Effectiveness and safety of adalimumab compared with leflunomide in patients with Takayasu arteritis: a retrospective cohort study.

OBJECTIVE: This study aims to evaluate the effectiveness and safety of adalimumab (ADA) compared with leflunomide (LEF) in patients with Takayasu arteritis (TAK). METHOD: A retrospective cohort study was performed with the following inclusion criteria: the fulfilment of the 2022 American College Classification/European Alliance of Associations for Rheumatology criteria for TAK, age ≥18 years, and written informed consent. Forty-four patients were treated with LEF (n=28) or ADA (n=16) therapy due to relapsing/refractory disease or toxicity from previous therapy. Patients were evaluated at baseline (T0), at a median of 7.0 months (T1) and at 15.0 months of follow-up (T2). Data regarding disease activity, daily dose of prednisone, side effects and angiographic progression were analysed. RESULTS: LEF and ADA groups had similar features on the baseline visit. However, intravenous methylprednisolone was more frequently prescribed for the ADA group (p=0.019). On T1 and T2 visits, complete response rates were similar for ADA and LEF groups (75.0% and 88.5%; p=0.397 and 62.5% vs 78.3%; p=0.307), respectively. The differences remained non-significant after adjusting for baseline variables by propensity score matching. Although the ADA group had a higher median daily prednisone on visit T1 (p=0.004), it was similar on visit T2 (p=0.595). Similar rates of angiographic progression were observed in ADA and LEF groups (40% vs 25%; p=0.467). Mild-to-moderate adverse events were observed only in the LEF group (17.9%). CONCLUSION: LEF and ADA had comparable outcomes after a median of 15.0 months of follow-up. However, withdrawal from therapy and mild-to-moderate adverse events were only observed in the LEF group.

Therapeutic response to leflunomide in combo therapy and monotherapy is associated to serum teriflunomide (A77 1726) levels.

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

Causes of synthetic disease-modifying drug discontinuation in rheumatoid arthritis: Data from a large real-life cohort.

The treatment of rheumatoid arthritis (RA) has evolved rapidly in recent years. Nonetheless, conventional synthetic disease-modifying drugs (csDMARDs) remain the gold standard for RA treatment. The treatment for RA is expensive and this has a negative impact on public health. Given the low cost of csDMARDs compared to those of other treatment strategies, it is important to manage this type of treatment properly. Information on the duration of use of each drug and the reasons for their discontinuation is relevant to medical practitioners as it could improve the information available regarding side effects and their proper management. Moreover, data from clinical practice in the population can provide health care managers with information for resource allocation and optimization of csDMARD use with a consequent cost reduction in the treatment of RA. In this cross-sectional study, we aimed to describe the use of csDMARDs in public health services in Brazil, emphasizing on the duration of use and reasons for discontinuation of each drug. This study is a part of the REAL, a multicenter project that evaluated Brazilian patients with RA from eleven rheumatology services from August to October 2015. Patients were examined clinically, and an analysis of complementary exams and medical records was performed. A total of 1125 patients were included. 98.5% were women with a median age of 55.6 years. 36% and 90.84% patients were using biological disease-modifying drugs (bDMARDs) and csDMARDs, respectively. The duration of use and doses of each medication and the causes of suspension were analyzed. Most of the patients analyzed in this study were using csDMARDs for prolonged periods and methotrexate showed the longest duration of use. Interruption indexes due to ineffectiveness and side effects were analyzed. The knowledge of common adverse effects may alert attending physicians to the proper management of effective and low-cost therapeutic groups.

Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis.

