Benefit of measuring vedolizumab concentrations in inflammatory bowel disease patients in a real-world setting

Objectives We set out to determine the reasons for serum vedolizumab (VDZ) trough concentration (TC) measurements in inflammatory bowel disease (IBD) patients and to evaluate treatment modifications after therapeutic drug measurement (TDM). We also evaluated the effect of increased dosing on patients' response to VDZ therapy. Methods We performed a retrospective cohort study of IBD patients who received VDZ therapy at Helsinki University Hospital and whose VDZ levels were measured between June 2014 and December 2018. Results Altogether, 90 patients (32 Crohn's disease and 58 ulcerative colitis) and 141 VDZ TC measurements were included. 24.1% of measurements took place during induction and 75.9% during the maintenance phase. During induction, 64.7% reached the target TC >20 mu g/ml. During maintenance therapy, 82.2% of VDZ TCs were within or exceeded the suggested target range of 5-15 mu g/ml. Reasons for TDM were: secondary nonresponse (44.0%), assessment of adequate VDZ TC (25.5%), primary nonresponse (12.8%), adverse events (6.4%), and other (11.3%). No treatment changes occurred after 60.3% of VDZ measurements. Increased dose frequency was used after 25.5% of VDZ measurements and 33.3% of these patients experienced improvement. Altogether, 31 (34.4%) patients discontinued the therapy due to inadequate treatment response. No anti-vedolizumab antibodies were detected. Conclusions During the maintenance of VDZ therapy, the majority of VDZ TCs were within the suggested range. Measurement of VDZ TC did not lead to any treatment changes in two-thirds of patients. Dose optimization occurred in a quarter of patients and a third of them benefited from it.Peer reviewe

Rintasyövän neoadjuvanttihoidon toteutuminen ja tulokset

publishedVersionPeer reviewe

Physicians discuss the risks of smoking with their patients, but seldom offer practical cessation support

Abstract Background Our aim was to study the smoking cessation-related 1) attitudes & experiences and 2) consultation practices of Finnish physicians and to determine if there is a relationship between the two. Methods An online survey on smoking cessation was sent to 39 % of all Finnish physicians, with emphasis on physicians working in fields relevant to smoking cessation. A total of 1141 physicians (response rate 15 %) responded to the online survey, 53 % of whom were employed in primary health care. A total of 1066 respondents were eligible for the analysis. The questionnaire included questions on the physician’s own smoking status, their attitudes and experiences on smoking cessation, and the implementation of smoking cessation in clinical practice. Two sub-scales concerning smoking-related consultation activities were constructed: one for conversation, and another for practical actions. Results The most common consultation activities (respondents who reported doing the following actions “nearly always”) were asking how much the patient smokes (65 %), marking smoking status in patient records (58 %) and recommending quitting to the patient (55 %). The least common activity was prescribing withdrawal medication (4 %). Primary care physicians were more active than those working in secondary health care in nearly all activities mapped. A positive attitude and experiences on smoking cessation were associated with actively offering withdrawal support. Those who were familiar with the local treatment guidelines for tobacco addiction were 30 % more active in offering practical cessation help to their patient. The respondents were more active in discussing smoking with their patients than in offering practical cessation help. Conclusion Physicians offer their patients practical cessation support relatively infrequently. Practical cessation calls for continuous education of physicians about the nature of tobacco and nicotine addiction, the role of smoking as a risk factor for various diseases, and the practical measures needed for smoking cessation. Secondary care physicians should acknowledge the authority they pose toward smoking patients

Effectiveness of mepolizumab in patients with severe eosinophilic asthma : results from real-world clinical practice in Finland

Objectives Mepolizumab treatment provides clinical benefits for patients with severe eosinophilic asthma in randomized controlled trials. However, real-world data for patients in Finland are lacking. Methods This retrospective, non-interventional, chart review study included patients with severe eosinophilic asthma >= 18 years of age initiating mepolizumab between January 1, 2016 and January 31, 2019 at three investigational sites in Finland. Patient characteristics during the 12 months prior to mepolizumab initiation (baseline) were recorded and primary and secondary endpoints included changes from baseline in disease outcomes during follow-up (up to 24 months following mepolizumab initiation). Exploratory endpoints included association between patient characteristics and exacerbation frequency/annual cumulative oral corticosteroid (OCS) dose. Results Overall, 51 patients were included (mean 17.8 months follow-up). At baseline, patients had a mean (standard deviation) blood eosinophil count of 550 (410) cells/mu L; impaired lung function and health-related quality of life; poor symptom control; frequent exacerbations (2.78/year); and 90% were using OCS (mean: 9.80 mg/day). At the last follow-up visit, reductions from baseline in blood eosinophil count (84%) and fractional exhaled nitric oxide (26%) were observed, as were improvements in Asthma Quality of Life Questionnaire score (36%) and Asthma Control Test score (34%). Reductions in the mean number of annual exacerbations (82%) and mean daily OCS dose (39%) were also seen; reductions were observed even after adjustment for several patient baseline characteristics. Conclusions Results are consistent with previous randomized clinical trials, indicating that Finnish patients experience clinically relevant improvements when treated with mepolizumab in real-world clinical practice.Peer reviewe

