| 1. |
- Askling, Johan, et al.
(författare)
-
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
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:11, s. 3180-3189
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Askling, Johan, et al.
(författare)
-
Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas : relative risks and time trends in the Swedish Biologics Register
- 2009
-
Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 0003-4967 .- 1468-2060. ; 68:5, s. 648-653
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 3. |
- Askling, Johan, et al.
(författare)
-
Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
- 2005
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 4. |
- Askling, Johan, et al.
(författare)
-
Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 5. |
- Bengtsson, Karin, 1980, et al.
(författare)
-
Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population : A register-based study from Sweden
- 2018
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:4, s. 541-548
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To describe the incidence of atrioventricular (AV) block II-III, atrial fibrillation (AF), pacemaker implantation (PM) and aortic regurgitation in patients with ankylosing spondylitis (AS), undifferentiated spondyloarthritis (uSpA) and psoriatic arthritis (PsA) compared with the general population (GP) and with each other. Methods A prospective nationwide study with cohorts of patients with AS (n=6448), PsA (n=16 063) and uSpA (n=5190) and a GP (n=2 66 435) cohort, identified in 2001-2009 in the Swedish National Patient and Population registers. Follow-up began on 1 January 2006 and ended at event, death, emigration or 31 December 2012. Age-standardised and sex-standardised incidence rates and hazard ratios (HRs) were calculated. Results The highest incidence rates were noted for AF (5.5-7.4 events per 1000 person-years), followed by PM (1.0-2.0 events per 1000 person-years). HRs for AV block, AF, PM and aortic regurgitation were significantly increased in AS (HRs 2.3, 1.3, 2.1 and 1.9), uSpA (HRs 2.9, 1.3, 1.9 and 2.0) and PsA (HRs 1.5, 1.5, 1.6 and 1.8) compared with the GP cohort. The highest HRs were seen for AV block in male uSpA (HR 4.2) and AS (HR 2.5) compared with GP. Compared with PsA, significantly increased HRs were noted for PM (HR 1.5) in AS and for AV block (HR 1.8) in uSpA. Conclusions Patients with SpA are at increased risk of aortic regurgitation, cardiac rhythm disturbances and, as a probable consequence, also PM. Particularly for AF, the most common arrhythmia, increased caution is warranted, whereas AV block should be looked for especially in men with AS or uSpA.
|
|
| 6. |
- Holmqvist, Marie E., et al.
(författare)
-
Risk of Venous Thromboembolism in Patients With Rheumatoid Arthritis and Association With Disease Duration and Hospitalization
- 2012
-
Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 308:13, s. 1350-1356
-
Tidskriftsartikel (refereegranskat)abstract
- Context Recent reports suggest that rheumatoid arthritis (RA) may be a risk factor for venous thromboembolism (VTE), particularly in conjunction with hospitalization. Using hospitalization data to identify RA and VTE may identify patients when they are at elevated risk for other reasons, obscuring the incompletely understood underlying association between RA and VTE and leading to inappropriate institution or timing of interventions. Objective To estimate risks for VTE in patients with RA, including the relation of these risks to disease duration and hospitalization. Design, Setting, and Patients Prospective, population-based cohort study of 1 prevalent RA cohort (n = 37 856), 1 incident RA cohort (n = 7904), and matched general population comparison cohorts, all from Sweden, with follow-up from 1997 through 2010. Main Outcome Measure First-time VTE. Results Patients with prevalent RA were at greater risk of VTE than the general population (rate, 5.9 [95% CI, 5.1-6.6] vs 2.8 [95% CI, 2.6-3.1] per 1000 person-years (adjusted hazard ratio [HR], 2.0 [95% CI, 1.9-2.2]; P < .001). By the time of RA symptom onset, there was no statistically significant association between a history of VTE and RA (odds ratio, 1.2 [95% CI, 1.0-1.4]; P = .08; 150 events in the RA cohort vs 587 in the comparison cohort). Counting from RA diagnosis, an increased rate in the RA cohort vs the comparison cohort (3.8 [95% CI, 2.5-5.2] vs 2.4 [95% CI, 1.9-2.9] per 1000 person-years; HR, 1.6 [95% CI, 1.1-2.5]; P = .02) was detected within the first year and did not increase further during the first decade. Although rates for VTE following hospitalization were higher, the 1-year rate of VTE per 1000 person-years was not higher in the RA cohort than in the comparison cohort after hospital discharge (11.8 [95% CI, 8.6-15.1] vs 13.1 [11.3-14.8]; HR, 1.0 [95% CI, 0.7-1.4]; P = .90). The rates of VTE increased with age but were largely similar across sex and rheumatoid factor status, as were the HRs for VTE across age, sex, and rheumatoid factor status. Conclusions Compared with the general population, Swedish patients with RA had an elevated risk for VTE that was stable over the first 10 years after diagnosis. Although hospitalization was a risk factor for VTE the first year after discharge, the excess risk was not greater in patients with RA than in the general population.
|
|
| 7. |
|
|
| 8. |
- Holmqvist, Marie E, et al.
