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1.
Rev Med Suisse ; 16(685): 487-491, 2020 Mar 11.
Artículo en Francés | MEDLINE | ID: mdl-32167250

RESUMEN

Targeted therapies are nowadays commonly used in connective tissue diseases and vasculitis. Experts recommend the use of belimumab and rituximab in refractory and/or severe cases of lupus. Rituximab can be also considered in difficult to treat cases of Sjögren's disease or myositis. Nintedanib seems a very promising weapon in the management of systemic sclerosis-associated pulmonary fibrosis. Regarding vasculitis, rituximab has become the preferred treatment for granulomatosis with polyangiitis and microscopic polyangiitis. Finally, tocilizumab is recommended as a steroid-sparing agent in giant cell arteritis. Further clinical trials are warranted to study the efficacy of other targeted therapies in connective tissue diseases and vasculitis.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Rituximab/uso terapéutico , Vasculitis/tratamiento farmacológico , Arteritis de Células Gigantes/tratamiento farmacológico , Humanos , Miositis/tratamiento farmacológico , Síndrome de Sjögren/tratamiento farmacológico
2.
BMJ ; 368: m421, 2020 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-32188597

RESUMEN

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a small to medium vessel vasculitis associated with excess morbidity and mortality. This review explores how management of AAV has evolved over the past two decades with pivotal randomized controlled trials shaping the management of induction and maintenance of remission. Contemporary AAV care is characterized by approaches that minimize the cumulative exposure to cyclophosphamide and glucocorticoids, increasingly use rituximab for remission induction and maintenance, and consider therapies with less toxicity (for example, methotrexate, mycophenolate mofetil) for manifestations of AAV that do not threaten organ function or survival. Simultaneously, improvements in outcomes, such as renal and overall survival, have been observed. Additional trials and observational studies evaluating the comparative effectiveness of agents for AAV in various patient subgroups are needed. Prospective studies are necessary to assess the effect of psychosocial interventions on patient reported outcomes in AAV. Despite the expanding array of treatments for AAV, little guidance on how to personalize AAV care is available to physicians.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Azatioprina , Ciclofosfamida/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Metotrexato/uso terapéutico , Ácido Micofenólico/uso terapéutico , Inducción de Remisión , Rituximab/uso terapéutico
3.
Medicine (Baltimore) ; 99(8): e19193, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080104

RESUMEN

BACKGROUND: This meta-analysis aimed to explore the efficacy and safety of rituximab combined with methotrexate (MTX) versus MTX alone in the treatment of rheumatoid arthritis (RA). METHODS: We performed an electronic search of PubMed (1950-January 2018), EMBASE (1974-January 2018), the Cochrane Library (January 2018 Issue 3), the Google database (1950-January 2018), and the Chinese Wanfang database (1950-January 2018). Only randomized controlled trials (RCTs) were included. The American College of Rheumatology 20% improvement criteria (ACR20), ACR50, ACR70, total complication rate, and infection rate were the outcomes. A fixed/random effects model was used according to the heterogeneity assessed by the I statistic. Data analysis was performed using Stata 12.0 software. RESULTS: A total of five RCTs with 3299 patients (rituximab combined with MTX group = 1787, MTX only group = 1512) were included in the meta-analysis. The pooled risk ratio showed that the administration of rituximab combined with MTX was associated with more ACR20, ACR50, and ACR70 than the administration of MTX only (P < .05). There were no significant differences between the two groups in terms of the total complication rate and the infection rate (P > .05). CONCLUSION: The administration of rituximab combined with MTX was effective and safe for RA patients. Additional high-quality RCTs with long-term follow-ups should be conducted in the future to identify the potential complications in the long term.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/uso terapéutico , Rituximab/uso terapéutico , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Productos Biológicos/uso terapéutico , Quimioterapia Combinada , Humanos , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Rituximab/administración & dosificación
4.
Medicine (Baltimore) ; 99(6): e18590, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32028388

