Risk of malignant melanoma and non-melanoma skin cancer in rheumatoid arthritis patients initiating methotrexate versus hydroxychloroquine: a cohort study.

OBJECTIVES: To characterise the incidence rate of skin cancer associated with methotrexate and hydroxychloroquine in older adults with rheumatoid arthritis (RA). METHODS: RA patients aged ≥65 years who initiated methotrexate or hydroxychloroquine as their first disease modifying antirheumatic drugs (DMARDs). The primary outcome was new occurrence of any skin cancer (i.e. malignant melanoma or non-melanoma skin cancer; NMSC) based on validated algorithms (positive predictive value >83%). Secondary outcomes were malignant melanoma, NMSC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We estimated the incidence rates (IRs) and hazard ratios (HRs) for each outcome in the 1:1 propensity score (PS)-matched methotrexate and hydroxychloroquine groups. RESULTS: We included 24,577 PS-matched pairs of methotrexate and hydroxychloroquine initiators. Compared with hydroxychloroquine (IR 25.20/1,000 person-years), methotrexate initiators (IR 26.21/1,000 person-years) had a similar risk of any skin cancer [HR 1.03 -(95%CI 0.92, 1.14)] over a mean follow-up of 388 days. The HR (95%CI) associated with methotrexate was 1.39 (0.87, 2.21) for malignant melanoma, 1.01(0.90, 1.12) for NMSC, 1.37 (1.13, 1.66) for BCC, and 0.79 (0.63, 0.99) for SCC compared with hydroxychloroquine. CONCLUSIONS: In this large cohort of older RA patients initiating methotrexate or hydroxychloroquine as their first DMARD, we found no difference in the risk of skin cancer including malignant melanoma and NMSC. However, for specific components of NMSC, methotrexate initiators had higher risk of BCC but lower risk of SCC compared with hydroxychloroquine initiators.

Validation of serostatus of rheumatoid arthritis using ICD-10 codes in administrative claims data.

PURPOSE: To determine the accuracy of International Classification of Diseases- Tenth Revision (ICD-10) diagnosis codes for rheumatoid arthritis (RA) serostatus using a U.S. claims database (Optum Clinformatics Data Mart, Optum) and to compare the results to a previous validation study performed in IBM Marketscan Research Database (sensitivity 73%, positive predictive value, PPV, 84%). METHODS: In Optum (01/01/2016-03/31/2020) linked with laboratory results, we selected RA patients based on ≥2 ICD-10 diagnosis codes for RA (M05 or M06) and at least one dispensing of RA treatments. We included individuals with at least one laboratory result for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) performed 365 days prior to and including the cohort entry date. An individual was "seropositive" if at least one of the 2 diagnosis codes used to define RA status was M05. "Seronegative" patients were required to have only M06. Secondary analyses were performed using subsets of M05 and M06 diagnosis codes. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of M05 and M06 against the prespecified reference standard laboratory data. RESULTS: We identified 14 490 adult RA patients who had at least 1 RF or anti-CCP result. The number of patients identified for each reference standard definition ranged from 3315 (reference standard definition: high + anti-CCP) to 13 636 (any + RF). PPV for seropositive RA, M05, was 77.1%. The PPV of M06 for seronegative RA was 61.6%. When we applied more restricted definitions of M05 and M06, the PPV for seropositive RA increased to 79.2%. The PPV for seronegative RA also notably increased to 89.5%. CONCLUSION: ICD-10 codes (M05 and M06) can help identify RA serostatus in claims data, but their limitations should be acknowledged. The PPVs for seropositive and seronegative RA found in the Optum database were lower than those found in MarketScan, perhaps related to database variability or differing patient characteristics and clinical practice. When more restricted definitions of M05 and M06 were used, the PPVs for seropositive and seronegative RA improved to 79.2% and 89.5%, respectively.

Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses: Results of 32 Clinical Trials.

