389 research outputs found
Epidemiological studies of host susceptibility in malignant lymphomas and colorectal cancer
No full textThe aim of this thesis was to investigate the role of host susceptibility in malignant lymphomas and colorectal cancer. Specifically, the associations between infection and malignant lymphomas, skin cancer and survival from subsequent cancer, and the association between inflammatory bowel disease, familial disease, and colorectal cancer were assessed using Swedish population-based and nation-wide registers.To investigate the role of chronic infections in the epidemic increase of non-Hodgkin's lymphomas, 5,199 individuals diagnosed or treated for tuberculosis 1939-1960 were followed-up for cancer occurrence through 1996. Overall, there was a moderately increased risk of nonHodgkin's lymphoma, with particularly elevated risks among patients with severe tuberculosis diagnosed before 1952.The risk of Hodgkin's disease following infectious mononucleosis was assessed in one Swedish cohort of 21,510 individuals hospitalised with infectious mononucleosis 1964-1994, and in one Danish cohort of 17,052 individuals with a positive Paul-Bunnell test 1943-1978. The risk of Hodgkin's disease was more than doubled, increased with age at infectious mononucleosis, decreased with time since infectious mononucleosis, but remained elevated up to 20 years after the infectious mononucleosis. The highest risk was observed in the age-group 15-34 years.The prognostic significance of a history of squamous cell skin cancer was assessed in five cohorts of patients with non-Hodgkin's lymphoma (n=36,629), colon cancer (n=77,039), breast cancer (n=139,767), prostate cancer (n=121,280), or lung cancer (n=60,681). In each cohort, the mortality among patients with a previous registration of squamous cell skin cancer was compared to that of same-site cancer patients without such history. In the cohorts, a history of squamous cell skin cancer was associated with a 20-30% increased risk of death.To assess the significance of familial colorectal cancer and familial inflammatory bowel disease on the risk of colitis-associated colorectal cancer, 19,459 patients with inflammatory bowel disease 1955- 1995 were followed-up for cancer occurrence 1958-1995. Familial colorectal cancer (assessed through record-linkage) was associated with a doubled risk of colitis-associated colorectal cancer, but familial inflammatory bowel disease had no significance.To test the hypothesis of a common genetic determinant for inflammatory bowel disease and colorectal cancer, the risk of colorectal cancer among first-degree relatives of patients with inflammatory bowel disease was assessed. Among 114,102 first-degree relatives, no increased occurrence of colorectal cancer could be detected.The results suggest that tuberculosis and infectious mononucleosis are risk factors for non-Hodgkin's lymphoma and Hodgkin's disease, respectively, that a history of squamous cell skin cancer is a marker of poor survival among patients with cancer, that inflammatory bowel disease and colorectal cancer do not share a common genetic cause, and that familial colorectal cancer (but not familial inflammatory bowel disease) is a risk factor for colitis-associated colorectal cancer.List of scientific papersI. Askling J, Ekbom A (2001). "Risk of non-Hodgkins lymphoma following tuberculosis. " Br J Cancer 84(1): 113-5 https://pubmed.ncbi.nlm.nih.gov/11139323II. Hjalgrim H, Askling J, Sorensen P, Madsen M, Rosdahl N, Storm HH, Hamilton-Dutoit S, Eriksen LS, Frisch M, Ekbom A, Melbye M (2000). "Risk of Hodgkins disease and other cancers after infectious mononucleosis. " J Natl Cancer Inst 92(18): 1522-8 https://pubmed.ncbi.nlm.nih.gov/10995808III. Askling J, Sorensen P, Ekbom A, Frisch M, Melbye M, Glimelius B, Hjalgrim H (1999). "Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer? " Ann Intern Med 131(9): 655-9 https://pubmed.ncbi.nlm.nih.gov/10577327IV. Askling J, Dickman PW, Karlen P, Brostrom O, Lapidus A, Lofberg R, Ekbom A (2001). "Family history as a risk factor for colorectal cancer in inflammatory bowel disease. " Gastroenterology 120(6): 1356-62 (In Print) https://pubmed.ncbi.nlm.nih.gov/11313305V. Askling J, Dickman PW, Karlen P, Brostrom O, Lapidus A, Lofberg R, Ekbom A (2001). "Colorectal cancer rates among first-degree relatives of patients with inflammatory bowel disease: a population-based cohort study. " Lancet 357(9252): 262-6 https://pubmed.ncbi.nlm.nih.gov/11214128</p
Obituary – Anders Ekbom
No full textJonas F Ludvigsson,1 Johan Askling,1 Sven Cnattingius,1 Per Hall,1 Lars Klareskog,1 Olof Nyren,1 John A Baron,2 Henrik Toft Sørensen3 1Karolinska Institutet, Solna, Sweden; 2University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3Aarhus University, Aarhus, DenmarkCorrespondence: Jonas F Ludvigsson, Email [email protected]
Serologic Analysis of Returned Travelers with Fever, Sweden
No full textWe studied 1,432 febrile travelers from Sweden who had returned from malaria-endemic areas during March 2005-March 2008. In 383 patients, paired serum samples were blindly analyzed for influenza and 7 other agents. For 21% of 115 patients with fever of unknown origin, serologic analysis showed that influenza was the major cause.Original Publication: Helena H Askling, Birgitta Lesko, Sirkka Vene, Angerd Berndtson, Per Bjorkman, Jonas Blackberg, Ulf Bronner, Per Follin, Urban Hellgren, Maria Palmerus, Karl Ekdahl, Anders Tegnell and Johan Struwe, Serologic Analysis of Returned Travelers with Fever, Sweden, 2009, EMERGING INFECTIOUS DISEASES, (15), 11, 1805-1808. http://dx.doi.org/10.3201/eid1511.091157 Copyright: National Center for Infectious Diseases http://www.cdc.gov/ncidod/eid/index.htm</p
Does autoimmune thyroid disease affects rheumatoid arthritis disease activity or response to methotrexate?
