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Comparison of the pharmacoeconomic profiles of treatment regimens for field pattern actinic keratoses
3167
3673
Association of melanoma and nonmelanoma skin cancer with antihypertensive drugs: A report from the Research on Adverse Drug events And Reports project Kimberly Sable, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Sara Majewski, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Beatrice Nardone, MD, PhD, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Ahuva Cices, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Dennis P. West, PhD, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Anne E. Laumann, MBChB, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
Evaluation of risk of SSRI-associated impotence and low libido in men exposed to finasteride Tina Kiguradze, Department of Dermatology, Northwestern University, Chicago, IL, United States; William H. Temps, Department of Dermatology, Northwestern University, Chicago, IL, United States; Robert Kantor, Department of Dermatology, Northwestern University, Chicago, IL, United States; Sarah Lyon, Department of Dermatology, Northwestern University, Chicago, IL, United States; Dennis P. West, PhD, Department of Dermatology, Northwestern University, Chicago, IL, United States; Steven M. Belknap, MD, Department of Dermatology, Northwestern University, Chicago, IL, United States
Introduction: Some antihypertensive drugs may increase the risk of skin cancer, but findings are inconsistent regarding the possible association of exposure to these agents including angiotensin-converting enzyme inhibitors (ACEis), angiotensinreceptor blockers (ARBs) and thiazides (TZs) with occurrence of malignant melanoma (MM), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The aim of this study was to investigate further these possible associations. Methods: The Northwestern Medicine Enterprise Data Warehouse repository was searched to detect patients, age 18-89 years, with two consecutive prescriptions for an ACEi, ARB or TZ. Subsequent diagnoses of MM, BCC or SCC occurring at least 2 months after exposure to one of these drugs were identified using ICD9 codes. The control population, from the same repository, consisted of non-antihypertensive drug-exposed individuals. Adjusted odds ratio was obtained using logistic regression analyses. Results: Between Jan. 2010 and Feb. 2015, a total of 635,687 individuals with documented age, race and gender were detected. Of 5772 patients with prior exposure to an ARB: 23 MM, 45 BCC and 18 SCC were detected. Of 13,617 patients with prior exposure to an ACEi: 28 MM, 94 BCC and 35 SCC were detected. Of 3400 patients exposed to a TZ: 9 MM, 18 BCC and 13 SCC were detected. After adjusting for age, gender and race, a significant increased risk of melanoma was determined for ARBs (OR: 2.21; 95% CI 1.45-3.36) and TZ (OR: 2.03; 95% CI: 1.04-3.92). An increased risk of basal cell carcinoma was determined for ARBs (OR: 1.36; 95% CI: 11.83) and ACEis (OR: 1.31; 95% CI: 1.06-1.62). Finally, an increased risk of squamous cell carcinoma was determined for ARB, ACE and TZ (OR: 1.75; 95% CI: 1.08-2.8; OR: 1.59; 95% CI: 1.12-2.25; OR: 3.47; 95% CI: 1.99-6.04; respectively). Conclusions: These findings serve to delineate the association of malignant melanoma and nonmelanoma skin cancer subsequent to ACEi, ARB and TZ exposure. This may have clinical relevance related to the choice of antihypertensive agent, particularly for patients with known risk factors for skin cancer. Given the widespread use of these drugs, increased pharmacovigilance, along with education for both patients and health practitioners, are warranted.
Introduction: Finasteride (F) exposure is associated with sexual dysfunction and depression when used to treat androgenic alopecia in men. Another class of drugs, selective serotonin reuptake inhibitors (SSRI), such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline are prescribed for depression, are also associated with sexual dysfunction. Methods: To evaluate sexual dysfunction adverse drug-drug interactions between F and SSRIs, we searched a large, urban, academic-based electronic medical record archive (3 million individual records, May 1998-June 2015) to detect all men exposed to oral F # 1.25 mg/day, and with no record of impotence, low libido, nor phosphodiesterase-5 inhibitor (sildenafil, tadalafil, and vardenafil) use prior to F exposure. Results: We detected 6803 men (median age 33, interquartile range 28.5-41 years) exposed to F # 1.25 mg/day of whom 864 also were prescribed an SSRI. Data were analyzed using globally optimal classification tree analysis (GO-CTA), a nonparametric statistical methodology for which no distributional assumptions are required and that explicitly maximizes model classification accuracy for each specific sample and hypothesis. For GO-CTA, the index of classification accuracy is effect strength for sensitivity (ESS), a normed index on which ESS ¼ 0 indicates the accuracy that is expected by chance, and ESS ¼ 100 indicates perfect, errorless prediction. The rate of impotence diagnosis was 76 of 864 (8.8%) among men prescribed both F and an SSRI vs 207 of 5,939 (3.5%) among men prescribed F and no SSRI (risk ratio 2.5; number needed to harm 5.3; effect strength score 14.8%; P \.001). The rate of low libido diagnosis was 34 of 864 (3.9%) among men prescribed both F and an SSRI vs 84 of 5,939 (1.4%) among men prescribed only F and no SSRI (risk ratio 2.3; number needed to harm 60; effect strength score 16.4%; P ¼ .001). Limitations: Limitations of this study include a need to evaluate causality since these findings warrant further exploration of this drug-drug interaction and their associations with low libido and impotence. Conclusions: There is evidence that exposure to both F and an SSRI results in a clinically significant drug-drug interaction with an associated increased risk of both impotence and low libido in men who were prescribed both F and an SSRI in this study population. Commercial support: None identified.
