P6558Malignancies in the ustekinumab psoriasis clinical development program:Final report with up to 5 years of follow-up

Kim Papp, MD, Probity Medical Research, Waterloo, Canada; Kenneth Gordon,MD, Northwestern University, Feinberg School of Medicine, Skokie, IL, UnitedStates; Philippe Szapary, MD, Janssen Research and Development, LLC, SpringHouse, PA, United States; Vincent Ho, MD, University of British Columbia,Vancouver, Canada

Objective: To report rates and types of malignancies observed in the ustekinumab(UST) psoriasis clinical development program with up to 5yrs of follow-up.Methods: Data were pooled across psoriasis trials [Phase2 trial (n ¼ 320), ACCEPT(n ¼ 903), PHOENIX1 (n ¼ 766), and PHOENIX2 (n ¼ 1230)] including 3117 UST-treated patients (8998 patient-years of follow-up[PY]). Patients with a prior historyof malignancy were generally excluded from these studies. Rates (events/100PY,95%CI) and types of nonmelanoma skin cancers (NMSCs, including basal [BCC] andsquamous [SCC] cell carcinomas) and other malignancies were reported. Formalignancies other than NMSC, standardized incidence ratios (SIRs) comparedobserved rates of malignancies in UST-treated patients to rates expected in thegeneral US population from the NIH SEER database; adjusted for age, sex and race tocontrol for some of the differences between the general and trial populations.

Results: Through year 5, cumulative rates of NMSCs per 100 PY (95% CI) for UST 45mg, UST 90 mg, and combined UST groups were 0.64 (0.41, 0.95), 0.44 (0.28, 0.66),and 0.52 (0.39, 0.70), respectively. 47 patients reported NMSCs (40 BCC and 10 SCC[3 patients reported both BCC and SCC]), for a BCC to SCC ratio of 4:1. Rates ofNMSC per 100 PY (95% CI) by year of follow-up for the combined UST group were0.94 (0.61, 1.41), 0.49 (0.21, 0.96), 0.40 (0.15, 0.87), 0.42 (0.15, 0.91), and 0.16(0.03, 0.47), respectively in years 1, 2, 3, 4, and 5. Cumulative rates of othermalignancies per 100 PY (95% CI) for the UST 45mg, UST 90mg, and combined USTgroups were 0.59 (0.37, 0.89), 0.61 (0.42, 0.87), and 0.60 (0.45, 0.78), respectively.54 patients reported other malignancies; most commonly reported were prostate,melanoma, colorectal, and breast. Rates of other malignancies per 100 PY (95% CI)for the combined UST group by year of follow-up were 0.39 (0.19, 0.72), 0.97 (0.56,1.58), 0.40 (0.15, 0.87), 0.77 (0.38, 1.37), and 0.59 (0.29, 1.05), respectively in years1, 2, 3, 4, and 5. Rate of other malignancies reported in the combined UST groupwascomparable to that expected in the general US (SEER) population (SIR ¼ 0.98, 95%CI:0.74, 1.29).

Conclusion: With up to 5 years of follow-up, rates of malignancies remainedconsistent with earlier analyses and no apparent dose effect was observed. Rateswere generally stable over time, and the ratio of BCC:SCC was preserved. Observedrate of other malignancies was consistent with the expected rate in the general USpopulation.

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P6448Malignancy events in the psoriasis longitudinal assessment and registry(PSOLAR) study: Current status of observations

Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada; BruceStrober, MD, University of Connecticut School of Medicine, Farmington, CT,United States; Marc Chevrier, MD, Janssen Services, LLC, Horsham, PA, UnitedStates; Mark Lebwohl, MD, Mount Sinai Medical Center, New York, NY, UnitedStates

Objective: To report malignancy events observed in PSOLAR, a multicenter,longitudinal, observational study.

Methods: PSOLAR captures events following exposure to systemic therapies. Safetyobservations captured for ustekinumab- and infliximab-exposed pts support spon-sor regulatory commitments. Prevalence and incidence of malignancy in moderateto severe psoriasis populations using systemic immunomodulatory therapies arebeing evaluated. Accrual of malignancies by exposure subgroups through August 23,2011 are summarized. Malignancies reported here are inclusive of all types exceptnon-melanoma skin cancer (NMSC, ie, basal/squamous cell carcinomas).

Results: 9495 pts enrolled in PSOLAR (13, 733 cumulative pt-years). Unadjusted ratesof malignancy excluding NMSC, were generally similar across groups as follows (inorder of attribution): ustekinumab 0.60 events/100 pt years of observation (PYO) [14events/2332 PYO], anti-TNF sponsor biologics (infliximab and golimumab) 0.65/100PYO [14/2158], nonsponsor biologics (almost exclusively etanercept/adalimumab)0.60/100 PYO [39/6458], nonbiologic therapy 0.61/100 PYO [17/2784], and overall0.61/100 PYO [84/13733]. (Exposure definition: event counts add to exposure groupwith highest position in the order of attribution, before/at the time of AE.) 57% ofustekinumab pts were exposed at/after entry into PSOLAR; ustekinumab cohortrepresents a balance of new and prior/ongoing exposure to sample event rates atvarying levels of exposure. To better compare rates observed in pts with differentexposure patterns, more malignancy events than currently available are needed toundertake rigorous, comparative statistical analyses.

Limitations: Because of channeling of therapy, differences in subgroup character-istics (eg, more pts aged [65 yrs not exposed to biologics exist, which couldinfluence malignancy rate, given long latency of cancer events and prevalence in theelderly). Any formal comparison will require statistical modeling to better adjust forpt characteristics and risks, including consideration of multiple treatments.