Importance: Nonrandomized studies using insurance claims databases can be analyzed to produce real-world evidence on the effectiveness of medical products. Given the lack of baseline randomization and measurement issues, concerns exist about whether such studies produce unbiased treatment effect estimates. Objective: To emulate the design of 30 completed and 2 ongoing randomized clinical trials (RCTs) of medications with database studies using observational analogues of the RCT design parameters (population, intervention, comparator, outcome, time [PICOT]) and to quantify agreement in RCT-database study pairs. Design, Setting, and Participants: New-user cohort studies with propensity score matching using 3 US claims databases (Optum Clinformatics, MarketScan, and Medicare). Inclusion-exclusion criteria for each database study were prespecified to emulate the corresponding RCT. RCTs were explicitly selected based on feasibility, including power, key confounders, and end points more likely to be emulated with real-world data. All 32 protocols were registered on ClinicalTrials.gov before conducting analyses. Emulations were conducted from 2017 through 2022. Exposures: Therapies for multiple clinical conditions were included. Main Outcomes and Measures: Database study emulations focused on the primary outcome of the corresponding RCT. Findings of database studies were compared with RCTs using predefined metrics, including Pearson correlation coefficients and binary metrics based on statistical significance agreement, estimate agreement, and standardized difference. Results: In these highly selected RCTs, the overall observed agreement between the RCT and the database emulation results was a Pearson correlation of 0.82 (95% CI, 0.64-0.91), with 75% meeting statistical significance, 66% estimate agreement, and 75% standardized difference agreement. In a post hoc analysis limited to 16 RCTs with closer emulation of trial design and measurements, concordance was higher (Pearson r, 0.93; 95% CI, 0.79-0.97; 94% meeting statistical significance, 88% estimate agreement, 88% standardized difference agreement). Weaker concordance occurred among 16 RCTs for which close emulation of certain design elements that define the research question (PICOT) with data from insurance claims was not possible (Pearson r, 0.53; 95% CI, 0.00-0.83; 56% meeting statistical significance, 50% estimate agreement, 69% standardized difference agreement). Conclusions and Relevance: Real-world evidence studies can reach similar conclusions as RCTs when design and measurements can be closely emulated, but this may be difficult to achieve. Concordance in results varied depending on the agreement metric. Emulation differences, chance, and residual confounding can contribute to divergence in results and are difficult to disentangle.

Emulating Randomized Clinical Trials With Nonrandomized Real-World Evidence Studies: First Results From the RCT DUPLICATE Initiative.

BACKGROUND: Regulators are evaluating the use of noninterventional real-world evidence (RWE) studies to assess the effectiveness of medical products. The RCT DUPLICATE initiative (Randomized, Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology) uses a structured process to design RWE studies emulating randomized, controlled trials (RCTs) and compare results. We report findings of the first 10 trial emulations, evaluating cardiovascular outcomes of antidiabetic or antiplatelet medications. METHODS: We selected 3 active-controlled and 7 placebo-controlled RCTs for replication. Using patient-level claims data from US commercial and Medicare payers, we implemented inclusion and exclusion criteria, selected primary end points, and comparator populations to emulate those of each corresponding RCT. Within the trial-mimicking populations, we conducted propensity score matching to control for >120 preexposure confounders. All study measures were prospectively defined and protocols registered before hazard ratios and 95% CIs were computed. Success criteria for the primary analysis were prespecified for each replication. RESULTS: Despite attempts to emulate RCT design as closely as possible, differences between the RCT and corresponding RWE study populations remained. The regulatory conclusions were equivalent in 6 of 10. The RWE emulations achieved a hazard ratio estimate that was within the 95% CI from the corresponding RCT in 8 of 10 studies. In 9 of 10, either the regulatory or estimate agreement success criteria were fulfilled. The largest differences in effect estimates were found for RCTs where second-generation sulfonylureas were used as a proxy for placebo regarding cardiovascular effects. Nine of 10 replications had a standardized difference between effect estimates of <2, which suggests differences within expected random variation. CONCLUSIONS: Agreement between RCT and RWE findings varies depending on which agreement metric is used. Interim findings indicate that selection of active comparator therapies with similar indications and use patterns enhances the validity of RWE. Even in the context of active comparators, concordance between RCT and RWE findings is not guaranteed, partially because trials are not emulated exactly. More trial emulations are needed to understand how often and in what contexts RWE findings match RCTs. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03936049, NCT04215523, NCT04215536, NCT03936010, NCT03936036, NCT03936062, NCT03936023, NCT03648424, NCT04237935, NCT04237922.

Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study.

OBJECTIVES: Recent results from 'ORAL Surveillance' trial have raised concerns regarding the cardiovascular safety of tofacitinib in patients with rheumatoid arthritis (RA). We further examined this safety concern in the real-world setting. METHODS: We created two cohorts of patients with RA initiating treatment with tofacitinib or tumour necrosis factor inhibitors (TNFI) using deidentified data from Optum Clinformatics (2012-2020), IBM MarketScan (2012-2018) and Medicare (parts A, B and D, 2012-2017) claims databases: (1) A 'real-world evidence (RWE) cohort' consisting of routine care patients and (2) A 'randomised controlled trial (RCT)-duplicate cohort' mimicking inclusion and exclusion criteria of the ORAL surveillance trial to calibrate results against the trial findings. Cox proportional hazards models with propensity score fine stratification weighting were used to estimate HR and 95% CIs for composite outcome of myocardial infarction and stroke and accounting for 76 potential confounders. Database-specific effect estimates were pooled using fixed effects models with inverse-variance weighting. RESULTS: In the RWE cohort, 102 263 patients were identified of whom 12 852 (12.6%) initiated tofacitinib. The pooled weighted HR (95% CI) comparing tofacitinib with TNFI was 1.01 (0.83 to 1.23) in RWE cohort and 1.24 (0.90 to 1.69) in RCT-duplicate cohort which aligned closely with ORAL-surveillance results (HR: 1.33, 95% CI 0.91 to 1.94). CONCLUSIONS: We did not find evidence for an increased risk of cardiovascular outcomes with tofacitinib in patients with RA treated in the real-world setting; however, tofacitinib was associated with an increased risk of cardiovascular outcomes, although statistically non-significant, in patients with RA with cardiovascular risk factors. TRIAL REGISTRATION NUMBER: NCT04772248.

Giant cell arteritis treatment patterns and rates of serious infections.

OBJECTIVES: Giant cell arteritis (GCA) afflicts older adults who may have age- and comorbidity-related risks for infection and is treated with immunosuppressants that increase risk of infection. We examined GCA treatment patterns and rates of serious infections in two real-world cohorts in the U.S. METHODS: We identified two GCA cohorts using two U.S. health insurance databases, Medicare (public, 2007-2017) and MarketScan (commercial, 2015-2019), by applying a validated claims-based algorithm with positive predictive value 79.0% for GCA. We required age ≥50 years and assessed baseline comorbidities, dispensing of immunosuppressants and prophylactic antibiotics, and vaccine administration. We calculated incidence rates (IR) of serious infections, defined as bacterial or viral infections requiring hospitalisation based on primary inpatient diagnosis code. Multivariable Cox proportional hazards models estimated hazard ratios for risk of serious infection for prespecified covariates. RESULTS: The Medicare cohort included 734 patients, 28% male, mean age 77.1; the MarketScan cohort included 1022 patients, 30% male, mean age 68.4. More than 85% used prednisone ≥60mg daily at index date and <10% used tocilizumab. Serious infections developed in 27.9% of Medicare and 7.2% of MarketScan patients: IR per 100 person-years = 10.7 (95% CI 9.3, 12.2) in Medicare and 6.3 (95% CI 5.0, 7.9) in MarketScan. Older age and higher frailty score were significantly associated with increased risk for serious infection. CONCLUSIONS: In these two U.S. GCA cohorts, high-dose glucocorticoids were the most common initial treatment, and over 25% of Medicare and 7% of MarketScan patients developed serious infection during follow-up. Older age and higher frailty score were associated with higher risk of serious infections, though maximum daily prednisone dose was not. Pneumocystis jiroveci pneumonia was rare in two GCA cohorts despite infrequent use of prophylactic antibiotics.

Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study.

BACKGROUND: The role of differing levels of frailty in the choice of oral anticoagulants for older adults with atrial fibrillation (AF) is unclear. OBJECTIVE: To examine the outcomes of direct oral anticoagulants (DOACs) versus warfarin by frailty levels. DESIGN: 1:1 propensity score-matched analysis of Medicare data, 2010 to 2017. SETTING: Community. PATIENTS: Medicare beneficiaries with AF who initiated use of dabigatran, rivaroxaban, apixaban, or warfarin. MEASUREMENTS: Composite end point of death, ischemic stroke, or major bleeding by frailty levels, defined by a claims-based frailty index. RESULTS: In the dabigatran-warfarin cohort (n = 158 730; median follow-up, 72 days), the event rate per 1000 person-years was 63.5 for dabigatran initiators and 65.6 for warfarin initiators (hazard ratio [HR], 0.98 [95% CI, 0.92 to 1.05]; rate difference [RD], -2.2 [CI, -6.5 to 2.1]). For nonfrail, prefrail, and frail persons, HRs were 0.81 (CI, 0.68 to 0.97), 0.98 (CI, 0.90 to 1.08), and 1.09 (CI, 0.96 to 1.23), respectively. In the rivaroxaban-warfarin cohort (n = 275 944; median follow-up, 82 days), the event rate per 1000 person-years was 77.8 for rivaroxaban initiators and 83.7 for warfarin initiators (HR, 0.98 [CI, 0.94 to 1.02]; RD, -5.9 [CI, -9.4 to -2.4]). For nonfrail, prefrail, and frail persons, HRs were 0.88 (CI, 0.77 to 0.99), 1.04 (CI, 0.98 to 1.10), and 0.96 (CI, 0.89 to 1.04), respectively. In the apixaban-warfarin cohort (n = 218 738; median follow-up, 84 days), the event rate per 1000 person-years was 60.1 for apixaban initiators and 92.3 for warfarin initiators (HR, 0.68 [CI, 0.65 to 0.72]; RD, -32.2 [CI, -36.1 to -28.3]). For nonfrail, prefrail, and frail persons, HRs were 0.61 (CI, 0.52 to 0.71), 0.66 (CI, 0.61 to 0.70), and 0.73 (CI, 0.67 to 0.80), respectively. LIMITATIONS: Residual confounding and lack of clinical frailty assessment. CONCLUSION: For older adults with AF, apixaban was associated with lower rates of adverse events across all frailty levels. Dabigatran and rivaroxaban were associated with lower event rates only among nonfrail patients. PRIMARY FUNDING SOURCE: National Institute on Aging.

Validation of claims-based algorithms to identify patients with psoriasis.

PURPOSE: Accurately identifying patients with psoriasis (PsO) is crucial for generating real-world evidence on PsO disease course and treatment utilization. METHODS: We developed nine claims-based algorithms for PsO using a combination of the International Classification of Diseases (ICD)-9 codes, specialist visit, and medication dispensing using Medicare linked to electronic health records data (2013-2014) in two healthcare provider networks in Boston, Massachusetts. We calculated positive predictive value (PPV) and 95% confidence interval (CI) for each algorithm using the treating physician's diagnosis of PsO via chart review as the gold standard. Among the confirmed PsO cases, we assessed their PsO disease activity. RESULTS: The nine claims-based algorithms identified 990 unique patient records. Of those, 918 (92.7%) with adequate information were reviewed. The PPV of the algorithms ranged from 65.1 to 82.9%. An algorithm defined as ≥1 ICD-9 diagnosis code for PsO and ≥1 prescription claim for topical vitamin D agents showed the highest PPV (82.9%). The PPV of the algorithm requiring ≥2 ICD-9 diagnosis codes and ≥1 prescription claim for PsO treatment excluding topical steroids was 81.1% but higher (82.5%) when ≥1 diagnosis was from a dermatologist. Among 411 PsO patients with adequate information on PsO disease activity in EHRs, 1.5-5.8% had no disease activity, 31.3-36.8% mild, and 26.9-35.1% moderate-to-severe across the algorithms. CONCLUSIONS: Claims-based algorithms based on a combination of PsO diagnosis codes and dispensing for PsO-specific treatments had a moderate-to-high PPV. These algorithms can serve as a useful tool to identify patients with PsO in future real-world data pharmacoepidemiologic studies.

