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BACKGROUND: Lupus nephritis affects 40 to 70% of Systemic Lupus Erythematous(SLE) patients increasing their morbi-mortality; therefore, successful treatments are required to improve outcomes. RESEARCH DESIGN AND STUDY SAMPLE: In this paper 20 patients who participated in the BLISS LN trial at a single center (OMI) in Argentina were studied. All the patients continued Mycophenolate (MMF) treatment when the trial was finished and until a second biopsy was performed to determine the withdrawal of the immunosuppression according to the achieved clinical and histological response. Ten patients treated with MMF + Placebo versus 10 receiving MMF + Belimumab, were compared evaluating the complete clinical (CCR) and complete histological response (CHR) and the flares in each group. RESULTS: All the patients in the Belimumab group showed a CCR and 7 in the Placebo one; CHR was found in 9 and 5 patients of the Belimumab and Placebo group, respectively. None of the patients in the Belimumab group flared meanwhile two of the Placebo one did it. CONCLUSIONS: Although the number of patients is insufficient to be able to draw unquestionable conclusions, adding Belimumab to the standard of care treatment with MMF would seem to increase the possibility of achieving a CCR, CHR, and a lower rate of relapses during treatment and long follow-up.

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O lúpus eritematoso sistêmico (LES) é uma doença de caráter imunomediado, ocasionada por fatores hormonais, ambientais e genéticos. Caracteriza-se pela presença de autoanticorpos reativos para diferentes células e tecidos, apresentando manifestações clínicas diversificadas, períodos de exacerbação e remissão, o que dificulta o tratamento desses pacientes. Este relato de caso destaca o progresso do uso de anticorpo monoclonal humano em uma paciente do gênero feminino, diagnosticada com LES em maio de 2019, aos 30 anos, e, por ser refratária ao tratamento medicamentoso convencional, utilizou o tratamento com anticorpo monoclonal humano belimumabe, com início em setembro de 2019. O belimumabe é um anticorpo monoclonal humano que se liga à proteína estimuladora de linfócito B (BLyS) solúvel, inclusive dos autorreativos, e desta maneira, reduz a diferenciação de linfócitos B em plasmócitos, diminuindo os níveis de IgG sérica e dos anticorpos anti-dsDNA, além de melhorar o quadro clínico dos pacientes. Apesar de ser um medicamento biológico de alto custo, diminui drasticamente os sintomas clínicos do LES, possibilitando a redução do uso do corticoide e os efeitos consequentes de seu uso, além de reestabelecer os parâmetros laboratoriais alterados pela doença, sem alteração de indicadores hepáticos e renais. O LES não tem cura, logo, o objetivo do tratamento é diminuir os sintomas e conter as fases ativas da doença.

Systemic lupus erythematosus is an immune-mediated disease caused by hormonal, environmental and genetic factors. It is characterized by the presence of reactive autoantibodies to different cells and tissues, with diverse clinical manifestations and periods of exacerbation and remission, which complicates treatment. This case report highlights progress with the use of a human monoclonal antibody in a woman diagnosed with systemic lupus erythematosus in May 2019 (at age 30). Since she was refractory to conventional drugs, belimumab treatment was begun in September 2019. Belimumab is a human monoclonal antibody that binds to soluble B lymphocyte-stimulating proteins, including self-reactive ones, and reduces the differentiation of B lymphocytes into plasma cells, decreasing the serum IgG and anti-dsDNA antibody levels, in addition to improving patient clinical status. Despite being a high-cost biological drug, it drastically reduces the clinical symptoms of systemic lupus erythematosus, enabling reduced used of corticosteroids and their effects, in addition to reestablishing laboratory parameters altered by the disease, without changing liver and kidney indicators. Since systemic lupus erythematosus has no cure, the goal of treatment is to reduce symptoms and the active phases of the disease.