No full textPublisher's version (útgefin grein)Objective: To investigate if autoimmune thyroid disease (AITD) impacts rheumatoid arthritis (RA) disease activity or response to methotrexate. Methods A nationwide register-based cohort study of 9 004 patients with new-onset RA from the Swedish Rheumatology Quality Register year 2006-2016, with linkage to other nationwide registers to identify comorbidity with AITD defined as thyroxine prescription before RA diagnosis, excluding non-autoimmune causes. We compared RA disease activity using 28-joint Disease Activity Score (DAS28) and its components, and EULAR response, between patients with and without AITD, using logistic regression. Results At diagnosis, patient reported outcome measures (PROMs; patient global, Health Assessment Questionnaire Disability Index and pain) but not objective disease activity measures (erythrocyte sedimentation rate and swollen joint count) were significantly higher (p<0.05 for all PROMs) among RA patients with AITD compared with those without. The level of DAS28 was 5.2 vs 5.1. By contrast, AITD had little influence on EULAR response to methotrexate at 3 months (OR of non/moderate response=0.95, 95% CI 0.8 to 1.1), nor at 6 months. When stratified by age, however, AITD was more common among EULAR non/moderate responders at 3 and 6 months in patients below 45 years resulting in ORs of non/moderate response of 1.44 (0.76-2.76) and 2.75 (1.04-7.28). Conclusion At diagnosis, RA patients with concomitant AITD score worse on patient reported but not on objective RA disease activity measures, while DAS28 was only marginally elevated. The overall chance of achieving a EULAR good response at 3 or 6 months remains unaffected, although among a limited subgroup of younger patients, AITD may be a predictor for an inferior primary response. © Author(s) (or their employer(s))This work was supported by research grants from the Swedish Research Council, the Swedish Cancer Society, the Swedish HeartLung Foundation, Nordforsk, Vinnova and FOREUM. Financial support information: Dr Askling has acted or acts as PI in agreements between Karolinska Institutet and the following entities, mainly related to the safety monitoring of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, Pfizer, Roche, Samsung Bioepis, Sanofi.Peer Reviewe
Risk of neurological adverse events during tumour necrosis factor inhibitor treatment for arthritis:a population-based cohort study from danbio and artis
No full textBackground Tumor necrosis factor alpha inhibitors (TNFi) have successfully been used for the treatment of immune-mediated inflammatory disorders including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) since 1998. However, several case reports and series have indicated that different neurological disorders including multiple sclerosis (MS), inflammatory neuropathies, demyelinating diseases and optic neuritis may be a serious, although rare, adverse event following TNFi treatment. The relationship is complex, as some studies show that RA is protective of MS and vice versa.Objectives To investigate the association between new-onset neurological events following TNFi treatment in arthritis patients compared to non-TNFi-treated arthritis patients from Denmark and Sweden.Methods 40,927/62,702 patients registered with a diagnosis of either RA, AS or PsA in DANBIO/ARTIS between January 1, 2000 and January 20, 2017 were included. Complete follow-up on mortality, emigration and incident neurological diseases suspected to be associated with use of TNFi until May 10, 2017 were obtained by linkage to the Danish and Swedish National Patient Registry and the Civil Registration Systems. Cox proportional hazard models were used to examine the association between use of TNFi and risk of a neurological event.Results The DANBIO/ARTIS arthritis cohorts contributed 612,347 person-years of observation and 221 patients were diagnosed with demyelinating disease or inflammatory neuropathy during follow-up with 117 cases among TNFi-treated patients and 104 cases among non-TNFi-treated patients. TNFi treatment among RA patients was not associated with an increased risk of a neurological event (DANBIO: HR=1.09, 95% Confidence Interval (CI) 0.60-1.99)/(ARTIS:HR=0.83, 95%CI 0.52-1.35) adjusted for age, gender and year of inclusion. However, TNFi-treated PsA and AS patients had an increased risk of neurological events (DANBIO:HR=2.57, 95%CI 1.17-5.65)/(ARTIS:HR=2.17, 95%CI 0.88-5.35). In TNFi-treated PsA/AS patients, 7 cases of inflammatory polyneuropathies were observed in DANBIO/ARTIS respectively versus 1 and 0 cases among non-TNFi treated. In on-drug models, the HR for neurologic events was 1.17 (ARTIS 95% CI: 0.41-3.35) and 1.66 (DANBIO 95% CI: 0.70-3.92) in PsA/AS.Conclusion The use of TNFi for the treatment of arthritis may be associated with increased risk of demyelinating disease or inflammatory neuropathies among patients with PsA and AS. Since these