Real-world treatment patterns and outcomes for patients with multiple myeloma in Denmark, Finland and Sweden: An analysis using linked Nordic registries.

AIM: The Health outcomes and Understanding of MyelomA multi-National Study (HUMANS) was a large-scale, retrospective study conducted across Denmark, Finland and Sweden using linked data from national registries. We describe the characteristics, treatment patterns and clinical outcomes for patients with newly diagnosed multiple myeloma (NDMM) over 2010-2018. METHODS: Patients with NDMM who received MM-specific, first-line treatments, were categorised by treatment (autologous stem cell transplantation [ASCT] or a combination chemotherapy regimen based on bortezomib, lenalidomide or melphalan-prednisolone-thalidomide). RESULTS: 11,023 patients received treatment over 2010-2018. Time between diagnosis and treatment was shortest in Denmark (0.9 months), then Sweden (2.9 months) and Finland (4.6 months). Around one third of patients underwent ASCT. Lenalidomide-based regimens were prescribed to 23-28% of patients in Denmark and Finland, versus 12% in Sweden. Patients receiving lenalidomide had the longest wait for treatment, from 3.2 months (Denmark) to 12.1 months (Sweden). Treatment persistence was highest among patients receiving melphalan-prednisolone-thalidomide (7-8 months) in Finland and Sweden and lowest among those receiving bortezomib (3.5 months) in Finland. Overall survival (OS) was longest among patients with ASCT (7-10 years). Among patients receiving chemotherapy, OS (from diagnosis/treatment initiation), varied between cohorts. In a sensitivity analysis excluding patients with smouldering MM, OS decreased for all; for patients receiving bortezomib or lenalidomide, OS from diagnosis was 40-49 and 27-54 months, respectively. CONCLUSIONS: This population-based study of patients with NDMM receiving first-line MM-specific treatment, provides real-world data on treatment patterns and outcomes to complement data from randomised clinical trials.

Real-world biologic treatment patterns and healthcare resource utilization in psoriasis patients using an insurance claims database in Japan.

BACKGROUND: With advent of newer treatments for psoriasis, real-world use of biologics in Japan is evolving. METHODS: This retrospective study utilized data from patients with ≥1 psoriasis-related biologic claims record between January 2016 and December 2020 in Japan to evaluate treatment patterns, healthcare resource utilization (HCRU), and associated costs. Data were analyzed using descriptive statistics. RESULTS: Of 1,614 eligible patients, 72.5% were male, 29.2% had comorbid hypertension and 26.6% had comorbid cardiovascular disease. Interleukin (IL)-17 and tumor necrosis factor alpha (TNFα) inhibitors were commonly prescribed across lines of treatment, while IL-23 inhibitors were most considered for switches (92% of switches were from IL-12/23/IL-17/TNFα inhibitors). The overall mean adherence rate for all classes was 80.1%, but adherence varied across biologics. Infliximab and IL-23 inhibitor users exhibited optimal medical possession ratios, reflecting the best adherence rates. Overall HCRU (visits/patient-year) was 9.05 for outpatient visits, 0.09 for inpatient hospitalization, and 0.5 for psoriasis-related phototherapy. HCRU associated with hospitalization was slightly higher for bio-experienced patients and so was the overall costs per patient-year relative to bio-naïve patients. CONCLUSION: Variable adherence rates observed suggest the need for improvement in treatment management with different biologics. Bio-experienced patients burdened by disease progression and treatment switches may result in increased HCRU.

Use of Linked Nordic Registries for Population Studies in Hematologic Cancers: The Case of Multiple Myeloma.

Purpose: Linked health-care registries and high coverage in Nordic countries lend themselves well to epidemiologic research. Given its relatively high incidence in Western Europe, complexity in diagnosis, and challenges in registration, multiple myeloma (MM) was selected to compare registries in Denmark, Finland, and Sweden. Patients and Methods: Data were obtained from four archetypal registries in each country (spanning January 2005-October 2018): National Patient Registry (NPR), Prescribed Drug Registry (PDR), Cancer Registry (CR), and Cause of Death Registry. Patients newly diagnosed with MM who received MM-specific treatment were included. PDR/NPR treatment records were used to assess incident NPR cases. The registration quality of MM-specific drugs in the PDR of each country was also evaluated. Results: In Denmark, only 6% of patients in the NPR were not registered in the CR; in Sweden, it was 16.9%. No systematic differences were identified that could explain this discrepancy. In Denmark, lenalidomide and bortezomib were registered in the NPR with high coverage, but less expensive drugs typically given in combination with bortezomib were not covered in any of the registries. In Finland and Sweden, bortezomib records were not identified in the PDR, but some were in the NPR; other drugs had good coverage in the PDR. Conclusions: The registries evaluated in this study can be used to identify the MM population; however, given the gaps in MM registration in the Finnish and Swedish CRs, Danish registries provide the most comprehensive datasets for research on treatment patterns for MM.

Adherence to oral antiretroviral therapy in Canada, 2010-2020.

OBJECTIVE: To assess antiretroviral therapy (ART) adherence among people with HIV (PWH) in Canada and identify baseline characteristics associated with suboptimal adherence (<95%). DESIGN: Retrospective observational study using data from the National Prescription Drug Utilization Information System and Régie de l'assurance maladie Quebec (RAMQ) Public Prescription Drug Insurance Plan. METHODS: This analysis included PWH aged 18 years or older who initiated an ART regimen and were followed for at least 12 months (2010-2020). Patient characteristics were summarized using medical/pharmacy claims data from seven provinces (Alberta, Manitoba, New Brunswick, Newfoundland and Labrador, Ontario, Saskatchewan, and Quebec). ART regimen at index date (first dispensing of a regimen including a core agent) was defined as a single-tablet or multitablet regimen (MTR). Adherence was calculated using a Proportion of Days Covered approach, based on ART dispensing, recorded between April 2010 and the last available date. Multivariate linear regression analysis was used to determine correlations between suboptimal adherence and baseline characteristics. RESULTS: We identified 19 322 eligible PWH, 44.7% of whom had suboptimal adherence (<95%). Among 12 594 PWH with evaluable baseline data, 10 673 (84.8%) were ART-naive, 74.2% were men, mean age was 42.9 years, and 54.1% received a MTR as their ART. Based on multivariate regression analysis, suboptimal adherence was significantly associated with multitablet ART ( P  < 0.001) and younger age ( P  < 0.001) but not sex. CONCLUSION: Almost half of adult PWH in Canada had suboptimal adherence to ART. Better understanding of factors influencing adherence may help address gaps in current care practices that may impact adherence.

Epidemiology, Treatment Patterns, Comorbidities, and Concomitant Medication in Patients with ADHD in Sweden: A Registry-Based Study (2018-2021).

OBJECTIVE: To evaluate treatment patterns for ADHD in Sweden. METHOD: Observational retrospective study of patients with ADHD from the Swedish National Patient Register and Prescribed Drug Register, 2018 to 2021. Cross-sectional analyses included incidence, prevalence, and psychiatric comorbidities. Longitudinal analyses (newly diagnosed patients) included medication, treatment lines, duration, time-to-treatment initiation, and switching. RESULTS: Of 243,790 patients, 84.5% received an ADHD medication. Psychiatric comorbidities were common, particularly autism among children, and depression in adults. Most frequent first-/second-line treatments were methylphenidate (MPH; 81.6%) and lisdexamfetamine dimesylate (LDX; 46.0%), respectively. In the second-line, LDX was most frequently prescribed (46.0%), followed by MPH (34.9%), then atomoxetine (7.7%). Median treatment duration was longest for LDX (10.4 months), followed by amphetamine (9.1 months). CONCLUSION: This nationwide registry study provides real-life insights into the current epidemiology of ADHD and the changing treatment landscape for patients in Sweden.

Treatment Patterns among Patients with Atopic Dermatitis in Secondary Care: A National, Observational, Non-interventional, Retrospective Study in Sweden.

This non-interventional, observational, longitudinal study describes treatment patterns of atopic dermatitis (AD) in Sweden. Data from 3 Swedish registries were merged, and included patients who received an AD diagnosis (during the period 1997 to 2019) and had AD treatment prescribed (during the period 2006 to 2020). Treatment persistence, treatment sequencing, time-to-event analysis, and 12-month prevalence were analysed. Overall, data for 99,885 patients with AD were included, of whom 4,086 (4.1%) received systemic treatments. Median persistence rates were 12.6 (95% CI 11.9, 13.4) months for methotrexate, 10.8 (9.1, 13.0) months for azathioprine, 5.6 (3.8, 6.2) months for mycophenolate, 5.1 (4.4, 5.7) months for alitretinoin and 3.4 (3.2, 3.7) months for cyclosporine. Median (Q1, Q3) time from first secondary care visit for AD to first systemic treatment was 5.8 (2.2, 11.0) years overall and 4.4 (1.3, 9.1) years in the Stockholm region. Methotrexate was a prominent first- and second-line treatment used during the period 2006 to 2020. Dupilumab was introduced during the study period and was increasingly used as first- or second-line therapy over time. The 12-month prevalence of AD generally remained steady, with a gradual increase observed over time for the overall population. A steep increase was observed in Stockholm from 2011. This study shows that a small proportion of patients with AD are offered systemic treatments in Sweden, with long periods in secondary care prior to systemic treatments and low persistence on systemic treatments. Regional differences highlight a need for national treatment guidelines.