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Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

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Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

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OBJECTIVE: To describe clinical effectiveness of belimumab for systemic lupus erythematosus (SLE) in real-world practice in Argentina. METHODS: This retrospective, observational study analysed medical record data of patients with SLE treated with belimumab in 15 centres in Argentina. Primary endpoint: overall clinical response (assessed on a scale similar to the 6-point Physician Global Assessment) at months 6, 12, 18 and 24, all versus index (belimumab initiation). Secondary endpoints: improvement in disease activity (SELENA-SLEDAI), SLE manifestations, and corticosteroid dose change. RESULTS: Records for 81 patients (91% female) were analysed. Clinical improvements were reported for 95%, 95%, 98% and 100% patients at 6, 12, 18, and 24 months post index, respectively. Mean SELENA-SLEDAI score decreased from 11.21 at index to 4.76, 3.77, 3.86 and 2.17 at 6, 12, 18, and 24 months post index, respectively. Number of flares decreased from 1.05 at index to 0.21, 0.09, 0.22 and 0.30 at 6, 12, 18, and 24 months post index, respectively. Mean corticosteroid dose was 14.59 mg/day at index, and 6.45, 5.18, 5.17 and 4.78 mg/day at 6, 12, 18, and 24 months post index, respectively. CONCLUSIONS: Real-world patients with SLE treated with belimumab in Argentina demonstrated clinical improvements and reductions in corticosteroid dose.

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Management of systemic lupus erythematosus patients is challenging because of disease heterogeneity. Although treatment of renal nephritis is more standardized, treating non-renal lupus activity remains controversial. Our objective was to identify non-renal, non-neurologic persistent active systemic lupus erythematosus patients in our cohort and described therapeutic behaviors in them. All systemic lupus erythematosus patients (American College of Rheumatology and/or Systemic Lupus Erythematosus International Collaborating Clinics criteria) seen at a university hospital between 2000 and 2017 were included and electronic medical records manually reviewed. Persistent lupus activity was defined as a patient with a Systemic Lupus Erythematosus Disease Activity Index score ≥ 6 (without renal and central nervous system manifestations) despite being on a stable treatment regimen for ≥ 30 days. Stable treatment could include prednisone alone (7.5-40 mg/d) or combined with antimalarial drugs and immunosuppressant therapies. A total of 257 lupus patients were included, 230 females (89.5%, 95% confidence interval 85.1-92.7), mean age at diagnosis 29.9 years (SD 16.4). After a median cohort follow-up of 5.7 years (interquartile range 2.4-10.2), 14 patients (5.4%, 95% confidence interval 3.2-9.0) showed persistent non-renal non neurologic lupus activity, with a median disease duration of 11.3 years (interquartile range 3.6-19.4). At that time, 12/14 (85.7 %, 95% confidence interval 52.6-97.0%) had low complement and 11/14 (78.6 %, 95% confidence interval 46.5-93.9%) had positive antiDNA antibodies. The main reasons for being refractory were mucocutaneous disease (50%, 95% confidence interval 23.5-76.5) and arthritis (42.9%, 95% confidence interval 18.5-71.2). Therapeutic choices after being refractory were: only increasing corticosteroid dose in one patient, starting rituximab in four, belimumab in eight, and in one mycophenolate and rituximab; with good response in all of them. In conclusion, 5.4% of systemic lupus erythematosus patients in our cohort were considered to have non-renal non neurologic persistent lupus activity, with mucocutaneous and arthritis the main manifestations. In total, 92.8% of these patients started a biologic treatment at this point (rituximab or belimumab).

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INTRODUCTION: Systemic lupus erythematous is an autoimmune disease with diverse clinical features and has its development associated with a complexity of genetic, hormonal and environmental factors and the development of autoantibodies. Identification of new treatments is currently an area of intense investigation. Belimumab is the first biologic approved for the treatment of the disease inhibiting the excessive B cell activity observed in these patients and consequently reduction of autoantibodies. AIM: To review the current transition of the evidence available of its use in real life patients with persistent active disease while on conventional therapies. EVIDENCE: The results observed on the large series of patients (over 50 patients) followed for at least six months confirm the observations from phase 3 trials. In clinical practice close to two third of the patients remained on belimumab and one third discontinued mostly due to evaluation by the doctor or the patient or both of no detectable positive response. The presence of adverse events was considerably low and the subgroups with skin and joint manifestations appear to benefit the most. Daily steroid use is usually reduced to a significantly low when compared with the intake before introduction of the biologic Although not seen on trials in real life the addition of belimumab to the conventional therapy in lupus nephritis is being reported in several patients. Cost of the medication is still an issue that hampers its use. Further evidence of its use in certain specific groups is under investigation and its results should shed light on additional indications. PLACE IN THERAPY: Considering what is currently published on the evidence here reviewed in the use of belimumab in clinical practice it is our understanding that belimumab it will be gradually incorporated in the armamentarium of treatment not necessarily on refractory patients. We believe that with the upcoming of the subcutaneous route in the near future should also help in widen the use of the belimumab to be considered in first line combination set ups.

