P2866 P2867. Author disclosure: Consultant to Genentech, Inc. 100% sponsored by Genentech, Inc.

Transcription

1 P2864 Case studies of efalizumab in hand and foot psoriasis Jeffrey Sobell, Tufts-New England Medical Center, Boston, MA, United ; Scott Fretzin, MD, Indiana University Medical Center, Indianapolis, IN, United Hand and foot psoriasis can manifest as a plaque-type disease or a pustular disease (also called palmoplantar pustulosis). Psoriasis localized to the hands and feet is difficult to treat and associated with symptoms that severely impact the patient s quality of life, potentially leading to functional disability. Efalizumab, a recombinant humanized monoclonal IgG1 antibody, inhibits multiple key T-cell-mediated processes in the psoriasis immune cascade and is approved to treat moderate to severe chronic plaque psoriasis in adults. We present case studies of 4 patients with hand and foot psoriasis successfully treated with efalizumab 1 mg/kg/wk. Case 1: A 31- year-old man who had a 6-year history of psoriasis, with painful fissures on his soles and elbows, had been unsuccessfully treated with topical steroids, acitretin, methotrexate, and phototherapy. After 8 weeks of efalizumab therapy 1 mg/kg/wk, his feet were clear, remaining clear after 5 months of continuous therapy with efalizumab. Case 2: A 36-year-old woman with a 5-year history of pruritic, painful, fissured plaques on her palms and soles, and mild elbow involvement failed to respond to phototherapy, systemic immunosuppressants, and the biologic immunosuppressant etanercept. Two weeks after starting efalizumab therapy, she experienced a decrease in pain: A 50% improvement was observed after 4 weeks, and by 12 weeks her psoriasis was essentially clear. Case 3: A 60-year-old man with an 18-month history of palmoplantar pustulosis and a past history of hypertension, hypercholesterolemia, and coronary artery disease had previously been treated with oral antibiotics, topical steroids, anthralin, immunosuppressive agents, and etanercept with no or little improvement. A full response was observed after 8 weeks of efalizumab monotherapy 1 mg/kg per week, and more than 18 months after starting treatment, his palmoplantar psoriasis remains.95% clear. Case 4: A 60-year-old woman with a 7-year history of hand and foot psoriasis and a medical history of hypercholesterolemia and coronary heart disease had been unsatisfactorily treated with topical steroids, antibiotics, acitretin, systemic immunosuppressive agents, and etanercept. Soon after efalizumab therapy was started, the condition of her hands and soles improved markedly. She remains clear 1 year after initiating treatment with efalizumab 1 mg/kg/wk. In these 4 patients, efalizumab provided a good therapeutic option for this difficult-to-treat condition. P2866 Author disclosure: Consultant to Genentech, Inc. 100% sponsored by Genentech, Inc. P2865 Clinical efficacy, safety and inhibition of joint destruction of adalimumab in the treatment of moderate to severe psoriatic arthritis: 48-week results of the ADEPT trial Philip Mease, MD, Swedish Medical Center, Seattle, WA, United ; Dafna Gladman, MD, University of Toronto, Toronto, ON, Canada; Christopher Ritchlin, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY, United ; Mark Weinberg, MD, Abbott Laboratories, Abbott Park, IL, United Objective: ADEPT has demonstrated adalimumab (ada) is efficacious for joint and skin disease of psoriatic arthritis (PsA) for #24 weeks. This report describes the effects of ada on arthritis and psoriasis (Ps) after an additional 24 weeks, including impact on joint damage. Methods: ADEPT was a phase III, controlled study of ada in patients with moderate to severe PsA ( $ 3 SJC and $ 3 TJC) who had failed NSAID therapy. Patients were stratified by MTX use (yes/no) and extent of Ps (,3% and $ 3% BSA), and randomized to ada 40 mg or placebo (PBO) every other week (eow) for 24 weeks. Patients who had completed the initial 24-week trial could enroll in an open-label extension (OLE), during which they received ada 40 mg eow. After 12 weeks of OLE therapy, patients with an inadequate response could increase to 40 mg weekly. ACR and PASI analyses were by NRI, and HAQ was by LOCF. PASI responses were evaluated for patients with $ 3% BSA Ps at BL. X-rays of hands/feet were taken at BL, and 24 and 48 weeks, and assessed by a modified total Sharp score (mtss) including additional joints involved in PsA. Results: Of 313 patients randomized, 285 continued into the OLE. BL data were indicative of moderate to severe PsA and well matched between arms. For the 151 patients on ada, the 24-week ACR20/50/70 response rates were 57/39/23 and mean D HAQ was ÿ0.4 (P,.001 vs PBO for both). For the 69 of these 151 patients who had BSA $ 3% Ps at BL, the PASI50/75/90 response rates were 75/59/42, and the mean% D in PASI was ÿ66% (P,.001 vs PBO for both). These results were maintained through week 48. PBO patients achieved similar responses in the OLE after 24 weeks of ada. ACR responses were similar between patients on ada alone and those on MTX. PASI responses were slightly higher in MTX patients, but the difference was not statistically significant BL mtss values for ada (n = 144) versus PBO patients (n = 152) were 22.7 versus Radiographs taken at BL and weeks 24 and 48 showed significant differences, with mean D mtss at week24 of ÿ0.2 for ada and 1.0 for PBO (P,.001). The 48-week analysis showed ada patients had a mean D vs BL in mtss of 0.1 (n = 128). PBO patients who began receiving ada at week 24 had a mean D mtss of 0.1 (n = 134) (week 48 vs week 24). Ada was generally well tolerated. The OLE safety profile was consistent with that reported for the initial 24 weeks and that observed for ada in RA. Conclusion: Ada was efficacious in treating PsA, with significant reductions in the burden of joint disease, skin disease, and disability for 1 year. P2867 Author disclosure: Drs Mease, Gladman and Ritchlin are ADEPT investigators. Dr Weinberg is an Abbott employee. 100% sponsored by Abbott Laboratories. AB214 J AM ACAD DERMATOL MARCH 2006

