Pooled analysis of three pharmacokinetic studies comparing biosimilar MB02 and reference bevacizumab.

AIM: The aim of this study was to add robustness and provide further evidence on the bioequivalence, safety and immunogenicity between MB02 and reference bevacizumab. No similar study has been performed before with a biosimilar monoclonal antibody. METHODS: Population analysis by pooling data from three independent pharmacokinetic (PK) studies was performed. The studies had a single-dose, double-blind, three-arm, parallel-group design and two studies, MB02-A-02-17 and MB02-A-05-18, compared MB02 to EU- and US-bevacizumab in Caucasian subjects, while study MB02-A-04-18 compared MB02 and EU-bevacizumab in Japanese participants. Primary endpoints included maximum observed serum concentration (Cmax ), area under the serum concentration-time curve (AUC) from time zero and extrapolated to infinity (AUC0-∞ ) and AUC from time zero to the time of last quantifiable concentration (AUC0-t ). Secondary endpoints included other PK parameters, safety and immunogenicity. A sensitivity analysis using actual protein concentration as a correction factor was applied to primary PK parameters. RESULTS: Point estimates and 90% confidence intervals for the geometric mean ratios of primary PK parameters for MB02, EU- and US-bevacizumab were all contained within the predefined bioequivalence margins (80%-125%) for all pairwise comparisons. The same results for all pairwise comparisons were observed when protein-corrected primary PK parameters were analyzed. Safety and immunogenicity were similar between MB02 and the EU- and US-reference bevacizumab in healthy subjects. CONCLUSIONS: This pooled analysis of three comparable PK studies further supports the bioequivalence of biosimilar MB02 to EU- and US-reference bevacizumab. No clinically meaningful differences in safety or immunogenicity were observed.

Sequential combined therapy with omalizumab and rituximab: a new approach to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disease, and a significant percentage of AD patients have severe forms. Inflammation based on type 2 helper T cells (T(H)2), autoantibodies, and CD8+ T cells could play a relevant role in this disease. When the patient requires systemic immunosuppressors for disease control, side effects are frequent. We propose a sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti-immunoglobulin [Ig] E) and rituximab (anti-CD20), which might induce clinical benefit with few side effects in selected individuals with AD. METHODS: We report 6 cases of severe AD refractory to conventional therapy. The patients underwent sequential switch therapy with omalizumab and rituximab. Clinical response was assessed by means of the decrease in body surface affected. Immunological parameters and side effects were also monitored. RESULTS: Four patients received omalizumab before a high-dose cycle of rituximab. In the case of recurrences, either low-dose cycles of rituximab or omalizumab were administered. A long-term clinical benefit was observed in 3 out of 4 patients. Two patients first received high-dose rituximab followed by either low-dose rituximab or omalizumab, and one of them achieved a response at 17 months. No severe side effects were recorded. Serum IgE level and B-cell counts decreased with therapy, the latter returning to baseline levels 10 to 11 months after treatment. Specific antibody responses remained protective during the study. CONCLUSIONS: With our proposed switch therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel strategy targets different arms of the immune response and might be a good alternative for patients with severe AD.

Sequential Combined Therapy With Omalizumab and Rituximab: A New Approach to Severe Atopic Dermatitis

Antecedentes: La dermatitis atópica (DA) es una enfermedad crónica de la piel. En un porcentaje elevado de pacientes con formas graves de DA, es probable que existan autoanticuerpos y linfocitos T CD8+ actuando junto con células Th2 en la fisiopatología. En los pacientes que requieren inmunosupresores sistémicos para controlar la enfermedad, los efectos adversos son frecuentes. En este trabajo proponemos la administración secuencial de dos terapias con anticuerpos monoclonales (omalizumab, anti-IgE y rituximab, anti-CD20) como estrategia terapéutica eficaz con un grado aceptable de efectos adversos. Métodos: Presentamos 6 pacientes con DA grave y recalcitrante a inmunosupresores convencionales que recibieron terapia secuencial con omalizumab (Xolair®)/Rituximab (MabThera®). La respuesta clínica se evaluó mediante la variación en la superficie corporal afectada. Se monitorizaron parámetros inmunológicos y efectos adversos. Resultados: Cuatro pacientes recibieron omalizumab seguido de un ciclo de alta dosis de rituximab (HR). En las siguientes recaídas se administró un ciclo de baja dosis de rituximab (LR) u omalizumab. Tres de los 4 pacientes consiguieron mejoría clínica prolongada. En 2 pacientes se administró primero HR seguido o bien por LR, o por omalizumab. Uno de ellos consiguió remisión durante 17 meses. No se registraron efectos adversos graves. La IgE y las células B séricas disminuyeron tras la terapia; estas últimas no recuperaron su nivel basal hasta 10-11 meses después. Las respuestas específicas de anticuerpos permanecieron en niveles protectores durante el estudio. Conclusiones: Con esta terapia, 4 de los 6 pacientes con DA grave consiguieron una mejoría significativa. Esta estrategia se dirige específicamente a varios mecanismos efectores del sistema inmunológico y podría ser una alternativa para un grupo seleccionado de pacientes con DA grave (AU)

