Feature: Psoriasis Update - Larisa Hubbs, Executive Editor, and Stefanie Tuleya, Managing Editor The latest news and research to keep you up to date. Biologic Therapy for Psoriasis: The Importance of Being Earnest By Jesse Kramer, M.D. Biologics are an effective treatment option for the management of moderate to severe psoriasis. In fact, because psoriasis often requires decades of treatment to manage the condition, the use of traditional systemic therapies often runs into problems with various toxicities and adverse side effects. Therefore, biologics have been a huge help to my patients. The better question is “Which biologic should I prescribe?” While the majority of patients respond to a biologic agent, all patients do not respond to one specific biologic or one class of biologic. Some patients may experience no response or partial response that is unsatisfactory. Other patients may have an initial positive response that erodes over time. Therefore, as dermatologists, it is our responsibility to ensure that our patients receive the best treatment for their disease. Changing Up Therapy I recently had the opportunity to examine six patients with an extensive history of moderate to severe psoriasis. Each of the patients was previously on etanercept (Enbrel) and was experiencing an inadequate response. In fact, one patient had a 40% affected body surface area (BSA) even while using the treatment. In each case, I switched these patients from their current biologic treatment to efalizumab (Raptiva), a recombinant, humanized, monoclonal IgG1 antibody that blocks T-cell activation, reactivation, and trafficking and modulates T-cell behavior.1 Due to the different mechanism of action, I thought efalizumab may work even after etanercept did not. All six patients showed significant improvement after transitioning to efalizumab, with each patient achieving 3% or less affected BSA, including the patient who had 40% affected BSA prior to the switch.2 Unfortunately, there’s not one way to decipher when to prescribe one biologic over another. In fact, most of the time, you’ll have to experiment with several treatment options to find the best approach. For example, one particular patient, a 29-year-old female who had psoriasis for 5 years, tried several therapies before efalizumab. Her psoriasis was fairly moderate (15% affected BSA) therefore topical creams, systemics and light therapy were experimented with prior to trying a biologic. However, after those treatments proved to be unsuccessful, the biologic etanercept was prescribed. Unfortunately, etanercept was also unsuccessful for this patient. I eventually prescribed efalizumab treatment. Within a few weeks we began to see progress — the patient’s plaques began to fade and eventually the psoriasis cleared completely. These are just a few examples that demonstrate the value of experimenting with several treatments before finding the best approach. As demonstrated here, when one biologic has inadequate response, you may want to try switching to another biologic. What the Research Shows Multiple Phase III clinical trials have demonstrated the safety, efficacy and health-related quality of life benefits of efalizumab treatment for patients suffering from moderate to severe psoriasis. Additionally, a clinical study presented at the 2005 Annual Meeting of the American Academy of Dermatology, showed that efalizumab monotherapy resulted in sustained improvement in psoriasis symptoms over a 3-year course of treatment, with 73% of patients completing 36 months of therapy achieving PASI 75 or greater and 40% of patients showing PASI 90 or greater improvement in symptoms.3 During the maintenance treatment, the percentage of patients achieving PASI 90 continued to increase through the first 18 months, and stabilizing thereafter.1 There’s no one right answer for all patients with psoriasis. It is helpful to be able to offer patients all the new options. Dr. Kramer has been in clinical practice for 15 years. For the last 10 years he has been in solo private practice in Redding, CA. DISCLOSURES: Dr. Kramer has been a consultant and lecturer on behalf of Amgen, Abbott and Genentech. References 1. Gottlieb A, Hamilton T, Caro I, Kwon P, Compton P, Leonardi C. Long-term continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis: Updated results from an ongoing trial. JAm Acad Dermatol, 2006;54(4 suppl 1): S154-163. 2. Kramer J, Turner J, Kircik L, Krussinski P, Snyder R. Efalizumab therapy of patients who respond inadequately to etanercept. Presented at 2006 Summer Academy, American Academy of Dermatology. 