2 P2868 Comparative efficacy of calcipotriene/betamethasone combination product after 1, 2, 4 weeks of treatment of mild, moderate, and severe psoriasis Alan Menter, MD, PA, Baylor University Medical Center, Dallas, TX, United Introduction: Decreases in the PASI are useful for assessing efficacy. We report pooled results from 6 randomized, double-blind, vehicle- and/or active-controlled studies using calcipotriene 50 mg/g and betamethasone dipropionate 0.5 mg/g (C/BD) in mild to severe psoriasis. Methods: Treatments were applied 13/day to lesions on the trunk/limbs over 4 weeks. One-, 2-, and 4-week PASI efficacy results are reported. Patients were grouped according to baseline severity with the use of a correlation between IGA and PASI, although all studies did not include assessment of both PASI and IGA. Mild disease severity according to IGA corresponded to PASI #6, IGA moderate disease to PASI 6.1 to #12 and IGA severe/very severe disease to PASI.12. Results: At baseline, severity was mild (PASI #6) in 26% of patients, moderate (PASI 6.1 to #12) in 49% and severe (PASI.12) in 25%. At the end of 1-, 2-, and 4-weeks, the mean percent PASI reduction from baseline with C/BD was 38.7%, 56.7%, and 67.6%, respectively, in mild disease; 37.8%, 55.3%, and 68.1%, respectively, in moderate disease; and 41.2%, 59.5%, and 71.5%, respectively, in severe disease. Comparator results were reported as mean percent change in PASI from baseline. Data tables will be provided. Conclusions: We show that after 1-, 2-, and 4-weeks of therapy, combined calcipotriene 50 mg/g and betamethasone dipropionate 0.5 mg/g ointment applied 13/day had a faster onset of action than the comparators in treating mild, moderate, or severe psoriasis. Supported by Warner Chilcott. P2870 Complete resolution of arthritis- and dermatologic-related functional loss with adalimumab in patients with Psoriatic arthritis Dafna Gladman, MD, University of Toronto Department of Medicine, Toronto, ON, Canada; Philip Mease, MD, Swedish Medical Center, Seattle, WA, United ; Jay Chmiel, PhD, Abbott Laboratories, Abbott Park, IL, United ; Lisa Melilli, PhD, Abbott Laboratories, Abbott Park, IL, United Background: Psoriatic arthritis (PsA) is associated with debilitating arthritic and psoriatic effects that can result in significant functional loss. Objective: This analysis assessed whether a clinical trial of adalimumab (ada) 40 mg eow demonstrated complete resolution of these effects, compared with placebo, in patients with moderate to severe PsA. Methods: The ADEPT study, a randomized, controlled trial, was conducted to assess the efficacy and safety of ada 40 mg eow in adult patients with moderate to severely active PsA ($3 swollen and $3 tender joints) with an inadequate response to NSAIDs A subset of patients had significant psoriatic involvement at entry, as measured by an affected BSA of 3% or greater. Patients were stratified for methotrexate use (yes/no) and extent of psoriasis ( $3% or,3% BSA), and received ada 40 mg or placebo subcutaneously every other week for 24 weeks. The disability index of the HAQ was used to measure changes in functional loss in all patients. HAQ scores range from 0 to 3, with higher scores indicating greater disability. The DLQI was used to measure changes in dermatologic-related functional limitations in the subset of patients with BSA.3%. DLQI scores range from 0 to 30, with lower scores indicating less impairment. The percent of patients with complete resolution of functional loss, defined as HAQ or DLQI equal to 0, was assessed at weeks 12 and 24, between ada and placebo patients in an as-observed, intention-to-treat analysis. Results: Of 313 patients, 151 received ada 40 mg eow and 162, placebo; approximately 45% in each group had $ 3% BSA. Mean baseline HAQ was 1.0 in both groups. Mean DLQI total scores were 8.6 (SD = 6.61) in the ada group and 10.3 (7.49) in the placebo group. At week 12, 34% of ada patients had an HAQ equal to 0 versus 14% of placebo patients (P,.0001). This between-group difference was sustained at 24 weeks (34% versus 13%, P,.0001). In terms of dermatologic-related functional loss, 37% of ada patients versus. 5% of placebo patients demonstrated DLQI equal to 0 at week 12 (P,.0001), and 45% versus 5%, respectively, at week 24 (P,.0001). Conclusion: Complete resolution of joint- and skin-related functional loss was seen in one third of patients treated with adalimumab at week 12. These results suggest the importance of anti-tnf treatment with adalimumab in PsA for reversing debilitating disease effects early in the course of treatment. Author disclosure: Drs Gladman and Mease are ADEPT investigators. Drs Chmiel and Melilli are Abbott employees. 