Background: Atopic dermatitis (AD) is a common chronic skin disease, and a significant percentage of AD patients have severe forms. Inflammation based on type 2 helper T cells (TH2), autoantibodies, and CD8+ T cells could play a relevant role in this disease. When the patient requires systemic immunosuppressors for disease control, side effects are frequent. We propose a sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti-immunoglobulin [Ig] E) and rituximab (anti-CD20), which might induce clinical benefit with few side effects in selected individuals with AD. Methods: We report 6 cases of severe AD refractory to conventional therapy. The patients underwent sequential switch therapy with omalizumab and rituximab. Clinical response was assessed by means of the decrease in body surface affected. Immunological parameters and side effects were also monitored. Results: Four patients received omalizumab before a high-dose cycle of rituximab. In the case of recurrences, either low-dose cycles of rituximab or omalizumab were administered. A long-term clinical benefit was observed in 3 out of 4 patients. Two patients first received high-dose rituximab followed by either low-dose rituximab or omalizumab, and one of them achieved a response at 17 months. No severe side effects were recorded. Serum IgE level and B-cell counts decreased with therapy, the latter returning to baseline levels 10 to 11 months after treatment. Specific antibody responses remained protective during the study. Conclusions: With our proposed switch therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel strategy targets different arms of the immune response and might be a good alternative for patients with severe AD (AU)

Omalizumab en el tratamiento de la dermatitis atópica / Omalizumab for the Treatment of Atopic Dermatitis

La atopia se acompaña de forma casi constante de una producción elevada de inmunoglobulina E (IgE). Omalizumab es un anticuerpo monoclonal anti-IgE, que actualmente está indicado en pacientes con asma que cumplen determinados criterios. Se han publicado algunos estudios sobre la utilidad del omalizumab en el tratamiento de la dermatitis atópica (DA), con resultados variables. Presentamos nuestra experiencia en 9 pacientes con dermatitis atópica grave, refractaria al menos a dos fármacos sistémicos. Todos los pacientes tratados referían una disminución del prurito y una mejoría en su calidad de vida. Los que presentaban asma consiguieron un buen control desde el punto de vista respiratorio, sin precisar otros tratamientos adicionales. En dos casos se consiguió un buen control en monoterapia, apreciándose una discreta mejoría de las lesiones de eccema en 4 de ellos. El omalizumab es un fármaco bien tolerado y seguro. Puede ser útil en el tratamiento de pacientes con DA grave, refractaria a otros tratamientos sistémicos. Este anticuerpo monoclonal anti-IgE abre la puerta a los tratamientos inmunomoduladores sistémicos para el manejo de la DA, lo que supone un gran avance terapéutico (AU)

Atopy is almost always associated with an elevated immunoglobulin (Ig) E production. Omalizumab is a monoclonal anti-IgE antibody that is currently indicated for the treatment of cases of asthma that satisfy certain criteria. A number of studies have been published on the usefulness of omalizumab in the treatment of atopic dermatitis, and the results have been variable. We present our experience in the treatment of 9 patients with severe atopic dermatitis refractory to at least 2 systemic drugs. All patients reported a decrease in pruritus and an improvement in quality of life. Good control of the skin disease was achieved with omalizumab in monotherapy in 2 patients, and there was a slight improvement in the eczematous lesions in 4 patients. Those patients who also had asthma achieved good control of their respiratory symptoms and did not require additional therapy. Omalizumab is a well-tolerated and safe drug that can be useful for the treatment of severe atopic dermatitis refractory to other systemic therapies. This monoclonal anti-IgE antibody is a major therapeutic advance as it opens the door to the management of atopic dermatitis using systemic immunomodulating therapies (AU)

Omalizumab for the treatment of atopic dermatitis.

