BACKGROUND: Anti-interleukin (IL)-17 biological agents (BAs) have significant efficacy in the treatment of psoriasis and psoriatic arthritis; however, adverse events (AEs) are common, and their safety has not been systematically evaluated.
OBJECTIVES: The purpose of this systematic review and meta-analysis was to summarize the number and corresponding rates of AEs caused by anti-IL-17 BAs in patients with psoriasis and psoriatic arthritis to improve clinical decision-making regarding their use.
METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were independently searched by three authors for articles on the treatment of psoriasis with anti-IL-17 BAs that were published before March 1, 2022, and included at least one AE. Dichotomous variables and 95% confidence intervals (CI) were analyzed using R software (version 4.1.3) and the Meta and Metafor software packages. Funnel plots and meta-regression were used to test for the risk of bias, I2 was used to assess the magnitude of heterogeneity, and subgroup analysis was used to reduce heterogeneity.
RESULTS: A total of 57 studies involving 28,424 patients with psoriasis treated with anti-IL-17 BAs were included in the meta-analysis. Subgroup analysis showed that anti-IL-17A (73.48%) and anti-IL-17A/F (73.12%) BAs were more likely to cause AEs than anti-IL-17R BAs (65.66%). The incidence of AEs was as high as 72.70% with treatment durations longer than one year, and long-term use of medication had the potential to lead to mental disorders. Infection (33.16%), nasopharyngitis (13.74%), and injection site reactions (8.28%) were the most common AEs. Anti-IL-17 BAs were most likely to cause type α (33.52%) AEs. Type δ AEs (1.01%) were rarely observed.
CONCLUSIONS: Anti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.
Síntesis amplia/ Revisión panorámica de revisiones sistemáticas
BACKGROUND: This is an update of the 2009 Cochrane overview and network meta-analysis (NMA) of biologics for rheumatoid arthritis (RA).
OBJECTIVES: To assess the benefits and harms of nine biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab) and small molecule tofacitinib, versus comparator (MTX, DMARD, placebo (PL), or a combination) in adults with rheumatoid arthritis who have failed to respond to methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs), i.e., MTX/DMARD incomplete responders (MTX/DMARD-IR).
METHODS: We searched for randomized controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (via The Cochrane Library Issue 6, June 2015), MEDLINE (via OVID 1946 to June 2015), and EMBASE (via OVID 1947 to June 2015). Data extraction, risk of bias and GRADE assessments were done in duplicate. We calculated both direct estimates using standard meta-analysis and used Bayesian mixed treatment comparisons approach for NMA estimates to calculate odds ratios (OR) and 95% credible intervals (CrI). We converted OR to risk ratios (RR) which are reported in the abstract for the ease of interpretation.
MAIN RESULTS: This update included 73 new RCTs for a total of 90 RCTs; 79 RCTs with 32,874 participants provided usable data. Few trials were at high risk of bias for blinding of assessors/participants (13% to 21%), selective reporting (4%) or major baseline imbalance (8%); a large number had unclear risk of bias for random sequence generation (68%) or allocation concealment (74%).Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with a statistically significant and clinically meaningful improvement in ACR50 versus comparator (RR 2.71 (95% confidence interval (CI) 2.36 to 3.10); absolute benefit 24% more patients (95% CI 19% to 29%), number needed to treat for an additional beneficial outcome (NNTB) = 5 (4 to 6). NMA estimates for ACR50 in tumor necrosis factor (TNF) biologic+MTX/DMARD (RR 3.23 (95% credible interval (Crl) 2.75 to 3.79), non-TNF biologic+MTX/DMARD (RR 2.99; 95% Crl 2.36 to 3.74), and anakinra + MTX/DMARD (RR 2.37 (95% Crl 1.00 to 4.70) were similar to the direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with a clinically and statistically important improvement in function measured by the Health Assessment Questionnaire (0 to 3 scale, higher = worse function) with a mean difference (MD) based on direct evidence of -0.25 (95% CI -0.28 to -0.22); absolute benefit of -8.3% (95% CI -9.3% to -7.3%), NNTB = 3 (95% CI 2 to 4). NMA estimates for TNF biologic+MTX/DMARD (absolute benefit, -10.3% (95% Crl -14% to -6.7%) and non-TNF biologic+MTX/DMARD (absolute benefit, -7.3% (95% Crl -13.6% to -0.67%) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was associated with clinically and statistically significantly greater proportion of participants achieving remission in RA (defined by disease activity score DAS < 1.6 or DAS28 < 2.6) versus comparator (RR 2.81 (95% CI, 2.23 to 3.53); absolute benefit 18% more patients (95% CI 12% to 25%), NNTB = 6 (4 to 9)). NMA estimates for TNF biologic+MTX/DMARD (absolute improvement 