100% sponsored by Abbott Laboratories. P2869 Comparison of biologic therapies for the treatment of psoriasis William Abramovits, MD, Texas Dermatology Research, Dallas, TX, United This poster will be an improved and updated version of the highly covered, often requested poster presented at AAD 2004 and 2005 comparing the 5 biologics (adalimumab, alefacept, efalizumab, etanercept, and infliximab) currently indicated for psoriasis and psoriatic arthritis. Data on effectiveness will be extended to cover 48 to 52 weeks, and 1 and 2 years, if available. Safety concerns reported during 2005 up to print date will be added. The costs of therapy for each of the biologics will be adjusted to the current year, and new data on the more recently approved indications presented in a very objective way. Author disclosure: Consultant: received research support; lecturer: Amgen, Centocor, Genentech, Abbott, Biogen. P2871 Consistency of infliximab response across subgroups of patients with psoriasis: Integrated results from randomized clinical trials K. Reich, MD, Georg-August-University, Gottingen, Germany; AB Gottlieb, MD, University of Medicine and Dentistry of New Jersey - Robert Wood Johnson Medical Center, New Brunswick, NJ, United ; A. Kimball, MD, MPH, Brigham and Women s Hospital, Boston, MA, United ; S. Li, PhD, Centocor, Inc, Malvern, PA, United Introduction: Infliximab (IFX), a monoclonal antibody to TNFa, is approved for the treatment of psoriatic arthritis. Two phase III studies were conducted to confirm the efficacy of IFX for induction therapy observed in phase II in patients with psoriasis and to determine if continuous therapy would maintain this response. Objective: To assess the consistency of response of IFX among different subgroups of patients with moderate to severe psoriasis. Methods: Three randomized, placebo (PBO)-controlled clinical trials (EXPRESS, EXPRESS II) evaluated the use of IFX in patients with moderate to severe psoriasis who were candidates for phototherapy or systemic therapy or who had previously received PUVA or other systemic therapy (SPIRIT). SPIRIT and EXPRESS II evaluated IFX 3 mg/kg and 5 mg/kg, and EXPRESS evaluated IFX 5 mg/kg. All patients received IFX at 0, 2, and 6 weeks. The common primary endpoint was the proportion of patients achieving. 75% improvement in PASI from baseline (PASI75) at week 10. Results: From the integrated data through week 10 (n = 1462 patients), the proportion of patients achieving PASI75 was 70.6% and 79.3% in the IFX 3 mg/kg and 5 mg/kg groups, respectively, compared with 2.7% in the PBO group (both P,.001). Consistent response in the proportion of patients in the IFX group (3 and 5 mg/kg groups combined) who achieved the primary endpoint was observed within subgroups of patients on the basis of baseline demographic and disease characteristics. The proportions of patients achieving PASI75 at week 10 were consistent in subgroups defined by baseline demographic characteristics including gender, age (, 40 years,. 40 years), race, and BMI (normal [, 25 kg], overweight [25 to, 30 kg], obese [. 30 kg]). The proportions of patients achieving PASI75 improvement at week 10 were consistent in subgroups defined by baseline disease characteristics including PASI severity (PASI, 20, PASI. 20), BSA (BSA, 30%, BSA. 30%), prior use of systemic therapies (. 2,, 2), and presence of psoriatic arthritis. Consistent results were also observed regardless of previous use of psoriasis medications (including methotrexate, acitretin, cyclosporine) and UVB or PUVA. Conclusion: IFX was consistently effective across subgroups defined by a variety of baseline demographic and disease characteristics in patients with psoriasis. Author disclosure: K. Reich, AB Gottlieb and A. Kimball have received research grants from Centocor, Inc. AB Gottlieb and A. Kimball are consultants for Centocor, Inc. S. Li is an employee of Centocor, Inc. Study sponsored by Centocor, Inc. MARCH 2006 J AM ACAD DERMATOL AB215

3 P2872 Consistency of response of infliximab 5mg/kg maintenance therapy: Data from EXPRESS and EXPRESS II A. Menter, MD, Baylor University Medical Center, Dallas, TX, United ; R. Matheson, MD, Oregon Medical Research Center, Portland, OR, United ; C. E. M. Griffiths, MD, University of Manchester, Manchester, United Kingdom; S. Li, PhD, Centocor, Inc, Malvern, PA, United Objective: To assess the consistency of response of infliximab (IFX) 5 mg/kg maintenance therapy from two phase III trials through 1 year. Methods: EXPRESS (n = 378) and EXPRESS II (n = 835) were randomized, doubleblind, placebo (PBO)-controlled trials in patients with moderate to severe psoriasis who were candidates for phototherapy or systemic therapy. Both trials shared a common induction regimen of IFX at weeks 0, 2, and 6, and a primary endpoint of. 75% improvement in PASI from baseline at week 10. EXPRESS evaluated IFX 5 mg/kg and EXPRESS II evaluated both IFX 3 and 5 mg/kg; patients in both trials received maintenance therapy with IFX 5 mg/kg q 8 wks. Other endpoints assessed at week 10 include.50% and.90% improvement in PASI from baseline (PASI50, PASI 90), and improvements in the DLQI and PGA scores. High responders (patients with a DLQI score of 0, PASI scores of 0, a PGA of clear) were also evaluated. Results on the basis of the IFX 5 mg/kg dose at week 10, week 26, and week 50 were evaluated. Results: Across both studies, psoriasis improved