Association of additional malignancies not previously recognized in the FDA Full Prescribing Information for ustekinumab: An analysis of the FDA Adverse Event Reporting System (FAERS)

PHARMACOLOGY 3335 A report of tigecycline-associated angiokeratoma formation Michael Isaacs, Indiana University School of Medicine, Indianapolis, IN, United States; Jami Miller, MD, Vanderbilt University School of Medicine, Nashville, TN, United States Introduction: Angiokeratomas represent benign growth of abnormally dilated vascular tissue. They are often observed as cutaneous manifestations of certain enzymatic deficiencies, but they can also occur in asymptomatic individuals. Recently, angiokeratoma formation has been reported in association with certain medications. We describe the first reported case of angiokeratoma appearance associated with the use of tigecycline, an intravenous antibiotic reserved for multidrug resistant bacterial infections. Case report: A fifty-nine year old female on chronic immunosuppression due to severe rheumatoid arthritis presented with a one-week history of two dark-colored papules, one on each lower extremity. The first papule had appeared several days following cessation of a six-week course of intravenous tigecycline for an unrelated soft tissue infection. Standard laboratory evaluation and infectious workup were negative. A biopsy revealed histopathologic features consistent with an angiokeratoma. Five more similar-appearing papules erupted over the next two weeks, culminating in a total of seven newly appearing angiokeratomas over a three-week span. Since these lesions were asymptomatic, treatment was deferred. Seven weeks following the initial papule’s appearance, six of the angiokeratomas had spontaneously resolved without any treatment, leaving no cutaneous signs of their former locations. Discussion: The timeline of gradual angiokeratoma progression and resolution in this patient suggests that a temporary factor was associated with the pathogenesis of angiokeratoma formation. Despite the onset of angiokeratoma appearance occurring a few days after discontinuing tigecycline, the time course of the angiokeratoma eruption in relation to the course of tigecycline suggests that this antibiotic may have been associated with their formation. We hypothesize that subcutaneous formation of angiokeratomas began prior to tigecycline cessation, but only cutaneously appeared after tigecycline was stopped. Due to its lengthy half-life of sixty hours, over 25% of the steady state concentration may still have been present in the patient’s serum on the day of the first angiokeratoma appearance, four days after tigecycline cessation. Finally, the resolution of angiokeratomas in the absence of tigecycline suggests it may have been associated with their formation. Future investigations are warranted to delineate the pathogenesis of tigecycline-associated angiokeratomas.

2647 Antimalarials for oral erosive lichen planus: A retrospective study of 8 patients Nancy Rivas-Tolosa, MD, Instituto Valenciano de Oncologıa, Valencia, Spain; Celia Requena, MD, Instituto Valenciano de Oncologıa, Valencia, Spain; Laura Calomarde, MD, Instituto Valenciano de Oncologıa, Valencia, Spain; Beatriz Llombart, MD, Instituto Valenciano de Oncologıa, Valencia, Spain; Carlos SerraGuillen, MD, Instituto Valenciano de Oncologıa, Valencia, Spain; Eduardo Nagore, MD, Instituto Valenciano de Oncologıa, Valencia, Spain; Carlos Guillen, MD, Instituto Valenciano de Oncologıa, Valencia, Spain; Onofre Sanmartın, MD, Instituto Valenciano de Oncologıa, Valencia, Spain Background: Treatment of oral erosive lichen planus (OELP) is considered a therapeutic challenge. Various systemic and topical agents that are aimed at the control of symptoms, rather than cure the lesions, have been used with varying results. Objective: In this study, we review the therapeutic response to antimalarial drugs in eight patients with OELP. All of them had been previously treated with other drugs without obtaining a favorable response. Methods: Eight patients diagnosed with oral erosive lichen planus were treated with antimalarial agents. The first clinical evaluation was made after a month of treatment and then every 2 to 3 months. Baseline ophthalmologic examinations were performed, and laboratory values were monitored before and during treatment. Results: Six women and two men from 56 to 82 years (mean 66 years) received oral antimalarials drugs. The ratio of interval required for a favorable clinical response was 1-5 months (mean 2.4 months). Pain relief and reduced erythema and erosions were observed after of a mean of 2.4 months. Conclusion: Antimalarials may be useful for the treatment of oral erosive lichen planus. They are easily administered and affordable with few adverse effects. Commercial support: None identified.

Commercial support: None identified.