Racial characteristics of alopecia areata in the United States.

BACKGROUND: Epidemiologic studies on the association between race and alopecia areata (AA) are limited. OBJECTIVE: To characterize racial differences of AA in the United States. METHODS: Cross-sectional study of self-registered AA patients and noncases in the National Alopecia Areata Registry (NAAR). We evaluated odds of AA and its subtypes for 5 ethnic/racial groups using logistic regression. A sex-stratified analysis and a sensitivity analysis among dermatologist-confirmed cases were also performed. RESULTS: We identified 9340 AA patients and 2064 noncases. Compared with whites, African Americans had greater odds of AA (odds ratio, 1.77; 95% confidence interval, 1.37-2.28) and Asians had lower odds (odds ratio, 0.40; 95% confidence interval, 0.32-0.50) of AA. The results were consistent in AA subtypes, dermatologist-confirmed cases, and by sex. LIMITATIONS: Residual confounding due to limited number of covariates. Recall or recruitment bias not representative of the entire disease spectrum. Also, outcome misclassification was possible because not all AA cases in the registry were confirmed by dermatologists. CONCLUSION: Our findings suggest higher odds of AA in African Americans and lower odds in Asians compared with whites. Future studies examining racial disparity in AA from clinical and genetic perspectives are warranted for a better understanding of the disease pathogenesis.

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.

A Retrospective Study of Methylprednisolone Mini-Pulse Therapy Combined with Narrow-Band UVB in Non-Segmental Vitiligo.

BACKGROUND: Systemic corticosteroids have been used to arrest the progression of vitiligo. However, side effects have been a constant issue. OBJECTIVE: We evaluated the clinical efficacy and side effect of oral methylprednisolone (MPD) mini-pulse therapy combined with narrow-band UVB (NBUVB) for adults with non-segmental vitiligo retrospectively. METHODS: 32 patients with extensive and/or spreading vitiligo received 0.5 mg/kg MPD on 2 consecutive days per week with NBUVB therapy for at least 3 months. RESULTS: All of the 32 patients (100%) showed progression arrest within 12 weeks. Nineteen out of 32 patients (59.4%) presented repigmentation on more than 25% of lesions. Thirteen patients (40.6%) achieved satisfactory repigmentation in more than 50% of lesions. Only 2 patients discontinued the medication due to gastrointestinal trouble. CONCLUSION: Oral MPD mini-pulse therapy combined with NBUVB appears effective in arresting vitiligo progression and rapidly inducing repigmentation with minimal side effects.

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization.

BACKGROUND: Atopic dermatitis (AD) shows very high prevalence in Asia, with a large unmet need for effective therapeutics. Direct comparisons between European American (EA) and Asian patients with AD are unavailable, but earlier blood studies detected increased IL-17(+)-producing cell counts in Asian patients with AD. OBJECTIVE: We sought to characterize the Asian AD skin phenotype and compare it with the EA AD skin phenotype. METHODS: We performed genomic profiling (real-time PCR) and immunohistochemistry on lesional and nonlesional biopsy specimens from 52 patients with AD (25 EAs and 27 Asians), 10 patients with psoriasis (all EAs), and 27 healthy subjects (12 EAs and 15 Asians). RESULTS: Although disease severity/SCORAD scores were similar between the AD groups (58.0 vs 56.7, P = .77), greater acanthosis, higher Ki67 counts, and frequent parakeratosis were characteristics of lesional epidermis from Asian patients with AD (P < .05). Most (24/27) Asian patients had high IgE levels. A principal component analysis using real-time PCR data clustered the Asian AD phenotype between the EA AD and psoriasis phenotypes. TH2 skewing characterized both Asian and EA patients with AD but not patients with psoriasis. Significantly higher TH17 and TH22 (IL17A, IL19, and S100A12 in lesional and IL-22 in nonlesional skin; P < .05) and lower TH1/interferon (CXCL9, CXCL10, MX1, and IFNG in nonlesional skin; P < .05) gene induction typified AD skin in Asian patients. CONCLUSION: The Asian AD phenotype presents (even in the presence of increased IgE levels) a blended phenotype between that of EA patients with AD and those with psoriasis, including increased hyperplasia, parakeratosis, higher TH17 activation, and a strong TH2 component. The relative pathogenic contributions of the TH17 and TH2 axes in creating the Asian AD phenotype need to be tested in future clinical trials with appropriate targeted therapeutics.