3. Leonardi C, Gordon K, Hamilton T, Caro I, Kwon P, Chastain R, Gottlieb A. Maintenance of Efficacy and Safety with Continuous Efalizumab Therapy in Patients with Moderate to Severe Chronic Plaque Psoriasis: Final Phase IIIb Study Results. Presented at 2005 Winter Academy, American Academy of Dermatology.   Adalimumab (Humira) Achieves Significant Clearance Rates In the first study to evaluate a biologic agent against a standard systemic treatment for psoriasis, adalimumab (Humira) was reported to attain “significant superior efficacy”, according to data presented during the European Academy of Dermatology and Venereology (EADV) Congress in Rhodes, Greece, this past fall. More than twice the percentage of patients (80%) with moderate to severe psoriasis receiving Abbott’s adalimumab achieved at least 75% improvement in disease extent and severity after 16 weeks compared to patients receiving methotrexate (36%). Adalimumab, a TNF-alpha inhibitor approved for treating psoriatic arthritis and inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis, among other conditions, was evaluated in the Comparative Study of HUMIRA vs. Methotrexate vs. Placebo In PsOriasis PatieNts (CHAMPION) trial that included 271 patients from eight European countries and Canada. The three-arm, 16-week study evaluated the treatment effect of adalimumab in comparison to methotrexate (MTX) or placebo, each dosed as monotherapy. Patients were randomized to receive either adalimumab in its standard dose of 40 mg subcutaneous injection every other week beginning at 1 week following an initial single dose of 80 mg, or MTX or placebo. The primary efficacy endpoint was the percentage of patients achieving at least a 75% reduction in disease activity at week 16 as measured by PASI 75. In the study, patients achieved the following PASI 75 scores at week 16: • nearly 80% of patients receiving adalimumab • 35.5% of patients receiving MTX (p<0.001) • 18.9% of patients receiving placebo (p<0.001). Patients also rapidly responded to treatment with adalimumab: Mean PASI improvement of 57% was attained by the fourth week. In addition, at week 16 of treatment, 73% of patients taking adalimumab had physicians global assessments (PGA) of “clear” or “minimal” compared to 30% of patients taking MTX (p<0.001) and 11% of patients taking placebo (p<0.001). Adalimumab’s safety profile in the study was consistent with previously reported studies of this biologic. Adverse events occurring in more than 5% of adalimumab patients included injection site reaction, hepatic events, nasopharyngitis, arthralgia and headache. Abbott expects to submit a regulatory application for a psoriasis indication in Europe and the United States during the first half of this year. Poster Authors: J Saurat, G Stingl, L Dubertret, K Papp, J Ortonne, K Unnebrink, M Kaul and A Camez. Liver Damage from Methotrexate: How At-Risk Are Your Patients? Liver injury was not associated with cumulative or weekly prescribed doses of methotrexate, nor was a patient’s age or duration of treatment, a recent study of 125 psoriasis patients revealed. Patients in the study (58 females and 67 males, mean age 45), which was published in Alimentary Pharmacology & Therapeutics, underwent therapy with methotrexate for a median time of 228 weeks. They received median cumulative methotrexate doses of 2113 mg. Analysis was performed on 278 liver biopsies during this retrospective chart review of patient charts from the years 1976 to 2005. Liver biopsy results indicated that most patients experienced mild changes in their livers (Roenigk grades I, II, IIIa). The findings were as follows: Roenigk Grade I — 71% Roenigk Grade II — 14% Roenigk Grade IIIa — 14% Roenigk Grade IIIb — 2% Roenigk Grade IV — 2% Researchers concluded that liver damage caused by methotrexate treatment in psoriasis patients is much less frequent than previously thought. Most patients suffered from liver damage when they received cumulative doses of <6000 mg. Significant risk factors for developing liver damage while undergoing methotrexate therapy were diabetes and being overweight. n Source: Berends MAM, Snoek J, De Jong EMGJ, Van De Kerkhof PCM, Van Oijen MGH, Van Krieken JH, and Drenth JPH. Liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent. Alimentary Pharmacology & Therapeutics; 24(5):805-811. Multiple Approvals for Remicade The anti-TNF-alpha treatment infliximab (Remicade) received FDA approval in late 2006 for the treatment of adult patients