Epidemiology and Treatment Patterns of Patients with Vitiligo: A Real-World Analysis.

INTRODUCTION: Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological conditions. Our current understanding of vitiligo burden and management in the real world is limited. This real-world analysis presents data on vitiligo epidemiology, comorbidities, and treatment of patients in Israel. METHODS: This retrospective study analyzed data from the Maccabi Health Services database. Prevalent patients with vitiligo in 2021 were matched to patients in the general population on the basis of age group, gender, and socioeconomic status. Patient demographics, vitiligo incidence and prevalence, comorbidities, and treatment patterns are reported. Data are presented as percentages, mean, median, P values, and standard mean differences (SMD). RESULTS: In this analysis, 11,412 patients with vitiligo were matched to patients from the general population. Incidence and prevalence rates increased over time from 2005 to 2021. Compared to the general population, patients with vitiligo were more likely to have an immune-mediated comorbidity (29.7% vs 18.4% [P < 0.001; SMD 0.27]) or psychological comorbidity (18.7% vs 15.9% [P < 0.001; SMD 0.07]). Comorbidities included atopic dermatitis (patients with vitiligo vs general population 12.5% vs 8.4%), psoriasis (5.8% vs 3.6%), Hashimoto's thyroiditis (2.9% vs 1.1%), alopecia areata (2.2% vs 0.9%), depression (10.8% vs 9.5%), and sleep disorder/insomnia (5.9% vs 4.4%). Only 74.8% of all patients with vitiligo had ever received treatment, with topical corticosteroids (51.5%) and calcineurin inhibitors (36.5%) most commonly prescribed. At the end of 2021, 83.7% of patients were untreated. CONCLUSION: Patients with vitiligo are more likely to have various immune-related and psychological comorbidities, highlighting the significant impact of the condition on well-being. Nearly a quarter of patients had never received treatment, with many receiving only topical treatments, and medication persistence was low. This highlights the lack of adequate treatment in this population and the need for more effective management options.

Real-World Data of Adherence and Drug Survival of Biologics in Treatment-Naïve and Treatment-experienced Adult Patients with Rheumatoid Arthritis.

INTRODUCTION: Biologic disease-modifying anti-rheumatics drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are important treatments for rheumatoid arthritis (RA). As more of these drugs become available, there is a greater need to assess their real-world adherence and drug survival. METHODS: Treatment-naïve and treatment-experienced patients with RA who initiated treatment with bDMARDs and tofactinib during 2015-2018 in a large Israeli health maintenance organization were included. Adherence and time to treatment suspension were recorded. Odds for adherence were estimated using a multivariable logistic regression model. Risk for treatment suspension was estimated using a mixed-effect Cox proportional hazard model. RESULTS: The analysis included 753 eligible patients (61.8% treatment-naïve) treated with 1287 treatment episodes (tofacitinib 24.2%, tocilizumab 17.5%, etanercept 16.0%, adalimumab 10.4%, abatacept 9.9%, rituximab 9.0%, golimumab 6.9%, certolizumab pegol 3.6%, infliximab 1.9%, and sarilumab 0.5%). Good adherence was measured for almost all drugs, yet over 50% of all treatment episodes were suspended. Older age was associated with reduced risk for treatment suspension while higher number of primary care visits and higher Charlson's comorbidity score were associated with increased risk. Compared to etanercept, treatment with adalimumab, certolizumab, or rituximab was associated with increased risk for treatment suspension (HR 1.68 95% CI 1.27-2.22, HR 1.62 95% CI 1.00-2.60, and HR 2.72 95% CI 2.02-3.67, respectively). CONCLUSION: Treatment choice primarily depends on disease activity and prognosis. Real-world data, showing differences in drug survival of bDMARDs and tsDMARD, can also be used in the variety of considerations when choosing treatment. Future studies could separate patients with RA into subgroups, which would also account for potential drug survival differences and enable personalized therapy.

Hormone-Replacement Therapy and Its Association with Breast Cancer Subtypes: A Large Retrospective Cohort Study.

