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1.
Rheumatology (Oxford) ; 59(3): 559-567, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31722431

RESUMEN

OBJECTIVES: To compare cervical screening attendance and cytology (high- and low-grade cervical dysplasia [HGCD and LGCD]) between women with RA and the English general population and between biologic DMARD (bDMARD)-naïve and exposed women. METHODS: The British Society for Rheumatology Biologics Register for RA (BSRBR-RA), a national prospective study of RA treatment outcomes, was linked to the National Health Service Cervical Screening Programme, providing data for 12 785 women to compare with national screening data. Rates of HGCD/LGCD were compared with rates of negative smears using risk difference calculations between BSRBR-RA and national statistics. Within the BSRBR-RA, coverage was compared between those with low and high physical disability scores, while coverage and cytology results were compared between bDMARD-naïve and -exposed RA patients. RESULTS: The mean 5 year screening coverage was significantly higher in BSRBR-RA (83%) compared with the general population (79%), but lower in women with high disability (78%) compared with lesser disability (85%). Risk differences for HGCD were lower in the BSRBR-RA compared with national statistics, whereas risk differences for LGCD were higher. There was no statistically significant difference in the rates of HGCD or LGCD between bDMARD-exposed and -naïve women. CONCLUSION: This first-ever British analysis of cervical screening rates in RA has shown that women with RA have higher screening rates than the general population. Disability negatively impacts attendance, but treatment type does not. Women with RA did not have an increased risk of HGCD compared with national statistics, which was also not influenced by bDMARD exposure.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Prueba de Papanicolaou/estadística & datos numéricos , Displasia del Cuello del Útero/epidemiología , Frotis Vaginal/estadística & datos numéricos , Adulto , Anciano , Artritis Reumatoide/epidemiología , Detección Precoz del Cáncer , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Sistema de Registros , Resultado del Tratamiento
2.
Rheumatology (Oxford) ; 58(1): 80-85, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30137485

RESUMEN

Objective: The aim of this study was to compare the incidence of cancer and all-cause and cause-specific mortality rates among a cohort of patients with severe PsA receiving TNF inhibitor (TNFi) with those of the general UK population. Methods: Cancers and deaths were identified from the national cancer and the national death registers in patients with PsA included in the British Society for Rheumatology Biologics Register from start of TNFi until 31 December 2012. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated using published cancer and death rates for the general population. SIRs were calculated for both overall cancer risk and non-melanoma skin cancer. SMRs were calculated for (1) all-cause mortality, (2) death from malignancy and (3) death from circulatory disease. Gender-specific analyses were also performed. Results: Thirty-four cancers and 41 deaths among 709 patients were observed. The risk of malignancy overall was not increased (SIR 0.94; 95% CI: 0.65, 1.34). However, there was a significantly increased incidence of non-melanoma skin cancer (SIR 2.12; 95% CI: 1.19, 3.50). The all-cause mortality rate in our cohort was increased (SMR 1.56; CI: 1.12, 2.11). Death from malignancy was not increased, but death from coronary heart disease was increased (SMR 2.42; 95% CI: 1.11, 4.59). Conclusion: In our cohort of patients with severe PsA, the overall incidence of malignancy was similar to that of the general population, although the incidence of non-melanoma skin cancer was increased. All-cause mortality was significantly increased, in part due to excess of deaths attributed to coronary heart disease.


Asunto(s)
Antirreumáticos/efectos adversos , Artritis Psoriásica/mortalidad , Productos Biológicos/efectos adversos , Neoplasias/mortalidad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Artritis Psoriásica/tratamiento farmacológico , Causas de Muerte , Enfermedad Coronaria/inducido químicamente , Enfermedad Coronaria/mortalidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/inducido químicamente , Sistema de Registros , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/mortalidad , Reino Unido/epidemiología
3.
Ann Rheum Dis ; 77(6): 848-854, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29475855