Real-world dose adjustments of biologic treatments in psoriasis and their economic impact: a Swedish national population study.

BACKGROUND: To date, evidence on the dose adjustments of biologics in the real-world treatment of psoriasis is limited. However, dose adjustments may have important clinical and economic implications. AIMS: To study the dose adjustments of individual biologics over time in real-world practice in Sweden. METHODS: A retrospective observational study of adults with moderate to severe psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Treatment episodes were identified for individual patients from the date of drug dispensation to the end of the supply of the drug. Dosing data were expressed as the proportion of treatment episodes with accumulated syringes/vials equal to, above or below the recommended guidelines. Real-world costs were calculated and compared with costs predicted from dosing guidelines. RESULTS: The mean dose was above recommended levels for all biologics investigated. Weighted mean dose adjustments for adalimumab, etanercept, secukinumab and ustekinumab were 13%, 23%, 8% and 3%, respectively, over the entire treatment period. Higher doses translate to higher costs, including notable increases over time vs. expected costs for secukinumab. CONCLUSIONS: Dose adjustments of biologics are frequent in clinical practice but differ for the various biologics. The mean observed increases in dose above guideline recommendations might indicate perceptions of suboptimal efficacy for biologics, with implications for the cost and cost-effectiveness of these treatments. Further research is warranted to understand the reasons for dose adjustments in clinical practice.

Overall survival of patients with metastatic breast cancer in Sweden: a nationwide study.

BACKGROUND: Breast cancer is the most common cancer among women in Sweden. Whereas survival for the overall breast cancer population is well-documented, survival of patients with metastatic breast cancer (MBC) is harder to quantify due to the lack of reliable data on disease recurrence in national cancer registers. METHODS: This study used machine learning to classify the total MBC population in Sweden diagnosed between 2009 and 2016 using national registers, with the aim to estimate overall survival (OS). RESULTS: The total population consisted of 13,832 patients-2528 (18.3%) had de novo MBC whereas 11,304 (81.7%) were classed as having a recurrent MBC. Median OS for patients with MBC was found to be 29.8 months 95% confidence interval (CI) [28.9, 30.6]. Hormone-receptor (HR)-positive MBC had a median OS of 37.0 months 95% CI [35.9, 38.3] compared to 9.9 months 95% CI [9.1, 11.0] for patients with HR-negative MBC. CONCLUSION: This study covered the entire MBC population in Sweden during the study time and may serve as a baseline for assessing the effect of new treatment strategies in MBC introduced after the study period.

Drug Persistence of Biologic Treatments in Psoriasis: A Swedish National Population Study.

INTRODUCTION: Biologic treatments for psoriasis are commonly switched. Treatment persistence represents an important parameter related to long-term therapeutic performance. The objective of the study was to analyse the real-world persistence with biologics over time in the treatment of psoriasis. METHODS: A retrospective observational study of adults with psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Patients included were treated with a biologic between 2010 and 2018. Treatment episodes were identified from the drug's date of dispensation recorded in the Prescribed Drug Register to the end of supply of the drug. Median persistence was estimated by Kaplan-Meier survival curves for patients who received adalimumab, etanercept, secukinumab, ustekinumab and ixekizumab. Descriptive analysis of change in persistence over time for 3-year running cohorts was also carried out. RESULTS: A total of 2292 patients were analysed. Patients who received ustekinumab had the longest median persistence [49.3 months, 95% confidence interval (CI) 38.0-59.1] and etanercept the shortest (16.3 months, 95% CI 14.5-19.0). Median persistence was longer in biologic-naive than biologic-exposed patients. Persistence for ustekinumab decreased by almost 50% over the study period, from a median of 62.3 (95% CI 45.6-∞) months in 2010-2011 to 32.7 (21.2-49.3) months in 2014-2016. CONCLUSIONS: Persistence with biologics was, on average, relatively low, given the chronic nature of psoriasis. Changes in persistence over time seemed to be attributable to changes in the therapeutic landscape, providing patients with more options to switch biologic treatments if their current management was considered suboptimal.

