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OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.
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OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.
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Antirreumáticos , Artritis Psoriásica , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Sistema de Registros , Espondiloartritis , Inhibidores del Factor de Necrosis Tumoral , Humanos , Artritis Reumatoide/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Masculino , Femenino , Artritis Psoriásica/tratamiento farmacológico , Persona de Mediana Edad , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Espondiloartritis/tratamiento farmacológico , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Adulto , Anciano , Cumplimiento de la Medicación/estadística & datos numéricosRESUMEN
This study assessed whether genetic variants coding for certain enzymes involved in xenobiotic detoxification, antioxidant defences and DNA repair, along with exposure to environmental chemicals, were associated with an increased prostate cancer (PCa) risk. The study population consisted of 300 men (150 PCa cases and 150 controls) which underwent prostate biopsy as their serum prostate specific antigen (PSA) levels were greater than 4â¯ng/ml. Genetic variants in GSTM1, GSTP1, SOD2, CAT, GPX1, XRCC1 were determined and data for chemical exposures was obtained through a structured questionnaire and by biomonitoring in a subsample of cases and controls. High serum PSA levels were associated with a greater risk of PCa, while physical exercise appears to exert a protective effect against its development. In addition, elevated urinary levels of certain organic pollutants, such as benzo(a)pyrene (BaP), bisphenol A (BPA), and ethyl-paraben (EPB), were associated with an increased risk of PCa.
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Contaminantes Ambientales , Estrés Oxidativo , Antígeno Prostático Específico , Neoplasias de la Próstata , Xenobióticos , Masculino , Humanos , Neoplasias de la Próstata/genética , Estrés Oxidativo/efectos de los fármacos , Persona de Mediana Edad , Anciano , Contaminantes Ambientales/orina , Contaminantes Ambientales/toxicidad , Antígeno Prostático Específico/sangre , Estudios de Casos y Controles , Exposición a Riesgos Ambientales/efectos adversos , Glutatión Transferasa/genéticaRESUMEN
Background: The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications. Objectives: To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions. Design: Retrospective non-interventional database analysis. Methods: Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated. Results: 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]). Conclusion: With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab.
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Anticuerpos Monoclonales , Antirreumáticos , Artritis Psoriásica , Artritis Reumatoide , Humanos , Femenino , Masculino , Anticuerpos Monoclonales/uso terapéutico , Persona de Mediana Edad , Artritis Reumatoide/tratamiento farmacológico , Estudios Retrospectivos , Artritis Psoriásica/tratamiento farmacológico , Adulto , Antirreumáticos/uso terapéutico , Anciano , Resultado del Tratamiento , Espondiloartritis Axial/tratamiento farmacológico , Sistema de RegistrosRESUMEN
OBJECTIVE: To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients. METHODS: Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3). RESULTS: Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model. CONCLUSIONS: Risk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3's discrimination ability and SCORE2's calibration accuracy.
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Artritis Psoriásica , Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/complicaciones , Estudios Prospectivos , Estudios Retrospectivos , Artritis Psoriásica/complicaciones , Teorema de Bayes , Estudios de Seguimiento , AlgoritmosRESUMEN
INTRODUCTION: This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment. METHODS: Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures t-test. RESULTS: A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (p value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (p value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit. CONCLUSIONS: The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials.
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The use of non-invasive liquid biopsy-based cell-free DNA (cfDNA) analysis is an emerging method of cancer detection and intervention. Different analytical methodologies are used to investigate cfDNA characteristics, resulting in costly and long analysis processes needed for combining different data. This study investigates the possibility of using cfDNA data converted for methylation analysis for combining the cfDNA fragment size with copy number variation (CNV) in the context of early colorectal cancer detection. Specifically, we focused on comparing enzymatically and bisulfite-converted data for evaluating cfDNA fragments belonging to chromosome 18. Chromosome 18 is often reported to be deleted in colorectal cancer. We used counts of short and medium cfDNA fragments of chromosome 18 and trained a linear model (LDA) on a set of 2959 regions to predict early-stage (I-IIA) colorectal cancer on an independent test set. In total, 87.5% sensitivity and 92% specificity were obtained on the enzymatically converted libraries. Repeating the same workflow on bisulfite-converted data yielded lower accuracy results with 58.3% sensitivity, implying that enzymatic conversion preserves the cancer fragmentation footprint in whole genome data better than bisulfite conversion. These results could serve as a promising new avenue for the early detection of colorectal cancer using fragmentation and methylation approaches on the same datasets.
