P2518Rapidly progressive ashy dermatosis responsive to hydroxychloroquine

Jennifer Janiga, MD, Henry Ford Hospital, Detroit, MI, United States; Holly Kerr,MD, Henry Ford Hospital, Detroit, MI, United States; Henry Lim, MD, Henry FordHospital, Detroit, MI, United States

Ashy dermatosis, also referred to as erythema dyschromicum perstans, is a rarepigmentary disorder most common in Central and South America. It is a chronicdisease of unknown origin characterized by asymptomatic blue-gray patches,sometimes presenting with an erythematous border. This condition is difficult totreat with reported success with clofazimine, dapsone, and oral corticosteroids inthe literature. We report a case of a 54-year-old African American woman withrapidly progressive lesions consistent with ashy dermatosis on biopsy that hadclinical response to hydroxychloroquine at 200 mg twice a day after failing a trialwith ruby laser.

FEBRUARY

cial support: None identified.

Commer

PSORIASIS AND OTHER PAPULOSQUAMOUSDISORDERS

P2600A 2-week multiple ascending dose, double-blind, placebo-controlled studyto evaluate the safety, tolerability, pharmacokinetics, and efficacy of oralAEB071, a protein kinase C inhibitor, in moderate to severe psoriasispatients

Hans Skvara, MD, Dermatology, Division of Immunology, Allergy and Inf Diseases,Medical University of Vienna, Vienna, Austria; Markus Dawid, MD, Dermatology,Division of Immunology, Allergy and Inf Diseases, Medical University of Vienna,Vienna, Austria; Georg Stingl, MD, Dermatology, Division of Immunology, Allergyand Inf Diseases, Medical University of Vienna, Vienna, Austria; ChristopherGriffiths, MD, University of Manchester, Manchester, United Kingdom

AEB071, a novel, selective inhibitor of protein kinase C (PKC), is being developed asan oral formulation for the treatment of autoimmune diseases and the prevention oftransplant rejection. Here, we report data from the first multiple dose trial inpsoriasis. A total of 32 patients with moderate to severe plaque psoriasis weresequentially randomised to one of four doses of the study drug (25, 100, 200, and300 mg bid AEB071) or placebo. Patients were treated for 2 weeks and followed-upfor another 2 weeks off treatment. AEB071 concentrations in blood increasedlinearly. Skin concentrations were 2- to 4-fold lower than blood levels. AEB071 waswell tolerated at all test doses, and different laboratory parameters did not indicate aspecific safety signal. Clinically, a remarkable dose-dependent improvement of thedisease was observed reaching a mean of 70% change of the PASI score after 2 weeksover baseline in the 300-mg bid cohort, which compares favorably with what hasbeen reported for potent TNF-a antagonists. Comparably, a dose-dependentreduction of infiltrating T cells in the epidermis and dermis was observed after 2weeks. The number of Ki-67 proliferating keratinocytes tended to decrease alreadyafter one week of treatment. AEB071 levels in blood correlated well with PASIchanges and sIL-2R levels in plasma. In conclusion, this first multiple dose study inpatients with psoriasis demonstrates that AEB071 is not only well tolerated at dosesup to 300 mg bid, but also, induces a clinically significant reduction in PASI scores in14 days. Considering these data, AEB071 might be a promising addition to thetherapeutic armamentarium in patients with psoriasis in the future.

cial support: None identified.

Commer

2008

P2604Adalimumab safety profile in global clinical trials and reduction instandardized mortality ratios (SMR) across multiple indications

Gerd Burmester, MD, Charite-University Medicine, Berlin, Germany; KennethGordon, MD, Evanston Northwestern Healthcare, Evanston, IL, United States;John Perez, MD, Abbott, Parsippany, NJ, United States; Aileen Pangan, MD,Abbott, Abbott Park, IL, United States

Objective: To evaluate the safety of adalimumab (ADA) in global clinical trials acrossmultiple indications.

Methods: Safety data were routinely collected in all randomized placebo-controlledand open-label clinical trials of ADA in rheumatoid arthritis (RA, including early RA),psoriatic arthritis (PsA), ankylosing spondylitis (AS), juvenile rheumatoid arthritis(JRA), psoriasis (Ps), and Crohn’s disease (CD). Rates of adverse events (AE) ofinterest to physicians prescribing anti-TNF therapy were assessed per 100 patient(pt) years (E/100PY). SMRs were also calculated using the World HealthOrganization 2000 US mortality data as comparator.