rapidly, with comparable numbers of patients in the IFX groups achieving PASI 75 at week 6. At week 10, the proportions of patients achieving PASI75 were 80.4% versus 2.6% (EXPRESS) and 75.5% versus 1.9% (EXPRESS II) for the IFX and PBO groups, respectively (both P,.001 versus PBO). The proportions of patients achieving PASI 90 were 57.1% versus 1.3% (EXPRESS) and 45.2% versus 0.5% (EXPRESS II) for the IFX and PBO groups, respectively. Improvements in DLQI from baseline were observed by week 10 in both studies (IFX vs PBO, ÿ9.0 vs 0.0, P,.001 for both studies). The proportions of patients with a PGA of cleared, excellent/minimal were 82.9% versus 3.9% (EXPRESS) and 76.0% versus 1.0% (EXPRESS II) for the IFX and PBO groups, respectively (both P,.001 vs PBO). Also at week 10, a significant proportion of patients were high responders. The response achieved at week 10 was sustained through week 26 in both EXPRESS and EXPRESS II (81.4% and 78.0% of patients achieved PASI.75 improvement from baseline, respectively). The majority of patients maintained PASI75 response at week 50. IFX was generally well tolerated in the majority of patients. Conclusions: IFX 5 mg/kg induction therapy resulted in substantial improvement in psoriasis as evaluated by PASI, PGA, and DLQI. P2874 Development of a large-scale, longitudinal survey to assess the prescribing practices of Canadian dermatologists in the treatment of psoriasis and the impacts of such treatments upon psoriasis patient Aditya Gupta, MD, PhD, MBA, Department of Medicine, Sunnybrook and Women s College Health Sciences Center (Sunnybrook site) and the University of Toronto, Toronto, Ontario; Mediprobe Research Inc, London, Ontario, Canada, London, ON, Canada; Charles Lynde, MD, University of Toronto, Dermatology, Markham, ON, Canada; Wayne Gulliver, MD, Memorial University, St John s, NF, Canada Psoriasis is a chronic skin disorder known for its ability to impact on the quality of life of affected subjects. Psoriasis impacts patients physically, affecting daily activities such as dressing, walking, and ability to work. Treatment may require substantial time and money on behalf of patients. Psoriasis may also impact patients psychologically and has been associated with a relatively high rate of depression and suicidal ideation. A long-term large-scale epidemiologic survey of Canadian dermatologists is ongoing, and investigates the use of psoriasis therapies and the impact of prescribed therapies on patient quality of life. This study uses patient and physician surveys to capture psoriasis visit data for each patient over a 3-year period. Physicians are instructed to provide treatments as per their usual recommendation(s) to patients in the clinic. The survey will collect data from at least 2 follow-up visits per year. The frequency of evaluation of patients will be based on the judgment and usual practice of the participating dermatologist. A baseline questionnaire will be given to patients to collect baseline data on general medical history and psoriasis history, including current medications and their current perceptions of their condition. Follow-up visits will collect data on how the subject s psoriasis is reacting to the active therapy since the previous visit, any adverse events that occur, and how the condition is affecting quality of life. The participating dermatologist will perform clinical evaluation of psoriasis at all visits using the PASI scoring and IGA score to evaluate psoriasis. Concomitant medications and adverse events will be monitored by the study coordinators/primary investigator at all follow-up visits. Initial data will provide a portrait of psoriasis presentations, patient characteristics, and prescribed treatments currently being used. As the study progresses, a general picture of typical psoriasis treatment in Canada will be obtained, looking specifically at treatment patterns in psoriasis patients and impacts of treatment on patient quality of life. Author disclosure: A. Menter and C. E. M. Griffiths are consultants and speakers and have also received research grants from Centocor, Inc. R. Matheson has received research grants from Centocor, Inc. S. Li is an employee of Centocor, Inc. Study sponsored by Centocor, Inc. P2873 Correlation between amount of drug used versus efficacy of calcipotriene/ betamethasone in severe psoriasis during a 52-week study Linda Stein Gold, MD, Henry Ford Health System, West Bloomfield, MI, United Introduction: Decreases in the PASI are effective in determining efficacy. We report a correlation between efficacy and amount of drug used at 52 weeks of treatment with combined calcipotriene 50 mg/g and betamethasone dipropionate 0.5 mg/g (C/BD) ointment in severe psoriasis. Methods: Six hundred thirty-four patients were randomized to treatment with either 52 weeks of C/BD (group 1), 52 weeks of alternating 4-week periods of C/BD and calcipotriene (group 2), or 4 weeks of C/BD followed by 48 weeks of calcipotriene (group 3). Treatments were used once daily as required. At each 4-week visit, the IGA of psoriasis was categorized as satisfactory (absence of, very mild. or mild disease according to IGA) or not satisfactory (moderate, severe, or very severe disease), and the patients assessment of treatment was categorized as satisfactory, not satisfactory, or not applicable, as not used. Results: IGA of severity at week 52 showed that 35.8% (76/212) of