P697LOCAL TOLERABILTY OF TISOCALCITATE OINTMENT IN HUMANSAngelika Jahreis, Eugene O’Keefe, Schering AG, Center of Dermatology, Berlin, Germany

Background: Vitamin D analogues are first line treatment options for plaque type psori-asis. Tisocalcitate ointment contains a novel Vitamin D derivative.

Objective: To evaluate the local tolerability (irritant potential) of Tisocalcitate ointmentcompared with 50 �g/g calcipotriol ointment (reference product) and vehicle.

Methods: A double-blind, single-center, reference- and vehicle-controlled study over aperiod of 21 days on healthy skin of 26 volunteers was performed. Twenty-six healthyvolunteers underwent 15 occlusive applications (5 times a week for 3 weeks) of theinvestigational products (Tisocalcitate ointment 25 and 50 �g/g in combination with urea0%, 5%, 10% or 20% w/w), 50 �g/g calcipotriol ointment (reference product) and vehicle.Finn Chambers (8-mm diameter) were applied to the skin of the back containing 0.02 mLointment. Irritation was assessed clinically using a visual 5-point scale as follows from 1 �no reaction to 5 � marked erythema, strong infiltration, papules or vesicles. A cumulativeirritancy index (CI) was calculated for each product and each subject.

Results: Twenty-four volunteers were included in the intent-to-treat analysis and com-pleted the study. The mean of the CI for the 8 Tisocalcitate ointment treated areas variedbetween 2.5 and 4.3, whereas for the calcipotriol ointment treated areas the mean of theCI was 9.5 showing that the reference product had the highest irritant potential. AllTisocalcitate ointment formulations had a significantly better local tolerability than thereference ointment (Dunnett’s 2-sided t test, � � 0.05).

Conclusions: All Tisocalcitate ointment formulations had a significantly better localtolerability than the reference ointment (Dunnett’s 2-sided t test, � � 0.05). In summary,Tisocalcitate ointments were tolerated well and were safe to use on healthy skin in thisstudy.

Disclosure not available at press time.

P698SAFETY OF LARGE AREA APPLICATION OF A NOVEL VITAMIN D ANALOGUE(TISOCALCITATE OINTMENT) IN PATIENTS WITH CHRONIC PLAQUE TYPE PSO-RIASISMarion Schneider, Thomas Staks, Schering AG, Clinical Pharmacology, Berlin, Germany,Angelika Jahreis, Eugene O’Keefe, Schering AG, Center of Dermatology, Berlin, Germany

Background: Vitamin D analogues are first line treatment options for plaque type psori-asis. One of the drawbacks of therapy with topical vitamin D analogues is their potentialto influence calcium metabolism.

Objective: To determine the safety of ascending doses of Tisocalcitate ointment inpatients with plaque type psoriasis, with special focus on the effects on calcium ho-meostasis.

Methods: Single-center, randomized, double blind, placebo-controlled, dose-escalation,interindividual study to investigate the safety of ascending doses of Tisocalcitate ointmentfor 14 days under highly standardized study conditions. Ten male and female patients ofnon-childbearing potential were allocated to each dose group, 7 patients were treatedwith Tisocalcitate ointment and 3 patients were treated with placebo ointment. A doserange from 525 �g Tisocalcitate/day to 2100 �g Tisocalcitate/day on 45% BSA wasevaluated applied as 25 �g/g of Tisocalcitate ointment on 45% BSA, 50 �g/g of Tisocal-citate ointment on 45% BSA and twice daily 50 �g/g of Tisocalcitate ointment on 45%BSA.

Results: Thirty patients with psoriasis were treated for 14 days. All 3 doses were welltolerated by the patients. Serum calcium was within the normal range for all patientsduring the study. No tendency towards an increase in serum calcium levels or 24-hoururine calcium excretion was observed for any single value or the mean value. There wasno change in PTH levels during the study. There were no serious adverse events reported.

Conclusions: Tisocalcitate ointment, containing a novel vitamin D analogue, shows anexcellent systemic safety profile. There was no tendency of Tisocalcitate ointment to havean effect upon single values or mean values of calcium metabolism during large areaapplication of up to 50 �g/g Tisocalcitate ointment twice daily over 45% BSA in patientswith chronic plaque type psoriasis.

Disclosure not available at press time.

P699COST EFFICACY COMPARISON OF BIOLOGICS IN THE TREATMENT OF PSORIASISLee A. Wanke, MS, Amgen, Thousand Oaks, CA; Daniel Malone, PhD; University ofArizona, Tucson, AZ; Chiun-Fang Chiou, PhD; Zynx Health, Cerner Corporation, BeverlyHills, CA; Michael Woolley, PhD, Amgen, Thousand Oaks, CA

Objective: To compare the cost-efficacy of biologics in the treatment of psoriasis usingthe Psoriasis Area and Severity Index (PASI) response criteria as the efficacy endpoint.

Methods: A cost-efficacy analysis was conducted comparing biologics used in the treat-ment of psoriasis. This aspect focuses on alefacept 7.5mg IV weekly (qw) or 15mg IM qwand etanercept 25mg subcutaneous (SQ) twice weekly (biw) or 50mg SQ biw. Theperspective of this analysis was a US managed care organization. A three-month timehorizon was chosen based on the availability of efficacy data (PASI-50 and PASI-75) fromcomparable clinical trials. Medication costs were based on US average wholesale price(AWP). Other direct costs, including those for physician office visits, laboratory monitor-ing, and drug administration, were based on Medicare reimbursement rates and theMEDSTAT DRG Guide. Adverse events were assumed to be equal for all treatment armsbased on reporting in package inserts; they were grouped into mild, moderate or severefor calculation of their treatment costs. It was assumed that 5% of patients dropped outof each treatment arm at 6 weeks due to severe adverse events. Sensitivity analyses wereconducted on drug costs, adverse event rates and efficacy measures.

Results: The total cost for each regimen over the three-month time course, adjusted forthe dropout rate, was: etanercept 25mg � $4130; etanercept 50mg � $7945; alefaceptIV � $9504; alefacept IM � $12850. Efficacy measures for each regimen were: etanercept25mg, PASI-50 � 0.44 and PASI-75 � 0.30; etanercept 50mg, PASI-50 � 0.0.60 andPASI-75 � 0.45; alefacept IV, PASI-50 � 0.28 and PASI-75 � 0.10; alefacept IM, PASI-50� 0.24 and PASI-75 � 0.16. The cost per PASI-50 responder for alefacept 7.5mg IV qwand 15mg IM qw were $33939 and $53542, respectively. The cost per PASI-50 responderfor etanercept 25mg SQ biw and 50mg SQ biw were $9386 and $13240 respectively. Thecost per PASI-75 responder for alefacept 7.5mg IV qw and 15mg IM qw were $95030 and$80313, rsepectively. The cost per PASI-75 responder for etanercept 25mg SQ biw and50mg SQ biw were $13767 and $17653 respectively. The results were sensitive to bothdrug cost and efficacy rate. Etanercept dominated alefacept in each analysis (that is, hadlower cost and higher efficacy). Results from analyses with other biologics will also bepresented.

Conclusions: Results suggest that etanercept is associated with a lower cost per PASI-50and PASI-75 responder and therefore is more cost-efficacious compared to alefacept forthe treatment of psoriasis.

Supported by Amgen.

P179MARCH 2004 J AM ACAD DERMATOL