RESUMEN

RATIONALE: The specific pathogenesis of the diffuse large B-cell lymphoma(DLBCL)is still indefinite and argumentative. It is known that DLBCL is the most common type of non-Hodgkin's lymphomas (NHL). A lot of cases of DLBCL such as primary gastric diffuse large B-cell lymphoma(PG-DLBCL) are reported. However, primary intestinal diffuse large B-cell lymphoma(PI-DLBCL) is unusual. PATIENT CONCERNS: We present a case of a 57-year-old male diagnosed in the Gastroenterology Department, which presented a bleeding duodenal ulcer with irregular borders. DIAGNOSES: The immunohistochemical staining showed: CD20(+++), CD10(+) and Ki-67>40%. INTERVENTIONS: The patient was successfully treated by Poly-chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vindesine and prednisolone). OUTCOMES: After 6 courses of chemotherapy treatment, the duodenal ulcer was completely healed by reviewing the UGIE. LESSONS: Our report might give further strength to avoiding the erroneous and missed diagnosis for PI-DLBCL which is different from common duodenal ulcer.


Asunto(s)
Úlcera Duodenal/etiología , Neoplasias Intestinales/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Diagnóstico Diferencial , Doxorrubicina/uso terapéutico , Humanos , Inmunohistoquímica , Neoplasias Intestinales/complicaciones , Neoplasias Intestinales/diagnóstico por imagen , Neoplasias Intestinales/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéutico
5.
N Engl J Med ; 382(7): 622-631, 2020 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-32053298

RESUMEN

BACKGROUND: More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS: Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Glucocorticoides/administración & dosificación , Fallo Renal Crónico/prevención & control , Intercambio Plasmático , Administración Oral , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Terapia Combinada , Ciclofosfamida/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Quimioterapia de Inducción , Enfermedades Renales/complicaciones , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Intercambio Plasmático/efectos adversos , Rituximab/uso terapéutico
6.
Harefuah ; 159(1): 31-33, 2020 Jan.
Artículo en Hebreo | MEDLINE | ID: mdl-31930805

RESUMEN

INTRODUCTION: Pemphigus is a chronic autoimmune bullous disease. To date there is no curative treatment for the disease. The standard treatment has been based on systemic corticosteroids and immune-suppressants. Rituximab is a monoclonal antibody against CD20 cells which leads to B cell depletion, resulting in decreased antibody production. In recent years increasing evidence on promising efficacy and safety of rituximab in the treatment of pemphigus has emerged. This review presents the key publications and the Israeli experience with rituximab treatment at the Rabin and the Sheba Medical Centers. Disclosure: Prof. Daniel Mimouni participated in an advisory board of Roche.


Asunto(s)
Enfermedades Autoinmunes , Factores Inmunológicos/uso terapéutico , Pénfigo/tratamiento farmacológico , Rituximab/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Humanos , Inmunosupresores
7.
Hematol Oncol ; 38(1): 67-73, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31724191

RESUMEN

BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m2 for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was -20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (-12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Antineoplásicos Inmunológicos/farmacocinética , Biosimilares Farmacéuticos/farmacocinética , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/patología , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Pronóstico , Rituximab/farmacocinética , Distribución Tisular
8.
J Oral Pathol Med ; 49(1): 91-95, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31420993