Commercial support: None identified.
3166 Comparison of the pharmacoeconomic profiles of treatment regimens for field pattern actinic keratoses Todd Schlesinger, MD, Dermatology & Laser Center of Charleston, Charleston, SC, United States; Lyndsay Zotian, PharmD, MBADUSA Pharmaceuticals, Inc, Wilmington, MA, United States; Amit Om, Medical University of South Carolina, Charleston, SC, United States Actinic keratosis (AK) is a common premalignant skin condition estimated to have an estimated prevalence of 39.5 million persons and warrants 5.2 million office visits in the United States each year. Currently, there is no universal agreement on the treatment of AKs. The objective of this paper is to create a model for health care providers to employ in determining the most cost effective treatment modality for AKs. The model is based on the efficacy of the treatment, of which compliance rate is an inherent factor. This study will introduce a static model comparing different treatment options taking into account compliance rates, the average wholesale price, and efficacy data from pivotal studies to determine the relative efficacy of the different treatment options. We collected efficacy data from package inserts based on the treatment regimen used in the package insert or off-label common practice usage, cost data from Medi-Span Price Rx, and compliance data from various clinical trials (for therapies with similar regimens since AK data was not available) to estimate compliance data for our studied treatments of AKs. The model also allows providers to input their own data to generate relative efficacy rates based on their own practice. The drugs studied included: 5% fluorouracil cream, 0.5% fluorouracil cream, aminolevulanic acid plus blue light photodynamic therapy, 3% diclofenac sodium gel, 3.75% imiquimod cream, 0.015% ingenol mebutate gel, and 5% imiquimod cream. Using the best available compliance data combined with efficacy and cost, aminolevulanic acid plus photodynamic therapy is the most effective treatment option for AKs (66% efficacy). We ran the model a second time with a theoretical 100% compliance rate of all treatment modalities and aminolevulanic acid plus photodynamic therapy was still the most effective (69% efficacy). This paper aims to provide guidance to physicians considering field pattern treatment of AKs and to choose the most efficient treatment considering price, patient adherence, and outcome. Using the best available compliance data, aminolevulanic acid plus photodynamic therapy is the most efficacious treatment option for AKs. While this study does have limitations, such as lack of available compliance trials for the treatment regimens and therefore, coming up with estimates for best available rates, we hope it can serve as a guideline for providers in choosing a cost effective modality for the treatment of AKs. Supported by a grant from DUSA Pharmaceuticals.
MAY 2016
3599 Lichenoid dermatitis from interferon alpha-2a in a patient with metastatic renal cell carcinoma and seronegative HCV Amelia Bush, UT Houston Medical School, Houston, TX, United States; Sirunya Silapunt, MD, University of Texas Medical School at Houston, Houston, TX, United States; Sharon Hymes, MD, University of Texas MD Anderson Cancer Center, Houston, TX, United States Cutaneous reactions to interferon, including a lichenoid drug reaction, are most commonly reported in patients undergoing treatment for hepatitis C virus (HCV) infection. There have been case reports of interferon-induced lichen planus in seronegative HCV patients with lymphoproliferative disorders and melanoma. We report the case of a 71-year-old man undergoing treatment with interferon for metastatic renal cell carcinoma (RCC) who developed an eruption 2 months after starting interferon. Clinical and histological findings from biopsies supported a diagnosis of interferon-induced lichen planus. To our knowledge, this is the first known case of a lichenoid drug eruption from interferon in a seronegative HCV patient with metastatic RCC. Commercial support: None identified.