Conclusion: These are preliminary observations and PSOLAR will follow pts for upto 8yrs, providing more robust results. Although the numbers of malignancy eventsare small, initial rates are generally similar to those in registrational programs withustekinumab/infliximab. PSOLAR is a powerful resource for tracking safety events ofinterest among pts eligible to receive systemic therapies.

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P6037Metabolic syndrome in psoriasis: Unusual findings from a South Indiancohort

Deepika Lunawat, MBBS, Sri Ramachandra Medical College and ResearchInstitute, Chennai, Tamil Nadu, India; Anandan Subramanian, MD, SriRamachandra Medical College and Research Institute, Chennai, Tamil Nadu, India

Background: Psoriasis, a chronic immune-mediated inflammatory disorder, has anestimated prevalence ranging between 0.6% and 4.8%. Several studies acrossdifferent ethnicities have suggested a strong link between psoriasis and theindividual components of metabolic syndrome.

Objective: To investigate the prevalence of metabolic syndrome in South Indianpatients accessing the psoriasis clinic of a tertiary care center and to evaluatespecific disease characteristics for risk of metabolic syndrome.

Methods: Adult patients registered at an outpatient psoriasis clinic at a tertiary carecenter in South India, were assessed on the following variables: age, gender,psoriasis type, height, weight, obesity, blood pressure, blood glucose, blood lipids,presence of cardiovascular disease, cerebrovascular accident, smoking, alcohol,tobacco consumption, physical activity, menopause, family history of psoriasis, ageof disease onset, disease duration, nail and scalp involvement, arthropathy andmetabolic syndrome, over a 1-year study period. Metabolic syndromewas diagnosedusing the National Cholesterol Education Program Adult Treatment Panel III criteria.Statistical analysis of the data was done using SPSS 15.

Results: A total of 141 patients (63 males, 44.7%) were enrolled with a median age of48 years. Of these, 44% had systemic arterial hypertension, 51.8% had impairedfasting plasma glucose levels, 61% had low HDL levels, 39% had hypertriglyceride-mia and 42.6% were obese. Nearly half, 45.4%, had metabolic syndrome. Psoriasispatients with metabolic syndrome (50.59yrs) were found to be significantly olderthan those without metabolic syndrome (42.90yrs) (P\.001). Scalp involvement inpsoriasis was found to be significantly associated with metabolic syndrome (P ¼.003). Males were found to have more severe psoriasis than females. No correlationwas found between metabolic syndrome and psoriasis disease duration or with typeof psoriasis.

Conclusion: Our study found an unusually high prevalence of metabolic syndrome,dyslipidemia and impaired glucose metabolism, in patients with psoriasis, comparedto national and international data frommost previous studies. The strong correlationbetween scalp involvement and metabolic syndrome has never been reported so far.We report these findings, to highlight the need for screening for metabolic syndromein all cases of psoriasis, to help prevent morbidity and improve patients’ quality oflife.

cial support: None identified.

Commer

P6378Palmoplantar hyperkeratotic psoriasis with a combination of adalimumaband alitretinoin: Clinical and histologic finding

Nevena Skroza, MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’Sapienza University of Rome, Polo Pontino, Italy; Claudio Di Cristofano, MD,PhD, Department of Medical-Surgical Sciences and Biotechnologies ExperimentalMedicine University of Rome ‘‘Sapienza,’’ Polo Pontino, Italy; Concetta Potenza,MD, PhD, Department of Dermatology ‘‘Daniele Innocenzi,’’ Sapienza Universityof Rome, Polo Pontino, Italy; Ilaria Proietti, MD, PhD, Department ofDermatology ‘‘Daniele Innocenzi,’’ Sapienza University of Rome, Polo Pontino,Italy

Background: Palm and sole psoriasis occours approximately in 15% of patients.Occupational manual workers are especially at risk and the isomorphic Koebnerreaction may actually contribute to significant palmar hyperkeratosis even refrac-tory to biologics. Oral alitretinoin (9-cis retinoic acid), which has been emerging asnovel treatment for recalcitrant chronic hand eczema, is a vitamin A derivative withimmunomodulatory and antiinflammatory activities. The specific alitretinoin mech-anism of actionwhich finally leads to skin inflammatory changes improvement is stillfar from being understood. We evaluated the therapeutic effect of alitretinoin plusadalimumab in patients with recalcitrant palmoplantar psoriasis thus investigatingsubsequent immunopathological alterations.

Methods: Fifteen patients with palmoplantar psoriasis were treated with oralalitretinoin 30 mg once daily for 12 weeks plus adalimumab 40 mg once every 2weeks. Efficacy was assessed by PASI, Palmoplantar Pustular Psoriasis Area andSeverity Index (PPPASI), visual analogue scales (VAS) on intensity of pain andpruritus along with an overall patient assessment. Immunostaining for TNFa, p40IL12-23, RAR, and RXRwas performed from skin lesions biopsied before and after 12weeks of treatment.

Results: PASI, PPPASI and VAS for pruritus and pain decreased significantly after 12weeks of treatment with adalimumab plus alitretinoin. The overall patient assess-ment ranged from 60 to 90% clinical improvement. A significant reduction of TNFa,p40 IL12-23, RAR and RXR at immunohistochemistry was also observed reflectingclinical improvement.

Discussion: Our findings suggest how alitretinoin may be used effectively incombination with adalimumab in patients with refractory palmoplantar hyperker-atotic psoriasis. Future randomized trials are required to confirm the safety andefficacy of such therapeutic option.

cial support: None identified.

Commer

APRIL 2013