Evaluation of the fragility of pivotal trials used to support US Food and Drug Administration approval for plaque psoriasis.

BACKGROUND: Over the last 5 years, there has been a rapid growth in the number of clinical trials used to support a US Food and Drug Administration (FDA) approval for systemic therapies with labeled indications for plaque psoriasis. OBJECTIVE: We aim to evaluate the fragility of clinical trial data used to support FDA approval of therapies for psoriasis. METHODS: We reviewed the primary endpoints of the pivotal trials of all systemic medications with a labeled indication for plaque psoriasis available from Drugs@FDA. RESULTS: Sixty-nine clinical trial primary endpoints met inclusion criteria and were assessed for robustness, yielding a median fragility index of 72 and a median fragility quotient of 0.19. LIMITATIONS: Efficacy and statistical analysis data for several approved medications were not available on the product label or on Drugs@FDA. CONCLUSIONS: When compared with randomized controlled trials for FDA approval across various diseases, pivotal trials in psoriasis appear quite robust to changes in outcomes.

Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas.

Importance: Shared gene variants in benign-malignant process pairs, such as BRAF mutations common to benign nevi and melanoma, are associated with differing phenotypic manifestations. Study of gene mechanisms underlying cherry angioma may uncover previously unknown disease relationships. Objective: To identify somatic mutations present in cherry angioma specimens by using targeted next-generation sequencing. Design, Setting, and Participants: In a single-center case series, 10 formalin-fixed, paraffin-embedded cherry angioma specimens from biopsies performed at Massachusetts General Hospital in Boston from July 10, 2016, to January 23, 2018, were obtained and underwent sequencing across a panel of 323 genes most relevant to cancer. Somatic mutations were curated by excluding variants that were presumed to be germline or of low mapping quality. Main Outcomes and Measures: Identification of somatic mutations associated with cherry angiomas. Results: In 10 cherry angioma tissue samples originating from 6 female and 4 male patients with a median (range) age of 54 (26-79) years, 5 samples (50%) revealed somatic missense mutations in GNAQ (Q209H, Q209R, and R183G) and GNA11 (Q209H). Individually, these mutational hot spots are known to be involved in entities that include congenital and anastomosing hemangiomas, hepatic small-vessel neoplasms (Q209), port-wine stains, and Sturge-Weber syndrome (R183). Both hot spots are associated with blue nevi, melanoma associated with blue nevus, and uveal melanoma. Conclusions and Relevance: In this case series study, the high prevalence of 5 known genetic drivers within the benign cherry angioma entity appears to support the context-dependent role of gene alterations in both benign and malignant proliferations from various cellular origins.

Rate of serious infection in patients who are prescribed systemic biologic or nonbiologic agents for psoriasis: A large, single center, retrospective, observational cohort study.

BACKGROUND: Systemic biologic and nonbiologic agents used to treat psoriasis may or may not contribute to serious infection (SI) risk. Safety data, particularly for biologic agents, and associated risk for SI, are scarce. The study's aim was to explore the risk for SI in psoriasis patients exposed to systemic biologic or nonbiologic agents. METHODS: A large, single-center electronic medical record repository was searched between January 2010 and December 2014. Records for patients prescribed a systemic agent for psoriasis (SAP) with psoriasis or psoriatic arthritis diagnoses were included (ICD-9 codes 696.1 and 696.0, respectively). SIs were those who required hospitalization, and/or injectable antibacterial, antiviral or antifungal therapy. SIs occurring within 120 days after exposure to a SAP, were included for study. RESULTS: A total of 1,346 patients were exposed to a SAP between January 2010 and December 2014; 27 (2%) had a SI. Comparing biologic and nonbiologic agent exposure, no statistically significant difference for risk of SI was detectable (p = .83). CONCLUSION: In this population, the SI rate for biologic and nonbiologic systemic agents was clinically indistinguishable, thereby supporting consideration of the entire spectrum of available systemic therapeutic agents, both biologic and nonbiologic agents, for management of moderate to severe psoriasis.

Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials.

Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%.

Identifying the incidence of rash, Stevens-Johnson syndrome and toxic epidermal necrolysis in patients taking lamotrigine: a systematic review of 122 randomized controlled trials

ABSTRACT Lamotrigine is an antiepileptic drug used for the treatment of epilepsy, bipolar disorder and numerous off-label uses. The development of rash significantly affects its use. The most concerning of these adverse reactions is Stevens-Johnson syndrome/toxic epidermal necrolysis. We performed a systematic review of randomized controlled trials using lamotrigine as a monotherapy to quantify the incidence of cutaneous reactions, particularly Stevens-Johnson syndrome/toxic epidermal necrolysis. Of a total of 4,364 papers regarding lamotrigine, 122 studies met our inclusion and exclusion criteria. In total, 18,698 patients were included with 1,570 (8.3%) of patients experiencing an adverse dermatologic reaction. The incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis was 0.04%.

Patient Factors and Their Association with Nonmelanoma Skin Cancer Morbidity and the Performance of Self-skin Exams: A Cross-Sectional Study.