J AM ACAD DERMATOL
AB221
3673
Association of melanoma and nonmelanoma skin cancer with antihypertensive drugs: A report from the Research on Adverse Drug events And Reports project Kimberly Sable, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Sara Majewski, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Beatrice Nardone, MD, PhD, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Ahuva Cices, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Dennis P. West, PhD, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States; Anne E. Laumann, MBChB, Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
Evaluation of risk of SSRI-associated impotence and low libido in men exposed to finasteride Tina Kiguradze, Department of Dermatology, Northwestern University, Chicago, IL, United States; William H. Temps, Department of Dermatology, Northwestern University, Chicago, IL, United States; Robert Kantor, Department of Dermatology, Northwestern University, Chicago, IL, United States; Sarah Lyon, Department of Dermatology, Northwestern University, Chicago, IL, United States; Dennis P. West, PhD, Department of Dermatology, Northwestern University, Chicago, IL, United States; Steven M. Belknap, MD, Department of Dermatology, Northwestern University, Chicago, IL, United States
Introduction: Some antihypertensive drugs may increase the risk of skin cancer, but findings are inconsistent regarding the possible association of exposure to these agents including angiotensin-converting enzyme inhibitors (ACEis), angiotensinreceptor blockers (ARBs) and thiazides (TZs) with occurrence of malignant melanoma (MM), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The aim of this study was to investigate further these possible associations. Methods: The Northwestern Medicine Enterprise Data Warehouse repository was searched to detect patients, age 18-89 years, with two consecutive prescriptions for an ACEi, ARB or TZ. Subsequent diagnoses of MM, BCC or SCC occurring at least 2 months after exposure to one of these drugs were identified using ICD9 codes. The control population, from the same repository, consisted of non-antihypertensive drug-exposed individuals. Adjusted odds ratio was obtained using logistic regression analyses. Results: Between Jan. 2010 and Feb. 2015, a total of 635,687 individuals with documented age, race and gender were detected. Of 5772 patients with prior exposure to an ARB: 23 MM, 45 BCC and 18 SCC were detected. Of 13,617 patients with prior exposure to an ACEi: 28 MM, 94 BCC and 35 SCC were detected. Of 3400 patients exposed to a TZ: 9 MM, 18 BCC and 13 SCC were detected. After adjusting for age, gender and race, a significant increased risk of melanoma was determined for ARBs (OR: 2.21; 95% CI 1.45-3.36) and TZ (OR: 2.03; 95% CI: 1.04-3.92). An increased risk of basal cell carcinoma was determined for ARBs (OR: 1.36; 95% CI: 11.83) and ACEis (OR: 1.31; 95% CI: 1.06-1.62). Finally, an increased risk of squamous cell carcinoma was determined for ARB, ACE and TZ (OR: 1.75; 95% CI: 1.08-2.8; OR: 1.59; 95% CI: 1.12-2.25; OR: 3.47; 95% CI: 1.99-6.04; respectively). Conclusions: These findings serve to delineate the association of malignant melanoma and nonmelanoma skin cancer subsequent to ACEi, ARB and TZ exposure. This may have clinical relevance related to the choice of antihypertensive agent, particularly for patients with known risk factors for skin cancer. Given the widespread use of these drugs, increased pharmacovigilance, along with education for both patients and health practitioners, are warranted.
Introduction: Finasteride (F) exposure is associated with sexual dysfunction and depression when used to treat androgenic alopecia in men. Another class of drugs, selective serotonin reuptake inhibitors (SSRI), such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline are prescribed for depression, are also associated with sexual dysfunction. Methods: To evaluate sexual dysfunction adverse drug-drug interactions between F and SSRIs, we searched a large, urban, academic-based electronic medical record archive (3 million individual records, May 1998-June 2015) to detect all men exposed to oral F # 1.25 mg/day, and with no record of impotence, low libido, nor phosphodiesterase-5 inhibitor (sildenafil, tadalafil, and vardenafil) use prior to F exposure. Results: We detected 6803 men (median age 33, interquartile range 28.5-41 years) exposed to F # 1.25 mg/day of whom 864 also were prescribed an SSRI. Data were analyzed using globally optimal classification tree analysis (GO-CTA), a nonparametric statistical methodology for which no distributional assumptions are required and that explicitly maximizes model classification accuracy for each specific sample and hypothesis. For GO-CTA, the index of classification accuracy is effect strength for sensitivity (ESS), a normed index on which ESS ¼ 0 indicates the accuracy that is expected by chance, and ESS ¼ 100 indicates perfect, errorless prediction. The rate of impotence diagnosis was 76 of 864 (8.8%) among men prescribed both F and an SSRI vs 207 of 5,939 (3.5%) among men prescribed F and no SSRI (risk ratio 2.5; number needed to harm 5.3; effect strength score 14.8%; P \.001). The rate of low libido diagnosis was 34 of 864 (3.9%) among men prescribed both F and an SSRI vs 84 of 5,939 (1.4%) among men prescribed only F and no SSRI (risk ratio 2.3; number needed to harm 60; effect strength score 16.4%; P ¼ .001). Limitations: Limitations of this study include a need to evaluate causality since these findings warrant further exploration of this drug-drug interaction and their associations with low libido and impotence. Conclusions: There is evidence that exposure to both F and an SSRI results in a clinically significant drug-drug interaction with an associated increased risk of both impotence and low libido in men who were prescribed both F and an SSRI in this study population. Commercial support: None identified.