patients in group 1 achieved 100% satisfactory assessments (satisfactory response at all visits), compared with 27.7% (59/213) in group 2 (4/4 alt) and 24.4% (51/209) in group 3 (4/48) (P =.071, analysis of distribution). These results correlate with the amount of drug used between weeks 49 to 52. Patients in group 1, who showed the greatest response to therapy on the basis of IGA, also used the least amount of drug during this time period (102.0 g vs g for patients in group 2 and g for patients in group 3). Interestingly, the same results are evident when response to therapy is based on the patient s assessment, where 80 (37.7%) patients in group 1 achieved 100% satisfactory assessments, compared with 61 (28.6%) in group 2 and 60 (28.7%) in group 3 (P =.071, analysis of distribution). Conclusions: While topical therapies are capable of achieving moderate success in patients with severe psoriasis, they often do so at the expense of time and financial resources. Providing patients with a topical therapy that results in high rates of satisfaction and the application of less drug is the purpose behind the development of calcipotriene 50 mg/g and betamethasone dipropionate 0.5 mg/g. This analysis shows that after 52 weeks of therapy, patients with severe psoriasis achieve higher satisfaction rates with 13/day application of calcipotriene 50 mg/g and betamethasone dipropionate 0.5 mg/g compared with alternate regimens, with less drug. Author disclosure: Connetics Corporation Grant Support, Research Support, Consultant, Speakers Bureau; Warner Chilcott Consultant. Supported by Warner Chilcott. P2875 Effectiveness and safety of continuous versus intermittent etanercept therapy in patients with psoriasis: Analysis of the EASE trial Kenneth Gordon, MD, Loyola University, Stritch School of Medicine, Maywood, IL, United ; Sewon Kang, MD, University of Michigan Medical Center, Ann Arbor,MI,United;H.AmyXia,PhD,AmgenInc,ThousandOaks,CA, United ; Seth R. Stevens, MD, Amgen Inc, Thousand Oaks, CA, United Objective: To compare the effectiveness of continuous versus intermittent etanercept therapy in patients with psoriasis from the Etanercept Assessment of Safety and Effectiveness (EASE) trial. Methods: In this multicenter, randomized, open-label, 24-week, phase 3 study, patients were required to have stable, active plaque psoriasis involving 10% or more of body surface area. Patients were randomized to 1 of 2 groups: continuous therapy (group A; n = 1272) or intermittent therapy (group B; n = 1274). For the first 12 weeks, all patients received uninterrupted etanercept 50 mg twice a week by subcutaneous (SC) injection. Group A patients then received continuous etanercept 50 mg once a week (QW) SC for weeks 13 through 24. Group B patients who were responders (achieved a PGA of psoriasis responder status [score of #2, where 0 = clear, 5 = severe] and improved from baseline at week 12) discontinued therapy; upon relapse (loss of PGA responder status) patients initiated etanercept 50 mg QW through week 24. Group B patients who did not achieve responder status on the PGA at week 12 continued etanercept 50 mg QW without interruption through weeks 13 to 24. The primary efficacy endpoint was the proportion of patients who achieved PGA responder status at week 24. Adverse events, serious adverse events, and infections were monitored. Results: A total of 2546 patients (85% white, 62.4% men) received at least 1 dose of study drug. The mean age was 45.4 years; mean duration of psoriasis was 18.2 years. The proportion of responders at week 24 was 71.0% in group A and 59.5% in group B, a difference of 11.5% (95% CI: 7.8%, 15.2%; P,.0001) between the treatment arms. The proportion of patients who achieved a status of clear at week 24 was 15.0% in group A and 5.3% in group B, a difference of 9.8% (95% CI: 7.4%, 12.1%; P,.0001). At week 24, mean improvements from baseline in PGA scalp scores for group A and group B were 57.6% and 42.9%, respectively. Etanercept was well tolerated in both treatment arms. Conclusions: In this 24-week study of patients with psoriasis, etanercept was well tolerated and efficacious when used either continuously or intermittently. Significantly greater improvements were observed in patients who received continuous etanercept therapy, compared with patients who received intermittent therapy. AB216 J AM ACAD DERMATOL MARCH 2006

4 P2876 Efficacy and safety of alefacept in combination with narrowband UVB for the treatment of plaque psoriasis Heidi Jacobe, MD, Laura Winterfield, MD, UT Southwestern Medical Center, Dallas, TX, United Alefacept has a mechanism of action that provides remittive effects, with some patients maintaining response to alefacept for prolonged periods after treatment completion. The remittive effects of alefacept are attributed to reductions in memory T cells in lesional skin, which may take 6 to 8 weeks of therapy before a clinical effect is observed. An open-label study using alefacept in combination with ultraviolet B (UVB) light therapy (Ortonne et al, J Eur Acad Dermatol Venerol 2005) suggested that the onset of effect is faster with combination therapy than with alefacept alone. However, a comparison with UVB phototherapy alone was not done. In the present prospective, randomized, double-blind, placebo-controlled study, we compare the effects of treatment with alefacept plus narrowband (NB) UVB with NB-UVB