K.A. Orrell

Apremilast and suicidality – a retrospective analysis of three large databases: the FAERS, EudraVigilance and a large single-centre US patient population

438–443. 3 Seideg ard J, Vorachek WR, Pero RW, Pearson WR. Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion. Proc Natl Acad Sci USA 1988; 85: 7293–7297. 4 Sprenger R, Schlagenhaufer R, Kerb R et al. Characterization of the glutathione S-transferase GSTT1 deletion: discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype-phenotype correlation. Pharmacogenetics 2000; 10: 557–565. 5 Ibbotson SH, Dawe RS, Dinkova-Kostova AT et al. Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy. Br J Dermatol 2012; 166: 380–388. 6 Kanetsky PA, Holmes R, Walker A et al. Interaction of glutathione S-transferase M1 and T1 genotypes and malignant melanoma. Cancer Epidemiol Biomarkers Prev 2001; 10: 509–513. 7 Solak B, Karkucak M, Turan H et al. Glutathione S-transferase M1 and T1 gene polymorphisms in patients with chronic plaque-type psoriasis: a casecontrol study. Med Princ Pract 2015; 25: 155–158.

Inflammatory bowel disease events after exposure to interleukin 17 inhibitors secukinumab and ixekizumab: Postmarketing analysis from the RADAR (“Research on Adverse Drug events And Reports”) program

To the Editor:New onset or exacerbation of ulcerative colitis (UC) and Crohn’s disease (CD), have been reported during premarketing trials for secukinumab and ixekizumab; however, detailed postmarketing reports are limited. The aim of this study was to explore the frequency of UC-related and CD-related reports subsequent to secukinumab or ixekizumab exposure within real world-setting databases. By using RADAR (Research on Adverse Drug events And Reports), a previously described medical record data repository, the Northwestern Medicine Enterprise Data Warehouse (NMEDW,[5 million patients) provided data for patients exposed to secukinumab (Jan 2015-Aug 2017) or ixekizumab (Jan 2016-Aug 2017) who had a subsequent first diagnosis of CD (International Classification of Diseases, Ninth Revision, [ICD-9] code 555.9 or Tenth Revision [ICD-10] code K50.90) or UC (ICD-9 code 556, ICD-10 K51). In addition, the Food and Drug Administration Adverse Event Reporting System (FAERS) was searched for terms related to UC or CD combined with secukinumab (Q1 2015-Q1 2017) or ixekizumab (Q1 2016-Q1 2017). Proportional reporting ratio (PRR) was calculated to detect a safety signal, defined as a number of events [3, chi-squared result[4, and PRR[2. Also, 2 large non-US, publicly available adverse event (AE)ebased databases were searched for terms related to UC or CD combined with secukinumab and ixekizumab. NMEDW provided 142 secukinumab-exposed patients (mean exposure time 4.2 months; range

Malignant melanoma association with systemic lupus erythematosus in a large midwestern U.S. patient population: a retrospective study

were proposed, as well as topical retinoids at night to control comedonal acne and improve ice-pick scars. The last meta-analysis and systematic review carried out reported 45 clinical cases and eight case series with involvement of the cutaneous adnexa as AE in patients receiving targeted-tumor therapies. The mean age was 49.8 years with a discrete predominance of females, imatinib being the most common causative agent. Vandetanib is a potent inhibitor of vascular endothelial growth factor receptor-2 receptor tyrosine kinases (VEGFR-2, also known as kinase insertion domain receptor [KDR]), epidermal growth factor receptor (EGFR), and of the RET (rearranged during transfection). Its use is approved for the treatment of aggressive and symptomatic medullary thyroid cancer in patients with locally unresectable advanced or metastatic disease. There are only three cases published in the scientific literature regarding this type of AE. None of them showed the intensity and extent of dyschromia and comedonal acne that our patient presented. On the clinical trials with vandetanib, some other more incidental dermatological AD were reported, such as eczematous skin changes, delayed wound healing, and photosensitivity. Alterations on pigmentation may be observed as blue macules of scars, diffuse blue gray pigmentation, brown pigmentation, and peripheral dark blue-gray pigmentation with positivity on the immunostaining with Pearls Prussian and Fontana. Pathogenesis is unknown, although it seems to be related to the accumulation of the drug, its metabolites, melanin, iron, or else complexes made up of the latter. Patients who present with this type of reaction are strongly recommended to follow strict photoprotection with sun-blockers and physical measures (clothes and regulated sunglasses). The use of the Q-Switched 755-nm alexandrite laser has shown excellent results in the management of these pigmentation conditions because of its greater wavelength and dermal penetration.