Results: As of April 15, 2006, the following rates in E/100PY were reported in theRA/PsA/AS/JRA/Ps/CD trials for AEs of interest: serious infections 4.6/2.5/0.9/3.6/0.8/5.9; TB 0.3/0.3/0/0/0.2/0.2; opportunistic infections 1.0/0.5/0.5/0.7/0.2/2.0;malignancies 2.1/1.1/0.7/0/1.9/1.1; lymphomas 0.1/0.3/0.2/0/0/0.1; demyelinatingdisorders 0.1/0/0/0/0/0.1; CHF 0.4/0/0/0/0/0.1; and lupus-like syndrome0.2/0/0/0/0.2/0.3. Among the diseases studied, the RA indication has the largestnumber of pts (12,202) and pt-years of exposure (16,973.2) based on 9 years ofclinical trial data. When compared to rates from RA clinical trials, rates of AEs for theother indications were at least comparable, if not lower. The serious infection rate(4.6/100PY) for RA is comparable to published reports of anti-TNF na€ive RA pts.1,2 InRA trials, the calculated SMR of 0.63 (95% CI, 0.52-0.76) was much lower thanpreviously reported for RA pts before the advent of anti-TNF therapy. SMRs for theother disease indications (95% CI/indication)—0.37 (0.04, 1.33/PsA),3 0.40 (0.01,2.24/Ps), and 0.22 (0.00, 1.24/CD)—were likewise lower when compared topublished rates.4-6 AS and JRA trials have observed no deaths to date.

Conclusions: Overall, ADA therapy showed consistent safety profiles in globalclinical trials for other TNF-mediated diseases compared to that observed in RA. Nonew safety signals were identified. Current evidence suggests a decrease in mortalityin ADA-treated pts compared to a sex- and age-matched population.

References

1. Singh G, et al. Arthritis Rheum 1999;42(Suppl):S242.2. Doran MF, et al. Arthritis Rheum 2002;46:2287-9.3. Wolfe F, et al. Arthritis Rheum 1994;37:481-94.4. Wong K, et al. Arthritis Rheum 1997;40:1868-72.5. Poikolainen K, et al. Arch Dermatol 1999;135:1490-3.6. Wolters FL, et al. Aliment Pharmacol Ther 2004;20:483-96.

nsored by Abbott.

100% spo

P2605Cost comparison between two antitumor necrosis factor (anti-TNF) ther-apies in patients with psoriasis using average sales price (ASP)

Boxiong Tang, MD, PhD, Centocor, Inc., Horsham, PA, United States; HeidiThompson, MS, MBA, Centocor, Inc., Horsham, PA, United States; OmarDabbous, MD, Centocor, Inc., Horsham, PA, United States; Mirza Rahman, MD,MPH, Centocor, Inc., Horsham, PA, United States

Objective: To compareannualcosts ofanti-TNFtherapies in patientswithpsoriasis (PsO).

Method: A decision-model was created using TreeAge software with clinical trialdata and average sales price (ASP) 1 6% (2Q 2007) for drug costs. Two treatmentstrategies were compared, either etanercept first then switching to infliximab, orinfliximab first then switching to etanercept. The model assumed patients whofailed to achieve Psoriasis Area and Severity Index (PASI) 50 would switch to theother biologic after 24 weeks, and the efficacy rates after switch were assumed to bethe same as the first-line treatment. A sensitivity analysis changing the efficacy ratesafter switching, to 10% to 30% less than that of the initial treatment, was conducted.The cost of adverse events was not included in the model. Infusion fees ($237.92/in-fusion—2Q2007) were included for infliximab. The overall efficacy rate wascalculated for each treatment strategy.

Results: With infliximab, 90% of patients achieved PASI 50 at week 24 and continuedreceiving infliximab. Patients (10%) who failed to achieve PASI 50 were switched toetanercept. With etanercept, 77% of patients achieved PASI 50 at week 24 andcontinued etanercept treatment. Patients (23%) who failed to achieve PASI 50 wereswitched to infliximab. The etanercept-first strategy costs $22,113 annually andresults in an overall efficacy rate of 78.5%, which yields a cost efficacy (CE) of$28,171. The infliximab-first strategy costs $23,544 annually and results in an 89.4%efficacy rate, which yields a CE of $26,351. Compared with etanercept, theinfliximab-first strategy costs $1,820 less per PASI 50 response. The incrementalCE ratio per PASI 50 was $13,190. The sensitivity analysis indicated that the resultsare robust and in the same direction as the original assumption.

Conclusion: This decision model demonstrates that an infliximab-first strategy ismore cost-effective, by more than $1800 per PASI 50 response, than an etanercept-first strategy in the treatment of psoriasis. Knowing this may be helpful to themanaged care organizations seeking to develop a preferred biologic therapy strategyto increase value and reduce overall costs. Analyses using real-world data maydemonstrate further cost savings between biologics. Further studies to explore theimpact of anti-TNF therapy on patients’ clinical, economic, and humanisticoutcomes are recommended.

d by Centocor, Inc.

Supporte

J AM ACAD DERMATOL AB119