Feature: Psoriasis Update - By Larisa Hubbs, executive Editor A look at recent research highlights from the AAD meeting. T his year’s annual meeting of the American Academy of Dermatology highlighted an array of promising study findings for some of the biologic psoriasis treatments, as well as some of the topical agents under study. In this update, we’ll offer you a condensed version of some of the most interesting research results. In addition, we’ll take a look at the most comprehensive study yet conducted on the social and emotional impact of psoriasis, which were released by a new collaboration of healthcare professionals joined to study psoriasis. Intermittent use of Etanercept Assessing relapse rates and patient safety. Although etanercept (Enbrel) has been used for continuous treatment in rheumatoid arthritis patients without cumulative toxicity, researchers wanted to study the effects when the drug was used on an intermittent or rotational basis, which is more in tune with how dermatologists typically treat psoriasis. In this Phase III study, Drs. Alice Gottlieb, Kenneth Gordon, Andrea Wang and Ralph Zitnik studied 409 patients. These patients were designated as responders (they had PASI improvement that was >=50%) following 24 weeks of randomized treatment with varying doses of etanercept. These patients then had etanercept therapy halted and were observed on a monthly basis until their disease relapsed (or until all patients had completed at least 60 weeks). Researchers defined “relapse” as the loss of half of the PASI improvement that was achieved between baseline and week 24. Of the different therapy groups, researchers found the following: • Patients who received placebo and 25 mg b.i.w. of etanercept. Patients in this group experienced a median of 85 days until relapse. • Patients who received 25 mg q.w. of etanercept. Patients in this group experienced a median of 70 days until relapse. • Patients who received 25 mg b.i.w. of etanercept. Patients in this group experienced a median of 85 days until relapse. • Patients who received 50 mg b.i.w. of etanercept. Patients in this group experienced a median of 91 days until relapse. (46 patients from the study were still in remission when the study closed.) In addition to these findings, researchers found that withdrawal of etanercept was well tolerated by patients and wasn’t associated with severe flares or conversion of psoriasis morphology. Subsequently following this study, another study gauged the efficacy and safety of etanercept when used to retreat patients who’d been discontinued on the drug. The researchers, who included Drs. Craig Leonardi, Boni Elewski, Charles Camisa, Andrea Wang and Ralph Zitnik, wanted to find out if patients who’d relapsed and who were retreated would attain the same or similar control of their psoriasis as when they’d initially received etanercept. This study group consisted of 347 patients whose psoriasis had relapsed and they received treatment with the same etanercept regimen they’d previously received. The study culminated when all patients had completed at least 60 weeks. Researchers found that patients retreated with etanercept reacted well to treatment, experiencing the same or similar disease control with similar adverse event and infection profiles seen initially. Efalizumab and the first 12 weeks of therapy A look at a large cohort of patients. Rapid clinical benefit documented (measured by PASI) after efalizumab therapy. A study designed to test the safety and efficacy of the first 12 weeks of treatment with efalizumab (Raptiva) in patients with moderate to severe plaque psoriasis found that a significantly greater proportion of patients who received this drug alone had statistically significant improvement. Researchers, who included Drs. Kenneth Gordon, David Pariser, Richard Langley, Ivor Caro, Amy Chen Rundle and Mark Lebwohl, studied a total of 1,651 patients. These patients were randomized to receive either efalizumab (1,172 patients) in a 1 mg/kg/wk or in a 2 mg/kg/wk dosage or placebo (479 patients). The patients had participated in Phase III, randomized, placebo-controlled clinical trials. Researchers found the following: • PASI-75 achieved. This endpoint was reached in 27% of efalizumab-treated patients in both dosage groups and in only 4% of the placebo group. • PASI-50 achieved. 