RESUMEN

OBJECTIVE: To compare the 10-year outcome (disease activity, disability, mortality) of two cohorts of patients with inflammatory polyarthritis (IP) recruited 10 years apart. METHODS: Patients with IP were recruited to the Norfolk Arthritis Register from 1990 to 1994 (cohort 1 (C1)) and from 2000 to 2004 (cohort 2 (C2)). Demographic and clinical data were collected at baseline and at years 1, 2, 3, 5, 7 and 10. Longitudinal disease activity (swollen/tender 51 joint counts (SJC51/TJC51)) and disability (Health Assessment Questionnaire (HAQ)) were compared between the cohorts using population-average negative binomial regression and generalised estimating equation analysis, respectively. Risk of 10-year mortality was compared between cohorts using Cox models. Risk of cardiovascular disease (CVD) mortality was compared between cohorts using competing risks analysis. Mortality rate ratios (MRR), adjusted for changes in mortality risk of the general population, were calculated using Poisson regression. RESULTS: In total 1653 patients were recruited (C1=1022, C2=631). Patients in C2 had 17% lower SJC51 than C1 over 10 years (95% CI -23% to -10%), whereas TJC51 and HAQ were comparable. C2 patients had reduced risk of all-cause and CVD mortality compared with C1 (all-cause: HR 0.72, 95% CI 0.56 to 0.95; CVD: subhazard ratio 0.58, 95% CI 0.37 to 0.93). After accounting for changes in mortality risk in the general population, the difference in mortality was non-significant (all-cause: MRR 0.78, 95% CI 0.56 to 1.10; CVD: MRR 0.77, 95% CI 0.48 to 1.24). CONCLUSION: Disease activity significantly improved in the new millennium, whereas disability and mortality were unchanged.


Asunto(s)
Artritis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis/mortalidad , Artritis/fisiopatología , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/mortalidad , Artritis Reumatoide/fisiopatología , Enfermedades Cardiovasculares/mortalidad , Evaluación de la Discapacidad , Inglaterra/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Pronóstico , Sistema de Registros , Índice de Severidad de la Enfermedad , Adulto Joven
4.
Rheumatology (Oxford) ; 57(6): 1089-1096, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29566213

RESUMEN

Objectives: To investigate the long term persistence of rituximab (RTX) in a large observational RA cohort, investigate persistence of RTX when used as a first or second line biologic DMARD (bDMARD), to characterize subsequent bDMARD treatment following RTX. Methods: Patients with RA starting treatment with RTX (MabThera) between 2008 and 2011 were recruited into the British Society for Rheumatology Biologics Register for RA. Duration of RTX treatment over the first 4 years after initiation was estimated via Kaplan-Meier estimates and the reason for discontinuation was ascertained. Subsequent bDMARD use following RTX discontinuation was characterised. Treatment survival in bDMARD-naïve (first line RTX use) and experienced (second line RTX use) cohorts was described. Results: One thousand six hundred and twenty-nine patients were recruited (1371 bDMARD-experienced and 258 bDMARD-naïve). Sixty percent of the whole cohort remained on RTX after 4 years. Ineffectiveness (46%) and death (24%) were the most common reason for RTX discontinuation. RTX discontinuation was associated with RF negativity for the bDMARD-experienced cohort. Of those that discontinued RTX, 46% initiated treatment with another bDMARD, with tocilizumab being the most common. Conclusion: This large study of patients initiating RTX treatment for severe RA found that 60% persisted with treatment after 4 years. This study also identified that RTX is tolerated well when used as a first or second line bDMARD.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Sistema de Registros , Rituximab/uso terapéutico , Anciano , Artritis Reumatoide/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento , Reino Unido/epidemiología
5.
Rheumatology (Oxford) ; 57(9): 1533-1540, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28968862

RESUMEN

Objectives: Both TNF inhibitors (TNFi) and rituximab (RTX), a B-cell depleting biologic, can disrupt the immune system in RA. RTX is licensed in Europe for use following TNFi failure. However, safety data on serious infections (SIs) are scarce for RTX in daily practice. This analysis aims to compare the risk of SIs in the first year after a switch to either TNFi or RTX in patients who have failed a first TNFi. Methods: This study included patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR-RA) who switched to either a second TNFi or RTX after failing a first TNFi. Patients were followed until first SI, treatment discontinuation, last recorded follow-up or the end of the first year after the switch, whichever came first. SI was defined as requiring hospitalization, intravenous antibiotics or resulting in death. The risk of first SI was compared between TNFi and RTX using Cox proportional hazard models adjusted using propensity scores using inverse probability of treatment weighting. Results: This analysis included 3419 TNFi and 1396 RTX patients contributing 2765 and 1224 person-years (pyrs), respectively. SI occurred in 164 (4.8%) TNFi and 81 (5.8%) RTX patients giving a crude rate of 59 and 66 SI/1000 pyrs, respectively. The adjusted hazard ratio for SI was 1.0 (95% CI: 0.7, 1.4). Conclusion: The risk of SIs was comparable over the first year of treatment between TNFi and RTX treatment in patients who had failed a single prior TNFi.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Sistema de Registros , Rituximab/uso terapéutico , Sociedades Médicas , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antirreumáticos/uso terapéutico , Artritis Reumatoide/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Reino Unido/epidemiología
6.
Ann Rheum Dis ; 76(4): 654-660, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28073800