Treatment Patterns and Outcomes in a Cohort of Finnish NSCLC Patients with ALK Rearrangement Reflect Rapid Evolution in Treatment Practices

Background: In Finland approximately 2,500 people are diagnosed with lung cancer annually. A small proportion of non-small cell lung cancer (NSCLC) patients (3–7%) have tumorigenic rearrangement of the anaplastic lymphoma kinase (ALK) gene (ALK-positive). ALK tyrosine kinase inhibitors (TKI) are the standard of care for these patients, showing superior efficacy compared to traditional chemotherapy (CT). Due to the rapid development of novel next-generation ALK TKIs, treatment practices have undergone substantial changes. In Finnish real-life clinical practice the choice of treatment is largely determined by the reimbursement status of available drugs. We set out to assess the prevailing treatment practices and outcomes for NSCLC patients harbouring ALK rearrangement. Materials and methods: This was a retrospective, non-interventional, two-centre study. Adult NSCLC patients from the Hospital District of Southwest Finland and ALK-positive NSCLC patients from the Hospital District of Helsinki and Uusimaa diagnosed between 2013–2017 were included. Patients were followed until death or until the end of study period (May 2018). Data were extracted retrospectively from electronic health records from University Hospital data lakes. Results: A total of 1,260 patients were included, of which 60 were ALK-positive. ALK TKI regimens were mainly received in second and later lines of treatment. Median time-to-next treatment (TTNT) during ALK TKI treatment was 11.0 months (95% CI; 5.0–35.0) and during CT treatment 7.0 months (5.0–11.0) when assessed irrespective of treatment line (p=0.08). Patients who received at least one ALK TKI treatment regimen during the follow-up had median overall survival (OS) of 33.6 months (16.9–NR) from diagnosis vs. 11.5 months (4.6–NR) in patients who were treated with CT regimens only (p=0.054). Conclusions: ALK-positive patients benefit from treatment with ALK targeting agents in real-world clinical practice. </p

Effectiveness of mepolizumab in patients with severe eosinophilic asthma: results from real-world clinical practice in Finland

Objectives: Mepolizumab treatment provides clinical benefits for patients with severe eosinophilic asthma in randomized controlled trials. However, real-world data for patients in Finland are lacking.Methods: This retrospective, non-interventional, chart review study included patients with severe eosinophilic asthma ≥18 years of age initiating mepolizumab between January 1, 2016 and January 31, 2019 at three investigational sites in Finland. Patient characteristics during the 12 months prior to mepolizumab initiation (baseline) were recorded and primary and secondary endpoints included changes from baseline in disease outcomes during follow-up (up to 24 months following mepolizumab initiation). Exploratory endpoints included association between patient characteristics and exacerbation frequency/annual cumulative oral corticosteroid (OCS) dose.Results: Overall, 51 patients were included (mean 17.8 months follow-up). At baseline, patients had a mean (standard deviation) blood eosinophil count of 550 (410) cells/µL; impaired lung function and health-related quality of life; poor symptom control; frequent exacerbations (2.78/year); and 90% were using OCS (mean: 9.80 mg/day). At the last follow-up visit, reductions from baseline in blood eosinophil count (84%) and fractional exhaled nitric oxide (26%) were observed, as were improvements in Asthma Quality of Life Questionnaire score (36%) and Asthma Control Test score (34%). Reductions in the mean number of annual exacerbations (82%) and mean daily OCS dose (39%) were also seen; reductions were observed even after adjustment for several patient baseline characteristics.Conclusions: Results are consistent with previous randomized clinical trials, indicating that Finnish patients experience clinically relevant improvements when treated with mepolizumab in real-world clinical practice.</p

Real-world treatment outcomes and safety of natalizumab in Finnish multiple sclerosis patients