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3448 An evaluation of vasoconstriction potency response for fluticasone propionate gel, 0.025% compared to current marketed reference corticosteroid formulations of known potency Amit Verma, PhD, MPH, Merz North America, Inc, Raleigh, NC, United States; Alan Fleischer, MD, Merz North America, Inc, Raleigh, NC, United States Background: The vasoconstriction response produced from exposure to topical corticosteroids has proven to be an effective indicator of steroid delivery through the epidermal barrier of the skin. Although the vasoconstriction response to steroids is not known to be directly related to their biochemical activity in skin diseases, it is well known that the vasoconstriction response is an indicator of steroid delivery and to some extent predicts comparative efficacy in treatment of skin disease. Objective: Evaluate the vasoconstriction potency response of fluticasone propionate gel, 0.025% in comparison with fluticasone propionate cream, 0.05% and three other reference corticosteroid formulations of known potency. Methods: This was an open-label study on 24 healthy adults. Subjects had twelve 4cm2 sites demarcated on each forearm of which 10 per arm were evaluated for vasoconstriction response to five gel formulations which contained fluticasone propionate. Four reference formulations (diprolene cream af, 0.05%; betamethasone dipropionate cream, 0.05%; triamcinolone acetonide cream, 0.1%; fluticasone propionate cream, 0.05%) and 1 test formulation of fluticasone propionate gel, 0.025% (test gel) were each dosed onto two side by side site pairs on each arm for a 16-hour duration. All sites remained unoccluded after application and two sites on each forearm remained untreated to serve as controls. Two hours after all product removal, a visual blanching score was obtained and a chromameter assessment made. Higher scores of blanching correlated to a steroid product that is more potent than one which showed lower scores. The study was based on the McKenzieStoughton vasoconstriction potency method. This test shows statistical difference between formulations where there is a 2-level, or greater, potency difference. Results: The test gel was significantly different from diprolene cream AF, 0.05%, betamethasone dipropionate cream, 0.05%, and triamcinolone acetonide cream, 0.1%, but not significantly different from fluticasone propionate cream, 0.05%. The test gel has a potency ranking no greater than a 5, but a ranking of 6 was not ruled out. Adverse events were minimal and unrelated to the treatments. Conclusions: The test gel was found to have the same potency ranking as fluticasone propionate cream, 0.05% and was well tolerated. Supported by Merz North America, Inc.

AB220

J AM ACAD DERMATOL

Association of additional malignancies not previously recognized in the FDA Full Prescribing Information for ustekinumab: An analysis of the FDA Adverse Event Reporting System (FAERS) Aleksandra G. Florek, MD, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Beatrice Nardone, MD, PhD, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Shalini Thareja, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Gary Tran, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Francis J. Giles, MD, MBBCh, Northwestern Medicine Developmental Therapeutics Institute, Northwestern University, Chicago, IL, United States; Dennis P. West, PhD, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States Introduction: Ustekinumab (U) is an interleukin (IL)-12 and IL-23 inhibitor, approved for the treatment of moderate to severe psoriasis (Ps) and for active psoriatic arthritis (PsA). Two long-term studies, with up to 5 years of follow-up, concluded that U did not increase the rate of malignancy in patients with psoriasis. Moreover, according to the Full Prescribing Information (FPI), occurrence of malignancies other than nonmelanoma skin cancer in U-treated patients was similar to what would occur in the general U.S. population. Nevertheless, U has now been reported to be associated with lymphoma. The aim of this study was to determine if there is a detectable association between U and malignancy in the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: We searched the FAERS database (January 2004 through December 2013) for terms related to U combined with cancer/malignancy, and calculated the proportional reporting ratio (PRR) for detection of a safety signal, defined as number of events [3, chi-square result ([4) and the PRR ([2). Results: Similar to the FPI, signals for breast cancer, prostate cancer, colon cancer, rectal cancer, and melanoma were found in the FAERS database. Unlike the FPI, safety signals were detected for several additional malignancies, namely B-cell lymphoma (9), myeloid leukemia (N ¼ 10), bladder cancer (N ¼ 6), cervix carcinoma (N ¼ 4), epithelioid sarcoma (N ¼ 11), gastric cancer (N ¼ 4), lung cancer (N ¼ 22), esophageal cancer (N ¼ 109), ovarian cancer (N ¼ 5), metastatic ovarian cancer (N ¼ 10), plasmacytoma (N ¼ 6), renal cancer (N ¼ 8), testis cancer (N ¼ 44) and thyroid cancer (N ¼ 4). Conclusion: Safety signals from the FAERS database suggest that ustekinumab is associated with several malignancies not recognized in the full prescribing information. However, limitations to the interpretation of FAERS data are the voluntarily reported aspect of data collection and redundant reporting. Exploration of this finding that ustekinumab is associated with malignancies not previously recognized in the full prescribing information is warranted. Commercial support: None identified.

MAY 2016