RESUMEN

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of myocardial infarction (MI) compared with subjects without RA, with the increased risk driven potentially by inflammation. Tumour necrosis factor inhibitors (TNFi) may modulate the risk and severity of MI. We compared the risk and severity of MI in patients treated with TNFi with that in those receiving synthetic disease-modifying antirheumatic drugs (sDMARDs). METHODS: This analysis included patients with RA recruited from 2001 to 2009 to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis starting TNFi (etanercept/infliximab/adalimumab) and a biologic-naïve comparator cohort receiving sDMARD. All patients were followed via physician and patient questionnaires and national death register linkage. Additionally, all patients were linked to the Myocardial Ischaemia National Audit Project, a national registry of hospitalisations for MI. Patients were censored at first verified MI, death, 90 days following TNFi discontinuation, last physician follow-up or 20 April 2010, whichever came first. The risk of first MI was compared between cohorts using COX regression, adjusted with propensity score deciles (PD). MI phenotype and severity were compared using descriptive statistics. 6-month mortality post MI was compared using logistic regression. RESULTS: 252 verified first MIs were analysed: 58 in 3058 patients receiving sDMARD and 194 in 11 200 patients receiving TNFi (median follow-up per person 3.5 years and 5.3 years, respectively). The PD-adjusted HR of MI in TNFi referent to sDMARD was 0.61 (95% CI 0.41 to 0.89). No statistically significant differences in MI severity or mortality were observed between treatment groups. CONCLUSIONS: Patients with RA receiving TNFi had a decreased risk of MI compared with patients with RA receiving sDMARD therapy over the medium term. This might be attributed to a direct action of TNFi on the atherosclerotic process or better overall disease control.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Infarto del Miocardio/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Adulto , Anciano , Etanercept/uso terapéutico , Femenino , Humanos , Incidencia , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Índice de Severidad de la Enfermedad , Reino Unido/epidemiología
7.
Ann Rheum Dis ; 76(3): 497-503, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27502891

RESUMEN

OBJECTIVES: Patients 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. METHODS: Subjects 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. RESULTS: 11 931 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. CONCLUSIONS: In 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.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Linfoma/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Adulto , Anciano , Estudios de Casos y Controles , Etanercept/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Infliximab/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Reino Unido/epidemiología
8.
Rheumatology (Oxford) ; 56(9): 1510-1517, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28510734

RESUMEN

Objectives: To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years. Methods: Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression. Results: Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient's risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [ß = 0.17 (95% CI 0.03, 0.32)]. Conclusion: HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment.


Asunto(s)
Artritis Reumatoide/cirugía , Procedimientos Ortopédicos/métodos , Anciano , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Prevención Secundaria/métodos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Caminata
9.
Lancet ; 385 Suppl 1: S44, 2015 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-26312866