Positive reactions to nickel on a patch test do not predict clinical outcome of nickel alloy-based atrial septal defect occluder implantation.

BACKGROUND: Patch testing is thought to be necessary prior to metal device implantation to rule out metal allergy-related complications; however, there are controversies over the effects of nickel allergy on the outcome of nickel alloy-based device implantation. OBJECTIVE: This study aimed to evaluate the adverse events in a Korean population of nickel allergy patients who underwent atrial septal defect (ASD) closure with a nickel-titanium alloy-based device. METHODS: We retrospectively reviewed the medical records of patients who underwent ASD closure with a nitinol device. RESULTS: Among 38 patients who had ASD closure, 4 of 5 nickel-allergic patients and 10 of the 33 non-nickel-allergic patients had post-closure complications. All patients fared well, without device failure culminating in device removal. CONCLUSION: In this study, positive reactions to nickel in a patch test were not associated with adverse early or late outcomes following ASD closure with a nickel alloy-based device.

Insight into newly discovered innate immune modulation in atopic dermatitis.

Atopic dermatitis (AD) is a highly pruritic, chronic relapsing inflammatory skin disease characterized by innate and adaptive immune reactions. In AD, innate immune mechanisms such as pattern recognition receptors and antimicrobial peptides have been investigated in detail, but recently, epidermis-derived cytokines, namely thymic stromal lymphopoietin (TSLP), IL-25 and IL-33, were shown to participate in innate immune reactions independently of adaptive immunity. In addition to conventional innate cells, such as mast cells, basophils and eosinophils, Th2 cytokine-producing invariant natural killer T (iNKT) cells, innate lymphoid cells (ILCs) and Th17/Th22 cytokine-producing innate cells - iNKT cells and natural killer (NK)-like cells - can participate in innate immune modulation in AD. Accordingly, early control of innate immune responses in AD before activation of adaptive immune responses by conventional T and B cells that perpetuate chronic skin inflammation may adequately alleviate acute exacerbations of AD. Therefore, we hypothesized that select immune modulators targeting the innate immune response could potentially be used for individualized treatment of AD.

Treatment Patterns for Alopecia Areata in the US.