17% (95% Crl 11% to 23%)) and non-TNF biologic+MTX/DMARD (absolute improvement 19% (95% Crl 12% to 28%) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for inconsistency), radiographic progression (scale 0 to 448) was statistically significantly reduced in those on biologics + MTX/DMARDs versus comparator, MD -2.61 (95% CI -4.08 to -1.14). The absolute reduction was small, -0.58% (95% CI -0.91% to -0.25%) and we are unsure of the clinical relevance of this reduction. NMA estimates of TNF biologic+MTX/DMARD (absolute reduction -0.67% (95% Crl -1.4% to -0.12%) and non-TNF biologic+MTX/DMARD (absolute reduction, -0.68% (95% Crl -2.36% to 0.92%)) were similar to respective direct estimates.Based on direct evidence of moderate quality (downgraded for imprecision), results for withdrawals due to adverse events were inconclusive, with wide confidence intervals encompassing the null effect and evidence of an important increase in withdrawals, RR 1.11 (95% CI 0.96 to 1.30). The NMA estimates of TNF biologic+MTX/DMARD (RR 1.24 (95% Crl 0.99 to 1.57)) and non-TNF biologic+MTX/DMARD (RR 1.20 (95% Crl 0.87 to 1.67)) were similarly inconclusive and downgraded to low for both imprecision and indirectness.Based on direct evidence of high quality, biologic+MTX/DMARD was associated with clinically significantly increased risk (statistically borderline significant) of serious adverse events on biologic+MTX/DMARD (Peto OR [can be interpreted as RR due to low event rate] 1.12 (95% CI 0.99 to 1.27); absolute risk 1% (0% to 2%), As well, the NMA estimate for TNF biologic+MTX/DMARD (Peto OR 1.20 (95% Crl 1.01 to 1.43)) showed moderate quality evidence of an increase in the risk of serious adverse events. The other two NMA estimates were downgraded to low quality due to imprecision and indirectness and had wide confidence intervals resulting in uncertainty around the estimates: non-TNF biologics + MTX/DMARD: 1.07 (95% Crl 0.89 to 1.29) and anakinra: RR 1.06 (95% Crl 0.65 to 1.75).Based on direct evidence of low quality (downgraded for serious imprecision), results were inconclusive for cancer (Peto OR 1.07 (95% CI 0.68 to 1.68) for all biologic+MTX/DMARD combinations. The NMA estimates of TNF biologic+MTX/DMARD (Peto OR 1.21 (95% Crl 0.63 to 2.38) and non-TNF biologic+MTX/DMARD (Peto OR 0.99 (95% Crl 0.58 to 1.78)) were similarly inconclusive and downgraded to low quality for both imprecision and indirectness.Main results text shows the results for tofacitinib and differences between medications.
AUTHORS' CONCLUSIONS: Based primarily on RCTs of 6 months' to 12 months' duration, there is moderate quality evidence that the use of biologic+MTX/DMARD in people with rheumatoid arthritis who have failed to respond to MTX or other DMARDs results in clinically important improvement in function and higher ACR50 and remission rates, and increased risk of serious adverse events than the comparator (MTX/DMARD/PL; high quality evidence). Radiographic progression is slowed but its clinical relevance is uncertain. Results were inconclusive for whether biologics + MTX/DMARDs are associated with an increased risk of cancer or withdrawals due to adverse events.
OBJETIVO: Desarrollar una nueva pauta de tratamiento farmacológico basado en la evidencia para la artritis reumatoide (AR).
MÉTODOS: Se realizó una revisión sistemática para sintetizar la evidencia de los beneficios y los daños de diferentes opciones de tratamiento. Se utilizó la clasificación de las recomendaciones de la evaluación, la metodología de Evaluación (GRADE) Desarrollo y en evaluar la calidad de las pruebas. Empleamos un proceso de consenso del grupo para clasificar la fuerza de las recomendaciones (ya sean fuertes o condicionales). Una recomendación sólida indica que los médicos están seguros de que los beneficios de una intervención son muy superiores a los daños (o viceversa). Una recomendación condicional denota incertidumbre sobre el equilibrio entre los beneficios y los daños y / o una mayor variabilidad significativa en los valores y las preferencias del paciente.
RESULTADOS: La guía cubre el uso de los fármacos tradicionales modificadores de la enfermedad (DMARD) antirreumáticos, agentes biológicos, tofacitinib, y los glucocorticoides en los primeros 6 meses (<) y estableció (6 meses o más) RA. Además, proporciona recomendaciones sobre el uso de un enfoque de tratar al objetivo, se estrecha y descontinuar medicamentos y el uso de agentes biológicos y FAME en pacientes con hepatitis, insuficiencia cardíaca congestiva, enfermedad maligna, y las infecciones graves. La directriz se refiere a la utilización de las vacunas en pacientes que inician / recepción de FARME o agentes biológicos, la detección de la tuberculosis en pacientes que inician / recepción de agentes biológicos o tofacitinib, y la vigilancia de laboratorio para los DMARD tradicionales. La guía incluye 74 recomendaciones: 23% son fuertes y el 77% son condicionales.