RESUMEN

BACKGROUND: Anti-citrullinated protein antibodies (ACPA) predict increased disease activity and disability in patients with inflammatory arthritis such as rheumatoid arthritis. However, the absence of these antibodies does not confer universally good prognosis. Recently, a new set of antibodies, anti-carbamylated (anti-CarP) antibodies, have been identified in patients with rheumatoid arthritis. This study aimed to investigate the association between anti-CarP antibodies, disability, and disease activity in these patients. METHODS: Adults with two or more swollen joints for at least 4 weeks were recruited from the Norfolk Arthritis Register (NOAR). At baseline patients completed the health assessment questionnaire (HAQ). The Disease Activity Score in 28 joints (DAS28) was calculated and rheumatoid arthritis classification criteria applied. ACPA and anti-CarP antibodies were measured on stored serum samples obtained within the first year of the study. The HAQ was repeated after 1, 2, 3, 5, 7, 10, 12, 15, and 20 years, and DAS28 scores done every 5 years. Generalised estimating equations (GEE) tested the association between anti-CarP antibodies and longitudinal HAQ and DAS28 scores. FINDINGS: 1995 patients were included; 1310 (66%) were women and median age at onset was 55 years (IQR 43-66). Anti-CarP antibodies were positive in 460 patients (23%), and 1221 (61%) met rheumatoid arthritis classification criteria. Median follow-up was 7 years (IQR 5-11). Patients who were anti-CarP antibody positive had significantly more disability over time and higher levels of disease activity than those who were negative (multivariate GEE adjusted for age, sex, smoking status, ACPA, and year of recruitment to NOAR: ß coefficient for HAQ 0·13, 95% CI 0·03-0·23, and for DAS28 0·31, 0·12-0·49). Statistically significant associations were also seen in a subanalysis of 1092 ACPA-negative patients (HAQ 0·15, 0·02-0·29; DAS28 0·37, 0·11-0·63). In ACPA-positive and rheumatoid arthritis subgroups, anti-CarP antibodies were significantly associated with DAS28 (0·30 [0·02-0·57] and 0·21 [0·04-0·37], respectively), and positive associations were also seen with HAQ scores, but these did not meet statistical significance. INTERPRETATION: In this study the presence of anti-CarPA was associated with increased burden of disability as measured by the HAQ and higher disease activity in patients with inflammatory arthritis. Since GEE models include outcome data at all timepoints, these associations are long term. Our results suggest that anti-CarP antibodies might provide additional prognostic information to ACPA and in particular identify ACPA-negative patients with poor prognosis. FUNDING: Arthritis Research UK.

10.
Ann Rheum Dis ; 75(6): 1139-44, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26443608

RESUMEN

OBJECTIVES: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years' follow-up in a cohort of patients with inflammatory polyarthritis (IP). METHODS: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model. RESULTS: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate ß-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model. CONCLUSIONS: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA.


Asunto(s)
Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Carbamatos/inmunología , Adulto , Anciano , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Pronóstico , Sistema de Registros , Factor Reumatoide/sangre , Índice de Severidad de la Enfermedad
11.
Ann Rheum Dis ; 75(1): 317-20, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26386125

RESUMEN

OBJECTIVES: A recent study identified 16 genetic variants associated with N-glycosylation of human IgG. Several of the genomic regions where these single nucleotide polymorphisms (SNPs) reside have also been associated with autoimmune disease (AID) susceptibility, suggesting there may be pleiotropy (genetic sharing) between loci controlling both N-glycosylation and AIDs. We investigated this by testing variants associated with levels of IgG N-glycosylation for association with rheumatoid arthritis (RA) susceptibility using a Mendelian randomisation study, and testing a subset of these variants in a less well-powered study of treatment response and severity. METHODS: SNPs showing association with IgG N-glycosylation were analysed for association with RA susceptibility in 14 361 RA cases and 43 923 controls. Five SNPs were tested for association with response to anti-tumour necrosis factor (TNF) therapy in 1081 RA patient samples and for association with radiological disease severity in 342 patients. RESULTS: Only one SNP (rs9296009) associated with N-glycosylation showed an association (p=6.92×10(-266)) with RA susceptibility, although this was due to linkage disequilibrium with causal human leukocyte antigen (HLA) variants. Four regions of the genome harboured SNPs associated with both traits (shared loci); although statistical analysis indicated that the associations observed for the two traits are independent. No SNPs showed association with response to anti-TNF therapy. One SNP rs12342831 was modestly associated with Larsen score (p=0.05). CONCLUSIONS: In a large, well-powered cohort of RA patients, we show SNPs driving levels of N-glycosylation have no association with RA susceptibility, indicating colocalisation of associated SNPs are not necessarily indicative of a shared genetic background or a role for glycosylation in disease susceptibility.


Asunto(s)
Artritis Reumatoide/genética , Inmunoglobulina G/genética , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Productos Biológicos/uso terapéutico , Estudios de Casos y Controles , Sitios Genéticos , Predisposición Genética a la Enfermedad , Glicosilación , Humanos , Desequilibrio de Ligamiento , Análisis de la Aleatorización Mendeliana/métodos , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
12.
Ann Rheum Dis ; 75(10): 1797-805, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-26857699

RESUMEN

BACKGROUND: We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. METHODS: Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. RESULTS: The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. CONCLUSIONS: This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Anciano , Artritis Reumatoide/complicaciones , Sesgo , Enfermedades Cardiovasculares/etiología , Europa (Continente)/epidemiología , Femenino , Humanos , India/epidemiología , Japón/epidemiología , América Latina/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , América del Norte/epidemiología , Suecia/epidemiología , Resultado del Tratamiento
13.
Ann Rheum Dis ; 75(10): 1789-96, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26621482

