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Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: a cohort study based on nationwide prospectively recorded data from Sweden.

https://arctichealth.org/en/permalink/ahliterature104364
Source
Arthritis Rheumatol. 2014 May;66(5):1282-90
Publication Type
Article
Date
May-2014
Author
K. Hellgren
K E Smedby
C. Backlin
C. Sundstrom
N. Feltelius
J K Eriksson
E. Baecklund
J. Askling
Author Affiliation
Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden.
Source
Arthritis Rheumatol. 2014 May;66(5):1282-90
Date
May-2014
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Antirheumatic Agents - adverse effects - therapeutic use
Arthritis, Psoriatic - drug therapy - epidemiology
Case-Control Studies
Cohort Studies
Female
Humans
Incidence
Lymphoma - epidemiology
Male
Methotrexate - therapeutic use
Middle Aged
Prospective Studies
Registries
Regression Analysis
Retrospective Studies
Risk factors
Spondylitis, Ankylosing - drug therapy - epidemiology
Sulfasalazine - therapeutic use
Sweden - epidemiology
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Young Adult
Abstract
Data on lymphoma risk in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are scarce. This study was undertaken to assess the risk of lymphoma in AS and PsA overall and in relation to therapies, including tumor necrosis factor inhibitor (TNFi), for which lymphoma risks are a concern.
Through the Swedish National Patient Register we assembled nationwide prevalence cohorts of patients with AS (n = 8,707) and patients with PsA (n = 19,283) for whom data were obtained between 2001 and 2010. Each cohort member was matched to 5 population comparator subjects. Linkage with the nationwide Cancer Register identified all lymphomas recorded from 2001 to 2010. Through the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]), we identified patients exposed to TNFi in the AS cohort (n = 1,908) and the PsA cohort (n = 2,605) before lymphoma diagnosis. Hazard ratios (HRs) for lymphoma were estimated by Cox regression. Crude incidences of lymphoma in TNFi-exposed and TNFi-naive patients were compared.
For AS patients, the HR of having lymphoma versus the general population was 0.9 (95% confidence interval [95% CI] 0.5-1.6) (14 lymphomas). For PsA patients, the corresponding HR was 1.2 (95% CI 0.9-1.7) (45 lymphomas). For PsA patients treated with methotrexate and/or sulfasalazine, the HR of having lymphoma was 1.7 (95% CI 1.0-3.1). The numbers and incidence of lymphoma were not materially different in TNFi-exposed versus TNFi-naive AS and PsA patients, although the numbers of lymphomas were small.
In contrast to rheumatoid arthritis, the average risks of lymphoma in AS or PsA are not elevated, although increased risks in a subset of PsA patients cannot be excluded. Our findings indicate that TNFi does not affect the risk of lymphoma in AS or in PsA.
PubMed ID
24782185 View in PubMed
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Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome.

https://arctichealth.org/en/permalink/ahliterature101921
Source
Genes Immun. 2011 Mar;12(2):100-9
Publication Type
Article
Date
Mar-2011
Author
G. Nordmark
G. Kristjansdottir
E. Theander
S. Appel
P. Eriksson
L. Vasaitis
M. Kvarnström
N. Delaleu
P. Lundmark
A. Lundmark
C. Sjöwall
J G Brun
M V Jonsson
E. Harboe
L G Gøransson
S J Johnsen
P. Söderkvist
M-L Eloranta
G. Alm
E. Baecklund
M. Wahren-Herlenius
R. Omdal
L. Rönnblom
R. Jonsson
A-C Syvänen
Author Affiliation
Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Gunnel.Nordmark@medsci.uu.se
Source
Genes Immun. 2011 Mar;12(2):100-9
Date
Mar-2011
Language
English
Publication Type
Article
Keywords
B-Lymphocytes - immunology
Case-Control Studies
Cohort Studies
Female
Genetic Predisposition to Disease
Humans
Interferon Regulatory Factors - genetics
Interleukin-6 - genetics
Lymphocyte Activation
Male
Middle Aged
Norway
OX40 Ligand - genetics
Polymorphism, Single Nucleotide
Protein-Tyrosine Kinases - genetics
STAT4 Transcription Factor - genetics
Sjogren's Syndrome - enzymology - genetics - immunology
Sweden
Trans-Activators - genetics
Abstract
We performed a candidate gene association study in 540 patients with primary Sj?gren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 ? 10(-5), OR 1.68, the family with sequence similarity 167 member A-B-lymphoid tyrosine kinase (FAM167A-BLK) locus, P=4.7 ? 10(-4), OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 ? 10(-4), OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
PubMed ID
20861858 View in PubMed
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Do steroids increase lymphoma risk? A case-control study of lymphoma risk in polymyalgia rheumatica/giant cell arteritis.

