scholarly journals Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly

Rheumatology ◽  
2010 ◽  
Vol 50 (1) ◽  
pp. 124-131 ◽  
Author(s):  
J. B. Galloway ◽  
K. L. Hyrich ◽  
L. K. Mercer ◽  
W. G. Dixon ◽  
B. Fu ◽  
...  
Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Katie Bechman ◽  
Kapil Halai ◽  
Sam Norton ◽  
Andrew P Cope ◽  
Kimme L Hyrich ◽  
...  

Abstract Background Patients with rheumatoid arthritis (RA) are at an increased risk of infection. Most attention has been given to serious infections, but these are the tip of the iceberg. Non-serious infections (NSI) are far more frequent, and although not life-threatening, have potential to impact treatment outcomes (drug survival) and quality of life. Our objective was to describe frequency of NSI and compare incidence of NSI by biologic drug within the British Society for Rheumatology Biologics Register (BSRBR-RA). Methods The BSRBR-RA is a prospective observational cohort study. NSI was identified as not requiring hospitalisation, intravenous therapy or leading to disability or death. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered ‘at risk’ from the date of commencing biologic treatment for 3 years. Drug exposure was defined by agent; TNF inhibitor, IL-6 inhibitor, anti-CD20 or csDMARD only. To account for a high frequency of events, a multiple-failure Cox model was used. Multivariable adjustment included age, gender, DAS28-ESR, HAQ-DI, disease duration, smoking, steroid usage, year recruited to BSRBR-RA, line of biologic therapy and cumulative infection number. Results There were 17,304 NSI in 10,099 patients, with an event rate of 27.0 per year (95% CI 26.6 to 27.4). Increasing age, female gender, comorbidity burden, corticosteroid therapy, DAS28 and HAQ-DI were associated with an increased risk of NSI. The rate of NSI was numerically lowest with csDMARDs. Compared to TNFi, IL-6 inhibitor had a higher risk of NSI, whilst the csDMARD cohort had a lower risk. Between the TNFi agents, adalimumab had a higher risk than etanercept (Table 1). Conclusion These results confirm that NSI is a frequent occurrence for patients, which historically has received little attention in research literature. The data suggest biologics increase the risk of NSI, especially IL-6 inhibition. Whilst unmeasured confounding must be considered, the magnitude of effects are large and it seems likely that a causal link between targeted immunosuppression and NSI risk exists. Further research is needed to understand the impact of NSI on clinical outcomes including drug survival and quality of life. Disclosures K. Bechman: None. K. Halai: None. S. Norton: None. A.P. Cope: None. K.L. Hyrich: Honoraria; AbbVie paid to the institution and grant income from Pfizer and Bristol-Myers Squibb for activities outside of this work. J.B. Galloway: Honoraria; for speaking or attending conferences from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Pfizer and Union Chimique Belge.


2014 ◽  
Vol 74 (6) ◽  
pp. 1087-1093 ◽  
Author(s):  
Louise K Mercer ◽  
Mark Lunt ◽  
Audrey L S Low ◽  
William G Dixon ◽  
Kath D Watson ◽  
...  

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk.ObjectivesTo compare the risk of solid cancer in patients with RA treated with TNFi to that in patients treated with non-biologic (synthetic) disease modifying antirheumatic drugs (sDMARDs).MethodsPatients with a physician diagnosis of RA enrolled in the British Society for Rheumatology Biologics Register, a national prospective cohort study established in 2001 to monitor the long-term safety of TNFi, were followed via record linkage with the national cancer registries until first solid cancer, death, for 5 years, or until 2011. Rates of solid cancers in 11 767 patients without prior cancer who received TNFi were compared to those in 3249 patients without prior cancer treated with sDMARDs.Results427 solid cancers were reported in 52 549 patient-years follow-up for the TNFi group (81 (95% CI 74 to 89) per 10 000 patient-years) and 136 cancers were reported in 11 672 patient-years in the sDMARD cohort (117 (95% CI 98 to 138) per 10 000 patient-years). After adjusting for differences in baseline characteristics there was no difference in risk of solid cancer for TNFi compared to sDMARD treated patients: HR 0.83 (95% CI 0.64 to 1.07). There was no difference in the relative risk of cancer for any of the individual TNFi drugs.ConclusionsThe addition of TNFi to sDMARD does not alter the risk of cancer in RA patients selected for TNFi in the UK.