RESUMEN

BACKGROUND: The overall incidence of cancer in patients with rheumatoid arthritis (RA) is modestly elevated. The extent to which cancer rates in RA vary across clinical cohorts and patient subsets, as defined by disease activity or treatment is less known but critical for understanding the safety of existing and new antirheumatic therapies. We investigated comparability of, and means to harmonise, malignancy rates in five RA registries from four continents. METHODS: Participating RA registries were Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (several countries) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data, and sensitivity analyses of sub-cohorts defined by disease activity, treatment change, prior comorbidities and restricted by calendar time or follow-up, respectively. Malignancy rates with 95% CIs were estimated, and standardised for age and sex, based on the distributions from a typical RA clinical trial programme population (fostamatinib). RESULTS: There was a high consistency in rates for overall malignancy excluding non-melanoma skin cancer (NMSC), for malignant lymphomas, but not for all skin cancers, across registries, in particular following age/sex standardisation. Standardised rates of overall malignancy excluding NMSC varied from 0.56 to 0.87 per 100 person-years. Within each registry, rates were generally consistent across sensitivity analyses, which differed little from the main analysis. CONCLUSION: In real-world RA populations, rates of both overall malignancy and of lymphomas are consistent.


Asunto(s)
Artritis Reumatoide/complicaciones , Linfoma/epidemiología , Neoplasias/epidemiología , Sistema de Registros/estadística & datos numéricos , Anciano , Femenino , Humanos , Incidencia , Japón/epidemiología , Linfoma/etiología , Masculino , Persona de Mediana Edad , Neoplasias/etiología , América del Norte/epidemiología , Suecia/epidemiología , Reino Unido/epidemiología
14.
Rheumatology (Oxford) ; 55(11): 2033-2039, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27550304

RESUMEN

OBJECTIVE: To explore the influence of TNF inhibitor (TNFi) therapy and rituximab (RTX) upon the incidence of cancer in patients with RA and prior malignancy. METHODS: The study population comprised RA subjects with a prior malignancy reported to the UK national cancer registers, recruited to the British Society for Rheumatology Biologics Register from 2001 to 2013. We compared rates of first incident malignancy in a TNFi cohort, RTX cohort and synthetic DMARDs (sDMARD) cohort. RESULTS: We identified 425 patients with a prior malignancy from 18 000 RA patients in the study. Of these, 101 patients developed a new malignancy. The rates of incident malignancy were 33.3 events/1000 person-years (py) in the TNFi cohort, 24.7 events/1000 py in the RTX cohort and 53.8 events/1000 py in the sDMARD cohort. The age- and gender-adjusted hazard ratio was 0.55 (95% CI: 0.35, 0.86) for the TNFi cohort and 0.43 (95% CI: 0.10, 1.80) for the RTX cohort in comparison with the sDMARDs cohort. The 17.0% of patients in the sDMARDs cohort had a recurrence of the same cancer in comparison with the 12.8% and the 4.3% in the TNFi and RTX cohorts, respectively. CONCLUSIONS: Although numbers are still low, it seems that patients with RA and prior malignancy selected to receive either a TNFi or RTX in the UK do not have an increased risk of future incident malignancy.


Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/efectos adversos , Neoplasias/inducido químicamente , Rituximab/efectos adversos , Inhibidores del Factor de Necrosis Tumoral , Anciano , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Femenino , Humanos , Incidencia , Masculino , Recurrencia Local de Neoplasia/inducido químicamente , Neoplasias/epidemiología , Estudios Prospectivos , Factores de Riesgo , Reino Unido/epidemiología
15.
Rheumatology (Oxford) ; 55(9): 1601-9, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27220594