(författare)
-
No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis : results from two Swedish population-based rheumatoid arthritis cohorts.
- 2009
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:10, s. 2861-2869
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the relative importance of shared etiologies for rheumatoid arthritis (RA) and ischemic heart disease (IHD) in terms of the well-known increased risk of IHD in patients with RA, by assessing the occurrence of IHD up until the time of the onset of the first symptoms of RA. METHODS: We assessed the prevalence of a history of IHD, myocardial infarction (MI), and angina pectoris before the onset of RA symptoms in 2 large population-based case-control studies. Patients with newly diagnosed RA according to the criteria of the American College of Rheumatology were included as cases. We used data from the Swedish Early Arthritis Register study and the Swedish Epidemiologic Investigation of Rheumatoid Arthritis case-control study and from general population controls. Information on IHD, MI, and angina pectoris was obtained from the nationwide Hospital Discharge Register and from self reports. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) to compare the prevalence of a history of IHD/MI/angina pectoris among patients with RA with that among population controls. RESULTS: We could not detect any increased occurrence of IHD, MI, or angina pectoris before the onset of symptoms of RA, regardless of whether data on IHD were obtained from the Hospital Discharge Register or were self reported. As detected in the Hospital Discharge Register, the OR for IHD overall was 1.0 (95% CI 0.9-1.1), the OR for MI was 1.0 (95% CI 0.9-1.1), and the OR for angina pectoris was 1.0 (95% CI 0.9-1.2). CONCLUSION: Shared risk factors or susceptibilities for RA and IHD are likely to contribute less than RA-related factors to the increased occurrence of IHD in patients with manifest RA. Nonetheless, the existence of shared factors associated with longer latency until the occurrence of IHD cannot be excluded.
|
|
| 9. |
- Simard, Julia F., et al.
(författare)
-
Ten years with biologics : to whom do data on effectiveness and safety apply?
- 2011
-
Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 50:1, s. 204-213
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 10. |
- Raaschou, Pauline, et al.
(författare)
-
Tumor necrosis factor inhibitors and cancer recurrence in Swedish patients with rheumatoid arthritis A nationwide population-based cohort study
- 2018
-
Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 169:5, s. 291-299
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Use of tumor necrosis factor inhibitors (TNFi) in patients with a history of cancer remains a clinical dilemma. Objective: To investigate whether TNFi treatment in rheumatoid arthritis (RA) is associated with increased risk for cancer recurrence. Design: Population-based cohort study based on linkage of nationwide registers. Setting: Sweden. Participants: Patients with RA who started TNFi treatment between 2001 and 2015, after being diagnosed with cancer, and matched patients with RA and a history of the same cancer who had never received biologics. Measurements: The primary outcome was the first recurrence of cancer. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs), taking into account time, cancer type, and whether the cancer was invasive or in situ (or tumor, node, metastasis [TNM] classification system stage in a subset of patients). Results: Among 467 patients who started TNFi treatment (mean time after cancer diagnosis, 7.9 years), 42 had cancer recurrences (9.0%; mean follow-up, 5.3 years); among 2164 matched patients with the same cancer history, 155 had recurrences (7.2%; mean follow-up, 4.3 years) (HR, 1.06 [95% CI, 0.73 to 1.54). Hazard ratios were close to 1 in analyses of patient subsets matched on cancer stage or with similar time from index cancer diagnosis to the start of TNFi treatment, as well as in unmatched analyses. Several CIs had upper limits close to 2. Limitation: The outcome algorithm was partly nonvalidated, and channeling bias was possible if patients with a better index cancer prognosis were more likely to receive TNFi. Conclusion: The findings suggest that TNFi treatment is not associated with increased risk for cancer recurrence in patients with RA, although meaningful risk increases could not be ruled out completely.
|
|