OBJECTIVE: To assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD). METHODS: We performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected. In structured workshops for discussion and assessment of each article, 6 could be meta-analyzed for the primary and secondary outcomes: achievement of American College of Rheumatology (ACR) 20 and its core set components; and change of serum C-reactive protein (CRP) levels, Health Assessment Questionnaire Disability Index (HAQ-Di), liver enzyme aspartate transaminase/alanine transaminase ratio, new gastrointestinal (GI) side effects and infections. RESULTS: A total of 1984 patients were included: 986 took leflunomide and 998 methotrexate. The probability of achieving ACR 20 had an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.74, 1.06) with a trend toward favoring methotrexate; reduction of the swollen joint count was greater for methotrexate: mean difference=0.82 (95%CI 0.24, 1.39); tender joint count, physician global assessment, HAQ-Di, and serum CRP levels revealed no significant difference between groups. Increased liver enzymes were more frequent in the leflunomide group, OR=0.38 (95%CI 0.27, 0.53), and new GI complaints were more common with methotrexate (OR=1.44; 95%CI 1.17, 1.79). There was no difference in the incidence of non-severe infections. CONCLUSION: Leflunomide used as the first DMARD in RA seemed to be as efficacious as methotrexate; only the reduction of swollen joint count was more marked for methotrexate. Leflunomide was linked to a greater increase in liver enzymes, but there were fewer GI complaints.

Terapia biológica para el tratamiento de artritis reumatoide / Biological therapy for the treatment of arthritis rheumatoid

CONTEXTO: La artritis reumatoide (AR) es una condición crónica y progresiva que se caracteriza por la inflamación del tejido sinovial de las articulaciones. Puede causar sensibilidad y rigidez en las articulaciones, su destrucción progresiva y síntomas que incluyen dolor y fatiga. Su tratamiento implica un diagnóstico precoz e iniciar el tratamiento lo antes posible para evitar el daño articular y disminuir el deterioro en la calidad de vida. El objetivo del tratamiento debe ser alcanzar rápidamente la remisión clínica de la enfermedad y cuando no es posible, lograr la mínima actividad de la enfermedad. OBJETIVO: Analizar la evidencia disponible acerca del tratamiento de AR con medicamentos biológicos. Establecer una recomendación de diagnóstico, tratamiento y cobertura en pacientes con AR candidatos a terapia biológica. METODOLOGÍA: Se formuló una pregunta P.I.C.O. con la siguiente población como foco: pacientes con artritis reumatoide moderada / severa refractaria a DMARDs (Drogas modificadoras de la Artritits Reumatoide) no biológicos. Se realizó una búsqueda bibliográfica destinada a recuperar Guías de prácticas clínicas, Revisiones sistemáticas, informes de Evaluación de tecnologías sanitarias (ETS), Evaluaciones Económicas y/o recomendaciones de cobertura sobre drogas biológicas para el tratamiento de AR durante el período 2013-2019. Además, se planteó una estrategia para ponderar y calificar la evidencia hallada (Revisiones Sistemáticas) y de vincular la misma con la práctica clínica. El Comité Provincial de Tecnologías Sanitarias (CoPTeS) convocó a reumatólogos e inmunólogos de los hospitales de Mendoza, a fin de conocer su experiencia. Para tal fin se diseñó una planilla, que permitía a los especialistas, ponderar cuatro aspectos relevantes de la terapia: efectividad, seguridad, adherencia y costos. RESULTADOS: Se hallaron 35 documentos. Se priorizaron revisiones sistemáticas y guías de práctica clínica. En segundo plano se priorizaron informes de ETS, evaluaciones económicas y políticas de cobertura de países similares. Estos hallazgos se presentaron a los especialistas convocados. Golimumab y Tocilizumab cumplen con el mejor esquema de valoración en evidencias y preferencias clínicas (valoración de especialistas), como también de costos del tratamiento, asequible por el Ministerio de Salud, Desarrollo Social y Deportes (MSDSyD). CONCLUSIONES: El COPTES sugiere la cobertura de Golimumab y Tocilizumab para el tratamiento de AR refractaria bajo los criterios de inclusión: Pacientes adultos con AR Activa (DAS28-4 ≥ a 5,1) y Refractaria (a 3 medicamentos no biológicos, incluidos metrotexate y leflunomida, a dosis máximas, durante 6 meses) atendidos en establecimientos del MSDSyD con cobertura estatal exclusiva. El Comité debatió acerca de la importancia de que las drogas de primera línea estén disponibles para la prescripción de manera de evitar la progresión de las lesiones. El presente documento queda sujeto al uso del correcto criterio clínico y de gestión sanitaria que se maximicen los beneficios en toda la población bajo cobertura del Ministerio de Salud.(AU)