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Ácidos Nucleicos Libres de Células , Neoplasias Colorrectales , Sulfitos , Humanos , Ácidos Nucleicos Libres de Células/genética , Variaciones en el Número de Copia de ADN/genética , Metilación de ADN/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Biomarcadores de Tumor/genéticaRESUMEN
OBJECTIVE: To establish the predictive value of the QRESEARCH risk estimator version 3 (QRISK3) algorithm in identifying Spanish patients with ankylosing spondylitis (AS) at high risk of cardiovascular (CV) events and CV mortality. We also sought to determine whether to combine QRISK3 with another CV risk algorithm: the traditional SCORE, the modified SCORE (mSCORE) EULAR 2015/2016 or the SCORE2 may increase the identification of AS patients with high-risk CV disease. METHODS: Information of 684 patients with AS from the Spanish prospective CARdiovascular in ReuMAtology (CARMA) project who at the time of the initial visit had no history of CV events and were followed in rheumatology outpatient clinics of tertiary centers for 7.5 years was reviewed. The risk chart algorithms were retrospectively tested using baseline data. RESULTS: After 4,907 years of follow-up, 33 AS patients had experienced CV events. Linearized rate=6.73 per 1000 person-years (95 % CI: 4.63, 9.44). The four CV risk scales were strongly correlated. QRISK3 correctly discriminated between people with lower and higher CV risk, although the percentage of accumulated events over 7.5 years was clearly lower than expected according to the risk established by QRISK3. Also, mSCORE EULAR 2015/2016 showed the same discrimination ability as SCORE, although the percentage of predicted events was clearly higher than the percentage of actual events. SCORE2 also had a strong discrimination capacity according to CV risk. Combining QRISK3 with any other scale improved the model. This was especially true for the combination of QRISK3 and SCORE2 which achieved the lowest AIC (406.70) and BIC (415.66), so this combination would be the best predictive model. CONCLUSIONS: In patients from the Spanish CARMA project, the four algorithms tested accurately discriminated those AS patients with higher CV risk and those with lower CV risk. Moreover, a model that includes QRISK3 and SCORE2 combined the best discrimination ability of QRISK3 with the best calibration of SCORE2.
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Algoritmos , Enfermedades Cardiovasculares , Espondilitis Anquilosante , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/epidemiología , Persona de Mediana Edad , Adulto , Medición de Riesgo/métodos , Estudios de Seguimiento , España/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Estudios Retrospectivos , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Patients with Rheumatoid Arthritis (RA) have a higher prevalence of comorbidities compared to the general population. However, the implications of multimorbidity on therapeutic response and treatment retention remain unexplored. OBJECTIVES: (a) To evaluate the impact of multimorbidity on the effectiveness of the first targeted synthetic or biologic disease-modifying antirheumatic drug (ts/bDMARD), in patients with RA after 2-year follow-up; (b) to investigate the influence of multimorbidity on treatment retention rate. METHODS: Patients with RA from the BIOBADASER registry exposed to a first ts/bDMARDs were included. Patients were categorized based on multimorbidity status at baseline, defined as a Charlson Comorbidity index (CCI) score ≥ 3. A linear regression model, adjusted for sex and age, was employed to compare the absolute DAS28 score over time after ts/bDMARD initiation between the two groups. The Log-Rank test and Kaplan-Meier curve were used to compare the retention rates of the first ts/bDMARD between the groups. RESULTS: A total of 1128 patients initiating ts/bDMARD were included, with 107 (9.3%) exhibiting multimorbidity. The linear regression model showed significantly higher DAS28 (beta coefficient 0.33, 95%CI:0.07-0.58) over a two-year period in patients with multimorbidity, even after adjusting for age and sex. Finally, no differences in the ts/bDMARD retention rate were found between groups (median 6.94-6.96 years in CCI < 3 vs. 5.68-5.62 in CCI ≥ 3; p = 0.610). CONCLUSIONS: Multimorbidity in patients with RA was associated with greater DAS28 scores within the first two years after ts/bDMARD initiation, in comparison with patients without multimorbidity. A slightly shorter retention rate was found in patients with multimorbidity, although the difference was non-significant.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Humanos , Multimorbilidad , Estudios de Seguimiento , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Sistema de Registros , Productos Biológicos/uso terapéuticoRESUMEN
OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.