RESUMEN

OBJECTIVES: Early remission is the current treatment strategy for patients with inflammatory polyarthritis (IP) and RA. Our objective was to identify baseline factors associated with achieving remission: sustained (SR), intermittent (IR) or never (NR) over a 5-year period in patients with early IP. METHODS: Clinical and demographic data of patients with IP recruited to the Norfolk Arthritis Register (NOAR) were obtained at baseline and years 1, 2, 3 and 5. Remission was defined as no tender or swollen joints (out of 51). Patients were classified as NR or PR, respectively, if they were in remission at: no assessment or ⩾3 consecutive assessments after baseline, and IR otherwise. Ordinal regression and a random effects model, respectively, were used to examine the association between baseline factors, remission group and HAQ scores over time. RESULTS: A total of 868 patients (66% female) were included. Of these, 54%, 34% and 12% achieved NR, IR and SR, respectively. In multivariate analysis, female sex (odds ratio, OR 0.47, 95% CI: 0.35, 0.63), higher tender joint count (OR = 0.94, 95% CI: 0.93, 0.96), higher HAQ (OR = 0.59, 95% CI: 0.48, 0.74), being obese (OR = 0.70, 95% CI: 0.50, 0.99), hypertensive (OR = 0.67, 95% CI: 0.50, 0.90) or depressed (OR = 0.74, 95% CI: 0.55, 1.00) at baseline were independent predictors of being in a lower remission group. IR and SR were associated with lower HAQ scores over time and lower DAS28 at year 5. CONCLUSION: Women with higher tender joint count and disability at baseline, depression, obesity and hypertension were less likely to achieve remission. This information could help when stratifying patients for more aggressive therapy.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Edad de Inicio , Artritis Reumatoide/epidemiología , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión
16.
Ann Rheum Dis ; 74(6): 1087-93, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24685910

RESUMEN

BACKGROUND: Patients 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. OBJECTIVES: To 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). METHODS: Patients 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. RESULTS: 427 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. CONCLUSIONS: The addition of TNFi to sDMARD does not alter the risk of cancer in RA patients selected for TNFi in the UK.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Metotrexato/uso terapéutico , Neoplasias/epidemiología , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Sistema de Registros , Adalimumab , Adulto , Anciano , Artritis Reumatoide/epidemiología , Neoplasias de la Mama/epidemiología , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Etanercept , Femenino , Humanos , Infliximab , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Fumar/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Reino Unido/epidemiología
17.
Ann Rheum Dis ; 74(6): 963-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24827533

RESUMEN

OBJECTIVES: Our initiative aimed to produce recommendations on post-randomised controlled trial (RCT) trial extension studies (TES) reporting using European League Against Rheumatism (EULAR) standard operating procedures in order to achieve more meaningful output and standardisation of reports. METHODS: We formed a task force of 22 participants comprising RCT experts, clinical epidemiologists and patient representatives. A two-stage Delphi survey was conducted to discuss the domains of evaluation of a TES and definitions. A '0-10' agreement scale assessed each domain and definition. The resulting set of recommendations was further refined and a final vote taken for task force acceptance. RESULTS: Seven key domains and individual components were evaluated and led to agreed recommendations including definition of a TES (100% agreement), minimal data necessary (100% agreement), method of data analysis (agreement mean (SD) scores ranging between 7.9 (0.84) and 9.0 (2.16)) and reporting of results as well as ethical issues. Key recommendations included reporting of absolute numbers at each stage from the RCT to TES with reasons given for drop-out at each stage, and inclusion of a flowchart detailing change in numbers at each stage and focus (mean (SD) agreement 9.9 (0.36)). A final vote accepted the set of recommendations. CONCLUSIONS: This EULAR task force provides recommendations for implementation in future TES to ensure a standardised approach to reporting. Use of this document should provide the rheumatology community with a more accurate and meaningful output from future TES, enabling better understanding and more confident application in clinical practice towards improving patient outcomes.


Asunto(s)
Ensayos Clínicos Controlados Aleatorios como Asunto , Informe de Investigación/normas , Reumatología , Comités Consultivos , Técnica Delphi , Humanos , Proyectos de Investigación
18.
Rheumatology (Oxford) ; 54(10): 1780-91, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25972390