59% of patients treated with 1 mg/kg/wk of efalizumab reached PASI-50, compared with only 14% of the placebo group. Overall, study participants achieved a rapid, statistically significant improvement in PASI scores as early as week 2 when they were treated with efalizumab therapy, compared with placebo. In addition, the therapy was well tolerated with acute adverse events that were reported as mild to moderate, and by the third dose the events were similar in incidence between the patients treated with efalizumab and those treated with placebo. Psoriasis from the Patient and Non-Patient Perspectives Patients discuss how their relationships and self-esteem are affected; people without psoriasis share their knowledge and perceptions of the disease. In what is being called the most comprehensive study to date to determine the social and emotional effects of psoriasis, researchers gauged how much psoriasis affects all aspects of life. They also spoke to the general public to determine how well the disease is understood. The survey was conducted by Beyond Psoriasis: The Person Behind the Patient, a new program run by a conglomerate of groups including the National Psoriasis Foundation, The Dermatology Nurses Association, dermatologists and patients with psoriasis. Research done by the group is supported by Genentech. The top and middle graphs reflect data from interviews with 502 psoriasis patients. The bottom graph reflects a random survey of 1,000 members of the general public who didn’t have psoriasis. Questions were designed to determine general knowledge of and perceptions about psoriasis. The survey results were gleaned during a two-part phase, involving psoriasis patients and people not afflicted with the disease. In phase one of the study, 502 people with moderate-to-severe psoriasis were interviewed. Key findings included: • 73% of patients with severe psoriasis and 48% with moderate psoriasis said they had low self-confidence that affected all aspects of their lives because of the disease • 4 in 10 people with psoriasis (38%) said their sex life or intimacy with others was affected by psoriasis • 45% of those surveyed had a family member with the disease, with 62% of these study participants having at least one parent with psoriasis. When 1,000 members of the general public were surveyed regarding knowledge of psoriasis, some findings included the following: • 86% of survey respondents who had heard of psoriasis knew it wasn’t contagious, but they weren’t necessarily aware of what the disease looked like. • 93% of people surveyed who knew about psoriasis did not know that 4.5 million Americans have the disease. In addition, 74% didn’t know that the disease was as debilitating as diabetes or heart disease. They also didn’t know that psoriasis is incurable (53%). Additional findings from the survey are shown in the tables on page 77. Alefacept inCcombination with Other Therapies Preliminary findings for patients who received multiple courses of alefacept and other psoriasis therapies. In a study of 201 patients, Dr. Kenneth B. Gordon, M.D., sought to determine the safety and effectiveness of three treatment courses of alefacept (Amevive) in addition to one of the following concomitant psoriasis therapies: • Cyclosporine. Patients remained on this therapy for the entire study period. • Methotrexate. Patients on this therapy were discontinued on methotrexate by week 4. • Narrowband or broadband UVB. Patients underwent this type of therapy two to three times per week. • Prednisone. • Systemic retinoids. • Topical treatments. These included (but weren’t limited to) corticosteroids, vitamin D derivatives, vitamin D derivatives plus corticosteroids, retinoids and tars or anthralins. The study is designed so that during each course of alefacept therapy, patients received 15 mg per week of alefacept delivered intramuscularly. Injections were received once a week for 12 weeks followed by a 12-week observation period. The study is still ongoing, and the results mentioned here are based on the patients who completed the first course of therapy and some type of combination therapy. At the interim analysis, Dr. Gordon observed the following: • Most patients’ psoriasis was stable at baseline (as measured with the Physicians Global Assessment), and most were undergoing treatment with conventional therapies. • Overall, 17% of patients had severe psoriasis. • 38% had moderate to severe psoriasis. • 33% had moderate psoriasis. • Patients who received methotrexate or cyclosporine in combination with alefacept had psoriasis that was less severe than the patients in the other treatment groups. For more specific data regarding the interim results of this study, see the table titled “Baseline PGA.” Treating Plaque Psoriasis with Infliximab Patients who have psoriatic arthritis and plaque psoriasis see improvement. This chart reflects outcomes of patients who were treated with infliximab. Response rates are noted through week 26. In this retrospective