RESUMEN

BACKGROUND: Pemphigus vulgaris patients with exclusive oral involvement (OPV) treated with conventional immunosuppressive therapy may be non-responders or experience severe side effects and/or relapses. In such cases, rituximab could be used as an adjuvant in recalcitrant OPV patients. METHODS: A retrospective single-center study on patients with oral pemphigus vulgaris treated with RTX at a dose of 375 mg/m2 was performed, evaluating the complete clinical and immunological remission, side effects of RTX, and possible correlation between anti-desmoglein (Dsg) 3 antibodies and clinical remission. RESULTS: We treated 10 OPV patients, of which 60% had a moderate and 40% mild disease severity before therapy with RTX. Complete clinical remission (CCR) was achieved in 100% of OPV patients, of which 20% developed side effects and 20% experienced a relapse in a mean time of 15.2 ± 10.2 weeks. The mean time for CCR was achieved in 19.8 ± 10.3 weeks, whereas the duration of the CCR consisted in 37.4 ± 33.5 weeks. OPV patients underwent a mean follow-up of 57.2 ± 37.7 weeks. In all patients, the mean of pemphigus disease area index (PDAI) decreased from 20.3 ± 14.1 to 0.4 ± 0.0, whereas the mean Dsg3 value dropped from 157.1 ± 40.6 to 67.0 ± 26.6 after therapy with RTX. However, no correlation was found between PDAI and anti-Dsg3 antibodies before and after therapy with RTX (P > .05). CONCLUSIONS: RTX represents a valid and safe alternative as an adjuvant in OPV patients with low rate of relapses and side effects.


Asunto(s)
Pénfigo , Rituximab/uso terapéutico , Desmogleína 3 , Humanos , Inmunosupresores , Pénfigo/tratamiento farmacológico , Estudios Retrospectivos
9.
Autoimmun Rev ; 19(2): 102453, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31838163

RESUMEN

INTRODUCTION: The effectiveness of CD20 targeting in connective tissue diseases (CTD) with lung involvement is controversial. This paper aims to review the current evidence about rituximab (RTX) use in CTD-related interstitial lung disease (ILD). METHODS: We performed a systematic review of papers published between January 2009 and May 2019. We included clinical trials, case/control studies and cohort studies. We excluded letters, case reports, case series, reviews, and full articles when not in English. The selected studies listed as primary or secondary outcome a variation in pulmonary function tests or in the scores used to radiologically stage lung involvement, in CTD-related ILD patients after RTX. RESULTS: Out of 1206 potentially eligible articles, 24 papers were selected: 3 retrospectively described cohorts of patients with different CTD, 14 dealt with systemic sclerosis (SSc)-related ILD, 5 with idiopathic inflammatory myopathies (IIMs)-related ILD, and 2 with Sjögren's Syndrome-related ILD. A direct comparison of the selected studies was hampered by their heterogeneity for outcomes, follow-up duration, the severity of lung involvement, and clinical features of study populations. However, an overall agreement existed concerning the effectiveness of RTX in the stabilization of lung disease, with some studies reporting an improvement of functional parameters from baseline. IIM-related ILD appeared more responsive than other CTD-related ILD to CD20 targeting. CONCLUSION: RTX is a promising therapeutic tool in CTD-related ILD. This systematic review remarks the unmet need of multicenter prospective studies aiming to evaluate the effectiveness of RTX with adequate sample size and study design.


Asunto(s)
Antígenos CD20/inmunología , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Rituximab/inmunología , Rituximab/uso terapéutico , Humanos , Estudios Retrospectivos
10.
Lancet ; 394(10216): 2271-2281, 2020 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-31868632