Importance: Alopecia areata (AA) is characterized by hair loss ranging from patches of hair loss to more extensive forms, including alopecia totalis (AT) and alopecia universalis (AU). There is a lack of consensus for treatment. Understanding current practice patterns could help the identification of treatment needs and development of standards of care. Objective: To review treatment patterns for adults with AA in the US between 2015 and 2020. Design, Setting, and Participants: This retrospective cohort study used medicine and pharmacy claims for commercially insured individuals from the IBM MarketScan Research Database to assess adults (≥18 years) newly treated for AA between October 15, 2015, and February 28, 2020. Alopecia areata was identified based on having at least 1 diagnosis of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code L63.x. Patients were required to have at least 365 days of continuous health plan enrollment before and after the cohort entry date. Patients were required to be free of AA diagnosis codes 365 days before the cohort entry date. Statistical analyses were conducted between 2019 and 2023. Main Outcomes and Measures: Main outcomes were treatment patterns for all patients with AA and subgroups of (1) patients with AT or AU and (2) those cared for by a dermatologist on the cohort entry date. Longitudinal therapy course during the first year after the diagnosis was also examined. Results: The study cohort consisted of 45 483 individuals (mean [SD] age, 43.8 [14.2] years; 29 903 [65.7%] female). During the year of follow-up, 30 217 patients (66.4%) received at least 1 AA treatment. The most common treatments were intralesional (19 014 [41.8%]), topical (18 604 [40.9%]), intramuscular (17 328 [38.1%]), and oral (9378 [20.6%]) corticosteroids. Compared with patients without AT or AU, patients with AT or AU a lower frequency of intralesional steroid (359 [11.1%] vs 18 655 [44.1%], P < .001) and higher frequency of topical corticosteroid (817 [25.4%] vs 17 787 [42.1%], P < .001) use. Almost half of patients (21 489 [47.2%]) received no treatment on the day of diagnosis. By 12 months, 32 659 (71.8%) were not receiving any treatment, making no treatment the largest study group. Conclusions and Relevance: In this large cohort study of commercially insured individuals, corticosteroids were the most commonly used treatment for adults with AA between 2015 and 2020. At 365 days after diagnosis, more than two-thirds of patients were no longer receiving any AA treatment. Further studies are needed to understand the reasons for the absence of treatment.

Alopecia areata in underrepresented groups: preliminary analysis of the all of us research program.

Alopecia areata (AA) is an autoimmune condition characterized by patchy, nonscarring hair loss. Few studies of AA have adequately included participants from underrepresented groups when evaluating the burden of AA in the United States. We conducted a cross-sectional study of personal/demographic factors and AA using the ongoing All of Us (AoU) Research Program. AoU enrolls adults over 18 years either as direct volunteers or through participating Health Care Provider Organizations by prioritizing recruiting underrepresented groups. We linked data from surveys and electronic health records (EHRs) to estimate the prevalence of AA by race/ethnicity, physical disability, sexual orientation/gender identity (LGBTQIA +), income, and education. The latest AoU release (version 5) includes 329,038 participants. Average age was 51.8 years (standard deviation, SD 16.7), and 60.2% of participants were female. Of these, 251,597 (76.5%) had EHR data and 752 were diagnosed with AA (prevalence, 0.30%; 95% CI 0.28-0.32). We used multivariate logistic regression adjusted for age and other factors to estimate the odds ratio (OR) and 95% confidence intervals (CIs) for prevalence of AA. Compared to Whites, Blacks and Hispanics had higher odds of AA (OR, 1.72; 95% CI 1.39-2.11 and OR, 2.13; 95% CI 1.74-2.59, respectively). Lower odds of AA were observed in participants with less than a high school degree (OR, 0.80; 95% CI 0.59-1.08), household income ≤ $35,000 (OR, 0.67; 95% CI 0.54-0.83), and no health insurance (OR 0.35; 95% CI 0.20-0.56). In this diverse population of US adults, participants with skin of color had higher prevalence of AA. Lower prevalence of AA among individuals with lower education and income levels and those lacking health insurance may reflect limited access to dermatologic care and potentially higher levels of undiagnosed AA in these groups.

Trends in use of antipsychotics and psychoactive drugs in older patients after major surgery.

BACKGROUND: Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied. METHODS: This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha-2 receptor agonist dexmedetomidine in the postoperative period by hospital type. RESULTS: The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008-2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009-2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital-days declined for haloperidol (CHs: 33-21 days [p < 0.01]; AMCs: 24-15 days [p < 0.01]) and benzodiazepines (CHs: 261-136 days [p < 0.01]; AMCs: 150-77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non-ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10-6 days [p < 0.01]; AMCs: 4-3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126-56 days [p < 0.01]; AMCs: 30-27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type. CONCLUSIONS: The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs.

Head and neck dermatitis is exacerbated by Malassezia furfur colonization, skin barrier disruption, and immune dysregulation.