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Antirreumáticos , Artritis Psoriásica , Artritis Reumatoide , Espondilitis Anquilosante , Humanos , Artritis Psoriásica/tratamiento farmacológico , Estudios de Cohortes , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Quimioterapia CombinadaRESUMEN
INTRODUCTION: Long-term clinical success of non-splinted, posterior, and short implants still is unclear. This prospective cohort study reports the 10-year follow-up of 6-mm implants supporting single crowns in the posterior region, and patient-reported outcomes. METHODS: Baseline sample comprised 20 patients treated with 46 screw-retained crowns supported by 6-mm implants with moderately rough implant surface. Participants were recalled for a 10-year clinical follow-up to assess survival rates, biologic and mechanic conditions, quality of life (OHIP-14), and treatment satisfaction. Data were collected with clinical-radiographic exams and analyzed using descriptive and inferential statistics. RESULTS: Fourteen patients with 35 implant-crown units were examined after 127.6 ± 11.8 months. For the entire cohort period, 7/46 implants were lost (survival estimate: 77.7% at 133 months), and mechanic complications occurred in 14/46 units (survival estimate: 66.4% at 116 months). In the Cox models, "maximum occlusal force" had a significant effect for implant loss (p = 0.038) and for prosthetic screw loosening (p = 0.038); "arch" and "bruxism" were not significant. Peri-implant bone loss was 0.4 ± 0.6 mm at 10 years. For peri-implant bone level, "crown-to-implant ratio" (p < 0.001) and "time" (p = 0.001) were significant. Bone levels differed from baseline to 12, 48, and 120 months. Satisfaction VAS was 94.0 ± 7.9 mm and OHIP-14 was 2.3 ± 2.2. CONCLUSION: Single screw-retained crowns supported by 6-mm implants have an acceptable long-term clinical performance, with stable peri-implant bone levels after 10 years of function.
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Pérdida de Hueso Alveolar , Implantes Dentales , Humanos , Estudios de Cohortes , Estudios Prospectivos , Calidad de Vida , Fracaso de la Restauración Dental , Prótesis Dental de Soporte Implantado/efectos adversos , Coronas , Pérdida de Hueso Alveolar/etiología , Estudios de Seguimiento , Diseño de Prótesis Dental/efectos adversosAsunto(s)
Multiómica , Neoplasias de la Próstata , Masculino , Humanos , Genómica , Neoplasias de la Próstata/genéticaRESUMEN
OBJECTIVE: to investigate the occurrence and relative risk of incident malignancy in patients with rheumatic diseases and previous malignancies treated with biologic and targeted synthetic DMARDs (b/tsDMARDs). METHODS: Cohort study of patients included in BIOBADASER 3.0 up to 2021, treated with b/tsDMARDs and history of a previous malignancy. Incident cancer was defined as any cancer (new primary, local recurrence or metastases) during the drug exposure. Incidence rate ratios of cancer per 1,000 patients-year (PY) and 95 % confidence interval (CI) were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus TNFi were compared. RESULTS: A total of 352 patients from over 9,129 patients recorded in BIOBADASER 3.0 had a history of a previous malignancy. Overall, there were 47 incident malignancies (28 solid cancers, 18 non-melanoma skin cancers and 1 melanoma). The overall rate of incident malignancy was 47.4 (95 % CI 35.6-63.1) events/1,000 PY, ranging between 24.5 events/1000 PY in the anti-CD20 group to 93 events/1000 PY in the anti-CTLA-4 group. We did not find differences in the adjusted rate of incident cancer in patients exposed to JAKi [0.5 (95 % CI 0.2-1.7)], anti-CD20 [0.4(95 % CI 0.1-1)], or anti-IL6 [1.1(95 % CI 0.5-2.4)], anti-CTLA-4 [1.5 (95 % CI 0.7-3.1) or anti-IL17 [0.7 (95 % CI 0.2-2.4) versus TNFi therapy. CONCLUSIONS: We did not find differences in the risk of incident cancer in patients with rheumatic diseases and a previous malignancy between TNFi and other b/tsDMARDs. While incident cancers in our cohort were limited, our data is reassuring, awaiting validation in future studies.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Melanoma , Enfermedades Reumáticas , Humanos , Riesgo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/inducido químicamente , Estudios de Cohortes , Antirreumáticos/efectos adversos , Melanoma/tratamiento farmacológico , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Enfermedades Reumáticas/inducido químicamente , Productos Biológicos/efectos adversosRESUMEN
INTRODUCTION: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients. METHOD: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups. RESULT: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation. CONCLUSION: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.