PURPOSE: The study examined trends in breast cancer incidence, mammography testing rates, hormone-replacement therapy (HRT) use and breast cancer subtypes in a large Israeli health maintenance organization during 2000-2014. METHODS: Annual rates of mammography tests and HRTs use were analyzed in women age ≥45. Annual incidence rates of breast cancer were analyzed in women age ≥20. Estimated annual percentage changes were used to test changes in incidence rates. Invasive breast cancer subtypes were approximated by treatments received. We compared annual rates and duration of HRTs use between women diagnosed with breast cancer and those who were not, as well as HRT use between subtypes of invasive breast cancer. RESULTS: We identified 14,092 breast cancer cases (88% invasive, 12% in situ). The age-adjusted incidence rate of invasive breast cancer peaked in 2005, consistent with increased mammography screening that year, and decreased thereafter. HRT use decreased from 13.2% in 2002 to 4.6% in 2014. The subtypes distribution of 7771 patients diagnosed with invasive breast cancer during 2007-2014 was: luminal A and B without HER2 over-expression (HR+/HER2-), 69.7%; Luminal B with HER2 over-expression (HR+/HER2+), 8.9%; Hormone receptor-negative HER2 enriched (HR-/HER2+), 5.4%; triple negative (HR-/HER2-), 10.0%; unknown, 6.0%. Overall, in women age ≥45 diagnosed with invasive breast cancer, 76-86% did not have HRT exposure vs 14-24% who were current (within 1 year before the breast cancer diagnosis), recent (within 2-5 years), or past users (>5 years). Current/recent HRT use was statistically significantly higher in luminal vs non-luminal/unknown breast cancer subtypes (13.9% vs 8.9%, respectively; p < 0.001). CONCLUSION: Our results show a decrease in breast cancer incidence that parallels the global and local decrease in HRT use. Yet, our results imply that current/recent HRT exposure may contribute to the incidence of luminal breast cancer tumors in particular. The magnitude of the effect supports findings from population-based studies.

Proton pump inhibitors long term use-trends and patterns over 15 years of a large health maintenance organization.

BACKGROUND: Proton pump inhibitors (PPI) are used for a variety of indications. Despite reported associations with undesirable effects, their long-term use is on the rise, while appropriate indications, dose, and treatment duration may deviate from guideline recommendations. OBJECTIVES: Primary to examine the annual patterns of PPI use. Secondary- to assess indications for initiating PPI treatment, long-term use, and factors associated with long-term use in a large Israeli health maintenance organization. METHODS: A historical cohort study of 528 420 eligible PPI users during 2000-2015, analyzed PPI use using defined daily doses and the proportion of patients covered method. Data on indications for treatment initiation, clinical and socio-demographic parameters were captured as well. A multivariable logistic-regression model was used to identify factors associated with long-term use of PPI. RESULTS: The annual incidence rates of patients initiating PPI treatment were relatively constant, ranging between 2.4% and 3.1% of the adult population, with a monotonic increase in annual consumption and prevalence (reaching 12.7% in 2015). Reflux, functional symptoms, and Helicobacter pylori eradication were the most common indications for initiating PPI therapy. However, 27% of patients had no recorded indication for treatment. Fifteen percent of patients used PPI for over 6 months, especially in older age groups. CONCLUSIONS: Utilization of PPI increases steadily, mainly due to chronic use. Prolonged consumption is associated with specific clinical indications and older age. Health organizations should encourage awareness of appropriate use among physicians, specifically in the elderly, patients with reflux, and those with functional disorders.

Asthma in Youth and Early-onset Type 2 Diabetes: A Nationwide Study of 1.72 Million Israeli Adolescents.

BACKGROUND: The prevalence of both asthma and early-onset diabetes is on the rise; however, the association between them remains unclear. We examined a possible association of asthma at adolescence with type 2 diabetes in young adulthood. METHODS: This is a nationwide, population-based study of 1 718 541 Israeli adolescents (57% males; mean age 17.3 years; range 16-19 years), examined before compulsory military service between 1992 and 2016, with data linked to the Israeli National Diabetes Registry. Asthma diagnosis and severity were determined by a board-certified pulmonologist and based on spirometry tests. RESULTS: Type 2 diabetes developed in 58/9090 (0.64%), 507/97 059 (0.52%), 114/23 332 (0.49%), and 7095/1 589 060 (0.44%) persons with moderate-to-severe, mild, inactive, and no history of asthma, respectively, during a mean follow-up >13 years. The respective odds ratios (ORs) were 1.33 (95% CI, 1.02-1.74), 1.17 (1.06-1.28), and 1.09 (0.9-1.31), considering those without asthma history as the reference, in a model adjusted for birth year, sex, body mass index, and other sociodemographic variables. The association persisted when the analysis accounted for coexisting morbidities, and when persons without asthma, individually matched by age, sex, birth year, and body mass index were the reference. Both mild and moderate-to-severe asthma were associated with type 2 diabetes before age 35 years: ORs 1.18 (1.05-1.34) and 1.44 (1.05-2.00), respectively. The strength of the association was accentuated over time. The effect was unchanged when adjusted for oral and inhaled glucocorticoid use. CONCLUSION: Adolescents with active asthma have higher risk to develop type 2 diabetes. This seems related to disease severity, independent of adolescent obesity status, apparent before age 35 years, and more pronounced in recent years.