RESUMEN

BACKGROUND: Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis. METHODS: This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany. We enrolled patients aged 18-60 years, with stage I-II disease, normal serum lactate dehydrogenase concentration, ECOG performance status 0-1, and without bulky disease (maximal tumour diameter <7·5 cm). Randomisation was computer-based and done centrally in a 1:1 ratio using the Pocock minimisation algorithm after stratification for centres, stage (I vs II), and extralymphatic sites (no vs yes). Patients were assigned to receive either six cycles of R-CHOP or four cycles of R-CHOP plus two doses of rituximab. CHOP comprised cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1·4 mg/m2, with a maximum total dose of 2 mg), all administered intravenously on day 1, plus oral prednisone or prednisolone at the discretion of the investigator (100 mg) administered on days 1-5. Rituximab was given at a dose of 375 mg/m2 of body surface area. Cycles were repeated every 21 days. No radiotherapy was planned except for testicular lymphoma treatment. The primary endpoint was progression-free survival after 3 years. The primary analysis was done in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of assigned treatment. A non-inferiority margin of -5·5% was chosen. The trial, which is completed, was prospectively registered at ClinicalTrials.gov, NCT00278421. FINDINGS: Between Dec 2, 2005, and Oct 7, 2016, 592 patients were enrolled, of whom 295 patients were randomly assigned to receive six cycles of R-CHOP and 297 were assigned to receive four cycles of R-CHOP plus two doses of rituximab. Four patients in the four-cycles group withdrew informed consent before the start of treatment, so 588 patients were included in the intention-to-treat analysis. After a median follow-up of 66 months (IQR 42-100), 3-year progression-free survival of patients who had four cycles of R-CHOP plus two doses of rituximab was 96% (95% CI 94-99), which was 3% better (lower limit of the one-sided 95% CI for the difference was 0%) than six cycles of R-CHOP, demonstrating the non-inferiority of the four-cycles regimen. 294 haematological and 1036 non-haematological adverse events were documented in the four-cycles group compared with 426 haematological and 1280 non-haematological adverse events in the six-cycles group. Two patients, both in the six-cycles group, died during study therapy. INTERPRETATION: In young patients with aggressive B-cell non-Hodgkin lymphoma and favourable prognosis, four cycles of R-CHOP is non-inferior to six cycles of R-CHOP, with relevant reduction of toxic effects. Thus, chemotherapy can be reduced without compromising outcomes in this population. FUNDING: Deutsche Krebshilfe.


Asunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/administración & dosificación , Administración Intravenosa , Administración Oral , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Dinamarca , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Esquema de Medicación , Femenino , Alemania , Humanos , Cooperación Internacional , Israel , Italia , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Noruega , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Estudios Prospectivos , Rituximab/uso terapéutico , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/uso terapéutico , Adulto Joven
11.
Medicine (Baltimore) ; 98(50): e18393, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852157

RESUMEN

RATIONALE: Pyothorax-associated lymphoma (PAL) is a rare type of malignant pleural lymphoma. Most lymphomas are normally discovered around 20 to 50 years after tuberculosis infection. In China, there have been few reports about PAL cases so far. We report a case of a patient, whose tuberculosis and lymphoma were diagnosed concurrently. PATIENT CONCERNS: The patient, a 76-year-old male, was reported to our hospital on March 13, 2015. He had recurrent shortness of breath during the previous 2 years of routine activities solely. His symptoms became more serious which was manifested by edema of lower limbs 1 day before his admission to our hospital. DIAGNOSES: Doctors reached the diagnosis of PAL based on the patient's pathologic cell morphology and immunohistochemistry. The chest computed tomography examination revealed that there were pleural effusions on both sides, and some extent of compressive atelectasis in the lower parts of the inflamed lungs yet without space-occupying lesions. There were multiple small nodules which may be benign in the right upper lung. INTERVENTIONS: The current first-line treatment for diffuse large B-cell lymphoma is the cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) protocol. Given that the patient had cardiac diseases and cardiotoxicity of anthracyclines, doctors decided to adopt rituximab with cyclophosphamide, vincristine, and prednisone chemotherapy without anthracyclines. OUTCOMES: The treatment effect was obvious after one cycle of chemotherapy. The patient's pleural and pericardial effusions were significantly reduced. With the chemotherapy protocol above continuously adopted, pleural and pericardial effusions did not increase in multiple reexaminations on October 25, 2015, February 15, 2016, and August 10, 2016. LESSONS: Analytical research revealed that chemotherapy with rituximab can increase the complete remission rate of non-Hodgkin lymphoma, reduce the possibility of failure and relapse, and prolong disease-free and overall survival. Moreover, there is no significant increase in adverse drug reactions compared with the effect of chemotherapy with CHOP alone. In the case of this patient, chemotherapy with rituximab was safe and efficacious.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Empiema Pleural/etiología , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Masculino , Neoplasias Pleurales/diagnóstico
12.
Medicine (Baltimore) ; 98(51): e18139, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31860960