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Productos Biológicos , Enfermedades Reumáticas , Reumatología , Embarazo , Humanos , Femenino , Masculino , Estudios Prospectivos , Enfermedades Reumáticas/tratamiento farmacológico , Sistema de RegistrosRESUMEN
The development and progression of prostate cancer (PCa) depends on complex interactions between genetic, environmental and dietary factors that modulate the carcinogenesis process. Interactions between chemical exposures and genetic polymorphisms in genes encoding xenobiotic metabolizing enzymes (XME), antioxidant enzymes and DNA repair enzymes have been reported as the main drivers of cancer. Thus, a better understanding of the causal risk factors for PCa will provide avenues to identify men at increased risk and will contribute to develop effective detection and prevention methods. We performed a meta-analysis on 17,518 cases and 42,507 controls obtained from 42 studies to determine whether seven SNPs and one CNV pertaining to oxidative stress, xenobiotic detoxification and DNA repair enzymes are associated with the risk of PCa (GPX1 (rs1050450), XRCC1 (rs25487), PON1 (rs662), SOD2 (rs4880), CAT (rs1001179), GSTP1 (rs1695) and CNV GSTM1). A significant increased risk of PCa was found for SOD2 (rs4880) ORGG+GA vs. AA 1.08; 95%CI 1.01-1.15, CAT (rs1001179) ORTT vs. TC+CC 1.39; 95%CI 1.17-1.66, PON1 (rs662) ORCT vs. CC+TT 1.17; 95%CI 1.01-1.35, GSTP1 (rs1695) ORGG vs. GA+AA 1.20; 95%CI 1.05-1.38 and GSTM1 (dual null vs. functional genotype) ORN vs. NN1+NN2 1.34; 95%CI 1.10-1.64. The meta-analysis showed that the CNV GSTM1, and the SNPs GSTP1 (rs1695) and CAT (rs1001179) are strongly associated with a greater risk of PCa and, to a lesser extent, the genetic variants SOD2 (rs4880) and PON1 (rs662). Although several antioxidant enzymes and XME play an important role in the PCa development, other risk factors such as chemical exposures should also be considered to gain insight on PCa risk. The functional in silico analysis showed that the genetic variants studied had no clinical implication regarding malignancy, except for GPX1 (rs1050450) SNP.
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Antioxidantes , Neoplasias de la Próstata , Masculino , Humanos , Xenobióticos , Gutatión-S-Transferasa pi/genética , Genotipo , Neoplasias de la Próstata/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Estudios de Casos y Controles , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Arildialquilfosfatasa/genéticaRESUMEN
BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept. METHODS: Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals. RESULTS: Over 5000 patients with RA treated with abatacept were included. Most patients (78-85%) were female, and the mean age range was 52-58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y. CONCLUSIONS: Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.
