| 1. |
- Askling, Johan, et al.
(author)
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Anti-TNF therapy in RA and risk of malignant lymphomas Relative risks and time-trends in the Swedish Biologics Register
- 2008
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
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Journal article (peer-reviewed)abstract
- Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n = 6604) were identified. A general population comparator (n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365 026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998–2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.
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| 2. |
- Askling, Johan, et al.
(author)
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Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies : does the risk change with the time since start of treatment?
- 2009
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:11, s. 3180-3189
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.METHODS:By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.RESULTS:During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.CONCLUSION:During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
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| 3. |
- Askling, Johan, et al.
(author)
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Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
- 2005
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.METHODS:Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.RESULTS:During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.CONCLUSION:Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
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| 4. |
- Askling, Johan, et al.
(author)
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Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
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Journal article (peer-reviewed)abstract
- OBJECTIVES:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.METHODS:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.RESULTS:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.CONCLUSION:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
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| 5. |
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| 6. |
- Kalha, Curran, et al.
(author)
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Hard x-ray photoelectron spectroscopy : a snapshot of the state-of-the-art in 2020
- 2021
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In: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 0953-8984 .- 1361-648X. ; 33:23
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Research review (peer-reviewed)abstract
- Hard x-ray photoelectron spectroscopy (HAXPES) is establishing itself as an essential technique for the characterisation of materials. The number of specialised photoelectron spectroscopy techniques making use of hard x-rays is steadily increasing and ever more complex experimental designs enable truly transformative insights into the chemical, electronic, magnetic, and structural nature of materials. This paper begins with a short historic perspective of HAXPES and spans from developments in the early days of photoelectron spectroscopy to provide an understanding of the origin and initial development of the technique to state-of-the-art instrumentation and experimental capabilities. The main motivation for and focus of this paper is to provide a picture of the technique in 2020, including a detailed overview of available experimental systems worldwide and insights into a range of specific measurement modi and approaches. We also aim to provide a glimpse into the future of the technique including possible developments and opportunities.
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| 7. |
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| 8. |
- Schaedel, Charlotta, et al.
(author)
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Predictors of deterioration of lung function in cystic fibrosis.
- 2002
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In: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 33:6, s. 483-491
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Journal article (peer-reviewed)abstract
- The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.The severity of pulmonary disease was to some extent predicted by CFTR genotype. Furthermore, the present investigation is the first long-term study showing a significantly more rapid deterioration of lung function in patients with concomitant diabetes mellitus. Besides diabetes mellitus, pancreatic insufficiency and chronic Pseudomonas colonization were found to be negative predictors of pulmonary function. In contrast to several other reports, we found no significant differences in lung function between genders. Patients with pancreatic sufficiency have no or only a slight decline of lung function with age once treatment is started, but an early diagnosis in this group is desirable.
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| 9. |
- Simard, Julia F., et al.
(author)
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Ten years with biologics : to whom do data on effectiveness and safety apply?
- 2011
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In: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 50:1, s. 204-213
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Journal article (peer-reviewed)abstract
- Methods. We identified all adult patients with RA (n = 9612), PsA (n = 1417) and other SpA (n = 1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. Results. Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite < 50% drug retention at 5 years, most patients remained exposed to some biologic. Conclusions. The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.
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| 10. |
- Thorlacius, Guðný Ella, et al.
(author)
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Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome
- 2021
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In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 60:2, s. 837-848
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Journal article (peer-reviewed)abstract
- ObjectivesClinical presentation of primary Sjögren’s syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints.MethodsWe performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls.ResultsWe found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10−62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS.ConclusionTwo subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.
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