complex. Multiple genes are involved.
Here’s a quick look at what we know so far. One gene associated with psoriasis has been identified in the Class I region of the major histocompatibility locus (MHC), a region associated with immune function. We can expect to see high-profile research papers on this over the next 6 months. The involvement in psoriasis of a gene called PSORS2 (on chromosome 17q) has been confirmed by several groups. It is possible that more than one psoriasis susceptibility gene exists in the PSORS2 region. Another two genes that were initially associated with psoriasis have not yet been confirmed. Across the rest of the genome, there are several other genes that potentially may be involved in psoriasis, but they still need to be convincingly confirmed.
The future of the field lies in whole-genome association analysis, continued accrual of cases and controls as well as families, and in continued coordination efforts by the various laboratories working in the field. Dermatologists can help with these studies by making patients aware of this opportunity to work toward identification of the genes involved in psoriasis.
Hopefully, as those genes are teased out, we’ll be able to develop more specific, and potentially more effective, treatments for the disease.
Efficacy and Safety in Treating Overweight Psoriasis Patients
Because investigations of the prevalence of comorbidities associated with psoriasis have shown that obesity occurs significantly more often in patients with psoriasis than in control patients, researchers studied if the dose of systemic psoriasis medications need to be adjusted to account for variability in patient body mass. To determine whether the safety and efficacy profiles of 12 weeks of subcutaneous efalizumab (Raptiva) 1 mg/kg/wk differ between patients with high body weight (≥100 kg) and patients weighing <100 kg, a recent study analyzed pooled date from four phase III efalizumab clinical trials.
Analyses were performed on pooled date from four phase III studies for safety analysis and three phase III studies for efficacy. (One study was excluded from efficacy analysis because the study was designed primarily to evaluate safety.)
Patients included in the studies were 18 to 75 years of age, with a PASI score of at least 12 at screening, with at least 10% of body surface area (BSA) affected for at least 6 months and were already candidates for systemic therapy. All patients received an initial conditioning dose of 0.7 mg/kg followed by 11 weekly doses of 1 mg/kg or 12 weeks of placebo.
Safety and Efficacy Study Results
Overall, no weight-related differences in the incidence of adverse or serious adverse events were observed. (See Tables 1 and 2.)
Adverse events that occurred in ≥5% of the patients were similar in both weight groups.
No single serious adverse event occurred in more than one efalizumab-treated patient in the high-body-weight group.
Clinical responses to efalizumab therapy were similar between both weight groups, and this similarly was observed when the data are stratified for patients achieving either a PASI-50 or PASI-75 response. (See Figure 1.)
Poster Authors: Mark Lebwohl, Elyse S. Rafal, Ivor Caro, Biao Xing, Steven R. Feldman.
Gauging the Best Biologic
Selecting the right biologic agent can be confusing. Plenty of research is available; however, head-on comparisons between different therapies are rarely available. In this study, researchers attempt to determine which biologic is best by comparing and contrasting
the five newest biologic agents for psoriasis.
Researchers based their findings on data from published pivotal studies and package inserts. In cases where more than one RCT for each biologic was identified, a weighted average based upon the number of patients treated was determined. Medication costs were determined from the 2004 Drug Topics Red Book Average Wholesale Price (AWP) and non-drug costs were based on the treatment model in table I and using median Medicare reimbursement rates for costs.
Other Considerations to Weigh into the Decision
When selecting a biologic for your patient, your patient’s preference may be the most important determining factor. Route administration and dosing schedules are also important considerations.
Potential side effects and perceived long-term risks are also important to consider in the overall decision.
Although researchers concluded that there was no single best biologic agent for all patients, they did agree that the physician is central to the decision and, ultimately, patient preference may play the largest role in determining the “best” biologic agent.
Poster authors: Andrew Nelson, B.S., Daniel Pearce, M.D., Alan Fleischer Jr., M.D., Rajesh Balkrishnan, Ph.D., and Steven Feldman, M.D., Ph.D.