Hypothyroidism in Young Children Following Exposure to Iodinated Contrast Media: An Observational Study and a Review of the Literature.

While it is well documented that exposure to iodinated contrast media (ICM) can interfere with thyroid function in adults, much less is known about the incidence and risk factors associated with ICM induced hypothyroidism in young children. Using a computerized database we identified 843 children who were exposed to ICM between 1998 and 2015. The incidence rate of ICM induced hypothyroidism per 1000 person-years was 9.66 (95% CI: 4.17-19.04). When compared to the rest of the cohort, children with hypothyroidism were more likely to be younger, weigh less and to have undergone cardio-angiography. These results are supported by findings described in the literature review. The risk of ICM- induced hypothyroidism needs to be considered especially in young children with low weight, undergoing cardio-angiography examinations. Systematic monitoring of thyroid function should be conducted in this focused patient population to avoid potential adverse consequences on child development.

Silicone breast implants and the risk of autoimmune/rheumatic disorders: a real-world analysis.

Objectives: Several epidemiological studies have investigated the link between silicone breast implants (SBIs) and autoimmune/rheumatic disorders, reporting inconsistent results. We aimed to evaluate the association between SBIs and the most clinically relevant autoimmune/rheumatic disorders using a large, population-based database. Methods: In this cross-sectional study, we used the computerized databases of Maccabi Healthcare Services (MHS), which include up to 20 years of data on 2 million members. Women with SBIs were identified by procedure and diagnosis codes, clinical breast examinations and mammography referrals. Autoimmune/rheumatic disorders were identified using the International Classification of Diseases 9th revision (ICD-9) codes. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A Cox's proportional hazards model was used to calculate the hazard ratios (HRs) and 95% CIs among a subgroup of SBI recipients for whom the year of SBIs insertion was available. Results: We included 24 651 SBI recipients and 98 604 matched SBI-free women. The adjusted OR between SBIs and being diagnosed with any autoimmune/rheumatic disorders was 1.22 (95% CI 1.18-1.26). The strongest association with SBIs (OR > 1.5, p < 0.001) was recorded for Sjögren's syndrome, systemic sclerosis (SSc) and sarcoidosis (OR of 1.58, 1.63 and 1.98, respectively). Similar results were calculated when analysis was limited to women with no breast cancer history. A multivariable Cox regression model yielded a HR of 1.45 (95% CI 1.21-1.73) for being diagnosed with at least one autoimmune/rheumatic disorder in women with SBI compared with those without. Conclusions: SBIs seem to be associated with higher likelihood of autoimmune/rheumatic disorders diagnosis.

Characterization of adherence and persistence profile in a real-life population of patients treated with adalimumab.

AIMS: Published data on long-term adherence and persistence with adalimumab (Humira® ) in clinical practice are scarce and often limited to selected patient populations. This study assessed adherence with adalimumab across different indications and identified correlates and outcomes of poor adherence. METHODS: We analysed data originating from the electronic database of Maccabi Healthcare Services (MHS) that includes 2.1 million enrolees. We randomly selected patients with at least one dispense of adalimumab since it was included in the local health basket in Israel in 2008 until the end of 2013. Patients with the following indications (n = 1339) were included: Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriatic arthritis (PSA), ankylosing spondylitis (AS) and psoriasis. Adherence with therapy was assessed by the medication possession ratio (MPR) during the follow-up period. RESULTS: Good adherence (MPR ≥ 80%) was observed among 80% of study patients and was associated with lower risk for ≥1 hospitalization per year of follow-up (adjusted-OR = 1.94, 95% CI:1.15-3.28). Patients with AS and CD persisted on adalimumab therapy the most, reaching median use of 27.0 and 26.7 months, respectively. Half (52.4%) of the patients discontinued treatment during a mean (SD) follow-up of 3.07 (1.71) years. High socioeconomic status was associated with lower risk for discontinuation (adjusted-HR = 0.74; 0.60-0.91). UC and concomitant prednisolone use were associated with increased risk for treatment discontinuation (HR = 1.31; 1.00-1.72, and HR = 1.40; 1.17-1.68, respectively). CONCLUSION: Our results indicate encouraging persistence and adherence with adalimumab of patients with inflammatory conditions.