https://arctichealth.org/en/permalink/ahliterature17063
Source
Ann Rheum Dis. 2005 Dec;64(12):1765-8
Publication Type
Article
Date
Dec-2005
Author
J. Askling
L. Klareskog
H. Hjalgrim
E. Baecklund
M. Björkholm
A. Ekbom
Author Affiliation
Clinical Epidemiology Unit M9:01, Department of Medicine, Karolinska University Hospital Solna, SE-171 77 Stockholm, Sweden. johan.askling@medks.ki.se
Source
Ann Rheum Dis. 2005 Dec;64(12):1765-8
Date
Dec-2005
Language
English
Publication Type
Article
Keywords
Aged
Antirheumatic Agents - adverse effects - therapeutic use
Epidemiologic Methods
Female
Glucocorticoids - adverse effects - therapeutic use
Hodgkin Disease - chemically induced - epidemiology
Humans
Leukemia, Lymphocytic, Chronic - chemically induced - epidemiology
Lymphoma - chemically induced - epidemiology
Lymphoma, Non-Hodgkin - chemically induced - epidemiology
Male
Middle Aged
Polymyalgia Rheumatica - drug therapy
Research Support, Non-U.S. Gov't
Sweden - epidemiology
Temporal Arteritis - drug therapy
Abstract
BACKGROUND: Recent studies indicate increased risks of malignant lymphomas among individuals treated with corticosteroids, but have not taken into account the underlying reasons for steroid use, so the increased risks might be attributable to the underlying disease or concomitant treatments other than steroids. Polymyalgia rheumatica (PMR) and temporal arteritis (giant cell arteritis, GCA) are common inflammatory conditions treated with steroids as single immunosuppressive therapy, but data on lymphoma risk in GCA/PMR are limited. OBJECTIVE: To assess the risk of lymphoma associated with steroid treatment of GCA/PMR. METHODS: The association between GCA/PMR and malignant lymphomas (overall, and separately for non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic lymphatic leukaemia) was examined in a nationwide, population based, case-control study of 42,676 lymphoma cases and 78,487 matched population controls, using prospectively recorded data on lymphomas from the Swedish cancer register 1964-2000 and data on pre-lymphoma hospital admissions for GCA/PMR from the Swedish inpatient register 1964-2000. Odds ratios (OR) associated with a pre-lymphoma hospital admission for GCA/PMR were calculated using conditional logistic regression. RESULTS: 153 lymphoma cases and 345 population controls had a history of GCA/PMR, resulting in an overall OR for malignant lymphomas of 0.81 (95% confidence interval, 0.67 to 0.98). The OR varied little with lymphoma type, sex, age, and calendar period. The OR for GCA was 0.67 (0.48 to 0.98) and for PMR, 0.83 (0.67 to 1.04). CONCLUSIONS: Treated GCA is not associated with increased lymphoma risks, which suggests that even at considerable cumulative doses, steroids may not appreciably increase lymphoma risk.
PubMed ID
15843445 View in PubMed
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Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists.