RESUMEN

RATIONALE: Rituximab is recommended to induce remission of severe granulomatosis with polyangiitis (GPA). Plasma exchange (PE) may be considered in the setting of rapidly progressive glomerulonephritis (RPGN) with a serum creatinine increase of more than 5.6 mg/dl or diffuse alveolar hemorrhage (DAH). However, there are no sufficient studies on combination therapy with rituximab and PE in GPA. PATIENT CONCERNS: A 23-year-old woman was admitted with fever, abdominal pain, and diarrhea on suspicion of infectious colitis. Colonoscopy showed hemorrhagic colitis and antibiotic treatment was ineffective. Physical examination revealed episcleritis and skin lesions similar to Janeway lesions or Osler nodes on her palms and soles. Transesophageal echocardiogram (TEE) revealed mitral valve vegetation mimicking infective endocarditis. However, no pathogen was grown in the blood culture. Ten days after admission, blood-tinged sputum and respiratory distress developed. Imaging studies of lung, bronchoscopy, and bronchoalveolar lavage indicated DAH. Moreover, serum creatinine levels rapidly increased from 0.8 mg/dl to 6.1 mg/dl with proteinuria. DIAGNOSIS: The patient was diagnosed with GPA and non-infectious endocarditis, DAH, and RPGN, based on a biopsy which revealed pauci-immune crescentic glomerulonephritis with granuloma and leukocytoclastic vasculitis and antineutrophil cytoplasmic antibodies against proteinase 3- positivity. INTERVENTIONS: Initial methylprednisolone pulse therapy (1 g daily for 3 days) proved unsuccessful. After initiating PE, creatinine levels began to slowly decline, but DAH continued to deteriorate. Rituximab combined with PE therapy was considered. We performed PE every 2 to 3 days for 5 total treatments combined with rituximab (375 mg/m, once weekly for 4 weeks). OUTCOMES: After the combination treatment of rituximab and PE, alveolar hemorrhage stopped. Chest X-ray and laboratory data, including serum creatinine and hemoglobin, notably improved. Mitral valve vegetation was no longer observed in follow-up TEE. GPA remained stable with low dose prednisolone and immunosuppressants over a follow-up period of 5 years. LESSONS: This case suggests that the use of rituximab and concurrent PE may represent a promising combination for severe and refractory GPA.


Asunto(s)
Granulomatosis con Poliangitis/patología , Granulomatosis con Poliangitis/terapia , Intercambio Plasmático/métodos , Rituximab/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Biopsia con Aguja , Colitis/diagnóstico , Colitis/etiología , Colonoscopía/métodos , Terapia Combinada , Esquema de Medicación , Servicio de Urgencia en Hospital , Femenino , Estudios de Seguimiento , Granulomatosis con Poliangitis/diagnóstico , Humanos , Inmunohistoquímica , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto Joven
13.
Mayo Clin Proc ; 94(11): 2199-2208, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31685150

RESUMEN

OBJECTIVE: To evaluate the impact of the sequence of treatment with rituximab and/or splenectomy on time to relapse for patients with steroid-refractory immune thrombocytopenia (ITP). PATIENTS AND METHODS: Patients 18 years or older with steroid-refractory immune thrombocytopenia who underwent treatment with splenectomy or rituximab from January 1, 2002, through December 31, 2015, at Mayo Clinic. Evaluation included freedom from relapse (FFR) and response rates after treatment with rituximab or splenectomy as single or sequential interventions. RESULTS: A total of 218 eligible patients with ITP who were treated according to standard of care were included in this analysis. Patients failing steroids treated with splenectomy had a higher 5-year FFR than did those treated with rituximab (67.4% vs 19.2%; P<.001, propensity-score matched). Patients who failed splenectomy and were then treated with rituximab had a 2-year FFR similar to that of patients who failed rituximab and were then treated with splenectomy (73.4% vs 59.9%; P=.52). Patients treated with rituximab after splenectomy had a longer 2-year FFR than did patients treated with rituximab as a second-line treatment (73.4% vs 29.0%; P<.001). CONCLUSION: For patients with ITP that relapse after treatment with steroids, splenectomy provides longer FFR than rituximab as a second-line therapy. Among patients who fail second-line treatment with splenectomy or rituximab, those who end up receiving sequential splenectomy-rituximab or rituximab-splenectomy therapy seem to derive similar benefit in the long term. Patients who received rituximab after splenectomy seem to derive superior benefit than do those who are treated with rituximab with an intact spleen.