Rheumatology ◽  
2011 ◽  
Vol 50 (7) ◽  
pp. 1341-1342 ◽  
Author(s):  
J. B. Galloway ◽  
K. L. Hyrich ◽  
L. K. Mercer ◽  
W. G. Dixon ◽  
K. D. Watson ◽  
...  

2016 ◽  
Vol 76 (3) ◽  
pp. 497-503 ◽  
Author(s):  
Louise K Mercer ◽  
James B Galloway ◽  
Mark Lunt ◽  
Rebecca Davies ◽  
Audrey L S Low ◽  
...  

ObjectivesPatients with rheumatoid arthritis (RA) are at increased risk of lymphoma compared with the general population. There are concerns that tumour necrosis factor inhibitors (TNFi) may exacerbate this risk. However, since the excess risk of lymphoma in RA is related to the cumulative burden of inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the burden of inflammation. The aim of this study was to compare the risk of lymphoma in subjects with RA treated with TNFi with those treated with non-biological therapy.MethodsSubjects diagnosed by a rheumatologist with RA enrolled in the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective cohort study, were followed until first lymphoma, death or until 30 November 2013. Rates of lymphoma in the TNFi and non-biological-treated cohorts were compared using Cox regression.Results11 931 TNFi-treated patients were compared with 3367 biological-naive patients. 84 lymphomas (88 (95% CI 70 to 109) per 100 000 person-years) were reported in the TNFi cohort and 30 lymphomas (154 (95% CI 104 to 220)) in the biological-naive cohort. After adjusting for differences in baseline characteristics, there was no difference in the risk of lymphoma for the TNFi versus the biological-naive group: HR 1.00 (95% CI 0.56 to 1.80). No risk differences were observed for individual TNFi.ConclusionsIn medium-term follow-up, there is no evidence that tumour necrosis factor inhibition influences the risk of lymphoma over the background risk in subjects with RA.


2009 ◽  
Vol 69 (3) ◽  
pp. 522-528 ◽  
Author(s):  
W G Dixon ◽  
K L Hyrich ◽  
K D Watson ◽  
M Lunt ◽  
J Galloway ◽  
...  

BackgroundThe risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF) therapy, with a proposed differential risk between the anti-TNF drugs etanercept (ETA), infliximab (INF) and adalimumab (ADA).ObjectiveTo compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity.MethodsData from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504 ADA) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs.ResultsTo April 2008, 40 cases of TB were reported, all in the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA (144 events/100 000 person-years) and INF (136/100 000 person-years) than for ETA (39/100 000 person-years). After adjustment, the incidence rate ratio compared with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to 12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated. Patients of non-white ethnicity had a sixfold increased risk of TB compared with white patients treated with anti-TNF therapy.ConclusionThe rate of TB in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving INF and ADA than in those receiving ETA.


Rheumatology ◽  
2018 ◽  
Vol 57 (4) ◽  
pp. 651-655 ◽  
Author(s):  
Sujith Subesinghe ◽  
Andrew Ian Rutherford ◽  
Rachel Byng-Maddick ◽  
Kimme Leanne Hyrich ◽  
James Benjamin Galloway

2011 ◽  
Vol 70 (10) ◽  
pp. 1831-1834 ◽  
Author(s):  
Rebecca Davies ◽  
James B Galloway ◽  
Kath D Watson ◽  
Mark Lunt ◽  
Deborah P M Symmons ◽  
...  