https://arctichealth.org/en/permalink/ahliterature13750
Source
Ann Rheum Dis. 2005 Oct;64(10):1414-20
Publication Type
Article
Date
Oct-2005
Author
J. Askling
C M Fored
E. Baecklund
L. Brandt
C. Backlin
A. Ekbom
C. Sundström
L. Bertilsson
L. Cöster
P. Geborek
L T Jacobsson
S. Lindblad
J. Lysholm
S. Rantapää-Dahlqvist
T. Saxne
L. Klareskog
N. Feltelius
Author Affiliation
Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. johan.askling@medks.ki.se
Source
Ann Rheum Dis. 2005 Oct;64(10):1414-20
Date
Oct-2005
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Antirheumatic Agents - adverse effects - therapeutic use
Arthritis, Rheumatoid - drug therapy - epidemiology
Biological Response Modifiers - adverse effects - therapeutic use
Epidemiologic Methods
Female
Hematologic Neoplasms - chemically induced - epidemiology
Humans
Leukemia - chemically induced - epidemiology
Lymphoma - chemically induced - epidemiology
Male
Middle Aged
Research Support, Non-U.S. Gov't
Sweden - epidemiology
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Abstract
BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. OBJECTIVE: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. METHODS: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. RESULTS: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. CONCLUSION: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.
PubMed ID
15843454 View in PubMed
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Pediatric Organ Transplantation and Risk of Premalignant and Malignant Tumors in Sweden.

https://arctichealth.org/en/permalink/ahliterature99736
Source
Am J Transplant. 2011 Jan;11(1):146-151
Publication Type
Article
Date
Jan-2011
Author
J F Simard
E. Baecklund
A. Kinch
C. Brattström
A. Ingvar
D. Molin
J. Adami
P. Fernberg
H. Wilczek
A. Ekbom
K E Smedby
Author Affiliation
Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden Department of Medical Sciences, Section of Rheumatology Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden Department of Transplantation Surgery, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, Uppsala University, Uppsala, Sweden Department of Oncology, Karolinska University Hospital Solna, Stockholm, Sweden.
Source
Am J Transplant. 2011 Jan;11(1):146-151
Date
Jan-2011
Language
English
Publication Type
Article
Abstract
Increased cancer risks are well documented in adult organ transplant recipients. However, the spectrum of malignancies and risk in the pediatric organ transplant population are less well described. We identified all solid organ transplanted patients aged
PubMed ID
21199354 View in PubMed
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Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased?

https://arctichealth.org/en/permalink/ahliterature284133
Source
Arthritis Rheumatol. 2017 Apr;69(4):700-708
Publication Type
Article
Date
Apr-2017
Author
K. Hellgren
E. Baecklund
C. Backlin
C. Sundstrom
K E Smedby
J. Askling
Source
Arthritis Rheumatol. 2017 Apr;69(4):700-708
Date
Apr-2017
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Arthritis, Rheumatoid - complications
Cohort Studies
Female
Humans
Lymphoma - epidemiology - etiology
Male
Middle Aged
Risk assessment
Sweden - epidemiology
Young Adult
Abstract
Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, this study was undertaken to assess whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes.
We identified 12,656 cases of incident RA in the Swedish Rheumatology Quality Register 1997-2012 and obtained information on therapy and inflammatory activity during the first year after diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas, including subtypes, were identified. We assessed hazard ratios (HRs) using Cox regression.
Overall, the HR for lymphoma was increased in RA, to 1.6 (95% confidence interval [95% CI] 1.2-2.1). Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the first year after RA diagnosis nor ever use of tumor necrosis factor inhibitors (TNFi) increased lymphoma risk (HR 0.9 [95% CI 0.4-1.9]). Use of oral corticosteroids the first year after RA diagnosis was associated with a reduced risk (HR 0.5 [95% CI 0.3-0.9]). Inflammatory activity during the first year after RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic leukemia occurred less frequently, and Hodgkin's lymphoma occurred more frequently, in RA patients than in the general population.
The average lymphoma risk in recently diagnosed RA is similar in magnitude to that reported in historical cohorts. Standard antirheumatic treatment including TNFi did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.
PubMed ID
27992692 View in PubMed
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Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists.

