Implementation of a pharmacogenetic panel-based test for pharmacotherapy-based supportive care in an adult oncology clinic.

The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel-based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non-hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient-reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (n = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel-based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.

Ossifications in Albright Hereditary Osteodystrophy: Role of Genotype, Inheritance, Sex, Age, Hormonal Status, and BMI.

Context: Albright hereditary osteodystrophy (AHO) is caused by heterozygous inactivating mutations in GNAS. Depending on the parental origin of the mutated allele, patients develop either pseudohypoparathyroidism type 1A (PHP1A), with multihormone resistance and severe obesity, or pseudopseudohypoparathyroidism (PPHP), without hormonal abnormalities or marked obesity. Subcutaneous ossifications (SCOs) are a source of substantial morbidity in both PHP1A and PPHP. Objective: This study investigated the previously undetermined prevalence of SCO formation in PHP1A vs PPHP as well as possible correlations with genotype, sex, age, hormonal resistance, and body mass index (BMI). Design: This study evaluated patients with AHO for SCOs by physical examination performed by one consistent physician over 16 years. Setting: Albright Clinic, Kennedy Krieger Institute; Institute for Clinical and Translational Research, Johns Hopkins Hospital; Albright Center, Connecticut Children's Medical Center. Patients: We evaluated 67 patients with AHO (49 with PHP1A, 18 with PPHP) with documented mutations in GNAS. Main Outcome Measures: Relationships of SCOs to genotype, sex, age, hormonal resistance, and BMI. Results: Forty-seven of 67 participants (70.1%) had SCOs. Patients with PHP1A and PPHP had similar prevalences and degrees of ossification formation. Patients with frameshift and nonsense mutations had much more extensive SCOs than those with missense mutations. Males were affected more than females. There was no correlation with hormonal status or BMI. Conclusions: There is a similar prevalence of SCOs in PHP1A and PPHP, and the extent of SCO formation correlates with the severity of the mutation. Males are affected more extensively than females, and the SCOs tend to worsen with age.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) in a Psoriasis Patient Treated With Ustekinumab.

The use of monoclonal antibodies against interleukin (IL)-12 and -23, such as ustekinumab, has considerably reduced the disease burden in many patients with moderate to severe psoriasis. Reversible posterior leukoencephalopathy syndrome (RPLS) is a neurologic disorder that has been documented with increased frequency with the use of systemic and biologic agents. We report a case of a 58-year-old man with psoriasis who presented with confusion and memory difficulties after being on treatment with ustekinumab for over six years. Imaging with CT and MRI revealed mild parenchymal edema with the typical appearance and distribution of RPLS, confirming the diagnosis of this condition. This case reports the second case of RPLS associated with ustekinumab treatment, with the only other known case reported during clinical trials. With the increasing use of biologics in patients with moderate to severe psoriasis, it is critical that clinicians are cognizant of this potential associated adverse event.

J Drugs Dermatol. 2017;16(2):177-179.

Pustular psoriasis eruption with dabrafenib, a BRAF inhibitor.

Targeted BRAF inhibition with vemurafenib and dabrafenib has dramatically improved the survival rate in metastatic melanoma. These agents are now being tested for their efficacy against other tumors with BRAF mutations, including lung adenocarcinoma. While cutaneous adverse events are prevalent with BRAF inhibition, our patient, to our knowledge, is the first to develop a psoriatic eruption with BRAF inhibitors. We postulate that the elevation of tumor necrosis factor-alpha (TNF-α) and the paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway due to BRAF inhibition may be responsible for the eruption. More studies are needed to further elucidate the immunopathogenic mechanisms behind this adverse event. The response to MEK inhibitors and/or increased TNF-α inhibition may help support or debunk our hypothesis.