events are rare, larger multicentre studies are warranted to further characterize the risk.Acknowledgement The study is funded by FOREUM, NordForsk and Independent Research Fund DenmarkDisclosure of Interests Tine Iskov Kopp : None declared, Elizabeth Arkema: None declared, René Cordtz: None declared, Bénédicte Delcoigne: None declared, Johan Askling Grant/research support from: Karolinska Institutet (JA) has or has had research agreements with the following pharmaceutical companies, mainly in the context of the ATRIS national safety monitoring programme for rheumatology biologicals: Abbvie, BMS, MSD, Eli Lilly, Pfizer, Roche, Samsung Bioepis, and UCB., Consultant for: Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Lilly, Novartis, and Pfizer., Lene Dreyer Consultant for: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: UCB, MSD, Eli Lilly and Janssen Pharmaceuticals
Anti-TNF therapy and malignancy in patients with rheumatoid arthritis : studies on cancer incidence, recurrence and survival
No full textTumor necrosis factor i nhibitors (TNFi) h ave become a backbone treatment of rheumatoid arthritis (RA). TNF has multiple and incompletely understood functions in tumor biology, and cancer is considered a potential adverse event of TNFi treatment. The overarching aim of this thesis was to investiga te the risk - benefit balance in RA - patients treated with TNFi, focusing on skin cancer, breast cancer progress and post - cancer survival. To put the risks into context we also contrasted RA - patients never treated with biological drugs (biologics - naïve) to th e general population. We used data from medical files, national health and census registers and the RA quality of care register, to define clinically relevant subsets of RA and cancer - related outcomes among them . In study I we investigated the risk o f malignant melanoma and all - site cancer in TNFi - treated RA - patients (1998 - 2010), biologics - naïve RA - patients, and matched general population comparators. We detected a 50% increased risk of invasive malignant melanoma, but no increased risk of in situ mel anoma or all - site cancer among TNFi - treated compared to biologics - naïve RA - patients. In study II we investigated the risk of non squa mous cell cancer (SCC, 1998 - 2011 ) and b asal cell cancer (BCC, 2004 - 2011 ) in TNFi - treated RA - patients, biologics - naïve RA - pa tients, and matched general population comparators. We found a 20% increase in risk of in situ SCC among TNFi - treated compared to biologics - naïve RA - patients, but no increased risk of BCC. In biologics - naïve RA - patients, we detected a doubled risk of SCC, and a 20% increased risk of BCC compared to the general population . In study III we investigated the risk of breast cancer recurrence in 120 female RA - patients who started TNFi treatment (1999 - 2010) on average a decade after diagnosis of breast cancer. As comparator we used 120 biologics - naïve RA - patients with a history of breast cancer, matched on sex, age, year and cancer stage at diagnosis, and residency. We found no difference in risk of recurrent breast cancer and all - cause mortality between the two g roups, after adjusting for breast cancer related prognostic factors. In study IV we investigated the clinical stage at diagnosis, and post - cancer survival of cancers developing during or after TNFi treatment (1999 - 2007), compared to cancers among biologics - naïve RA - patients. We used both a matched and an unmatched approach. No major differences in cancer stage at diagnosis or in post - cancer survival were observed among TNFi - treated RA - patients, compared to biologics - naïve RA - patients with cancer.List of scientific papersI. Pauline Raaschou, Julia F Simard, Marie Holmqvist, Johan Askling for the ARTIS study group. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population-based prospective cohort study from Sweden. BMJ. 2013 Apr; 346, fl939. https://doi.org/10.1136/bmj.f1939. II. Pauline Raaschou, Julia F Simard, Charlotte Asker-Hagelberg, Johan Askling for the ARTIS study group. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of squamous cell and basal cell skin cancer- a nationwide population-based prospective cohort study from Sweden. [Manuscript]III. Pauline Raaschou, Thomas Frisell, Johan Askling for the ARTIS study group. TNF inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis - a nationwide cohort study. Ann Rheum Dis. 2015 Dec;74(12):2137-43. https://doi.org/10.1136/annrheumdis-2014-205745. IV. Pauline Raaschou, Julia F Simard, Martin Neovius, Johan Askling for the ARTIS study group. Does cancer that occurs during or after anti-TNF therapy have a worse prognosis? A national assessment of overall and site-specific cancer survival in rheumatoid arthritis patients treated with biologics. Arthritis & Rheumatism. 2011 Jul; 63(7):1812-22. https://doi.org/10.1002/art.30247. </p
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