P610INTERPRETATION OF POSITIVE PATIENT RESPONSE TO EFALIZUMAB FOR THETREATMENT OF MODERATE TO SEVERE PLAQUE PSORIASISStephen Stone, MD, Southern University School of Medicine, Springfield, IL, United States,Kim Papp, MD, Probity Medical Research, Waterloo, ON, Canada, Ivor Caro, MD, Genen-tech, South San Francisco, CA, United States, Brian Bresnahan, Genentech, South SanFrancisco, CA, United States

Numerous studies have shown that patients with plaque psoriasis experience reduceddermatology-related quality of life (DRQL), psychosocial distress and functional impair-ment. The clinical interpretation and real-world understanding of improvements ondermatology or psoriasis-specific scales has not been fully investigated. The impact ofpsoriasis on physical functioning and mental health has been shown to exceed that ofmany chronic diseases, including cancer, diabetes mellitus, and cardiac disease. Thesefindings highlight the need for novel psoriasis therapies that improve the physicalsymptoms of psoriasis, and improve patients’ well-being and ability to function. Efali-zumab, a humanized monoclonal IgG1 antibody, is a T-cell modulator that targets keysteps in the immunopathogenesis of psoriasis.

Data were pooled from three similarly designed Phase III randomized, double-blind,parallel-group, placebo-controlled, multicenter trials of patients with moderate to severeplaque psoriasis who received 12 weekly doses of 1 mg/kg/wk efalizumab or placeboadministered subcutaneously. The impact of efalizumab on DRQL for patients in the 3trials was measured using multiple pre-defined, dermatology- or psoriasis-specific patient-reported outcome (PRO) measures, including the Dermatology Life Quality Index (DLQI),Psoriasis Symptom Assessment (PSA), and the Itch Scale. Responses to individual ques-tions on these PRO scales were examined, and patient benefit categories for expandedclinical interpretation were developed. The impact of efalizumab on DRQL and diseaseburden was assessed, including a comparison of aggregate changes in DLQI, PSA, and ItchScale scores between efalizumab and placebo using statistical and clinical responsecriteria. Efalizumab-treated patients demonstrated significant improvement on all DRQLmeasures compared with placebo (P � .001, each measure). A greater percent ofefalizumab-treated patients experienced improvement in physical symptoms, functionalstatus, relief from itch, and social well-being, compared with placebo. The details andinterpretation of the item-level responses will be presented.

The results demonstrate that patients with moderate to severe plaque psoriasis experi-ence significant disease burden and poor DRQL at baseline. Efalizumab treatment signif-icantly lessened the impact of psoriasis on patients’ lives, improved patients DRQL andtheir ability to function.

Author is a consultant for Genentch, Inc.

Supported by Genentech, Inc.

P611LONG-TERM EFALIZUMAB THERAPY SAFELY MAINTAINS PSORIASIS AREA ANDSEVERITY INDEX IMPROVEMENT: PRELIMINARY RESULTS FROM AN OPEN-LA-BEL TRIALAlice Gottlieb, MD, PhD, UMDNJ-Robert Wood Johnson Medical School, New Brunswick,NJ, United States, Kenneth Gordon, MD, Loyola University Medical Center, Maywood, IL,United States, Ivor Caro, MD, Genentech, South San Francisco, CA, United States, CraigLeonardi, MD, Saint Louis University School of Medicine, Saint Louis, MO, United States

Psoriasis, an incurable disease characterized by periods of disease relapse and remission,often requires long-term treatment to manage symptoms. The risk of serious cumulativetoxicity precludes long-term administration with currently available systemic therapies.Efalizumab is an IgG1 humanized monoclonal antibody in development to address theneed for a safe, long-term therapy for continuous control of plaque psoriasis.

An ongoing, open-label study in patients with moderate to severe plaque psoriasis isassessing the efficacy, safety, and tolerability of long-term efalizumab therapy. DuringMonths 1 to 3 (84 days), patients received weekly subcutaneous (SC) injections ofefalizumab 2 mg/kg (with or without a topical corticosteroid during Days 56 to 84).Patients who achieved �50% Psoriasis Area and Severity Index improvement (PASI-50) oran Overall Lesion Severity (OLS) rating of Mild, Minimal, or Clear at Day 84 were eligibleto enter the open-label maintenance period, which is being analyzed in 3-month seg-ments. During maintenance treatment, subjects receive SC efalizumab 1 mg/kg/wk. In theevent of relapse (loss of �50% PASI improvement at Day 84), the efalizumab dose isincreased to 2 mg/kg or up to 4 mg/kg weekly. During the first 3-month period, 339patients were treated; 41% of all patients achieved a PASI-75 response, relative to baseline,and 82% achieved a PASI-50 response. Of these 339 patients, 290 (94%) entered into themaintenance period. PASI responses were analyzed using both intent-to-treat (ITT) (n �290 throughout maintenance treatment) and as-treated analyse (the number of subjectsdecreased each 3-month period due to discontinuations). As previously reported, of the194 patients who received 21 months of continuous efalizumab therapy, PASI-75 re-sponses were achieved in 55.9% of patients using the ITT analysis (n � 290) and 67.0%using the as-treated analysis (n � 194). PASI-90 responses increased from 13% at Month3 to 30.0% and 34.0% at month 21 in the ITT and as-treated analyses, respectively. No newcommon adverse events emerged during long-term efalizumab therapy. The incidence ofserious adverse events, adverse events leading to withdrawal, infection-related events,and malignancy remained stable during 21 months of treatment.