RESUMEN

OBJECTIVES: To investigate levels of self-reported adherence to biologic treatment and establish the contribution of demographic, physical and psychological factors to biologic medication adherence in an RA cohort. METHODS: Adalimumab-treated patients were recruited through the British Society for Rheumatology Biologics Register for RA between May 2007 and April 2009. Demographic and baseline psychological measures including illness and medication beliefs were collected. Disease activity (28-item DAS), physical function (HAQ) and quality of life (36-item Short Form Health Survey) were also measured at baseline and at 6, 12 and 18 months. Adherence was assessed at each follow-up using the patient self-completed Compliance Questionnaire for Rheumatology (CQR). Multilevel mixed effects modelling analysis was performed to investigate predictors of adherence. RESULTS: Of the 329 Adalimumab-treated patients included, low adherence (CQR score <65) was reported in 23%, with 41% reporting low adherence at at least one time point. After controlling for age and disease duration, factors independently predictive of increased adherence were increased belief in medication necessity, with baseline effect diminishing over time [ß coefficient 1.68 (s.e. 0.19), P = 0.0001], lower medication concerns [0.50 (0.15), P = 0.001], with this effect remaining throughout follow-up, increased professional or family member support [0.81 (0.32), P = 0.01], strong views of illness being chronic [0.32 (0.14), P = 0.025] and increased treatment control [0.41 (0.19), P = 0.032]. CONCLUSION: Wider recognition of the importance of psychological factors, particularly medication beliefs, in driving medication adherence could have substantial clinical and health economic benefits in RA. The psychological factors we have identified are putative targets for strategies to improve adherence in RA.


Asunto(s)
Adalimumab/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/psicología , Productos Biológicos/uso terapéutico , Cumplimiento de la Medicación/psicología , Cooperación del Paciente/psicología , Adulto , Cultura , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Autoinforme , Índice de Severidad de la Enfermedad , Apoyo Social , Encuestas y Cuestionarios , Factores de Tiempo , Reino Unido
19.
Curr Rheumatol Rep ; 17(5): 31, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25874347

RESUMEN

Juvenile idiopathic arthritis (JIA) is a poorly understood, heterogeneous, incurable, inflammatory syndrome. Long-term outcomes are uncertain, and this painful condition can result in lifelong disability. JIA is associated with considerable financial and humanistic burden for those affected and the healthcare system. Early diagnosis and effective treatment are indicated to optimise outcomes. Modern treatment aims to achieve remission and preserve joint function by using disease-modifying antirheumatic drugs (DMARDs) early. DMARDs can be classified as conventional/traditional or biologic. Biologic medications may be more effective but cost approximately ten times more than traditional DMARDs. Decision-makers in healthcare are increasingly comparing the cost and consequences of alternative treatment strategies to guide resource allocation decisions. There have been few economic evaluations to date to guide medicines optimisation in JIA. This systematic review highlights the lack of existing evidence relating to the humanistic and economic burden of JIA in the era of biologic medication.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Artritis Juvenil/economía , Productos Biológicos/uso terapéutico , Costo de Enfermedad , Antirreumáticos/economía , Artritis Juvenil/rehabilitación , Productos Biológicos/economía , Costos de los Medicamentos/estadística & datos numéricos , Humanos , Calidad de Vida
20.
Pharmacoepidemiol Drug Saf ; 24(11): 1121-32, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26303866

RESUMEN

PURPOSE: Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long-term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries. METHODS: We identified and characterized differences and similarities across five registries (Swedish Rheumatology Quality of Care Register, Consortium of Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register, Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA International), harmonized outcome definitions, and investigated whether restricted subcohorts improved comparability with trial populations. To address confounding, we identified risk predictors for outcomes of interest (mortality, cardiovascular disease, infection, and malignancy). We used patient-level analyses at each registry and central analysis of standardized group-level data. RESULTS: Despite data differences, the coordinated approach enabled consistent variable definitions for key baseline characteristics and outcomes. Selection of restricted subcohorts (e.g., using active joint count criteria) improved baseline comparability with trial patients for some rheumatoid arthritis disease activity measures, but less for other characteristics (e.g., age and comorbidity); however, such selection decreased sample size considerably. For most outcomes, age was the most important risk predictor, emphasizing the importance of age/sex standardization to address confounding. The prospective approach enabled use of recent relevant data; the distributed analysis safeguarded confidentiality of registry data. CONCLUSIONS: Compared with reliance on published data alone, a forward-looking coordinated approach across multiple observational data sources can improve comparability and consistency and better support sensitivity analyses and data interpretation, in contextualizing safety data from clinical trials. This approach may have utility to support safety assessments across diverse diseases and drug development programs and satisfy future regulatory requirements.


Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Diseño de Fármacos , Sistema de Registros/estadística & datos numéricos , Anciano , Aminopiridinas , Antirreumáticos/uso terapéutico , Artritis Reumatoide/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfolinas , Oxazinas/efectos adversos , Oxazinas/uso terapéutico , Estudios Prospectivos , Piridinas/efectos adversos , Piridinas/uso terapéutico , Pirimidinas , Proyectos de Investigación , Resultado del Tratamiento
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