Atopy is almost always associated with an elevated immunoglobulin (Ig) E production. Omalizumab is a monoclonal anti-IgE antibody that is currently indicated for the treatment of cases of asthma that satisfy certain criteria. A number of studies have been published on the usefulness of omalizumab in the treatment of atopic dermatitis, and the results have been variable. We present our experience in the treatment of 9 patients with severe atopic dermatitis refractory to at least 2 systemic drugs. All patients reported a decrease in pruritus and an improvement in quality of life. Good control of the skin disease was achieved with omalizumab in monotherapy in 2 patients, and there was a slight improvement in the eczematous lesions in 4 patients. Those patients who also had asthma achieved good control of their respiratory symptoms and did not require additional therapy. Omalizumab is a well-tolerated and safe drug that can be useful for the treatment of severe atopic dermatitis refractory to other systemic therapies. This monoclonal anti-IgE antibody is a major therapeutic advance as it opens the door to the management of atopic dermatitis using systemic immunomodulating therapies.

Pericardial tamponade in a patient with polymyalgia rheumatica.

We report a patient who developed pericarditis and pericardial tamponade coinciding with polymyalgia rheumatica onset. Our patient did not show any clinical sign of vasculitis; temporal artery biopsies were negative for giant cell arteritis. Pericardial biopsy in our case shows inflammatory perivascular lymphocytary infiltrates thus we believe pericardial effusion has an inflammatory-immunologic origin. Cardiac manifestations are exceptional in polymyalgia rheumatica, though it should be considered in the differential diagnosis in patients with pericarditis over 50 years. The recognition of this uncommon manifestation is very important due to the good response to corticosteroid treatment.

Partial response to cyclosporine in a patient with Schnitzler's syndrome.

Schnitzler's syndrome is an unusual clinical association of chronic urticaria, intermittent fever and monoclonal immunoglobulin M (IgM) gammopathy. The pathogenesis of the urticaria is unclear and treatment is problematic. We describe the case of a 61-year-old woman with a long history of chronic urticaria with severe pruritus, spiking fever and malaise. The IgM-kappa monoclonal component was detected in the patient's serum 4 years after symptom onset. After ineffective treatment with antihistamines and systemic corticosteroids, oral cyclosporine resulted in complete remission of the fever and malaise, which has persisted after an 18-month follow-up. Partial but maintained remission of the urticaria was also observed, allowing corticosteroid doses to be decreased.

Partial response to Cyclosporine in a patient with Schnitzler's syndrome / Reactividad cruzada entre la parietaria y la acelga

Schnitzler's syndrome is an unusual clinical association of chronic urticaria, intermittent fever and monoclonal immunoglobulin M (IgM) gammopathy. The pathogenesis of the urticaria is unclear and treatment is problematic. We describe the case of a 61-year-old woman with a long history of chronic urticaria with severe pruritus, spiking fever and malaise. The IgM-kappa monoclonal component was detected in the patient's serum 4 years after symptom onset. After ineffective treatment with antihistamines and systemic corticosteroids, oral cyclosporine resulted in complete remission of the fever and malaise, which has persisted after an 18-month follow-up. Partial but maintained remission of the urticaria was also observed, allowing corticosteroid doses to be decreased

La alergia a la acelga es muy rara. Hasta este momento ha habido solamente informes sobre el asma inducido por el vapor de la acelga cocinada. Presentamos un estudio de dos pacientes con rinitis alérgica y positividad al prick test por Parientaria y acelga solamente. En la hipótesis de una reactividad cruzada entre el polen de Parietaria y la acelga, realizamos algunos análisis del laboratorio que demostraron IgE acelga -específica en sueros de los dos pacientes y una reactividad cruzada posible entre Parietaria y la acelga en un paciente