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Antirreumáticos , Artritis Reumatoide , Humanos , Femenino , Persona de Mediana Edad , Masculino , Abatacept , Inhibidores del Factor de Necrosis Tumoral , Sistema de RegistrosRESUMEN
BACKGROUND: In patients with rheumatic diseases, the use of biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) after discontinuation of tumor necrosis factor inhibitors (TNFi) is known to be effective. However, data on the use of TNFi after discontinuation of non-TNFi bDMARDs or tsDMARDs (non-TNFi) are scarce. This study assessed the 4-years golimumab retention in patients with rheumatic diseases when used after discontinuation of non-TNFi. METHODS: Adults with rheumatoid arthritis (RA; n = 72), psoriatic arthritis (PsA; n = 30) or axial spondyloarthritis (axSpA; n = 23) who initiated golimumab after discontinuation of non-TNFi from the Spanish registry of biological drugs (BIOBADASER) were analyzed retrospectively. The retention rate (drug survival or persistence) of golimumab up to 4 years was evaluated. RESULTS: The golimumab retention rate was 60.7% (51.4-68.8) at year 1, 45.9% (36.0-55.2) at year 2, 39.9% (29.8-49.7) at year 3 and 33.4% (23.0-44.2) at year 4. Retention rates did not differ significantly whether golimumab was used as second, third, or fourth/subsequent line of therapy (p log-rank = 0.462). Golimumab retention rates were higher in axSpA or PsA patients than in RA patients (p log-rank = 0.002). When golimumab was administered as third or fourth/subsequent line, the 4-years retention rate after discontinuation of non-TNFi was similar to that after discontinuation of TNFi. CONCLUSION: In patients who discontinued non-TNFi, most of whom received golimumab as third/subsequent line of therapy, one-third of patients remained on golimumab at year 4. Retention rates were higher in patients with axSpA and PsA than in those with RA.
Asunto(s)
Antirreumáticos , Artritis Psoriásica , Artritis Reumatoide , Fiebre Reumática , Adulto , Humanos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/efectos adversosRESUMEN
Background In-stent restenosis (ISR) is commonly encountered even in the era of contemporary percutaneous coronary intervention (PCI). There is a paucity of data on the comparative outcomes of PCI for ISR lesions versus de novo lesions. Methods and Results An electronic search was conducted for MEDLINE, Cochrane, and Embase through August 2022 for studies comparing the clinical outcomes after PCI for ISR versus de novo lesions. The primary outcome was major adverse cardiac events. Data were pooled using a random-effects model. The final analysis included 12 studies, with a total of 708 391 patients, of whom 71 353 (10.3%) underwent PCI for ISR. The weighted follow-up duration was 29.1 months. Compared with de novo lesions, PCI for ISR was associated with a higher incidence of major adverse cardiac events (odds ratio [OR], 1.31 [95% CI, 1.18-1.46]). There was no difference on a subgroup analysis of chronic total occlusion lesions versus none (Pinteraction=0.69). PCI for ISR was associated with a higher incidence of all-cause mortality (OR, 1.03 [95% CI, 1.02-1.04]), myocardial infarction (OR, 1.20 [95% CI, 1.11-1.29]), target vessel revascularization (OR, 1.42 [95% CI, 1.29-1.55]), and stent thrombosis (OR, 1.44 [95% CI, 1.11-1.87]), but no difference in cardiovascular mortality (OR, 1.04 [95% CI, 0.90-1.20]). Conclusions PCI for ISR is associated with higher incidence of adverse cardiac events compared with PCI for de novo lesions. Future efforts should be directed toward prevention of ISR and exploring novel treatment strategies for ISR lesions.
Asunto(s)
Reestenosis Coronaria , Stents Liberadores de Fármacos , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/etiología , Reestenosis Coronaria/terapia , Stents Liberadores de Fármacos/efectos adversos , Factores de Riesgo , Infarto del Miocardio/epidemiología , Stents/efectos adversos , Constricción Patológica , Resultado del Tratamiento , Angiografía Coronaria/efectos adversosRESUMEN
BACKGROUND: The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. METHODS: An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. RESULTS: The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91-0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34-0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01-1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21-5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02-0.53). CONCLUSIONS: Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.