Objective: Mohs micrographic surgery is widely utilized for the treatment of nonmelanoma skin cancers with the advantage of tissue sparing and higher cure rate. The preoperative tumor size and post-Mohs micrographic surgery defect size are useful surrogate measures of nonmelanoma skin cancer morbidity. The authors sought to evaluate whether gender, Hispanic ethnicity, socioeconomic status, sun-safe practices and self-skin exams affected tumor size and Mohs micrographic surgery defect size. They also investigated factors associated with self-skin exams. Design: A cross-sectional survey-based study. Setting: Two dermatologic surgery clinics-one academic-associated and the other private. Participants: Patients receiving Mohs surgery for nonmelanoma skin cancers. Measurements: Tumor size and Mohs defect size and their relationship to patient factors ascertained from a survey, as well as the number of patients performing self-skin exams. The authors used t-tests and analysis of variance to compare tumor and defect sizes for each patient factor. Chi-squared tests were used to determine the factors associated with self-skin exams performance. Results: Lower education was associated with greater head and face tumor area (95mm2 vs. 41mm2, P=0.019), but not Mohs micrographic surgery defect size. Other studied patient factors were not associated with an increased morbidity. Hispanics performed self-skin exams at a lower rate than non-Hispanics (27% vs. 46%, p=0.03). Conclusion: This study innovatively uses tumor and Mohs micrographic surgery defect area as a measure of morbidity, allowing for identification of populations at need for improved education and prevention. (J Clin Aesthet Dermatol. 2016;9(9):16-22.).

Second Primary Malignancies in CTCL Patients from 1992 to 2011: A SEER-Based, Population-Based Study Evaluating Time from CTCL Diagnosis, Age, Sex, Stage, and CD30+ Subtype.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a diverse group of extranodal non-Hodgkin lymphomas with malignant T lymphocytes localizing in the skin. CTCL can mainly be classified as mycosis fungoides, Sézary syndrome, or primary cutaneous CD30+ lymphoma. Patients with CTCL have an increased risk of developing second primary malignancies. OBJECTIVE: Our objective was to analyze the overall incidence of second primary malignancies in patients with CTCL by age, sex, stage, and the primary cutaneous CD30+ lymphoproliferative subtype of CTCL, as this group has usually been excluded from previous analyses. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate CTCL cases diagnosed between 1992 and 2011. We calculated the multiple primary standardized incidence ratio, comparing the observed incidence of second primary malignant neoplasms in the CTCL patient population versus the general population. RESULTS: CTCL is associated with an overall increased risk of cancers. This incidence is greatest within the first year of diagnosis. The risk of secondary Hodgkin disease is greatest in patients aged ≥60 years; the risk of secondary non-Hodgkin lymphoma is greatest in patients aged 20-39. Males demonstrated a significantly increased risk of developing Hodgkin lymphoma, while females showed a significantly increased risk of developing bronchopulmonary malignancy. Overall, secondary malignancy incidence was significantly elevated for stage I and IV CTCL. Patients with CD30+ CTCL had a significantly higher incidence of Hodgkin lymphoma, non-Hodgkin lymphoma, and urinary cancers than the general population. CONCLUSION: Occult secondary malignancies, particularly lymphomas, should be considered in adult CTCL patients, including those with the CD30+ subtype.

An increased risk of non-Hodgkin lymphoma and chronic lymphocytic leukemia in US patients with Merkel cell carcinoma versus Australian patients: A clinical clue to a different mechanism of pathogenesis?

The US and Queensland populations both demonstrate an increased risk of secondary malignancies following the diagnosis of Merkel cell carcinoma (MCC). A recent Queensland study failed to demonstrate a significantly increased risk of developing non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukaemia (CLL) in these patients. In contrast, using the US Surveillance, Epidemiology, and End Results database, we demonstrate there is an increased risk in CLL and NHL following the diagnosis of MCC in the USA. We hypothesise that this difference may be a result of a differing pathogenesis.

A Systematic Review of Patients with Mucocutaneous and Respiratory Complications in Paraneoplastic Autoimmune Multiorgan Syndrome: Castleman's Disease is the Predominant Malignancy.

PURPOSE: Paraneoplastic autoimmune multiorgan syndrome (PAMS) is a rare disorder that manifests with severe mucocutaneous blistering and erosions accompanied by underlying malignancy. Constrictive bronchiolitis (CB) can occur in a subset of patients. We sought to characterize the particular group of PAMS patients with CB by comparing the underlying tumor in these patients versus all reported PAMS patients. METHODS: We performed a systematic review of the Medline/Pubmed and compared the incidence of the most frequent tumor type in the CB cohort with the previously reported incidences of tumors in all documented PAMS patients. RESULTS: There is an increased occurrence of Castleman's tumor in patients with mucocutaneous and pulmonary complications of PAMS OR 3.86, 95 % CI [2.2-6.7]. CONCLUSIONS: As PAMS is a syndrome with a heterogeneous presentation and autoantibody profile, the particular pathogenic pathway seen in Castleman's tumor may provide additional insight into the antigenic sites involved in PAMS-related CB.

Assessing the current market of sunscreen: a cross-sectional study of sunscreen availability in three metropolitan counties in the United States.

Sunscreen use is recommended for the prevention of sunburn and skin cancer. Little is known regarding sunscreen availability in high versus low income communities. We analyzed sunscreen availability in three large metropolitan counties to determine the relationship between availability and community demographics. We included sun care products in all pharmacies and supermarkets open as of July 2013 in representative high and low income zip codes in Cook County, Illinois, Miami-Dade County, Florida, and San Diego County, California. We recorded the percentage of tanning oil, sunscreens with a sun protection factor (SPF) < 15, SPF > 15, physical sunscreens, spray sunscreens, mean price per ounce (PPO), and mean SPF. Of the total products assessed, 11.0% were tanning oils, with physical sunscreens accounting for only 3.4% of the available sunscreens and 46.2% of sunscreens being spray-on. A comparison between higher and lower income zip codes demonstrated a significantly increased percentage of sunscreens with SPF < 15 in high income zip codes. Lower income zip codes had higher percentages of sunscreens with SPF > 15 and higher PPO, even when taking into account SPF. Further studies of sunscreen usage patterns in different populations must take into account sunscreen availability and price, as these significantly differ based on the community demographic.