Asunto(s)
Inmunosupresores/uso terapéutico , Púrpura Trombocitopénica Idiopática/terapia , Rituximab/uso terapéutico , Esplenectomía/métodos , Esteroides/uso terapéutico , Adulto , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/fisiopatología , Análisis de Supervivencia , Resultado del Tratamiento
14.
Medicine (Baltimore) ; 98(44): e17801, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689860

RESUMEN

RATIONALE: Anti-glomerular basement membrane (GBM) disease is a T cell-mediated disease that has a poor prognosis with conventional therapy. We tested rituximab as a primary therapy to reduce anti-GBM antibody produced by B cells. PATIENT CONCERNS: A 53-year old woman with complaints of a fever, headache and abdominal discomfort showed renal failure with elevated anti-GBM antibody, and renal biopsy revealed crescentic necrotizing glomerulonephritis with linear immunoglobulin G (IgG) 1 deposition along GBM. DIAGNOSES: The patient's plasma contained autoantibodies against Goodpasture antigen, which is the NC domain of collagen IVα3, and CD4-positive helper T cells were found surrounding crescent glomeruli with the coexistence CD20-positive B cells. INTERVENTIONS: Rituximab with steroid and plasma exchange. OUTCOMES: The levels of autoantibody for Goodpasture antigen were reduced, and the patient was able to temporarily withdraw from hemodialysis. LESSONS: B cell depletion with rituximab is effective as an initial therapy for anti-GBM disease.


Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Intercambio Plasmático/métodos , Rituximab/uso terapéutico , Esteroides/uso terapéutico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/sangre , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Autoanticuerpos/sangre , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Resultado del Tratamiento
15.
Medicine (Baltimore) ; 98(46): e17856, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31725626

RESUMEN

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a paraneoplastic limbic encephalitis, recently identified.To summarize our experience in the nursing care of patients with anti-NMDAR encephalitis managed with surgery and pharmacotherapy.This study included 45 patients treated between July 2015 and November 2016. Laparoscopic oophorocystectomy was performed in 11 female patients with teratomas. Eleven patients required tracheal intubation or tracheotomy and ventilation.The patients were hospitalized for an average of 25.2 days. The mental and neurological symptoms were significantly relieved 23.6 ± 4.8 days after surgery or immunotherapy. Near-normal function was restored in 11 patients, while 34 patients had varying degrees of dysfunction at discharge. After follow-up of 1 to 18 months, 24 patients were found to have permanent impairments.Appropriate symptomatic nursing care is required to ensure the safety of patients with anti-NMDAR encephalitis.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Encefalitis Antirreceptor N-Metil-D-Aspartato/enfermería , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Niño , Femenino , Humanos , Inmunoglobulina G/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/cirugía , Estudios Retrospectivos , Rituximab/uso terapéutico , Teratoma/complicaciones , Teratoma/cirugía , Adulto Joven
16.
Chem Commun (Camb) ; 55(96): 14506-14509, 2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31735949

RESUMEN

Polymers are an attractive anchoring platform for the synthesis of radioimmunoconjugates. They enable independent control over the amount of radioisotope loading and antibody attachment, which is pivotal in developing tailorable formulations for personalised medicine. Herein, we report the synthesis of p(HEMA-ran-GMA) for the conjugation of lutetium ions and rituximab as a functional platform for radioimmunotherapy. We demonstrate the suitability of this platform using non-Hodgkin's lymphoma cells.