The results of this study demonstrate the safety and maintained efficacy of long-termefalizumab administration in patients with moderate to severe plaque psoriasis. Updatedpreliminary results will be presented.

Disclosure not available at press time.

Supported by Genentech, Inc.

P612INFLIXIMAB IMPROVES SIGNS OF PLAQUE PSORIASIS IN PATIENTS WITH PSORI-ATIC ARTHRITISAlice B Gottlieb, MD, PhD, UMDNJ-Robert Wood Johnson Medical School, New Bruns-wick, NJ, United States, Robert Evans, RPh, Centocor, Inc., Malvern, PA, United States,Kamlesh Patel, MS, Centocor, Inc., Malvern, PA, United States, Robert Matheson, MD,Oregon Medical Research Center, Portland, OR, United States

Purpose: Psoriatic arthritis is a chronic inflammatory condition that affects both the skinand joints. Tumor necrosis factor alpha (TNF-alpha), a primary mediator of generalinflammation, plays a key role in the pathogenesis of both the articular and skin inflam-matory components. Infliximab (IFX) is a chimeric, anti-TNF-alpha monoclonal antibodythat specifically neutralizes both bound and secreted forms of TNF-alpha. Previous studieshave demonstrated improvement in rheumatoid arthritis when IFX is used in combinationwith MTX and in psoriasis when IFX used as monotherapy. This abstract assesses theeffects of IFX induction therapy on plaque psoriasis in patients with psoriatic arthritis.

Methods: In a retrospective analysis of a phase 2, multicenter, randomized, double-blind,placebo-controlled trial evaluating IFX induction therapy in patients with plaque-typepsoriasis (the SPIRIT trial), 78 patients had psoriatic arthritis as identified by medicalhistory. These patients were treated with placebo or 3 or 5 mg/kg IFX at weeks 0, 2 and6. Improvement from baseline in psoriatic lesions was assessed using the Psoriasis Areaand Severity Index (PASI) and Physician Global Assessment (PGA). Proportions of PASIresponders (�75% improvement in PASI), marked responders (�90% improvement inPASI), and patients achieving a PGA score of minimal or clear in the IFX dose groups werecompared with those of the placebo group at week 10 using a chi-square test.

Results: Response to infliximab treatment in the subset of patients with psoriatic arthritiswas similar to that of the general study population. At week 10, 68.8% and 89.7% ofpatients in the 3 and 5 mg/kg group, respectively, were rated as having minimal or cleardisease compared with 0 patients in the placebo group (p � 0.001). In addition, 75.0%and 86.2% of patients in the 3 and 5 mg/kg group, respectively, were classified as PASIresponders compared with 0 patients in the placebo group (p � 0.001). Strikingly, 53.1%and 44.8% of patients in the 3 and 5 mg/kg groups, respectively, achieved marked PASIresponse compared with 0 patients in the placebo group (p � 0.001).

Conclusions: IFX treatment resulted in a significantly greater improvement in plaquepsoriasis compared with placebo in patients with concurrent psoriatic arthritis.

Drs Gottlieb and Matheson have served as consultants to Centocor, Inc. R Evans and KPatel are Centocor, Inc. employees.

This study was sponsored by Centocor, Inc.

P613THE SAFETY OF EFALIZUMAB IN PATIENTS WITH MODERATE TO SEVEREPLAQUE PSORIASIS: SUMMARY OF CLINICAL TRIAL EXPERIENCECraig Leonardi, MD, St. Louis University School of Medicine, St. Louis, MO, United States,Bernard Goffe, MD, Minor and James Medical Clinic, Seattle, WA, United States, JeffSobell, MD, ORA Clinical Research, North Andover, MA, United States, Ivor Caro, MD,Genentech, South San Francisco, CA, United States

Lack of consistent treatment efficacy, inconvenience associated with topical therapiesand phototherapy, invasive monitoring for systemic therapies, the potential for seriouscumulative toxicity, and increased knowledge regarding the role of T cells in psoriasispathology have provided the impetus for the development of novel psoriasis therapies.Efalizumab is a humanized monoclonal IgG1 antibody in development for the treatmentof moderate to severe plaque psoriasis. Efalizumab has been studied in more than 2,700psoriatic patients in 13 controlled and uncontrolled trials. These trials have evaluated theeffects of efalizumab during 12- and 24-week treatment periods and long-term adminis-tration (up to 2 years). Results from these psoriasis trials were pooled, yielding the largestreported cohort of psoriasis patients treated with a biologic therapy to date.

Initiation of efalizumab therapy was associated with acute flu-like symptoms, typicallyobserved during the first one or two doses; by the third dose, the incidence wascomparable to that observed in placebo-treated patients. During long-term treatment, nonew pattern of treatment-emergent adverse events was observed. There was no evidenceof an increased risk of end-organ damage (renal, hepatic, and bone marrow), infection, ormalignancy in efalizumab-treated patients often compared with placebo-treated patientsor external cohorts of similar patients. The lack of end-organ damage obviates the needfor frequent or invasive laboratory monitoring during long-term therapy.

Efalizumab is well tolerated, with acute adverse events related primarily to the first twodoses. The lack of serious toxicity supports its long-term utility in psoriasis patients,offering a much-needed therapeutic option that could provide long-term control ofpsoriasis symptoms.

Author is consultant for Genentech, Inc.

Supported by Genentech, Inc.

P157MARCH 2004 J AM ACAD DERMATOL