Commercial support: None identified.
3166 Comparison of the pharmacoeconomic profiles of treatment regimens for field pattern actinic keratoses Todd Schlesinger, MD, Dermatology & Laser Center of Charleston, Charleston, SC, United States; Lyndsay Zotian, PharmD, MBADUSA Pharmaceuticals, Inc, Wilmington, MA, United States; Amit Om, Medical University of South Carolina, Charleston, SC, United States Actinic keratosis (AK) is a common premalignant skin condition estimated to have an estimated prevalence of 39.5 million persons and warrants 5.2 million office visits in the United States each year. Currently, there is no universal agreement on the treatment of AKs. The objective of this paper is to create a model for health care providers to employ in determining the most cost effective treatment modality for AKs. The model is based on the efficacy of the treatment, of which compliance rate is an inherent factor. This study will introduce a static model comparing different treatment options taking into account compliance rates, the average wholesale price, and efficacy data from pivotal studies to determine the relative efficacy of the different treatment options. We collected efficacy data from package inserts based on the treatment regimen used in the package insert or off-label common practice usage, cost data from Medi-Span Price Rx, and compliance data from various clinical trials (for therapies with similar regimens since AK data was not available) to estimate compliance data for our studied treatments of AKs. The model also allows providers to input their own data to generate relative efficacy rates based on their own practice. The drugs studied included: 5% fluorouracil cream, 0.5% fluorouracil cream, aminolevulanic acid plus blue light photodynamic therapy, 3% diclofenac sodium gel, 3.75% imiquimod cream, 0.015% ingenol mebutate gel, and 5% imiquimod cream. Using the best available compliance data combined with efficacy and cost, aminolevulanic acid plus photodynamic therapy is the most effective treatment option for AKs (66% efficacy). We ran the model a second time with a theoretical 100% compliance rate of all treatment modalities and aminolevulanic acid plus photodynamic therapy was still the most effective (69% efficacy). This paper aims to provide guidance to physicians considering field pattern treatment of AKs and to choose the most efficient treatment considering price, patient adherence, and outcome. Using the best available compliance data, aminolevulanic acid plus photodynamic therapy is the most efficacious treatment option for AKs. While this study does have limitations, such as lack of available compliance trials for the treatment regimens and therefore, coming up with estimates for best available rates, we hope it can serve as a guideline for providers in choosing a cost effective modality for the treatment of AKs. Supported by a grant from DUSA Pharmaceuticals.
MAY 2016
3599 Lichenoid dermatitis from interferon alpha-2a in a patient with metastatic renal cell carcinoma and seronegative HCV Amelia Bush, UT Houston Medical School, Houston, TX, United States; Sirunya Silapunt, MD, University of Texas Medical School at Houston, Houston, TX, United States; Sharon Hymes, MD, University of Texas MD Anderson Cancer Center, Houston, TX, United States Cutaneous reactions to interferon, including a lichenoid drug reaction, are most commonly reported in patients undergoing treatment for hepatitis C virus (HCV) infection. There have been case reports of interferon-induced lichen planus in seronegative HCV patients with lymphoproliferative disorders and melanoma. We report the case of a 71-year-old man undergoing treatment with interferon for metastatic renal cell carcinoma (RCC) who developed an eruption 2 months after starting interferon. Clinical and histological findings from biopsies supported a diagnosis of interferon-induced lichen planus. To our knowledge, this is the first known case of a lichenoid drug eruption from interferon in a seronegative HCV patient with metastatic RCC. Commercial support: None identified.
J AM ACAD DERMATOL
AB221