Introduction & objectives: Head and neck dermatitis (HND) is a refractory phenotype of atopic dermatitis (AD) and can be a therapeutic challenge due to lack of responsiveness to conventional treatments. Previous studies have suggested that the microbiome and fungiome may play a role in inducing HND, but the underlying pathogenic mechanisms remain unknown. This study aimed to determine the link between HND and fungiome and to examine the contribution of Malassezia furfur. Materials and methods: To identify the effect of the sensitization status of M. furfur on HND, 312 patients diagnosed with AD were enrolled. To elucidate the mechanism underlying the effects of M. furfur, human keratinocytes and dermal endothelial cells were cultured with M. furfur and treated with Th2 cytokines. The downstream effects of various cytokines, including inflammation and angiogenesis, were investigated by real-time quantitative PCR. To identify the association between changes in lipid composition and M. furfur sensitization status, D-squame tape stripping was performed. Lipid composition was evaluated by focusing on ceramide species using liquid chromatography coupled with tandem mass spectrometry. Results: Increased sensitization to M. furfur was observed in patients with HND. Additionally, sensitization to M. furfur was associated with increased disease severity in these patients. IL-4 treated human keratinocytes cultured with M. furfur produced significantly more VEGF, VEGFR, IL-31, and IL-33. IL-4/M. furfur co-cultured dermal endothelial cells exhibited significantly elevated VEGFR, TGF-ß, TNF-α, and IL-1ß levels. Stratum corneum lipid analysis revealed decreased levels of esterified omega-hydroxyacyl-sphingosine, indicating skin barrier dysfunction in HND. Finally, M. furfur growth was inhibited by the addition of these ceramides to culture media, while the growth of other microbiota, including Cutibacterium acnes, were not inhibited. Conclusions: Under decreased levels of ceramide in AD patients with HND, M. furfur would proliferate, which may enhance pro-inflammatory cytokine levels, angiogenesis, and tissue remodeling. Thus, it plays a central role in the pathogenesis of HND in AD.

Tofacitinib and Risk of Malignancy: Results From the Safety of Tofacitinib in Routine Care Patients With Rheumatoid Arthritis (STAR-RA) Study.

OBJECTIVES: Results of the ORAL Surveillance safety trial have indicated that there is an increased risk for the development of malignancies with tofacitinib therapy when compared to treatment with tumor necrosis factor inhibitors (TNFi). This study was undertaken to further examine this safety concern in rheumatoid arthritis (RA) patients in a real-world setting. METHODS: Using US insurance claims data from Optum Clinformatics (2012-2020), IBM MarketScan Research Databases (2012-2018), and Medicare (parts A, B, and D, 2012-2017), we created 2 cohorts of RA patients who had initiated treatment with tofacitinib or TNFi. The first cohort, designated the real-world evidence (RWE) cohort, included RA patients from routine care. For the second cohort, designated the randomized controlled trial (RCT)-duplicate cohort, we emulated the inclusion and exclusion criteria that were applied in the ORAL Surveillance trial of tofacitinib, which allowed us to assess the comparability of our results with the results of that trial. Cox proportional hazards models with propensity score fine-stratification weighting were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of any malignancy (excluding nonmelanoma skin cancer). Database-specific estimates were meta-analyzed using fixed-effects models with inverse-variance weighting. RESULTS: The RWE cohort consisted of 83,295 patients, including 10,504 patients (12.6%) who received treatment with tofacitinib. The pooled weighted HR for the primary outcome of any malignancy associated with tofacitinib treatment compared to any malignancy associated with TNFi therapy was 1.01 (95% CI 0.83, 1.22) in the RWE cohort and 1.17 (95% CI 0.85, 1.62) in the RCT-duplicate cohort (compared to the ORAL Surveillance trial HR of 1.48 [95% CI 1.04, 2.09]). CONCLUSION: We did not find evidence of an increased risk of malignancy development with tofacitinib therapy, in comparison with TNFi therapy, in RA patients treated in a real-world setting. However, our results cannot rule out the possibility of an increase in risk that may accrue with a longer duration of treatment with tofacitinib.