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Funding Information: Authorship note: JH and HK are co–first authors. AK and S Mustjoki are co–senior authors. Conflict of interest: OB has received consultancy fees from Novartis, Sanofi, and Amgen. BL is employed by and holds stock in BMS. PB is employed by Terveystalo, has a leadership role at Terveystalo, holds a consultant or advisory role at MSD Oncology, Ipsen, Faron Pharmaceuticals, Oncorena, TILT Biotherapeutics, EUSA Pharma, and Herantis Pharma, and owns stock in TILT Biotherapeutics, Faron Pharmaceuticals, and Terveystalo. MH has received honoraria from Pierre Fabre, Novartis, BMS, Merck Sharp & Dohme (MSD), Roche, Amgen, Sanofi, and Incyte. AK is employed by BMS. S Mustjoki has received honoraria and research funding from BMS, research funding from Novartis, Janpix, and Pfizer, and honoraria from Dren Bio. Copyright: © 2023, Huuhtanen et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Submitted: August 25, 2022; Accepted:January 25, 2023; Published: March 15, 2023. Reference information: J Clin Invest. 2023;133(6):e164809. https://doi.org/10.1172/JCI164809. Funding Information: We are deeply grateful to all the patients who participated in the study and generously contributed samples. This study was supported by the Cancer Foundation Finland, the Sigrid Juselius Foundation, the Signe and Ane Gyllenberg Foundation, the Relander Foundation, State funding for university-level health research in Finland, a Helsinki Institute of Life Sciences Fellow grant, the Academy of Finland (Decision 311081) (grant numbers 314442, 311081, 335432, and 335436), and an investigator-initiated research grant from BMS. JH was supported by the Finnish Hematology Association, the Blood Disease Research Foundation, the Helsinki Institute for Life Science, the Biomedicum Helsinki Foundation, the Finnish Medical Foundation, the K. Albin Johansson Foundation, the Kaute Foundation, the Finnish Cancer Foundation, the Paolo Foundation, and the Emil Aaltonen Foundation. We acknowledge the Turku Bioscience Centre Single-cell Omics Core Facility, the Finnish Functional Genomics Centre, the Institute for Molecular Medicine Finland (FIMM), and Biocenter Finland for infrastructure support and the computational resources provided by the Aalto Science-IT project. We acknowledge Susanna Miettinen and Kjersti Holmsen for providing patients' clinical details and Tiina Kasanen, Hanna Lähteenmäki and Jay Klievink for the processing of study samples. We acknowledge BMS Oncology team for providing clinical trial data. Figure 1 was created with BioRender.com. Funding Information: FUNDING. Cancer Foundation Finland, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, Relander Foundation, State funding for university-level health research in Finland, a Helsinki Institute of Life Sciences Fellow grant, Academy of Finland (grant numbers 314442, 311081, 335432, and 335436), and an investigator-initiated research grant from BMS. Funding Information: We are deeply grateful to all the patients who participated in the study and generously contributed samples. This study was supported by the Cancer Foundation Finland, the Sigrid Juselius Foundation, the Signe and Ane Gyllenberg Foundation, the Relander Foundation, State funding for university-level health research in Finland, a Helsinki Institute of Life Sciences Fellow grant, the Academy of Finland (Decision 311081) (grant numbers 314442, 311081, 335432, and 335436), and an investigator-initiated research grant from BMS. JH was supported by the Finnish Hematology Association, the Blood Disease Research Foundation, the Helsinki Institute for Life Science, the Biomedicum Helsinki Foundation, the Finnish Medical Foundation, the K. Albin Johansson Foundation, the Kaute Foundation, the Finnish Cancer Foundation, the Paolo Foundation, and the Emil Aaltonen Foundation. We acknowledge the Turku Bioscience Centre Single-cell Omics Core Facility, the Finnish Functional Genomics Centre, the Institute for Molecular Medicine Finland (FIMM), and Biocenter Finland for infrastructure support and the computational resources provided by the Aalto Science-IT project. We acknowledge Susanna Miettinen and Kjersti Holmsen for providing patients’ clinical details and Tiina Kasanen, Hanna Lähteenmäki and Jay Klievink for the processing of study samples. We acknowledge BMS Oncology team for providing clinical trial data. Figure 1 was created with BioRender.com. Publisher Copyright: © 2023, Huuhtanen et al. BACKGROUND. Relatlimab plus nivolumab (anti-lymphocyte-activation gene 3 plus anti-programmed death 1 [anti-LAG-3+anti-PD-1]) has been approved by the FDA as a first-line therapy for stage III/IV melanoma, but its detailed effect on the immune system is unknown. METHODS. We evaluated blood samples from 40 immunotherapy-naive or prior immunotherapy-refractory patients with metastatic melanoma treated with anti-LAG-3+anti-PD-1 in a phase I trial using single-cell RNA and T cell receptor sequencing (scRNA+TCRαβ-Seq) combined with other multiomics profiling. RESULTS. The highest LAG3 expression was noted in NK cells, Tregs, and CD8+ T cells, and these cell populations underwent the most significant changes during the treatment. Adaptive NK cells were enriched in responders and underwent profound transcriptomic changes during the therapy, resulting in an active phenotype. LAG3+ Tregs expanded, but based on the transcriptome profile, became metabolically silent during the treatment. Last, higher baseline TCR clonality was observed in responding patients, and their expanding CD8+ T cell clones gained a more cytotoxic and NK-like phenotype. CONCLUSION. Anti-LAG-3+anti-PD-1 therapy has profound effects on NK cells and Tregs in addition to CD8+ T cells. TRIAL REGISTRATION. ClinicalTrials.gov (NCT01968109) FUNDING. Cancer Foundation Finland, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, Relander Foundation, State funding for university-level health research in Finland, a Helsinki Institute of Life Sciences Fellow grant, Academy of Finland (grant numbers 314442, 311081, 335432, and 335436), and an investigator-initiated research grant from BMS.

The majority of registry studies on atopic dermatitis include only patients and diagnoses from specialized healthcare. The aim of this retrospective, real-world cohort study was to evaluate the effect of atopic dermatitis severity on comorbidities and total morbidity, with comprehensive data from both primary and specialty healthcare registries covering the entire Finnish adult population. In total, 124,038 patients were identified (median age 46 years; 68% female) and stratified by disease severity. All regression analyses (median follow-up 7.0 years) were adjusted at a minimum for age, sex, obesity, and educational level. Compared with mild atopic dermatitis, severe atopic dermatitis was significantly associated with multiple morbidities, including neurotic, stress-related and somatoform disorders, abscesses, erysipelas/cellulitis, impetigo, herpes zoster, extragenital herpes, bacterial conjunctivitis, septicaemia, lymphomas, alopecia areata, urticaria, other dermatitis, contact allergy, osteoporosis, and intervertebral disc disorders (p

Background A global My Migraine Voice survey was conducted in 31 countries among 11,266 adults who suffered from ≥4 monthly migraine days (MMD). The aim of this retrospective observational survey-based study was to analyse the country specific results in Finland in order to understand the impact of migraine based on disease severity. Methods The included participants (3%, n = 338/11,266) were stratified by mean MMDs into 4 ≤ MMD n = 133), 8 ≤ MMD n = 139) and MMD ≥ 15 (n = 66) subgroups. Comorbidities, migraine-related emotional burden and impact on daily living and work productivity and activity impairment (WPAI) were assessed. Subgroup analysis on healthcare resource utilization (HCRU) due to migraine was assessed by visits to healthcare practitioners (HCPs) during the past 6 months and by hospitalizations and emergency room (ER) visits during the past 12 months. The group difference was tested using the one-way ANOVA and for categorical variables using the Chi-squared test. The association between HCRU and MMD and number of comorbidities was assessed using negative binomial regression analysis. Results Mean age was 44 years, 93% were women and 67% (n = 227) were employed. Chronic migraine (CM, MMD ≥ 15) was reported in 19.5% of the respondents. The negative impact on daily functioning and emotional burden increased significantly by migraine frequency. Mean number of comorbidities was 2.4, and mean number of HCP visits during the previous 6 months was 5.9. Increase in migraine frequency and comorbidities was associated with higher HCRU. Eighty-eight percent of the respondents reported negative impact on working life and 52% experienced overall work productivity impairment. Over previous month, the mean number of missed working days for all respondents was 2.8 days of which 54% were paid sick leave days, and in CM up to 6.0 days and 30%, respectively. Both absenteeism and presenteeism were higher in the CM group. Conclusions The emotional and functional burden was high, and the societal burden increased by frequency and severity of migraine, as shown by higher HCRU and reduced work productivity. There is a need to improve quality of care in migraine and improve migraine management related issues in both healthcare and society in Finland.