https://arctichealth.org/en/permalink/ahliterature13754
Source
Ann Rheum Dis. 2005 Oct;64(10):1421-6
Publication Type
Article
Date
Oct-2005
Author
J. Askling
C M Fored
L. Brandt
E. Baecklund
L. Bertilsson
N. Feltelius
L. Cöster
P. Geborek
L T Jacobsson
S. Lindblad
J. Lysholm
S. Rantapää-Dahlqvist
T. Saxne
L. Klareskog
Author Affiliation
Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. johan.askling@medks.ki.se
Source
Ann Rheum Dis. 2005 Oct;64(10):1421-6
Date
Oct-2005
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Antirheumatic Agents - adverse effects - therapeutic use
Arthritis, Rheumatoid - drug therapy - epidemiology
Biological Response Modifiers - adverse effects - therapeutic use
Epidemiologic Methods
Female
Humans
Male
Middle Aged
Neoplasms - chemically induced - epidemiology
Research Support, Non-U.S. Gov't
Sweden - epidemiology
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Abstract
BACKGROUND: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. OBJECTIVE: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. METHODS: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. RESULTS: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. CONCLUSION: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.
PubMed ID
15829572 View in PubMed
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Time trends in risk and risk determinants of non-Hodgkin lymphoma in solid organ transplant recipients.

https://arctichealth.org/en/permalink/ahliterature131717
Source
Am J Transplant. 2011 Nov;11(11):2472-82
Publication Type
Article
Date
Nov-2011
Author
P. Fernberg
G. Edgren
J. Adami
A. Ingvar
R. Bellocco
G. Tufveson
P. Höglund
A. Kinch
J F Simard
E. Baecklund
B. Lindelöf
Y. Pawitan
K E Smedby
Author Affiliation
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. pia.fernberg@ki.se
Source
Am J Transplant. 2011 Nov;11(11):2472-82
Date
Nov-2011
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Antilymphocyte Serum - adverse effects
Case-Control Studies
Cohort Studies
Female
Follow-Up Studies
Humans
Immunosuppressive Agents - therapeutic use
Kidney Transplantation - adverse effects
Lymphoma, Non-Hodgkin - epidemiology
Male
Middle Aged
Risk
Sweden - epidemiology
T-Lymphocytes - immunology
Transplants - adverse effects
Abstract
Organ transplantation increases risk of non-Hodgkin lymphoma (NHL), but long-term risk and time trends have seldom been evaluated. Immunosuppressive drug load is an important risk determinant, but the details are unclear. We studied NHL risk in a nationwide Swedish cohort of 11 081 graft recipients transplanted 1970-2008. Relative risks (RRs) were estimated within the cohort and versus the general population by age, sex, follow-up time and calendar period. NHL risk was also assessed by cumulative and average doses of immunosuppressive treatments in a nested case-control design throughout 1997 using conditional logistic regression. We observed 153 NHL cases during 97 853 years of follow-up. Compared with the general population, NHL risk was eightfold increased (RR 7.9; 95% confidence interval [CI] 6.6-9.4), and increased risks persisted after =15 years of follow-up among kidney (6.1; 95% CI 3.5-10) and nonkidney recipients (44; 14-103). Among nonkidney recipients, NHL risk was lower in the 2000s compared with the 1990s (0.5; 95% CI 0.3-1.0; p = 0.04). A high average dose of antithymocyte immunoglobulin (ATG) conferred an eightfold increased risk of NHL (OR 8.5; 95% CI 1.9-38). To conclude, posttransplant NHL risk decreased during the last decade among nonkidney recipients, possibly because of a more careful use of ATG, the introduction of new drugs, or both.
PubMed ID
21883909 View in PubMed
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8 records – page 1 of 1.