Large-scale real-world data analyses of cancer risks among patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) affects 24.5 million people worldwide and has been associated with increased cancer risks. However, the extent to which the observed risks are related to the pathophysiology of rheumatoid arthritis or its treatments is unknown. Leveraging nationwide health insurance claims data with 85.97 million enrollees across 8 years, we identified 92 864 patients without cancers at the time of rheumatoid arthritis diagnoses. We matched 68 415 of these patients with participants without rheumatoid arthritis by sex, race, age and inferred health and economic status and compared their risks of developing all cancer types. By 12 months after the diagnosis of rheumatoid arthritis, rheumatoid arthritis patients were 1.21 (95% confidence interval [CI] [1.14, 1.29]) times more likely to develop any cancer compared with matched enrollees without rheumatoid arthritis. In particular, the risk of developing lymphoma is 2.08 (95% CI [1.67, 2.58]) times higher in the rheumatoid arthritis group, and the risk of developing lung cancer is 1.69 (95% CI [1.32, 2.13]) times higher. We further identified the five most commonly used drugs in treating rheumatoid arthritis, and the log-rank test showed none of them is implicated with a significantly increased cancer risk compared with rheumatoid arthritis patients without that specific drug. Our study suggested that the pathophysiology of rheumatoid arthritis, rather than its treatments, is implicated in the development of subsequent cancers. Our method is extensible to investigating the connections among drugs, diseases and comorbidities at scale.

Association of Postsurgical Opioid Refills for Patients With Risk of Opioid Misuse and Chronic Opioid Use Among Family Members.

Importance: The US health care system is experiencing a sharp increase in opioid-related adverse events and spending, and opioid overprescription may be a key factor in this crisis. Ambient opioid exposure within households is one of the known major dangers of overprescription. Objective: To quantify the association between the postsurgical initiation of prescription opioid use in opioid-naive patients and the subsequent prescription opioid misuse and chronic opioid use among opioid-naive family members. Design, Setting, and Participants: This cohort study was conducted using administrative data from the database of a US commercial insurance provider with more than 35 million covered individuals. Participants included pairs of patients who underwent surgery from January 1, 2008, to December 31, 2016, and their family members within the same household. Data were analyzed from January 1 to November 30, 2018. Exposures: Duration of opioid exposure and refills of opioid prescriptions received by patients after surgery. Main Outcomes and Measures: Risk of opioid misuse and chronic opioid use in family members were calculated using inverse probability weighted Cox proportional hazards regression models. Results: The final cohort included 843 531 pairs of patients and family members. Most pairs included female patients (445 456 [52.8%]) and male family members (442 992 [52.5%]), and a plurality of pairs included patients in the 45 to 54 years age group (249 369 [29.6%]) and family members in the 15 to 24 years age group (313 707 [37.2%]). A total of 3894 opioid misuse events (0.5%) and 7485 chronic opioid use events (0.9%) occurred in family members. In adjusted models, each additional opioid prescription refill for the patient was associated with a 19.2% (95% CI, 14.5%-24.0%) increase in hazard of opioid misuse in family members. The risk of opioid misuse appeared to increase only in households in which the patient obtained refills. Family members in households with any refill had a 32.9% (95% CI, 22.7%-43.8%) increased adjusted hazard of opioid misuse. When patients became chronic opioid users, the hazard ratio for opioid misuse among family members was 2.52 (95% CI, 1.68-3.80), and similar patterns were found for chronic opioid use. Conclusions and Relevance: This cohort study found that opioid exposure was a household risk. Family members of a patient who received opioid prescription refills after surgery had an increased risk of opioid misuse and chronic opioid use.

Real-world data analyses unveiled the immune-related adverse effects of immune checkpoint inhibitors across cancer types.

Immune checkpoint inhibitors have demonstrated significant survival benefits in treating many types of cancers. However, their immune-related adverse events (irAEs) have not been systematically evaluated across cancer types in large-scale real-world populations. To address this gap, we conducted real-world data analyses using nationwide insurance claims data with 85.97 million enrollees across 8 years. We identified a significantly increased risk of developing irAEs among patients receiving immunotherapy agents in all seven cancer types commonly treated with immune checkpoint inhibitors. By six months after treatment initialization, those receiving immunotherapy were 1.50-4.00 times (95% CI, lower bound from 1.15 to 2.16, upper bound from 1.69 to 20.36) more likely to develop irAEs in the first 6 months of treatment, compared to matched chemotherapy or targeted therapy groups, with a total of 92,858 patients. The risk of developing irAEs among patients using nivolumab is higher compared to those using pembrolizumab. These results confirmed the need for clinicians to assess irAEs among cancer patients undergoing immunotherapy as part of management. Our methods are extensible to characterizing the effectiveness and adverse effects of novel treatments in large populations in an efficient and economical fashion.

Variation in dental services by rurality among privately insured adults in the United States.

OBJECTIVES: Rurality is associated with reduced dental access and worse oral health outcomes. It is unknown whether there is variation in dental services received by rural adults who visit a dentist. METHODS: This was a retrospective analysis of claims data from a large private insurer. All individuals who had at least one dental visit in 2018 were included. Patient demographics, whether or not a patient's ZIP code was rural as defined by the Federal Office of Rural Health Policy, as well as ZIP code demographics were collected. Differences in the frequency of dental services received were evaluated using χ2 tests. Multilevel logistic regressions were used to evaluate the individual and ZIP code-level correlates of receiving a preventive dental procedure, a tooth extraction, or a denture-related dental procedure. RESULTS: Rates of preventive, oral and maxillofacial surgery, and denture-related procedures were higher among rural adults. Accounting for individual age and gender, and ZIP code average income and dentist density, rural dwellers were more likely to receive a preventive procedure [odds ratio (OR) 1.15, P < 0.0001] or tooth extraction (OR 1.08, P < 0.0001), and less likely to have a denture-related procedure (OR 0.94, P = 0.015) compared to nonrural dwellers. Female gender was the strongest predictor of receiving a preventive procedure (OR 1.30, P < 0.0001). CONCLUSIONS: Even among privately insured individuals with known access to dental care, rurality was associated with significant differences in the frequency of various dental procedures. Rural dental patients may have higher needs for oral surgical procedures, even when they have access to preventive care.

Autoimmune Effects of Lung Cancer Immunotherapy Revealed by Data-Driven Analysis on a Nationwide Cohort.

The autoimmune adverse effects of lung cancer immunotherapy are not fully understood at the population level. Using observational data from commercial health insurance claims, we compared autoimmune diseases risk of immune checkpoint inhibitors (including pembrolizumab and nivolumab) and that of chemotherapy using the matching method. By 6 months after treatment initialization, the cumulative incidence of new autoimmune diseases among patients receiving immunotherapy was 13.13% (95% confidence interval (CI), 10.79-15.50%) and that of the matched chemotherapy patients was 6.65% (95% CI, 5.79-7.50%), constituting a hazard ratio (HR) of 1.97 (95% CI, 1.58-2.48). Both pembrolizumab (HR = 2.06 (95% CI, 1.20-3.65), P = 0.0032) and nivolumab (HR = 1.76 (95% CI, 1.39-2.24), P < 0.0001) were associated with higher risks of developing autoimmune diseases, especially for hypothyroidism (P < 0.0001). Our findings suggest the need to monitor autoimmune side effects of immunotherapy.

Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study.

OBJECTIVE: To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population. DESIGN: Retrospective cohort study. SETTING: Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016. PARTICIPANTS: 1 015 116 opioid naive patients undergoing surgery. MAIN OUTCOME MEASURES: Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose. RESULTS: 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively. CONCLUSIONS: Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact.