Etanercept (ETN) is a disease-modifying anti-rheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA) that works as a tumor necrosis factor inhibitor (TNF inhibitor) by blocking the effects of naturally occurring TNF. This review will evaluate the effect of ETN as a monotherapy or combination therapy with methotrexate (MTX) in the treatment of RA. This systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. A systematic search was done on PubMed and Google Scholar from 1999 to 2023. Predefined eligibility criteria were set for selected studies, which include: free full-text articles published; randomized control trials (RCTs); systematic reviews and meta-analyses; and observational studies in a patient with RA treated with ETN as initial therapy or as an add-on to conventional disease-modified therapy. Hence, the data had been extracted, and a quality assessment of each study was done by two individual authors. When comparing patients who received 15-25 mg of MTX with those who also received 25 mg of ETN in combination, 71% achieved American College of Rheumatology 20 (ACR20) by 24 weeks, compared to 27% in the MTX and placebo groups (p<0.001), and 39% achieved American College of Rheumatology 50 (ACR50), compared to 3% in the placebo + MTX group (p<0.001). Low disease activity (DAS 28) was more common in patients who had both MTX and ETN (64.5% with DAS <2.4 and 56.3% with DAS 28 <3.2) compared to patients who received only one medication (44.4% with DAS <2.4 and 33.2% with DAS 28 <3.2 for ETN and 38.6% with DAS <2.4 and 28.5% with DAS 28 <3.2 for MTX, with P<0.01). ETN demonstrated smaller changes from baseline in the modified Sharp score (TSS) and erosion scores (ES) at 12 months and two years, as well as a decreased change in the ES score at one year (with a trend of P value = 0.06 for the TSS score), in comparison to those receiving DMARD. Reactions at the injection site (42% vs. 7%, P<0.001) were the only events that occurred significantly more frequently in the ETN plus-MTX group. Combining ETN and MTX appears to help control RA symptoms by decreasing the American College of Rheumatology (ACR) response and DAS score, as well as halting the disease's progression on X-rays. The most common adverse effects were reactions to ETN administered alone at the injection site, likely because of patient awareness of the treatment received. There was also concern about tuberculosis and malignancy, but no recent data is available. Therefore, a larger clinical trial with longer follow-up is required to ascertain long-term safety and benefits.
Background: Adalimumab, golimumab, infliximab, certolizumab, and etanercept are five anti-tumor necrosis factor (anti-TNF) medicines that have been approved for use in rheumatology. Apart from their well-established therapeutic usefulness, -it is unclear to what extent -they are linked to an increased risk of various side effects. The present meta-analysis was carried out to assess the risk of infection and other side effects after anti-TNF- α for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Methods: We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 23 articles were used for meta-analysis. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. In addition, a random-effects model was used to calculate the pooled odds ratio, and Forest plots were constructed to determine the risk of infections and cancer following the use of anti-TNF treatment. Results: Treatment with anti-TNFα agents resulted in an increase in the risk of serious infections (OR: 1.72, 95% CI: 1.56–1.90, p < 0.00001) and an increase in cancer risk (OR: 1.36, 95% CI: 1.20–1.53, p < 0.00001) whereas the risk of developing tuberculosis was not significantly different with anti-TNFα agents versus those without treatment with anti-TNFα agents (OR: 2.55, 95% CI: 0.40–16.23, p = 0.32) although the number of studies is limited to make a definitive conclusion. The risk of bias of the included studies was unclear to high across most domains, and there was evidence of publication bias for most outcomes. Conclusion: The present meta-analysis suggests an increased risk of infectious adverse events, including overall adverse events and cancer following anti-TNFα treatment, whereas the risk of tuberculosis was not significantly different. Although anti-TNF agents have shown promise to treat inflammatory conditions, their use should be balanced by the risk-benefit ratio as suggested by the meta-analysis.
This systematic review and meta-analysis aim to evaluate the remission rate of patients with rheumatoid arthritis (RA) in real-world studies and to summarize potential predictors of remission in RA. Studies reporting remission rate in patients with RA were searched from MEDLINE, EMBASE, and Scopus databases. Two reviewers independently assessed all studies according to eligibility criteria and extracted data. Generally, observational studies reporting remission rate in adult (≥ 18 years) patients with RA were included. Quality assessments were performed using the Newcastle-Ottawa Scale. Pooled analyses of remission rate were conducted using a random-effects model and data were analyzed in subgroups to identify potential source of heterogeneity. Sensitivity analyses were performed by serially excluding each study. Potential predictors of remission were summarized. Thirty-one studies with ~ 82,450 RA patients in total were included. Using the DAS28 remission criteria, the pooled 3-, 6-, 12-, and 24-month remission rates were 17.2%, 16.3%, 21.5%, and 23.5%, respectively. Subgroup analyses showed that 11.7% and 13.8% of TNFi inadequate responders reached remission after 6- and 12-month use of non-TNFi biologics. Predictors of remission included male, higher education level, and lower baseline disease activity, while initial use of corticosteroids was negative predictors of remission. Sustained remission was rare regardless of different criteria used. Remission was a reachable target in real-world studies, while attention should also be paid to achieve sustained remission.
OBJECTIVE: Biologic anti-rheumatic drugs are used with less frequency among older patients compared to young patients. This population is less represented in studies performed to evaluate the efficacy and safety of this drugs. We aimed to assess the efficacy and safety of biological agents between the older RA patients compared to young.
METHODS: A comprehensive, systematic search was conducted in major indexing databases using key terms for RA and each biological agent. The review process was completed by 2 investigators. Both randomized controlled trials and observational studies of at least 6-month duration conducted in adult RA patients were included. Outcomes of interest were clinical efficacy and safety. Effect-estimates were pooled using random-effects modeling if 4 or more studies used the same scale and time-frame for measuring outcomes.
RESULTS: 24 studies (16 focusing on anti-TNF agents) representing 63,705 patients (24% were older) were included. Older RA patients had worse baseline RA disease activity, longer disease duration at the time of enrollment in the trial (14.4 ± 3.6 vs. 10.9 ± 3.6 years; p < 0.001) and higher steroid use (73.2 vs. 64.7%, p < 0.001) than younger. 5 out of 6 studies assessing anti-TNF agents showed worse efficacy outcomes in older patients. The pooled OR of infection and ADRs with anti-TNF agents in older compared to young RA patients was OR 1.59 (95% CI: 1.45-1.76) and 1.40 (95% CI: 1.23-1.61) respectively.
CONCLUSIONS: Older patients had worse safety and efficacy with biological agents but also had worse baseline disease activity. There was significant heterogeneity in reporting outcomes and very limited studies in biological agents other than anti-TNF drugs.
OBJECTIVES: Compare the benefits and harms of drug therapies for adults with early rheumatoid arthritis (RA) within 1 year of diagnosis, updating the findings on early RA from the 2012 review.
DATA SOURCES: English-language articles identified through MEDLINE®, Cochrane Library, Embase®, International Pharmaceutical Abstracts, gray literature, the previous 2012 review, expert recommendations, reference lists of published literature, and supplemental evidence data requests from January 2011 to October 5, 2017.
REVIEW METHODS: Literature was synthesized qualitatively in narrative form and summary tables within and between corticosteroids and classes of disease-modifying antirheumatic drugs (DMARDs). Additionally, combination treatment strategies were examined. We conducted network meta-analysis for five outcomes: American College of Rheumatology 50-percent improvement (ACR50), remission based on Disease Activity Score (DAS), radiographic joint damage, all discontinuations, and discontinuations due to adverse events. Eligibility for network meta-analyses required the following: (1) patients with early RA had not attempted prior treatment with methotrexate (MTX), (2) doses of treatments were within ranges approved by the Food and Drug Administration (FDA), (3) length of followup was similar, and (4) studies were double-blinded randomized controlled trials of low or medium risk of bias.
RESULTS: We analyzed 49 studies: 41 RCTs and 8 observational studies reported in 124 published articles. All included studies enrolled patients with moderate to high disease activity at baseline as measured with mean or median DAS 28 scores. A combination of corticosteroids plus MTX achieved higher remission rates than with MTX monotherapy (low strength of evidence [SOE]). Combination therapy with TNF (tumor necrosis factor) or non-TNF biologics plus MTX improved disease control, remission, and functional capacity compared with monotherapy with either MTX or a biologic (low to moderate SOE). Network meta-analyses found higher ACR50 response for combination therapy of biologics plus MTX than for MTX monotherapy (range of relative risk, 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). In available data, consisting mostly of clinical trials, no significant differences emerged between any DMARDs for rates of discontinuation attributable to adverse events or serious adverse events (low SOE for adalimumab, certolizumab pegol, etanercept, infliximab, or abatacept with MTX, and moderate SOE for rituximab or tocilizumab with MTX). Data about subgroups (based on disease activity, prior therapy, demographics, and the presence of other serious conditions) were insufficient. No difference in findings were noted in MTX naïve and resistant populations. We found no studies of biosimilars for patients with early RA.
CONCLUSIONS: Qualitative synthesis and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics improves disease activity and remission when compared with biologic monotherapy or a conventional synthetic DMARD (csDMARD) monotherapy in patients with moderate to high disease activity at baseline as measured with mean or median DAS 28 scores. Overall rates of adverse events and discontinuation were similar among patients given csDMARDs, TNF biologics, and non-TNF biologics. We did not find eligible studies of biosimilars.
Inhibition of tumor necrosis factor (TNF) activity has profoundly changed the management of several immune-mediated inflammatory diseases with great benefit for patients. The application of TNF inhibitors (TNFi), however, also brings a new concern, malignancy. We performed a systemic review to collect the studies reporting cancer incidences and risks in TNFi users regardless of indications. TNFi were most frequently used in treating patients with rheumatoid arthritis (RA) and inflammatory bowel diseases (IBD). In RA patients without prior cancer history, the incidences of malignancies ranged from the lowest rate 0 per 1000 person-years in etanercept users regarding lymphoma to the highest rate 35.62 per 1000 person-years in adalimumab users on non-melanoma skin cancer (NMSC), while in those patients with prior cancer history, the recurrent incidences of malignancies ranged from the lowest rate 5.05 per 1000 person-years regarding melanoma to the highest rate 63.20 per 1000 person-years on basal cell carcinoma (BCC) in TNFi users. In IBD patients, incidences ranged from 0 per 1000 person-years in TNFi users on lymphoma to 34.0 per 1000 person-years in infliximab users on overall cancer. However, these incidence rates of overall cancer, lymphoma and melanoma were not higher in comparison with those patients who were not treated with TNFi. Compared to general population, incidences of lymphoma were elevated in RA patients and rates of NMSC were higher in patients with psoriasis, RA and IBD. In conclusion, cancer incidences vary across different studies, indications, cancer types and studies with different individual TNFi. Treatment with TNFi is not associated with increased malignant risks of overall cancer, lymphoma or melanoma. Results of NMSC risk were inconsistent among studies. A latest prospective registry study demonstrated a small increased risk of squamous cell cancer in RA patients treated with TNFi (one additional case for every 1600years of treatment experience). Further prospective studies are needed to verify whether TNFi users have higher NMSC risk than non-TNFi users.
OBJETIVOS: Evaluar la seguridad de los fármacos antirreumáticos modificadores de la enfermedad (DMARD) sintéticos y biológicos para el tratamiento de la artritis reumatoide (RA) para informar a la Liga Europea contra el Reumatismo de las recomendaciones para el tratamiento de la AR. MÉTODOS: Revisión sistemática de la literatura (SLR) de estudios observacionales comparando cualquier DMARD con otra intervención para el manejo de pacientes con AR. Se incluyeron todos los resultados de seguridad. Se requirió un grupo de comparación para incluir el estudio. El riesgo de sesgo se evaluó con la herramienta de Hayden. RESULTADOS: Veintiséis estudios observacionales que abordaron diversos resultados de seguridad del tratamiento con bDMARDs cumplieron con los criterios de elegibilidad (15 en infecciones graves, 4 en neoplasias malignas). La heterogeneidad sustancial impidió el metanálisis. Junto con la evidencia de la SLR 2013, basada en 15 estudios, 7 con bajo riesgo de sesgo, los pacientes en bDMARDs en comparación con los pacientes en sDMARDs convencionales tuvieron un mayor riesgo de infecciones graves (HR ajustada 1,1 a 1,8) A través de bDMARDs-un mayor riesgo de tuberculosis (aHR 2,7 a 12,5), pero no hay mayor riesgo de infección por herpes zoster. Los pacientes con bDMARDs no tuvieron un mayor riesgo de neoplasias malignas en general, linfoma o cáncer de piel no melanoma, pero el riesgo de melanoma puede estar ligeramente aumentado (aHR 1,5). CONCLUSIONES: Estos hallazgos confirman el patrón de seguridad conocido de los bDMARDs, incluyendo el inhibidor del factor de necrosis tumoral (TNFi) y no TNFi, para el tratamiento de la AR.
OBJETIVO: Comparar sistemáticamente el riesgo de acontecimientos adversos (AA) durante 13 inmunomoduladores específicos (TIM) indicado para la espondilitis anquilosante (EA), enfermedades inflamatorias del intestino, la artritis idiopática juvenil, psoriasis en placas, la artritis psoriásica (APs), o la artritis reumatoide (AR ).
MÉTODOS: Se realizaron búsquedas en bases de datos electrónicas hasta julio de 2015 para recuperar los ensayos controlados aleatorios (ECA) y estudios observacionales que comparan los EA entre dos o más TIM cabeza a cabeza. Nos informó sobre los siguientes resultados: número de eventos adversos, la interrupción debido a eventos adversos graves, AES, mortalidad, infecciones graves, tuberculosis, herpes zoster, y tumores malignos. Hemos sintetizado cualitativamente la literatura y se realizaron efectos aleatorios meta-análisis si tres o más estudios proporcionaron datos para un resultado.
RESULTADOS: Diez ECA de cabeza a cabeza y 51 estudios observacionales se incluyeron en esta revisión sistemática. La mayoría de los estudios (70%) se llevaron a cabo en pacientes con AR. Riesgo de interrupción del tratamiento debido a eventos adversos fue mayor con infliximab que con adalimumab o etanercept en la AR, APs y EA. Un mayor riesgo de infecciones graves se observó con infliximab que con abatacept, adalimumab, etanercept o en la AR. Riesgo de interrupción del tratamiento debido a acontecimientos adversos, infecciones graves, y la tuberculosis fue menor con etanercept que con adalimumab en la AR. La evidencia limitada sugiere diferencias comparativas en el riesgo de mortalidad, enfermedades malignas, y el herpes zoster de adalimumab, etanercept e infliximab en la AR.
CONCLUSIÓN: No se observaron diferencias importantes en el perfil de seguridad de los TIM en la AR, en general, a favor de abatacept, adalimumab, etanercept y el infliximab más. evidencia comparativa de cabeza a cabeza para otros TIM y poblaciones con AR no era suficiente para establecer conclusiones para la mayor parte de los resultados de seguridad. Este artículo está protegido por derechos de autor. Todos los derechos reservados.
Evaluar la proporción de pacientes con AR que suspendieron biológicos en los registros y bases de datos mundiales de cuidado de la salud y para identificar las causas y los factores predictivos de la interrupción.
Se utilizaron Medline, Embase, Cochrane Library y bases de datos electrónicas Web de Ciencia y ACR y EULAR resúmenes de reuniones: MÉTODOS. Se llevó a cabo de forma independiente la selección de estudios de los registros y bases de datos mundiales de atención médica, incluyendo los pacientes con AR tratados con fármacos biológicos. Los datos extraídos de artículos y resúmenes se combinaron mediante un modelo de efectos aleatorios. Los metanálisis de los porcentajes y proporciones de riesgo se utilizaron para evaluar la interrupción.
RESULTADOS: Noventa y ocho estudios con 200> 000 pacientes de 11 242 artículos y 119 resúmenes cumplieron los criterios de inclusión. En general las tasas de interrupción de los inhibidores del TNF en 0.5, 1, 2, 3 y 4 años fueron de 21, 27, 37, 44 y 52%, respectivamente. La interrupción de etanercept fue significativamente menor a los 3 y 4 años (35% y 41%, respectivamente) que infliximab y adalimumab (46% y 52%, respectivamente). Los predictores de tiempo para la suspensión fueron las proporciones de riesgo [etanercept (CR) de 0,58 y 0,77 en comparación con infliximab y adalimumab, respectivamente), el uso concomitante de FARME (HR 0,77), duración de la enfermedad (HR 1,01) y el sexo femenino (HR 1,18). Los estudios de los registros llevados a cabo después de 2005 y de los países con menor acceso biológicos mostraron mayores porcentajes de interrupción. los datos pertinentes sobre abatacept y tocilizumab faltaban.
CONCLUSIÓN: En la AR, el tratamiento con etanercept tiene un menor porcentaje de interrupción de infliximab y adalimumab. El uso concomitante de FARME, duración de la enfermedad antes del tratamiento con un producto biológico y el sexo femenino predecir el momento de la interrupción.
OBJETIVOS: Para actualizar la evidencia sobre la seguridad de las drogas sintéticas que modifican la enfermedad antirreumáticos (sDMARDs), glucocorticoides (GC) y los DMARD biológicos (MBE) en pacientes con artritis reumatoide (AR) para informar a la Liga Europea contra el Reumatismo (EULAR) recomendaciones para la el tratamiento de la AR.
Métodos: Revisión sistemática de la literatura (SLR) de los estudios observacionales (incluyendo registros). Las intervenciones fueron cualquier MBE (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab o certolizumab pegol) o sDMARD (metotrexato, leflunomida, hidroxicloroquina, sulfasalazina, oro / auranofin, azatioprina, clorambucil, la cloroquina, ciclosporina, ciclofosfamida, mofetil , se requirió la minociclina, penicilamina, tacrolimus o tofacitinib) y un comparador. La información sobre los GC se recogió de los estudios incluidos. Se incluyeron todos los resultados de seguridad.
RESULTADOS: Cuarenta y nueve estudios observacionales que abordan diversos resultados de seguridad de la terapia con MBE cumplieron con los criterios de elegibilidad. Heterogeneidad significativa impidió un metanálisis de cualquiera de los resultados. Los pacientes tratados con inhibidores del factor de necrosis tumoral (TNFi) en comparación con los pacientes en sDMARDs convencionales tenían un mayor riesgo de infecciones graves (HR ajustado (AHR) 01.01 a 01.08), un mayor riesgo de tuberculosis, y un mayor riesgo de infección por el herpes zoster no puede ser excluidos. Los pacientes en TNFi no tenían un mayor riesgo de tumores malignos en general, el cáncer de piel no melanoma o linfoma, pero el riesgo de melanoma se incrementó ligeramente (AHR 1,5). A partir de los estudios identificados en sDMARDs convencionales, no se encontraron nuevas señales de seguridad.
Conclusiones: Los resultados de esta SLR confirman el patrón de seguridad conocido de sDMARDs y MBE para el tratamiento de la AR.
Etanercept (ETN) is a disease-modifying anti-rheumatic drug (DMARD) used in the treatment of rheumatoid arthritis (RA) that works as a tumor necrosis factor inhibitor (TNF inhibitor) by blocking the effects of naturally occurring TNF. This review will evaluate the effect of ETN as a monotherapy or combination therapy with methotrexate (MTX) in the treatment of RA. This systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. A systematic search was done on PubMed and Google Scholar from 1999 to 2023. Predefined eligibility criteria were set for selected studies, which include: free full-text articles published; randomized control trials (RCTs); systematic reviews and meta-analyses; and observational studies in a patient with RA treated with ETN as initial therapy or as an add-on to conventional disease-modified therapy. Hence, the data had been extracted, and a quality assessment of each study was done by two individual authors. When comparing patients who received 15-25 mg of MTX with those who also received 25 mg of ETN in combination, 71% achieved American College of Rheumatology 20 (ACR20) by 24 weeks, compared to 27% in the MTX and placebo groups (p<0.001), and 39% achieved American College of Rheumatology 50 (ACR50), compared to 3% in the placebo + MTX group (p<0.001). Low disease activity (DAS 28) was more common in patients who had both MTX and ETN (64.5% with DAS <2.4 and 56.3% with DAS 28 <3.2) compared to patients who received only one medication (44.4% with DAS <2.4 and 33.2% with DAS 28 <3.2 for ETN and 38.6% with DAS <2.4 and 28.5% with DAS 28 <3.2 for MTX, with P<0.01). ETN demonstrated smaller changes from baseline in the modified Sharp score (TSS) and erosion scores (ES) at 12 months and two years, as well as a decreased change in the ES score at one year (with a trend of P value = 0.06 for the TSS score), in comparison to those receiving DMARD. Reactions at the injection site (42% vs. 7%, P<0.001) were the only events that occurred significantly more frequently in the ETN plus-MTX group. Combining ETN and MTX appears to help control RA symptoms by decreasing the American College of Rheumatology (ACR) response and DAS score, as well as halting the disease's progression on X-rays. The most common adverse effects were reactions to ETN administered alone at the injection site, likely because of patient awareness of the treatment received. There was also concern about tuberculosis and malignancy, but no recent data is available. Therefore, a larger clinical trial with longer follow-up is required to ascertain long-term safety and benefits.
Pregunta de la revisión sistemática»Revisión sistemática de intervenciones