phototherapy alone. Approximately 16 patients, $18 years of age, who are candidates for systemic therapy or phototherapy for chronic plaque psoriasis are being enrolled. Treatment with systemic agents, phototherapy including UVB and PUVA, biologic agents, and other immunosuppressants within 28 days before study drug administration is not allowed. Patients with CD41 T-cell counts below the lower limit of normal or a known history of photosensitivity are excluded. Patients are randomized into 1 of 2 treatment groups. Patients in group 1 receive alefacept 15 mg IM once a week and NB-UVB 3 times a week for 12 weeks. Patients in group 2 receive placebo by IM injection once weekly and NB-UVB 3 times a week for 12 weeks. Patients will be followed for 20 weeks after treatment is completed (up to week 32). Efficacy assessments using PASI and PGA are conducted at baseline, at weeks 4, 8, and 12 during the treatment period, and at weeks 16, 20, 26, and 32 during the follow-up period. In addition to PASI and PGA, additional efficacy assessments include the total number of NB-UVB treatments and the total dose of NB-UVB (millijoule) required to achieve at least a 50% and 75% reduction from baseline PASI (PASI50 and PASI75, respectively) and total clearance. Lymphocyte subset analyses are carried out at every other week throughout the treatment period. Adverse events are monitored throughout the study. Results from the study will provide further information on the safety and efficacy of alefacept in combination with NB-UVB and allow for comparison with NB-UVB phototherapy alone. Author disclosure: H.J.: investigator and speaker for Biogen Idec, speaker for Amgen and Valient; L.W.: investigator for Biogen Idec. Study supported by Biogen Idec, Inc, Cambridge, MA. P2878 Efficacy and safety of XP-828L in the treatment of mild to moderate psoriasis: A double-blind, placebo-controlled clinical study Yves Poulin, University Laval, Sainte-Foy (Quebec), CA, Canada; Robert Bissonnette, MD, Innovaderm, Montreal, CA, Canada Introduction: XP-828L is a growth factor complex extracted from bovine lactoserum that is administered orally. A double-blind, placebo-controlled clinical trial was done to evaluate XP-828L s safety and efficacy on psoriasis. Study Design: A randomized multicenter, double-blind, placebo-controlled crossover study involving 84 patients with mild to moderate psoriasis was undertaken. Two groups of 42 patients were compared over two consecutive periods of 56 days for a total of 112 days. In the first 56-day period, patients received XP-828L (2.5 g twice daily- 5 g/day) or placebo. Afterwards, patients under placebo received XP- 828L at a higher dose of the active compound (5 g twice daily-10 g/day). Patients who received the active product (XP-828L 5 g/day) remained on the same dose for the second 56 day-period of the study. The PGA (a 5-point scale) was used as the main endpoint. Results: First 56-day phase: At day 1 and 56 the PGA values (mean 6 SD) were and , respectively, for the placebo group; and , respectively, for the active treatment group. The difference between treatment groups was statistically significant (P =.0395). Twenty-one percent of patients receiving the active compound(xp-828l at a dose of 5 g daily) showed a decrease on the PGA score of at least one point. Second 56-day phase: The PGA scoring after 56 days of treatment with XP-828L at a dosage of 10 g/day was identical to that achieved with the dose of 5 g/day. Patients remaining under XP-828L at a dosage of 5 g/day maintained their initial improvement, without further benefit. No differences were found between the active treatment group and the placebo group with regard to laboratory monitoring and clinical adverse events. Conclusion: Results from this study are showing a trend toward improvement for mild to moderate psoriasis with the use of oral XP-828L with an adequate safety profile. Additional contributors: Patrice E. Poubelle, Centre de Recherche en Rhumatologie & Immunologie, CRCHUL, Quebec; Kim Cantin, Advitech, Quebec, Canada; Christina Juneau Advitech, Quebec, Canada. Supported by Advitech. P2877 Efficacy and safety of low-dose acitretin for the treatment of moderate to severe plaque-type psoriasis Jennifer Cather, MD, Baylor University Medical Center, Dallas, TX, United ; Gerald Krueger, MD, University of Utah, Salt Lake City, UT, United ; Mark Jackson, MD, University of Louisville, Louisville, KY, United ; Alexey Samtsov,MD,PhD,KirovRussianMilitaryMedicalAcademy,StPetersburg,Russia Objective: Evaluate the efficacy and safety of 2 low-dose regimens of acitretin administered over 24 weeks in adult subjects with moderate to severe plaque-type psoriasis. Design: This multicenter, open-label, randomized study in the United and Russia enrolled 213 adults.18 years of age with moderate to severe plaque-type psoriasis defined as.10% total body surface area involvement with psoriasis and an OLA score of.3. Subjects were randomized to acitretin 25 mg once daily for 24 weeks, or acitretin 25 mg once daily for 12 weeks followed by step-down dosing of acitretin 10 mg once daily for 12 weeks. Subjects who did not improve.2 grades (OLA scale) at week 12 could be increased to 35 mg/day at the investigator s discretion. Methods: Efficacy endpoints included the proportion of subjects who achieved an OLA score of 0 or 1 (none or minimal) at weeks 12 and 24, and the proportion of