Association of Sodium-Glucose Cotransporter-2 Inhibitors With Fracture Risk in Older Adults With Type 2 Diabetes.

Importance: Whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are associated with an increased risk of fractures in older adults with type 2 diabetes (T2D) outside of clinical trials remains unknown. Objective: To examine the association of incident fracture among older adults with T2D with initiating an SGLT-2i compared with initiating a dipeptidyl peptidase 4 inhibitor (DPP-4i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA). Design, Setting, and Participants: This is a population-based, new-user cohort study including older adults (aged ≥65 years) with T2D enrolled in Medicare fee-for-service from April 2013 to December 2017. Data analysis was performed from October 2020 to April 2021. Exposures: New users of an SGLT-2i, DPP-4i, or GLP-1RA without a previous fracture were matched in a 1:1:1 ratio using 3-way propensity score matching. Main Outcomes and Measures: The primary outcome was a composite end point of nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention within 30 days. After 3-way 1:1:1 propensity score matching, multivariable Cox proportional hazards regression models were used to generate hazard ratios (HRs) for SGLT-2i compared with DPP-4i and GLP-1RA and Kaplan-Meier curves to visualize fracture risk over time across groups. Results: Of 466 933 new initiators of study drugs, 62 454 patients were new SGLT-2i users. After 3-way matching, 45 889 (73%) new SGLT-2i users were matched to new users of DPP-4i and GLP-1RA, yielding a cohort of 137 667 patients (mean [SD] age, 72 [5] years; 64 126 men [47%]) matched 1:1:1 for analyses. There was no difference in the risk of fracture in SGLT-2i users compared with DPP-4i users (HR, 0.90; 95% CI, 0.73-1.11) or GLP-1RA users (HR, 1.00; 95% CI, 0.80-1.25). Results were consistent across categories of sex, frailty (nonfrail, prefrail, and frail), age (<75 and ≥75 years), and insulin use (baseline users and nonusers). Conclusions and Relevance: In this nationwide Medicare cohort, initiating an SGLT-2i was not associated with an increased risk of fracture in older adults with T2D compared with initiating a DPP-4i or GLP-1RA, with consistent results across categories of frailty, age, and insulin use. These findings add to the evidence base evaluating the potential risks associated with SGLT-2i use for older adults outside of randomized clinical trials.

Validation of claims-based algorithms to identify interstitial lung disease in patients with rheumatoid arthritis.

OBJECTIVE: To develop and validate claims-based algorithms to identify interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) METHODS: Using Medicare claims data linked with the electronic medical records (2012-2014), we first selected RA patients based on ≥2 diagnostic codes for RA and ≥1 disease-modifying antirheumatic drugs.Then, to identify ILD in RA, we developed eight claims-based algorithms using a combination of ICD-9 diagnosis codes and procedure codes related to the diagnosis or management of ILD. We assessed the positive predictive value (PPV) for each of the eight algorithms relative to confirmed ILD cases using chest computerized tomography or lung biopsy as the gold standard. RESULTS: A total of 5,214 RA patients were included in the study, and the ILD cases identified by each algorithm ranged from 181 to 993. The PPV of the diagnosis code-based algorithms ranged from 43.4% (≥1 diagnosis code by any physician) to 52.0% (≥2 diagnosis codes by any physician). When the algorithms further required ≥1 procedure code (e.g., imaging, bronchoscopy), the PPV did not improve. However, the algorithms that required ILD diagnosis codes by specialists (i.e., pulmonologist or rheumatologist) had PPVs of 61.5% with ≥1 code; 72.4% with ≥2 codes. CONCLUSIONS: In a cohort of RA patients, our algorithm that required ≥2 ILD diagnosis codes by specialists demonstrated a PPV of 72.4% in ascertaining ILD. Our results support the utility of the claims-based algorithm to identify a population-based cohort of RA patients with ILD using large administrative claims data.

Risk of Serious Infection Among Initiators of Tumor Necrosis Factor Inhibitors Plus Methotrexate Versus Triple Therapy for Rheumatoid Arthritis: A Cohort Study.

OBJECTIVE: To compare the risk of serious infections between the use of tumor necrosis factor inhibitors (TNFi) plus methotrexate (MTX) versus triple therapy among rheumatoid arthritis (RA) patients in a real-world setting. METHODS: Using claims data from Truven MarketScan (2003-2014), we conducted a cohort study to compare RA patients receiving MTX who added a TNFi (TNFi plus MTX group) versus MTX plus hydroxychloroquine and sulfasalazine (triple therapy group). The primary outcome was any serious infection (i.e., a composite end point of hospitalized bacterial and opportunistic infections or herpes zoster). Secondary outcomes were individual components of the composite end point. To adjust for baseline confounding, we used propensity score (PS)-based fine stratification and weighting. A weighted Cox proportional hazards model estimated the hazard ratio (HR) and 95% confidence interval (95% CI) of the outcomes. RESULTS: After PS stratification (PSS) and weighting, we included a total of 45,208 TNFi plus MTX initiators and 1,387 triple therapy initiators. Mean age was 53 years and 70% were female. The incidence rate of any serious infection per 100 person-years was 2.46 in the TNFi plus MTX group and 2.03 in the triple therapy group. The PSS-weighted HR for any serious infection comparing TNFi plus MTX versus triple therapy was 1.23 (95% CI 0.87-1.74). For the secondary outcomes, the PSS-weighted HR was 1.41 (95% CI 0.85-2.34) for bacterial infection and 0.80 (95% CI 0.55-1.18) for herpes zoster. CONCLUSION: In this real-world cohort of RA patients, we noted no substantially different risk of any serious infection, bacterial infection, or herpes zoster after initiating TNFi plus MTX versus triple therapy, although CIs were wide.

Validation of claims-based algorithms for psoriatic arthritis.

PURPOSE: An increasing number of new medications are being developed and approved for psoriatic arthritis (PsA). To generate real-world evidence on comparative safety and effectiveness of these drugs, a claims-based algorithm that can accurately identify PsA is greatly needed. METHODS: To identify patients with PsA, we developed seven claims-based algorithms based on a combination of diagnosis codes and medication dispensing using the claims data from Medicare parts A/B/D linked to electronic medical records (2012-2014). Two physicians independently conducted a chart review using the treating physician's diagnosis of PsA as the gold standard. We calculated the positive predictive value (PPV) and 95% confidence intervals of each algorithm. RESULTS: Of the total 2157 records identified by the seven algorithms, 45% of the records had relevant clinical data to determine the presence of PsA. The PPV of the algorithms ranged from 75.2% (algorithm 1: ≥2 diagnosis codes for PsA and ≥1 diagnosis code for psoriasis) to 88.6% (algorithm 7: ≥2 diagnosis codes for PsA with ≥1 code by rheumatologist and ≥1 dispensing for PsA medication). Having ≥2 diagnosis codes and ≥1 dispensing for PsA medications (algorithm 6) also had PPV of 82.4%. CONCLUSIONS: All seven claims-based algorithms demonstrated a moderately high PPV of 75% to 89% in identifying PsA. The use of ≥2 diagnosis codes plus ≥1 prescription claim for PsA appears to be a valid and efficient tool in identifying PsA patients in the claims data, while broader algorithms based on diagnoses without a prescription claim also have reasonably good PPVs.