Use of ALK-tyrosine kinase inhibitors (ALK TKI) in clinical practice, overall survival, and treatment duration - a Swedish nationwide retrospective study.

BACKGROUND: The real-world treatment and outcomes of patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer treated with ALK Tyrosine Kinase Inhibitor (TKI) drugs in Sweden is not well described. MATERIAL AND METHODS: A retrospective population-based cohort study was conducted using Swedish national registers. All patients with a filled prescription for an ALK TKI between January 2012 and October 2020 were included. The sequencing of ALK TKI and duration of treatment (DOT) were described, and overall survival (OS) was estimated using the Kaplan-Meier method. Patients were stratified based on treatment with frontline chemotherapy, presence of CNS metastases prior to the first ALK TKI, and generation of ALK TKI agent. RESULTS: Among the total of 579 patients, 549 (95%) underwent a therapy sequence in line with current clinical practice with 204 (37%) patients receiving frontline chemotherapy. Single-line ALK TKI was given to 366 patients (crizotinib: 211; alectinib: 146; ceritinib: 9), whereas 128 patients received two different ALK TKI (frontline crizotinib: 100, alectinib: 24, ceritinib: 4); 40 patients received three lines and 15 patients four ALK TKI lines or more. With frontline chemotherapy, the mean (standard deviation) DOT was 1.07 (1.25) years for the entire TKI therapy sequence compared to 1.23 (1.28) years with frontline ALK TKI. The median (95% confidence interval) OS was 1.83 (1.48-2.13) years for the entire cohort, 1.44 (0.89-1.98) years for patients given frontline chemotherapy, and 2.02 (1.60-2.58) years for patients given frontline ALK TKI. CONCLUSION: This study provides a unique overview of the patient population treated with ALK TKI in Sweden and reveals the treatment patterns applied in real clinical practice. More research is needed when longer follow-up data are available for later-generation ALK TKI, to fully understand ALK TKI sequencing and its effect on patient survival in a real-world setting.

Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden. METHODS AND RESULTS: Transthyretin amyloid cardiomyopathy patients were identified during 2008-2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to patients with non-ATTR heart failure (HF). An identical study design was used in each country to facilitate comparison and aggregation of results. A total of 1930 ATTR-CM patients were identified from national health registers in the four countries. In 2018, prevalence of ATTR-CM per 100 000 inhabitants ranged from 1.4 in Denmark to 5.0 in Sweden; a steep increase over time was observed in Sweden and Norway. Median survival from diagnosis was 30 months for ATTR-CM patients and 67 months for matched HF patients. Survival was significantly lower for female than for male ATTR-CM patients (median survival: 22 and 36 months), while no significant difference was observed in the HF cohort. CONCLUSIONS: This study provides the first nationwide estimates of the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using identical study design across several countries. Findings corroborate previous case series showing high mortality in ATTR-CM, two-fold higher than for other HF patients and higher in women than men, highlighting the need for more precise and early diagnosis to reduce the disease burden.

Healthcare resource use of patients with transthyretin amyloid cardiomyopathy.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is the cardiac manifestation of transthyretin amyloidosis (ATTR). The aim of this study was to estimate healthcare resource use for ATTR-CM patients compared with heart failure (HF) patients, in Denmark, Finland, Norway, and Sweden. METHODS AND RESULTS: Data from nationwide healthcare registers in the four countries were used. ATTR-CM patients were defined as individuals diagnosed with amyloidosis and cardiomyopathy or HF between 2008 and 2018. Patients in the ATTR-CM cohort were matched to patients with HF but without ATTR-CM diagnosis. Resource use included number of visits to specialty outpatient and inpatient hospital care. A total of 1831 ATTR-CM and 1831 HF patients were included in the analysis. The mean number of hospital-based healthcare contacts increased in both the ATTR-CM and HF cohort during 3 years pre-diagnosis and was consistently higher for the ATTR-CM cohort compared with the HF cohort, with 6.1 [CI: 5.9-6.3] vs. 3.2 [CI: 3.1-3.3] outpatient visits and 1.03 [CI: 0.96-1.1] vs. 0.7 [CI: 0.7-0.8] hospitalizations. In the first year following diagnosis, patients with ATTR-CM continued to visit outpatient care (10.2 [CI: 10.1, 10.4] vs. 5.7 [CI: 5.6, 5.9]) and were admitted to hospital more frequently (3.3 [CI: 3.2, 3.4] vs. 2.5 [CI: 2.5, 2.6]) than HF patients. CONCLUSIONS: Transthyretin amyloid cardiomyopathy imposes a high burden on healthcare systems with twice as many outpatient specialist visits and 50% more hospitalizations in the year after diagnosis compared with HF patients without ATTR-CM. Studies to investigate if earlier diagnosis and treatment of ATTR-CM may lower resource use are warranted.