subjects who achieved a PASI score reduction of 50% (PASI50 response) and 75% (PASI75 response) at weeks 12 and 24 relative to baseline. SGA scores were also evaluated. Results: An interim analysis of 54 subjects at 6 study centers in Russia was performed. The baseline OLA (range: 0-5) was 3 in 86% and.4 in 14% of subjects. After 12 weeks of treatment an improvement in OLA score of 2 grades or more from baseline was reported in 24% of the intent-to-treat (ITT) population and in 38% of the per-protocol population (PPP). Mean drug exposure was days (1 SD) for the ITT and days for PPP. Conclusions: A meaningful response to low-dose acitretin was achieved by 12 weeks. Twenty-four week efficacy and safety data will be reported. If confirmed, these data suggest that a low-dose regimen of acitretin may have utility in the treatment of moderate to severe psoriasis. Author disclosure: Drs Cather and Jackson are speakers, researchers, and consultants for Connetics; Dr Krueger is a researcher and consultant for Connetics; Dr Samtsov is a researcher for Connetics. 100% sponsored by Connetics Corporation, Palo Alto, CA. P2879 Etanercept and narrowband UVB combination therapy for plaque-type psoriasis shortens onset of action in both adults and children Angela Moore, MD, Eric Wright, MS, Lisa Ostrowski, PA, Todd Moore, MD, Arlington Center for Dermatology, Arlington, TX, United Optimizing therapy for patients with chronic plaque psoriasis requires balancing many factors, including safety, efficacy, onset of therapeutic benefit, duration of response, as well as convenience. Etanercept is a recombinant human fusion protein that binds free TNF to prevent interaction with cell surface TNF receptors. Although the mechanisms of action of narrowband UVB (NB-UVB) in psoriasis have not been fully elucidated, they appear to be broader in scope than TNF inhibition and include inhibition of DNA synthesis, reduction in basal layer overproliferation, and induction of T-cell apoptosis. Dermatologists often combine therapeutic modalities for the treatment of moderate to severe psoriasis. Combining etanercept with NB-UVB phototherapy, two relatively safe treatment modalities that work through different mechanisms of action, may benefit a greater proportion of psoriasis patients with quicker onset of action than either treatment used as a monotherapy. Purpose: To assess the onset of action and safety, we retrospectively analyzed 5 adults and children with moderate to severe plaque-type psoriasis who received etanercept in combination with NB-UVB. Results: Combining etanercept with NB-UVB 3 times a week increases efficacy without increased side effects. Conclusion: When etanercept is combined with NB-UVB, the onset of action decreases and efficacy increases without increased side effects. More studies need to be performed to show the additive and synergistic effects of etanercept and other biologic treatments with NB-UVB. MARCH 2006 J AM ACAD DERMATOL AB217

5 P2880 Etanercept in children and adolescents with psoriasis Elaine Siegfried, MD, Kids Dermatology, St Louis, MO, United ; Moise Levy, MD, Texas Children s Hospital, Houston, TX, United ; Angelika Jahreis, MD, PhD, Amgen Inc, Thousand Oaks, CA, United ; Amy Paller, MD, Children s Memorial Hospital, Chicago, IL, United Background: Although the prevalence of psoriasis in adolescents has been estimated at 0.3% (Larsson P, Liden S. Acta Derm Venereol 1980;60:415-23), this may be an underestimate in children because many are misdiagnosed as having eczema. Children and adolescents with moderate to severe psoriasis represent a vulnerable patient population with a need for safe and efficacious therapies. Etanercept, a soluble TNF receptor, has been approved for adult patients with chronic moderate to severe plaque psoriasis. Etanercept is FDA-approved in juvenile rheumatoid arthritis patients, but no systematic study has examined its use in the pediatric psoriasis population. Methods: A phase 3, randomized, double-blind, placebo-controlled clinical trial of etanercept in up to 200 pediatric patients with a $ 6 month history of psoriasis has been initiated. Patients 4 to 17 years of age are required to have stable moderate to severe plaque psoriasis with a PASI score of at least 12 during the screening period. Patients are randomized to receive either etanercept 0.8 mg/kg once weekly (QW) or placebo. The study consists of 3 treatment periods: a double-blind, placebocontrolled treatment period for 12 weeks; an open-label treatment period for 24 weeks; and a randomized, double-blind withdrawal and retreatment period for 12 weeks. The last period randomizes only those patients achieving a PASI75 response (a $ 75% decrease in PASI score, compared with baseline) to either placebo or etanercept QW. Preliminary Results: The 76 patients who received at least 1 dose of study drug as of April 2005 represent 38% of the planned population. Baseline characteristics were: 51.3% female, 84.2% white, 31.6% age 4 to 11 years old, mean age of 13.3 years, mean weight of 61.9 kg, and mean duration of psoriasis of 6.7 years. Conclusions: Pediatric psoriasis patients constitute a vulnerable population, with a need for safe and efficacious treatment options. A currently enrolling phase 3 clinical study in pediatric patients with psoriasis is examining the safety and efficacy of once-weekly etanercept in this population. P2882 Evaluation of alefacept