All SGLT2i had an elevated, though not statistically significant, risk for amputations.

No abstract

Background European studies reported an increased risk of non-melanoma skin cancer associated with hydrochlorothiazide (HCTZ)-containing products. We examined the risks of basal cell (BCC) and squamous cell carcinoma (SCC) associated with HCTZ compared to angiotensin-converting enzyme inhibitors (ACEIs) in a US population. Methods We conducted a retrospective cohort study in the US Food and Drug Administration’s Sentinel System. From the date of HCTZ or ACEI dispensing, patients were followed until a SCC or BCC diagnosis requiring excision or topical chemotherapy treatment on or within 30 days after the diagnosis date; or a censoring event. Using Cox proportional hazards regression models, we estimated the hazard ratios (HRs), overall and separately by age, sex, and race. We also examined site- and age-adjusted incidence rate ratios (IRRs) by cumulative HCTZ dose within the matched cohort. Results Among 5.2 million propensity-score matched HCTZ and ACEI users, the incidence rate (per 1,000 person-years) of BCC was 2.78 and 2.82 respectively, and 1.66 and 1.60 for SCC. Overall, there was no difference in risk between HCTZ and ACEIs for BCC (HR = 0.99, 95% CI = 0.97–1.00), but an increased risk for SCC (HR = 1.04, 95% CI = 1.02–1.06). HCTZ use was associated with higher risks of BCC (HR = 1.09, 95% CI = 1.07–1.11) and SCC (HR = 1.15, 95% CI = 1.12–1.17) among Caucasians. Cumulative HCTZ dose ≥50,000mg was associated with an increased risk of SCC in the overall population (IRR =1.19, 95% CI = 1.05–1.35) and among Caucasians (IRR = 1.27, 95% CI = 1.10–1.47). Conclusions Among Caucasians, we identified small increased risks of BCC and SCC with HCTZ compared to ACEI. Appropriate risk mitigation strategies should be taken while using HCTZ.

Based on limited evidence, the U.S. Food and Drug Administration (FDA) issued a black box warning for the use of tumor necrosis factor-alpha inhibitors (TNFIs) and risk of non-Hodgkin lymphoma (NHL). Our objective was to determine the risk of NHL associated with TNFI use by duration and type of anti-TNF agent. We performed a nested case-control study within a retrospective cohort of adults with rheumatologic conditions from a U.S. commercial health insurance database between 2009 and 2015. Use of TNFIs (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol) and conventional-synthetic disease-modifying antirheumatic drugs (csDMARDs) was identified, and conditional logistic regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL. From a retrospective cohort of 55,446 adult patients, 101 NHL cases and 984 controls matched on age, gender and rheumatologic indication were included. Compared to controls, NHL cases had greater TNFI use (33% vs. 20%) but were similar in csDMARD use (70% vs. 71%). TNFI ever-use was associated with nearly two-fold increased risk of NHL (OR = 1.93; 95% CI: 1.16-3.20) with suggestion of increasing risk with duration (P-trend = 0.05). TNF fusion protein (etanercept) was associated with increased NHL risk (OR = 2.73; 95% CI: 1.40-5.33), whereas risk with anti-TNF monoclonal antibodies was not statistically significant (OR = 1.77; 95% CI: 0.87-3.58). In sensitivity analyses evaluating confounding by rheumatologic disease severity, channeling bias was not likely to account for our results. Our findings support the FDA black box warning for NHL. Continued surveillance and awareness of this rare but serious adverse outcome are warranted with new TNFIs and biosimilar products forthcoming.