CONCLUSIÓN: Esta directriz RA debe servir como una herramienta para los médicos y pacientes (nuestros dos audiencias objetivo) para las decisiones de tratamiento farmacológico en situaciones clínicas más frecuentes. Estas recomendaciones no son prescriptivos, y las decisiones de tratamiento deben ser tomadas por los médicos y los pacientes a través de un proceso de toma de decisiones compartida, teniendo en cuenta los valores de los pacientes, las preferencias y las comorbilidades. Estas recomendaciones no deben ser utilizados para limitar o no permitir el acceso a las terapias.
Objetivo: Comparamos sistemáticamente la eficacia, la efectividad y la seguridad (eventos adversos) de abatacept, adalimumab, alefacept, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, natalizumab, rituximab, tocilizumab y ustekinumab en pacientes con artritis reumatoide juvenil idiopática Artritis, espondilitis anquilosante, artritis psoriásica, enfermedad de Crohn, colitis ulcerosa y psoriasis en placas. FUENTES DE DATOS: Para identificar los estudios publicados, se realizaron búsquedas en PubMed, EMBASE, CINAHL, Centro de Revisiones y Difusión, The Cochrane Library, y International Pharmaceutical Abstracts de 2009 (enero) a 2011 (octubre). También se realizaron búsquedas en el sitio web de la Administración de Alimentos y Medicamentos de los Estados Unidos para el sitio web de Evaluación e Investigación de Medicamentos para obtener datos adicionales no publicados, se solicitaron expedientes de información de los fabricantes farmacéuticos y se obtuvieron las citas pertinentes de las listas de referencias de los estudios incluidos. MÉTODOS DE REVISIÓN: La selección del estudio, la abstracción de los datos, la evaluación de la validez, la clasificación de la fuerza de la evidencia y la síntesis de los datos se realizaron de acuerdo con nuestros métodos de revisión estándar. RESULTADOS Y CONCLUSIÓN: En general, los moduladores inmunes dirigidos son medicamentos altamente eficaces para el tratamiento de la artritis reumatoide, la artritis idiopática juvenil, la espondilitis anquilosante, la artritis psoriásica, la enfermedad de Crohn, la colitis ulcerosa y la psoriasis en placa que mejoran sustancialmente la carga de la enfermedad y son generalmente seguros Para el tratamiento a corto plazo. Para la artritis reumatoide, las pruebas de baja y moderada fuerza indicaron que algunos moduladores inmunes dirigidos son más eficaces que otros. Estos resultados se basaron en tres ensayos de cabeza a cabeza, varios estudios observacionales grandes y comparaciones indirectas de ensayos controlados con placebo. La evidencia es actualmente insuficiente para determinar de manera fiable la eficacia comparativa de otras indicaciones y en subgrupos. Las pruebas de baja resistencia indicaron que las infecciones graves son menos frecuentes con el abatacept que las otras drogas y que la tasa de eventos adversos es mayor con infliximab que con adalimumab o etanercept. Asimismo, más pacientes que recibieron infliximab se retiraron debido a eventos adversos que abatacept, adalimumab, etanercept y golimumab. La infusión o las reacciones alérgicas contribuyeron a la diferencia en el riesgo.
Anti-interleukin (IL)-17 biological agents (BAs) have significant efficacy in the treatment of psoriasis and psoriatic arthritis; however, adverse events (AEs) are common, and their safety has not been systematically evaluated.
OBJECTIVES:
The purpose of this systematic review and meta-analysis was to summarize the number and corresponding rates of AEs caused by anti-IL-17 BAs in patients with psoriasis and psoriatic arthritis to improve clinical decision-making regarding their use.
METHODS:
PubMed, Embase, Cochrane Library, and Web of Science databases were independently searched by three authors for articles on the treatment of psoriasis with anti-IL-17 BAs that were published before March 1, 2022, and included at least one AE. Dichotomous variables and 95% confidence intervals (CI) were analyzed using R software (version 4.1.3) and the Meta and Metafor software packages. Funnel plots and meta-regression were used to test for the risk of bias, I2 was used to assess the magnitude of heterogeneity, and subgroup analysis was used to reduce heterogeneity.
RESULTS:
A total of 57 studies involving 28,424 patients with psoriasis treated with anti-IL-17 BAs were included in the meta-analysis. Subgroup analysis showed that anti-IL-17A (73.48%) and anti-IL-17A/F (73.12%) BAs were more likely to cause AEs than anti-IL-17R BAs (65.66%). The incidence of AEs was as high as 72.70% with treatment durations longer than one year, and long-term use of medication had the potential to lead to mental disorders. Infection (33.16%), nasopharyngitis (13.74%), and injection site reactions (8.28%) were the most common AEs. Anti-IL-17 BAs were most likely to cause type α (33.52%) AEs. Type δ AEs (1.01%) were rarely observed.
CONCLUSIONS:
Anti-IL-17 BAs used for the treatment of psoriasis and psoriatic arthritis caused a series of AEs, but the symptoms were generally mild.
