Use of a topical Janus kinase inhibitor in immune checkpoint inhibitor-induced eczematous reaction: a case report.

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. Our case report highlights a novel therapeutic option for an eczematous cirAE: the topical JAK 1/2 inhibitor, ruxolitinib. CirAEs can occur in up to 55% of patients on ICIs, a class of medications seeing rapidly increasing use in cancer therapy, and prior research has demonstrated that ICI-induced dermatitis may involve different pathways than traditionally observed in their spontaneous counterparts. Specifically, marked Th1 skewing is noted in ICI-induced dermatitis, as opposed to a predominant Th2 response which typically characterizes spontaneous atopic dermatitis. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

Prescriber Uncertainty as Opportunity to Improve Care of Type 2 Diabetes with Chronic Kidney Disease: Mixed Methods Study.

BACKGROUND: Over 5 million patients in the United States have type 2 diabetes mellitus (T2D) with chronic kidney disease (CKD); antidiabetic drug selection for this population is complex and has important implications for outcomes. OBJECTIVE: To better understand how providers choose antidiabetic drugs in T2D with CKD DESIGN: Mixed methods. Interviews with providers underwent qualitative analysis using grounded theory to identify themes related to antidiabetic drug prescribing. A provider survey used vignettes and direct questions to quantitatively assess prescribers' knowledge and preferences. A retrospective cohort analysis of real-world prescribing data assessed the external validity of the interview and survey findings. PARTICIPANTS: Primary care physicians, endocrinologists, nurse-practitioners, and physicians' assistants were eligible for interviews; primary care physicians and endocrinologists were eligible for the survey; prescribing data were derived from adult patients with serum creatinine data. MAIN MEASURES: Interviews were qualitative; for the survey and retrospective cohort, proportion of patients receiving metformin was the primary outcome. KEY RESULTS: Interviews with 9 providers identified a theme of uncertainty about guidelines for prescribing antidiabetic drugs in patients with T2D and CKD. The survey had 105 respondents: 74 primary care providers and 31 endocrinologists. Metformin was the most common choice for patients with T2D and CKD. Compared to primary care providers, endocrinologists were less likely to prescribe metformin at levels of kidney function at which it is contraindicated and more likely to correctly answer a question about metformin's contraindications (71% versus 41%) (p < .05). Real-world data were consistent with survey findings, and further showed low rates of use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (<10%) in patients with eGFR below 60 ml/min/1.73m2. CONCLUSIONS: Providers are unsure how to treat T2D with CKD and incompletely informed as to existing guidelines. This suggests opportunities to improve care.

Safety and effectiveness of metformin in patients with reduced renal function: A systematic review.

AIM: To examine clinical and safety outcomes associated with metformin use in patients with impaired renal function. MATERIALS AND METHODS: We searched PubMed and Embase databases from inception to August 2020, supplementing our search with a review of investigator files and reference lists of included studies. Any study reporting original data on metformin and patient-centred outcomes in patients with impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 , was included. Post hoc meta-analysis was performed for the outcomes of mortality, cardiovascular events and acidosis. RESULTS: Nine small prospective studies enrolling patients with significantly impaired renal function identified only one case of clinically apparent lactic acidosis. Among 13 larger retrospective studies, seven examined the risk of mortality across patient subgroups; meta-analysis showed reductions in overall mortality at an eGFR of 45 mL/min/1.73m2 or higher but not at an eGFR of less than 45 mL/min/1.73m2 . Eight retrospective studies evaluated acidosis as an outcome; meta-analysis showed no increase in risk of acidosis except at an eGFR of less than 30 mL/min/1.73m2 , in which group the HR was 1.97 (95% CI 1.03-3.77). CONCLUSIONS: The literature shows metformin to be associated with reduced mortality and no increased risk of acidosis at an eGFR of 45 mL/min/1.73m2 or higher. Metformin appears to be associated with fewer benefits and possible increases in the risk of acidosis at an eGFR of less than 30 mL/min/1.73m2 . Consistent with US Food and Drug Administration guidelines, metformin should not be used at an eGFR less than 30 mL/min/1.73m2 , and further research on its risk-benefit profile at eGFR values approaching 30 mL/min/1.73m2 is warranted.

Trial of restarting and tolerating metformin (TreatMet).

This randomized, double-blind, placebo-controlled, n-of-1 crossover study assessed whether metformin's side effects are reproducible in patients with a history of metformin intolerance. Participants completed up to four cycles of 2 weeks of metformin exposure and 2 weeks of placebo exposure. Participants completed surveys based on the Gastrointestinal Symptom Rating Scale and the Treatment Satisfaction Questionnaire for Medication. The primary hypotheses were that treatment satisfaction would be equal for placebo and metformin and that more than 30% of the study enrollees would be able to adhere to a higher dose of metformin 6 months after participation. Thirteen patients (all women, mean age 52.4 years) enrolled, three of whom were lost to follow-up or were non-adherent to study protocol. Metformin was associated with significantly lower global treatment satisfaction scores compared with placebo (39.58 vs. 53.75, P < .05 ) but participants could not distinguish metformin from placebo and did not report higher rates of gastrointestinal side effects on metformin. Two out of 10 participants adhered to a higher dose of metformin after trial completion. Metformin appears to have barriers to use beyond its classic gastrointestinal side effects.