Objectives: The primary objective was to evaluate long-term treatment persistence and safety of natalizumab in Finnish multiple sclerosis patients. The secondary objectives were to assess patient characteristics, use of natalizumab-related safety protocol, and treatment persistence in patients with different anti-John Cunningham virus antibody statuses (John Cunningham virus status). Materials & Methods: All adult multiple sclerosis patients in the Finnish multiple sclerosis register who started natalizumab between 1/2006 and 12/2018 were included in this study and followed retrospectively until treatment discontinuation or end of follow-up (12/2019). Results: In total, 850 patients were included. Median duration of natalizumab treatment was 7.8 years in John Cunningham virus negative (n = 229) and 2.1 years in John Cunningham virus positive patients (n = 115; p < 0.001). The most common cause for treatment discontinuation was John Cunningham virus positivity. After natalizumab discontinuation, patients who had a washout duration of less than 6 weeks had fewer relapses during the first 6 months (p = 0.012) and 12 months (p = 0.005) compared with patients who had a washout duration of over 6 weeks. During the median follow-up of 3.6 years, 76% of patients remained stable or improved on their Expanded Disability Status Scale. Conclusions: Treatment persistence was very high among John Cunningham virus negative patients. The study supports long-term effectiveness of natalizumab and a washout duration of less than 6 weeks after discontinuation.Peer reviewe

Hemofilian hoito ja kustannukset Suomessa

Lähtökohdat Hemofilia on harvinainen verenvuototauti. Potilaat suositellaan hoidettavan verenvuototautien hoitoon erikoistuneissa keskuksissa. HemoHEOR-tutkimuksessa kartoitimme aikuisten potilaiden hoidon toteutumista ja kustannuksia Suomen yliopistosairaaloissa.Menetelmät Tiedot yliopistosairaaloissa hoidossa olleiden täysi-ikäisten A- ja B-hemofiliapotilaiden (n = 168) terveyspalvelu- ja lääkekäytöstä sekä lääkemääräyksistä kerättiin potilaskertomuksista. Hoidon suorat kustannukset arvioitiin lääkkeiden tukkumyyntihintojen ja terveydenhuollon yksikkökustannusten perusteella.Tulokset Vuosien 2012–16 aikana arviolta 72 % aikuisista A-hemofilia- ja 67 % B-hemofiliapotilaista oli hoidossa yliopistosairaaloissa. Verenvuotojen vuosittaisen määrän mediaani oli aineistossa pieni, eikä neljäsosalla hemofiliapotilaista ollut vuotoja tutkimusjakson aikana. Enemmän kuin 80 % potilaista sai hyytymistekijäkorvaushoitoa, joka muodosti noin 97 % hemofilian hoidon suorista vuosittaisista kokonaiskustannuksista.Päätelmät Hemofilian hoidon tulokset suomalaisissa yliopistosairaaloissa ovat kansainvälisesti verrattuna erinomaisia ja hoitomuodon potilaskohtainen valinta onnistunutta. Potilaiden ohjaamista keskitetyn hoidon piiriin on edelleen tehostettava.</p

Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised

Tämä artikkeli ei ole avattavissa lehden sivuilta, koska linkit ja DOI vievät väärään artikkeliin samoin PDF sen ohessa. Kustantajalle ilmoitettu ja pyydetty korjausta.Abstract Background: Twin and family studies have indicated a strong genetic component in autism spectrum disorders, and genetic studies have revealed highly heterogeneous risk factors. The range and severity of the symptom presentation also vary in the spectrum. Thus, symptom-based phenotypes are putatively more closely related to the underlying biology of autism than the end-state diagnosis. Methods: We performed principal component analysis on Autism Diagnostic Interview-Revised algorithm for 117 Finnish families and 594 families from the Autism Genetic Research Exchange (AGRE). The resulting continuous component scores were used as quantitative phenotypes in family-based association analysis. In addition, K-means clustering was performed to cluster and visualize the results of the PCA. Unaffected siblings were included in the study. Results: The components were interpreted as Social Component (SC), communication component and Restricted and Stereotyped Behavior Component (RSBC). K-means clustering showed that, especially in SC, the range of the symptom severity was increased by the siblings. The association of neuroligin 1 with SC was increased, compared to a previous study where only the end-state diagnosis was used. In RSBC, the range of the symptom severity of siblings overlapped greatly with that of patients, which could explain why no association of reelin was found in previous studies in which only the end-state diagnosis was used, but a significant association of reelin with RSBC was now found in the Finnish families (Bonferroni-corrected p=0.029 for rs362644). Although, the Finnish sample is isolated and genetically very homogeneous, compared to the heterogeneous background of AGRE families, many single-nucleotide polymorphisms in reelin, showed modest association with RSBC in the AGRE sample, too. Conclusions: This study demonstrates how the quantitative phenotypes can affect the association analyses, and yields further support to the use of siblings in the study of complex neuropsychiatric disorders.Peer reviewe