with chronic severe plaque psoriasis. According to Centocor, the drug’s manufacturer, the indication is for patients who are candidates for systemic therapy when other systemic therapies are medically less appropriate. Delivered intravenously at a doctor’s office or clinic, Remicade is infused over a 2-hour period at a dosage of 5 mg/kg for psoriasis. Early in therapy, this treatment is administered at the patient’s initial visit and then at 2 weeks and 6 weeks. Afterward, patients receive treatment at 8-week intervals. FDA approval was based on data from two Phase III studies, EXPRESS and EXPRESS II, that included more than 1,200 patients. The data are as follows: EXPRESS. In this study, 8 out of 10 patients experienced a 75% improvement in their psoriasis as measured by the Psoriasis Area Severity Index (PASI 75) by week 10. EXPRESS II. Patients in this study maintained PASI 75 when evaluated at every 8-week interval up to 6 months. According to study data, the majority of patients continued to achieve PASI 75 at week 50, which was the last visit for both studies.   Remicade Also Received Expanded Approval The FDA also granted an additional indication for Remicade for inhibiting the progression of structural damage and improving physical function in patients with psoriatic arthritis. This indication is in addition to Remicade’s already approved indication in dermatology for reducing the signs and symptoms of active arthritis in patients who have psoriatic arthritis. The expanded indication is based on data from the double-blind placebo-controlled IMPACT and IMPACT 2 trials. Here are the key findings from those trials upon which approval was based: • IMPACT 2. An analysis of 1 year of radiographs revealed that patients treated with Remicade experienced significant inhibition of the progression of structural damage as compared with patients who received placebo, according to their van der Heijde-Sharp scores. • IMPACT. By week 16 in this trial, patients who received Remicade experienced significant improvement in functional status with a median improvement of 50% in their scores on the Health Assessment Questionnaire-Disability Index, as compared to a 2% improvement in this score for study participants in the placebo group. These scores were typically the same throughout the nearly 2-year study. • Improved Skin Symptoms. In addition to the above findings, 64% of patients in the IMPACT study achieved a 75% improvement from baseline in their psoriasis symptoms. These improvements also were maintained throughout the nearly 2-year study. In addition to these newest indication, Remicade is also indicated for the treatment of psoriatic arthritis, rheumatoid arthritis, Crohn’s disease, both for adults and pediatric patients, ulcerative colitis and ankylosing spondylitis. International Psoriasis Council Issues a Call to Action Research shows that physicians need to be vigilant about monitoring psoriasis patients for signs of co-morbid conditions. Following a collaborative Consensus Meeting convened by the International Psoriasis Council (IPC) held at the 15th European Academy of Dermatology and Venereology (EADV) Congress in October 2006, the IPC issued a call to action to physicians to elevate psoriasis on the public health agenda by undertaking a more thorough therapeutic approach. Recommendations include the need to review current guidelines to ensure a more holistic approach to the management of psoriasis, taking into account the many potential co-morbidities, to prevent this significant health burden from escalating. During the meeting, multi-disciplinary medical professionals from around the world discussed how psoriasis might be linked to co-morbid conditions such as obesity, cardiovascular disease (including hypertension, and myocardial infarction), type II diabetes and liver disease. Highlights from the meeting are detailed below. • Psoriasis and Obesity. Dr Bruce Strober, assistant professor in the department of dermatology at New York University School of Medicine, commented, “Mounting data suggest that psoriasis is a component of an inflammatory state that nurtures significant co-morbidities. It is likely that in some patients both psoriasis and obesity are co-dependent manifestations of an underlying dysfunctional pathophysiologic state. It is important that the overall management of psoriasis is significantly improved to ensure that patients are diagnosed early, appropriately treated and regularly monitored for signs of co-morbidity.” A statistical study of more than 10,000 patients in clinical trials conducted over the past 5 years, show that psoriasis patients are more likely to have body mass index (BMI) measurements in the overweight and obese ranges than members of the general population. Dr. Gerald Krueger of the University of Utah presented a study that indicated that psoriasis and obesity are endpoints of a shared etiology in which one may promote the other. • Psoriasis and Heart Disease. A study by Dr. Joel Gelfand of the University of Pennsylvania, recently published in the Journal of the American Medical Association, highlighted that psoriasis may be an independent risk factor for heart attack, particularly in young individuals with severe disease. Patients in their 40s with severe psoriasis were more than twice as likely to suffer a heart attack than people without the skin disease. Findings from the study also shed light on potential health risks for overweight psoriasis patients. These data are supported by a case-control study, which was also presented at the meeting showing that twice the number of psoriasis patients (60%) had coronary artery calcification than non-psoriasis patients (30%). • Psoriasis and Depression and Addiction. Some of the studies presented at the meeting indicated that psoriasis patients suffer more than previously understood. One trial showed that almost half of 1,000 psoriasis patients tested were likely to be clinically depressed, and another demonstrated an increased tendency to use alcohol and tobacco among psoriasis patients. More Research Needed The consensus group agreed there is overwhelmingly sufficient data supporting the linkage of psoriasis to increased co-morbid risk and to mandate future investigations funded by both government and industry. According to the IPC, a group of medical experts involved in the consensus group are currently working on a manuscript to summarize the consensus of the IPC meeting, investigate the relationship between psoriasis and co-morbidities, discuss important areas for research on these issues, and issue recommendations for clinical management of psoriasis patients at risk of developing co-morbid conditions. Psoriasis Therapeutics Market Growth Predicted According to a new study released in October 2006 from Kalorama Information, Psoriasis and Psoriatic Arthritis: a Strategic Analysis of the Market in the United States, the market for psoriasis therapeutics is expected to grow from its current $6.5 billion to more than $9 billion by 2016. Psoriasis is a very common disease with between 2% and 4% of the world population suffering from the disease. In the United States, approximately 7.8 million people, or about 2.6% of the population are affected. (See Table 1 below.) According to the report, a 1998 survey by the National Psoriasis Foundation (NPF) showed that among patients classified as having severe psoriasis, 90% were frustrated with ineffective treatments. Among psoriasis patients overall, 40% reported being frustrated with perceived ineffectiveness of the current therapies and 32% believed that their treatment was not aggressive enough. In 2005, another study by NPF showed that only about one-third of psoriasis sufferers said they were satisfied with their treatment. Though an improvement, the report indicates that better therapies are still needed. About 14% reported they are not in treatment either because they have given up (31%) or because of the cost of treatment (46%). The Current Market and Expected Growth The average cost of pharmaceutical treatment of psoriasis patients in 2006 was about $920 annually ($77 per month), according to data the report acquired from the American Academy of Dermatology. For psoriatic arthritis, the average cost of pharmaceutical treatment has increased significantly since the introduction of biologic disease-modifying antirheumatic drugs (DMARDs) and was about $2,200 per year ($183 per month) in 2006. This includes all levels of psoriasis and psoriatic arthritis staging. According to the report, the costs of medication account for between 70% to 80% of the total cost for a disease of this type, which means the average cost of total treatment per patient is about $1,227 annually ($102 per month) for psoriasis, and $2,933 annually ($244 per month) for psoriatic arthritis. Using these assumptions and others, the Kalorama report estimated the market for psoriasis therapeutics in the United States for 2006 to 2016. (See Table 2 below.)     Skin & Aging - ISSN: 1096-0120 - Volume 15 - Issue 1 - January 2007 - Pages: 56 - 60