analysis, Drs. A.B. Gottlieb, R. Matheson, R. Evans and K. Patel, looked at 78 patients who had psoriatic arthritis and plaque-type psoriasis. This chart reflects results of treatment with infliximab. Data reflect PGA responses through week 26. The Phase II, multicenter, randomized, double-blind, placebo-controlled trial evaluated the effects of infliximab (Remicade) therapy. Patients received either placebo or 3 mg/kg or 5 mg/kg of infliximab at weeks 0, 2 and 6, and researchers used PASI and PGA to assess lesions. At week 10, researchers noted a statistically significant improvement in the psoriasis of the patients who were treated with 5 mg/kg of infliximab as compared with those treated with placebo. In the 5 mg/kg group, 98.7% of patients were evaluated as having minimal disease or were rated clear. Researchers concluded the following: • By week 4, onset of >=75% improvement in PASI was rapid and noticeable in the group of patients who were treated with infliximab, compared with placebo. • By week 2, >=50% improvement in PASI was rapid and noticeable in the group of patients who were treated with infliximab, compared with placebo. • By week 2, minimal or clear improvement as gauged with PGA was rapid and notable in the infliximab-treated patients. • By week 2, patients with PGA mild or better was rapid and notable in the infliximab-treated patients. In addition to these results, the drug was found to be consistent with previous trials of infliximab with no serious infusion reactions noted. For more information on therapy results with infliximab for duration of up to 26 weeks, see the tables on the previous page and above. Duration of Treatment with Tazarotene Treatment lengths evaluated in patients with moderate to very severe psoriasis. This graph reflects the incidence of patients achieving >=75% global improvement in all psoriatic lesions after treatment with tazarotene. In this study, researchers conducted two multicenter, double-blind, randomized placebo-controlled studies that were identically designed. The researchers, who included Drs. J.Y.M. Koo, N.J. Lowe, J. Sefton and P.S. Walker, evaluated approximately 700 patients with moderate to very severe plaque psoriasis. Patients received once-daily treatment with either oral tazarotene (Tazorac, 4.5-mg capsule) or placebo for 12 weeks, followed by a 12-week post-treatment follow-up. The following treatment results were noted: • Therapy with tazarotene was statistically clinically superior when compared to placebo, and these efficacy levels were consistent throughout the 12-week post-treatment period. • Even at 12 weeks post-treatment, the clinical outcomes achieved with tazarotene were maintained at, or close to, the levels achieved after 12 weeks of therapy with this drug. The authors concluded that this therapy offers “continued efficacy after discontinuation of therapy and more prolonged clinical improvements than some other systemic antipsoriatic therapies.” Bexarotene Gel’s Success in Treating Psoriasis In this Phase II study, Drs. D. Breneman, P. Sheth and V. Stevens evaluated bexarotene gel 1%, the first RXR-selective retinoid (rexinoid) to be marketed, to determine its efficacy in treating patients who had mild to moderate plaque-type psoriasis. Twenty-four patients participated in the study, and they received scheduled, weekly, escalating dosages of bexarotene gel 1% in the following manner: 1% q.o.d. to 1% q.d., alternating with b.i.d. to 1% b.i.d. Both patients and investigators could elect to increase the frequency of the drug to t.i.d. or q.i.d. to obtain a response if they weren’t getting one. Patients were assessed using the physician’s global assessment (PGA) at weeks 2 and 8 and every 4 weeks afterward. Researchers concluded the following: • Bexarotene gel was active in treating mild to moderate plaque psoriasis with a 67% response rate (16 of 24 patients) for intent-to-treat patients. • Using the PGA to evaluate patients, it was determined that 8.3% of patients were clinically cleared of signs and symptoms; 33.3% improved by •75% to 99%. In addition, 25% of patients partially cleared by 50% to 75%. • Most patients achieved results by week 4 of the study and then improved slowly. • Patients who were completely cleared required 20 to 24 weeks of treatment. • Adverse events were mild or moderate; most were either erythema or irritation related to retinoids. Based on the cumulative results noted in this trial, researchers concluded that bexarotene gel may have a potential role in treating or maintaining skin clearance for many patients who have mild to moderate plaque psoriasis. Skin & Aging - ISSN: 1096-0120 - Volume 12 - Issue 04_2004 - April 2004 - Pages: 76 - 81