ObjectivesPast studies have reported conflicting rates of venous thrombotic events (VTEs) in rheumatoid arthritis (RA). The current study aimed to compare (1) the rates of VTEs in patients with RA treated with anti-tumour necrosis factor (anti-TNF) therapy versus those treated with non-biological disease-modifying antirheumatic drugs (nbDMARDs) alone and (2) the rates between each individual anti-TNF agent and nbDMARDs.MethodsUsing data from the British Society for Rheumatology Biologics Register, a national prospective observational cohort study of biological safety in patients with RA, the authors compared the incidence of VTEs between 11 881 anti-TNF- and 3673 nbDMARD-treated patients. Analysis was limited to the first VTE per person. HRs were calculated using Cox modelling. Adjustment was made for potential confounders including surgery performed during follow-up.ResultsA total of 196 first VTEs were reported (151 anti-TNF, 45 nbDMARD). Overall there was no difference in the rates of VTEs between anti-TNF- and nbDMARD-treated patients (adjusted HR 0.8 (95% CI 0.5 to 1.5)). The risk was similar across all anti-TNF agents. Rates of postoperative VTEs did not significantly differ between groups.ConclusionsThese data suggest that anti-TNF therapy is not associated with an increased risk of VTEs in RA patients.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 177.2-178
Author(s):  
E. Burn ◽  
L. Kearsley-Fleet ◽  
K. Hyrich ◽  
M. Schaefer ◽  
D. Huschek ◽  
...  

Background:The Observational and Medical Outcomes Partnerships (OMOP) common data model (CDM) provides a framework for standardising health data.Objectives:To map national biologic registry data collected from different European countries to the OMOP CDM.Methods:Five biologic registries are currently being mapped to the OMOP CDM: 1) the Czech biologics register (ATTRA), 2) Registro Español de Acontecimientos Adversos de Terapias Biológicas en Enfermedades Reumáticas (BIOBADASER), 3) British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), 4) German biologics register ‘Rheumatoid arthritis observation of biologic therapy’ (RABBIT), and 5) Swiss register ’Swiss Clinical Quality Management in Rheumatic Diseases’ (SCQM).Data collected at baseline are being mapped first. Details that uniquely identify individuals are mapped to the person table, with the observation_period table defining the time a person may have had clinical events recorded. Baseline comorbidities are mapped to the condition_occurrence CDM table, while baseline medications are mapped to the drug_exposure CDM table. This mapping is summarised in Figure 1.Figure 1.Overview of initial mappingResults:A total of 64,901 individuals are included in the 5 registries being mapped to the OMOP CDM, see table 1. The number of unique baseline conditions being mapped range from 17 in BSRBR-RA to 108 in RABBIT, while the number of baseline medications range from 26 in ATTRA to 802 in BSRBR-RA. Those registries which captured more comorbidities or medications generally allowed for these to be inputted as free text.Table 1.Summary of initial code mappingRegistryNumber of individualsNumber of mapped baseline conditionsNumber of mapped baseline medicationsATTRA5,3262626BIOBADASER6,4963051BSRBR-RA21,69517802RABBIT13,06210878SCQM18,3222633Conclusion:Due to differences in study design and data capture, the baseline information captured on comorbidities and drugs across registries varies greatly. However, these data have been mapped and mapping biologic registry data to the OMOP CDM is feasible. The adoption of the OMOP CDM will facilitate collaboration across registries and allow for multi-database studies which include data from both biologic registries and other sources of health data which have been mapped to the CDM.Disclosure of Interests:Edward Burn: None declared, Lianne Kearsley-Fleet: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Martin Schaefer: None declared, Doreen Huschek: None declared, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Jakub Zavada Speakers bureau: Abbvie, UCB, Sanofi, Elli-Lilly, Novartis, Zentiva, Accord, Markéta Lagová: None declared, Delphine Courvoisier: None declared, Christoph Tellenbach: None declared, Kim Lauper: None declared, Carlos Sánchez-Piedra: None declared, Nuria Montero: None declared, Jesús-Tomás Sanchez-Costa: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen


Sign in / Sign up

Export Citation Format

Share Document