Asunto(s)
Inmunoconjugados/química , Linfoma no Hodgkin/radioterapia , Radioinmunoterapia , Antineoplásicos Inmunológicos/química , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Química Clic , Compuestos Epoxi/química , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Lutecio/química , Metacrilatos/química , Polímeros/química , Rituximab/química , Rituximab/farmacología , Rituximab/uso terapéutico
17.
Presse Med ; 48(11 Pt 2): 319-327, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31759790

RESUMEN

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease related to the formation of microvascular thrombosis and subsequent organ failure. The disease is accompanied with microangiopathic haemolytic anaemia, consumptive thrombocytopenia and lies on a severe deficiency in ADAMTS13, the von Willebrand factor-cleaving protease. In the acquired, immune-mediated form, this deficiency is due to the production of autoantibodies directed against the enzyme. Therapeutic plasma exchange has been used empirically for decades and still represents the cornerstone of TTP treatment. However, a better understanding of pathophysiological mechanisms underlying the disease has led these last years to the development of highly effective targeted therapies that might in the future restraint the use of therapeutic plasma exchange.


Asunto(s)
Proteína ADAMTS13/deficiencia , Terapia Molecular Dirigida , Intercambio Plasmático , Púrpura Trombocitopénica Trombótica/terapia , Proteína ADAMTS13/inmunología , Acetilcisteína/uso terapéutico , Corticoesteroides/uso terapéutico , Anemia Hemolítica/complicaciones , Autoanticuerpos/inmunología , Ensayos Clínicos como Asunto , Predicción , Humanos , Factores Inmunológicos/uso terapéutico , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/inmunología , Rituximab/uso terapéutico , Anticuerpos de Dominio Único/uso terapéutico
18.
Clin Biochem ; 74: 31-35, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31672652

RESUMEN

BACKGROUND: In the chronic inflammation process in the course of rheumatoid arthritis (RA), many alterations in the expression of plasma proteins, as well as their posttranslational modifications (including glycosylation) can occur. Taking into account the disturbances in protein glycosylation and the emerging new treatment regimens, the aim of this study was to assess the serum profile of transferrin isoforms in RA patients treated with biological drugs. METHODS: The study included 20 patients (16 females and 4 males; mean age: 53.4 years; range: 24-67) with rheumatoid arthritis treated with rituximab. Serum samples were taken 3 times: before and 3 and 6 months during treatment. The isoforms of transferrin were separated by capillary electrophoresis (MINICAP electrophoretic system, Sebia, France) into five major fractions: asialo-, disialo-, trisialo-, tetrasialo- and pentasialotransferrin. The results were calculated as relative concentrations of each fraction. RESULTS: The median trisialotransferrin relative concentrations after 3 and 6 months treatment (4.40% and 4.10%, respectively) were significantly higher (p = 0.013, p = 0.009, respectively) than before treatment (3.50%). The levels of serum pentasialotransferrin were also increased 3 and 6 months following treatment (16.5% and 17.7%, p = 0.005 and p = 0.006, respectively) as compared to those before therapy (14.5%), while tetrasialotransferrin concentrations were lower (80.3% and 78.4%, p = 0.009 and p = 0.008, respectively) than before treatment (81.5%). Trisialotransferrin relative concentration correlated with Hb (p = 0.019), whereas pentasialotransferrin with PLT (p = 0.036) after treatment. CONCLUSIONS: This study indicates that treatment with rituximab of RA patients alters the serum profile of transferrin isoforms. Tri-, tetra- and pentasialotransferrin relative concentrations measurements can be a useful tool to monitor therapy.


Asunto(s)
Artritis Reumatoide/sangre , Artritis Reumatoide/terapia , Productos Biológicos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Rituximab/uso terapéutico , Transferrina/análisis , Adulto , Anciano , Biomarcadores/sangre , Monitoreo de Drogas/métodos , Electroforesis Capilar , Femenino , Estudios de Seguimiento , Glicosilación , Humanos , Masculino , Persona de Mediana Edad , Isoformas de Proteínas/sangre , Índice de Severidad de la Enfermedad , Transferrina/química , Resultado del Tratamiento , Adulto Joven
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