Prevalence of chronic hepatitis B and C in psoriasis patients: A cross-sectional study in a large US population

n/a, Not available; SD, standard deviation. REFERENCES 1. Administration FaD. Quality considerations in demonstrating biosimilarity of a therapeutic protein product to a reference product. 2015.; http://wwwfda.gov/downloads/Drugs/Guidance ComplianceRegulatoryInformation/Guidances/UCM291134. pdf. Accessed January 31, 2017. 2. Strober BE, Armour K, Romiti R, et al. Biopharmaceuticals and biosimilars in psoriasis: what the dermatologist needs to know. J Am Acad Dermatol. 2012;66(2):317-322. 3. Blauvelt A, Puig L, Chimenti S, et al. Biosimilars for psoriasis: clinical studies to determine similarity. Br J Dermatol. September 17, 2016. http://dx.doi.org/10.1111/bjd.15067 [Epub ahead of print]. 4. Blauvelt A, Cohen AD, Puig L, et al. Biosimilars for psoriasis: preclinical analytical assessment to determine similarity. Br J Dermatol. 2016;174(2):282-286.

Melanoma and chronic exposure to contraceptives containing microdoses of ethinylestradiol in young women: a retrospective study from the Research on Adverse Drug Events and Reports (RADAR) project comprising a large Midwestern U.S. patient population

An association between the use of contraceptives containing exogenous estrogen compounds and subsequent diagnosis for malignant melanoma (MM) has been suspected for decades. This is, in part, due to the finding that estrogen stimulates melanogenesis1 and the observation that the incidence of MM is greater in women vs. men before the age of 50, but lower than men after the age of 502, corresponding with the average age of menopause when estrogen levels dramatically decrease. Prior studies assessing the relationship between the incidence of MM and exposure to exogenous estrogen provide conflicting results3-6. This article is protected by copyright. All rights reserved.

Inverse association for diagnosis of Alzheimer's disease subsequent to both melanoma and non-melanoma skin cancers in a large, urban, single-centre, Midwestern US patient population

Although literature demonstrates a decreased risk of Alzheimers disease (AD) in individuals with various cancers, including squamous cell cancers (SCC) and basal cell cancers (BCC) comprising non‐melanoma skin cancers (NMSC), there is a paucity of literature to substantiate an association between malignant melanoma (MM) and AD.

Malignant melanoma associated with chronic once daily aspirin exposure in males: a large, single-center, urban, U.S. patient population cohort study from the Research on Adverse Drug events And Reports (RADAR) project

To the Editor: Conflicting evidence exists for the risk of malignant melanoma (MM) subsequent to chronic aspirin exposure. Although a study in the Journal of the American Academy of Dermatology demonstrated that chronic aspirin exposure before and after MM diagnosis in a large midwestern US population was associated with overall prolonged survival, the risk of MM subsequent to chronic aspirin exposure remains uncertain. The aim of this study, which was also conducted within a large midwestern US patient population, was to determine whether there was a detectable risk for MM after 1 year or more of chronic aspirin exposure. Using the methodology of the ‘‘Research on Adverse Drug events And Report’’, the Northwestern Medicine Enterprise Data Warehouse,

Skin cancer associated with commonly prescribed drugs: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and statins -weighing the evidence

ABSTRACT Introduction: Skin cancers, including both malignant melanoma (MM) and nonmelanoma skin cancer (NMSC), are the most commonly diagnosed cancers in the US. The incidence of both MM and NMSC continues to rise. Areas covered: Current evidence for an association between four of the most commonly prescribed classes of drugs in the U.S. and risk for MM and NMSC is reported. Medline was searched (January 2000 to May 2017) for each drug in the classes and for ‘basal cell carcinoma’, ‘squamous cell carcinoma’, ‘non-melanoma skin cancer’, ‘skin cancer’ and ‘melanoma’. Skin cancer risk information was reported for: tumor necrosis factor alpha inhibitors (TNF-αIs), angiotensin-receptor blockers (ARBs), phosphodiesterase type 5 inhibitors (PDE5Is) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins). Expert opinion: Since skin cancer risk is associated with all four classes of these commonly prescribed drugs that represent nearly 20% of the Top 100 drugs in the U.S., these important findings warrant enhanced education, especially for prescribers and those patients at high risk for skin cancer.