for the treatment of palmoplantar psoriasis Daniel Pearce, MD, Wake Forest University School of Medicine, Winston-Salem, NC, United ; Steven Feldman, MD, PhD, Wake Forest University School of Medicine, Winston-Salem, NC, United ; Bernard Goffe, MD, Dermatology Associates, Seattle, WA, United Given the refractory nature of palmoplantar pustular psoriasis (PPP) and the many limitations of traditional systemic therapies, we performed a pilot study to evaluate the efficacy and safety of alefacept for the treatment of PPP. Subjects $18 years of age with PPP requiring phototherapy or systemic therapy are eligible for enrollment. Alefacept is administered as an IM injection of 15 mg once weekly for 16 weeks; if there is no appreciable response after 8 weeks of treatment, the dose is increased to 30 mg weekly for the remainder of the study. A 12-week observation period follows the completion of treatment, for a total study duration of 28 weeks. Efficacy assessments include the PPSI and the PGA of palmoplantar psoriasis. Safety assessments include monitoring of CD41 T-cell counts and adverse events, and assessment of new or ongoing infections. A total of 15 subjects are enrolled at 2 sites (A and B) in this ongoing study; 6 subjects have completed the study, and 9 remain in treatment or follow-up. At week 16, mean PPSI scores at site A improved by 17.9%, and scores at site B improved by 44.9%. Mean PGA scores followed a similar trend, improving from 2.3 at week 4 to 1.8 at week 28 at site A, and from 2.4 at week 4 to 2.0 at week 16 at site B. During both the monthly (weeks 1-8) and weekly (weeks 9-16) T-cell-monitoring periods, no subject had CD41 T-cell counts below 250 cells/mm 3, and no doses of alefacept were withheld due to low counts. Alefacept was generally well tolerated, with no subjects withdrawing from the study due to adverse events. No serious adverse events or malignancies have been reported. These preliminary results indicate that treatment with alefacept offers clinical benefit to subjects with PPP. Additional efficacy and safety results from the completed study will be presented. Author disclosure: SF: Consultant or research support from 3M, Abbot, Acuderm, Allergan, Amgen, Aventis, Biogen Idec, Bristol Myers-Squibb, Centocor, Connetics, Curatek, Ferndale, Fujisawa, Galderma, Genderm, Hoffman LaRoche, Janssen, Novartis, Roche, Schering-Plough, Warner Chilcott. Study supported by Biogen Idec, Inc, Cambridge, MA. Author disclosure: Siegfried: Amgen Inc; Levy: Amgen, Novartis, 3M, GSK; Jahreis: Amgen Inc; Paller: Amgen Inc. Abstract supported by Immunex, a wholly owned subsidiary of Amgen, and by Wyeth Research. P2881 Etanercept therapy maintains high PASI responses in psoriasis patients independent of reported Psoriatic arthritis Mark Lebwohl, MD, Mount Sinai School of Medicine, New York, NY, United ; Jerold Powers, MD, Radiant Research, Scottsdale, AZ, United ; Kenneth B. Gordon, MD, Loyola University Medical Center, Maywood, IL, United ; Wolfram Sterry, MD, Humbolt University, Berlin, Germany Background: Psoriatic arthritis (PsA) is a spondyloarthropathy associated with psoriasis. Etanercept is safe and effective for the treatment of both indications. The efficacy of etanercept on psoriatic skin lesions in psoriasis patients with or without a history of PsA was investigated. Objective: To determine the treatment effect of etanercept therapy, as measured by the PASI, in a cohort of psoriasis patients with a history of PsA, compared with a cohort without PsA. Methods: Patients with psoriasis from three phase 3 trials (N = 1027) who received 12 weeks of either etanercept 25 mg twice weekly (BIW) or etanercept 50 mg BIW were stratified by the presence or absence of self-reported PsA. At screening, patients with PsA were identified by obtaining medical histories, which included the dates of PsA onset. The primary endpoint was a 75% or greater improvement in the PASI (PASI75) at 12 weeks. PASI50 and PASI 90 response rates were also assessed. Results: Among the 358 patients who received etanercept 25 mg BIW, 91 (25%) had PsA and 267 (75%) did not. Among the 669 patients who received etanercept 50 mg BIW, 194 were PsA patients (29%) and 475 were non-psa patients (71%). At week 12, PASI75 responses were comparable between patients with PsA and those without PsA in the etanercept 25 mg BIW group (37% vs 33%, P =.49). PASI75 responses to etanercept 50 mg BIW were also similar for patients with and without PsA (45% vs 50%, P =.24). Comparable PASI50 responses were observed between PsA and non- PsA patients in the etanercept 25 mg BIW group (60% vs 62%, P =.74) and in the etanercept 50 mg BIW group (74% vs 75%, P =.79). Patients with PsA also had PASI 90 response rates similar to those of patients without PsA in both the etanercept 25 mg BIW group (13% and 10%, P =.45) and the etanercept 50 mg BIW group (23% vs 20%, P =.40). Conclusions: A 12-week course of etanercept therapy in patients with psoriasis resulted in high PASI responses regardless of reported psoriatic arthritis. P2883 Author disclosure: Dr Lebwohl is a speaker, consultant, and investigator for Amgen; Dr Gordon has received honoraria and research support, and has been a consultant for Amgen. Nothing to disclose for Drs Powers and Sterry. Research funded by Immunex Corporation, a wholly-owned subsidiary of Amgen Inc, and by Wyeth Research. AB218 J AM ACAD DERMATOL MARCH 2006