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El lupus eritematoso sistémico (LES) esuna enfermedad de tipo autoinmune en donde existen múltiples factores que inducen una respuesta inmunológica no controlada en un individuo que genéticamente está predispuesto, presentándose una variedad de manifestaciones clínicas que muchas veces se convierten en un verdadero reto diagnóstico y terapéutico como es el caso de sus presentaciones en piel. Describiremos a continuación un caso de un paciente género masculino con diagnostico LES con lesiones cutáneas extensas severas con diagnóstico clínico yhistopatológico sugestivo de lupus ampolloso refractarias a tratamiento estándar con corticoterapia e inmunomoduladores con evolución tórpida en su curso, que requiere posteriormente inicio de terapia biológica con Belimumab observándose una remisión clínica significativa de las lesiones y contribuyendo además a disminuir las dosis de corticoides utilizadas desde su ingreso . Se revisaránaspectos en relación del LES en hombres en lo que refiere a epidemiologia, manifestaciones cutáneas, hallazgos histopatológicos, diagnóstico diferencial y opciones terapéuticas actuales.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which multiple factors induce an uncontrolled immune response in an individual who is genetically predisposed, presenting a variety of clinical manifestations that often become a real diagnostic challenge and Therapeutic as in the case of their skin presentations. We will now describe a case of a malepatient with a SLE diagnosis with severe extensive skin lesions with clinical and histopathological diagnosis suggestive of blistering lupus refractory to standard treatment with corticosteroid therapy and immunomodulators with a morphologic evolution in their course, which then requires the initiation of biological therapy with Belimumab observed a significant clinical remission of the lesions and also contributing to decrease the doses of corticosteroids used since their entry. We will review aspects related to SLE in men in terms of epidemiology, cutaneous manifestations, histopathological findings, differential diagnosis and current therapeutic options

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Resumen Introducción: El belimumab es un anticuerpo monoclonal tipo IgG1 que se une e inhibe la forma soluble de Blys (estimulador de linfocitos B) y ha mostrado efectividad en el manejo del lupus eritematoso sistémico (LES). Sin embargo, se desconoce su efectividad en una población tan variable étnicamente como la colombiana. Métodos: Se realizó un estudio prospectivo observacional entre febrero de 2015 y febrero de 2016, en pacientes con LES, con enfermedad activa a pesar del tratamiento estándar, quienes fueron tratados con belimumab. Resultados: El uso de belimumab se relacionó con una mejoría significativa en los compromisos articular, cutáneo y hematológico, con aumento de los niveles de complemento, disminución de las exacerbaciones por LES y de las hospitalizaciones, además de una menor actividad calculada por SLEDAI después de 3 meses de utilización y con una estabilidad mantenida hasta los 9 meses. Conclusiones: Se observó que el belimumab es útil en pacientes colombianos con LES que son refractarios a la terapia estándar, especialmente en manifestaciones articulares, hematológicas y cutáneas, en un entorno de pacientes de la vida real.

Abstract Introduction: Belimumab, a monoclonal type Ig G1 antibody that binds and inhibits the Belimumab soluble form of the Blys (B lymphocyte stimulator) has shown to be effective in the manamanagement of systemic lupus erythematosus (SLE). However, its effectiveness is unknown in an ethnically variable population, such as in Colombia. Methods: A prospective observational study was conducted between February 2015 and February 2016 on patients with active SLE disease despite being on standard treatment and who were treated with Belimumab. Results: Belimumab showed a significant improvement in joint, cutaneous and haematological involvement, with an increase in complement levels, a decrease in lupus crises and hospital admissions. After 3 months there was lower activity, calculated by SLEDAI, with stability for 9 months. Conclusions: In a real-life patient setting, it was observed that belimumab was useful in Colombian patients with SLE and refractory to standard therapy, especially in the joint, haematological, and cutaneous manifestations.

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