Use of classifiers to optimise the identification and characterisation of metastatic breast cancer in a nationwide administrative registry.

BAKGROUND: The prognosis for patients with metastatic breast cancer (MBC) is substantially worse when compared with patients with earlier stage disease. Therefore, understanding the differences in epidemiology between these two patient groups is important. Studies using population-based cancer registries to identify MBC are hampered by the quality of reporting. Patients are registered once (at time of initial diagnosis); hence only data for patients with de novo MBC are identifiable, whereas data for patients with recurrent MBC are not. This makes accurate estimation of the epidemiology and healthcare utilisation of MBC challenging. This study aimed to investigate whether machine-learning could improve identification of MBC in national health registries. MATERIAL AND METHODS: Data for patients with confirmed MBC from a regional breast cancer registry were used to train machine-learning algorithms (or 'classifiers'). The best performing classifier (accuracy 97.3%, positive predictive value 85.1%) was applied to Swedish national registries for 2008 to 2016. RESULTS: Mean yearly MBC incidence was estimated at 14 per 100,000 person-years (with 18% diagnosed de novo and 76% of the total with HR-positive MBC). CONCLUSION: To our knowledge, this is the first study to use machine learning to identify MBC regardless of stage at diagnosis in health registries covering the entire population of Sweden.

Patients With High-disease-activity Relapsing-Remitting Multiple Sclerosis in Real-world Clinical Practice: A Population-based Study in Sweden.

PURPOSE: This study aims to compare the disease progression and disease-modifying treatment-switching patterns between patients with high-disease-activity (HDA) relapsing-remitting multiple sclerosis (RRMS) and patients with low-disease-activity (LDA) RRMS in real-world clinical practice. METHODS: The confirmed disease progression and time to switch of 6647 patients from the Swedish multiple sclerosis registry were analyzed using a marginal structural model that compared patients with relapsing HDA (HDA-R) and lesion HDA (HDA-L) following definitions in European labels of disease-modifying therapies with patients with LDA. Time to milestone and stratified drug cohort analyses were used for internal validation. FINDINGS: A total of 262 patients with LDA, 985 patients with HDA-R, and 683 patients with HDA-L were included in the primary analysis. The HDA-R subgroup had statistically significant greater risk of disease progression (hazard ratio = 1.23; 95% CI, 1.03-1.46) and no difference in time to switch compared with the LDA subgroup. The HDA-L subgroup had statistically significant shorter time to switch (hazard ratio = 1.47; 95% CI, 1.31-1.66) and no difference in disease progression compared with the LDA subgroup. IMPLICATIONS: Compared with past research on HDA RRMS grounded mainly in randomized controlled trials of individual disease-modifying therapies, the main contribution of this study is that HDA, as identified by relapses, in real-world clinical settings has a clearer association with disease progression than HDA identified by new magnetic resonance imaging lesions. Taking into account that the HDA-L subgroup had a shorter time to switch, there is evidence of an unmet need for effective treatments in clinical practice for both the HDA-R and HDA-L subgroups.

Characterization of annual disease progression of multiple sclerosis patients: A population-based study.

BACKGROUND: Previous research characterizing factors influencing multiple sclerosis (MS) disease progression has typically been based on time to disease milestones (Kaplan-Meier, Cox hazard regression, etc.). A limitation of these methods is the handling of the often large groups of patients not reaching the milestone. OBJECTIVE: To characterize clinical factors influencing MS disease progression as annual transitions from each Expanded Disability Status Scale (EDSS). METHOD: The annual progression of 11,964 patients from the Swedish MS Registry was analysed with 10 multinomial logistic regressions, that is, one for transition from each full EDSS with explanatory variables age, sex, age at onset, time in current EDSS, highest prior EDSS, MS course and treatment. RESULTS: All factors (except sex) investigated had statistically significant impacts on transitions from at least one EDSS. However, significance and size of the effect are dependent on the EDSS state of the patient. Greater age, longer time in a state, highest prior EDSS, having progressive MS and treatment had significant impacts, whereas age at onset had minor impact. CONCLUSION: Our study confirms that established factors associated with MS disease worsening in time to disease milestones also have impacts on annual progression. This approach adds granularity to what EDSS these factors have an influence.