Nationwide prevalence and characteristics of transthyretin amyloid cardiomyopathy in Sweden.

OBJECTIVE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive and fatal condition caused by deposition of transthyretin amyloid fibrils in the heart. This study aims to identify all patients diagnosed with ATTR-CM in Sweden, estimate the prevalence of ATTR-CM, describe patient characteristics and mortality, assess the importance of early symptoms (red flags) for identification of ATTR-CM, and compare with patients with heart failure (HF). METHODS: This retrospective study combined multiple national health registers covering all specialist visits and prescriptions for the entire population of Sweden. Between January 2008 and December 2018, patients with ATTR-CM were identified retrospectively based on a combination of diagnosis codes and compared with matched, all-cause non-ATTR HF patients. RESULTS: Overall, a total of 994 patients diagnosed with ATTR-CM were identified, with an average age at diagnosis of 73 years, and 30% of whom were female. The prevalence of diagnosed ATTR-CM cases in 2018 was 5.0 per 100 000. The median survival from diagnosis was 37.6 months (CI 33.8 to 43.8), with a lower median survival in women (27.9 months, CI 23.3 to 33.8) compared with men (43.5 months, CI 37.6 to 49.6). Patients with ATTR-CM demonstrated reduced survival compared with patients with HF (p<0.001). Compared with patients with HF, clinical identification of carpal tunnel syndrome, spinal stenosis, and atrioventricular and left bundle branch block can facilitate earlier diagnosis of ATTR-CM. CONCLUSIONS: This study provides the first nationwide estimates of ATTR-CM prevalence and risk factors. The results reinforce the severity of the disease and the importance of earlier diagnosis, especially for female patients, in order to allow effective treatment and prevention of disease progression.

Impact of nutritional vitamin D supplementation on parathyroid hormone and 25-hydroxyvitamin D levels in non-dialysis chronic kidney disease: a meta-analysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common and major complication in chronic kidney disease (CKD), reflecting the increase of parathyroid hormone (PTH) in response to reduced vitamin D signalling and hypocalcaemia. This meta-analysis evaluated the impact of nutritional vitamin D (NVD) (cholecalciferol or ergocalciferol) on SHPT-related biomarkers. METHODS: A systematic literature search was performed in PubMed to identify relevant randomized control trials to be included in the meta-analysis. Fixed- and random-effects models were used to pool study-level results. Effects were studied within NVD study arms and relative to control groups (placebo/no treatment); the former in order to identify the effect of actively altering biomarkers levels. RESULTS: Reductions in PTH from supplementation with NVD were small when observed within the NVD study arms (pooled reduction: 10.5 pg/mL) and larger when compared with placebo/no treatment (pooled reduction: 49.7 pg/mL). NVD supplementation increased levels of 25-hydroxyvitamin D [25(OH)D] in both analyses (increase within NVD study arm: 20.6 ng/mL, increase versus placebo/no treatment: 26.9 ng/mL). While small and statistically non-significant changes in phosphate and fibroblast growth factor 23 were observed, NVD supplementation caused calcium levels to increase when compared with placebo/no treatment (increase: 0.23 mg/dL). CONCLUSIONS: Our results suggest that supplementation with NVD can be used to increase 25(OH)D to a certain extent, while the potential of NVD to actively reduce PTH in non-dialysis-CKD patients with SHPT is limited.

Differing impact of clinical factors on the risk of fracture in younger and older women in the general population and an osteoporosis clinic population.

This study assesses the impact of risk factors for fracture in women aged 80+ and 60-79. The results suggest that risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort. PURPOSE: This study assesses whether the impact of classical risk factors for fracture due to osteoporosis is different in women aged 80+ and women aged 60-79. Since most prior research on the contribution of risk factors is based on patients below 80 years of age, this study aims to fill this knowledge gap to increase the accuracy of risk assessment in the oldest old. METHODS: Retrospective, observational cohort study using Swedish national health register data and BMD data from osteoporosis clinics. Women aged at least 60 were identified from a random sample of the general population and from the BMD databases and allocated to two populations representing patients at different stages of risk assessment. The relative impact of risk factors on fracture risk was assessed using multivariate competing risk regression with fracture as outcome and death as competing event. RESULTS: A total of 163,329 women were included from the general population (52,499 aged 80+) and 22,378 from the BMD databases (4563 aged 80+). The clinical risk factors with relatively highest effect on fracture risk in the older patients were prior fracture and hip T-score below - 2.5 SD. Other included risk factors showed lower impact in the older compared to the younger strata. CONCLUSIONS: This study confirms our understanding of the key risk factors for fracture: age, prior fracture, and a low T-score. Regarding remaining risk factors, risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort.