The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies.
To evaluate the effects of abatacept in patients with persistent, ...active rheumatoid arthritis despite methotrexate treatment.
One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004).
116 centers worldwide.
652 patients with active rheumatoid arthritis despite methotrexate treatment.
Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo.
Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year.
Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points 95% CI, 19.8 to 36.7 percentage points), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points CI, 15.0 to 31.1 percentage points), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points CI, 7.0 to 19.5 percentage points), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points CI, 25.1 to 41.7 percentage points), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points CI, 21.8 to 38.5 percentage points), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points CI, 15.6 to 29.8 percentage points), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points CI, -2.5 to 9.1 percentage points) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points CI, -0.3 to 3.6 percentage points) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points CI, 0.9 to 8.4 percentage points; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points CI, 1.2 to 14.0 percentage points) compared with placebo recipients.
The study involved only 1 group of patients over 1 year.
Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.
Diffuse Alveolar Hemorrhage in Autoimmune Diseases Martínez-Martínez, Marco Ulises; Oostdam, David Alejandro Herrera-van; Abud-Mendoza, Carlos
Current rheumatology reports,
05/2017, Letnik:
19, Številka:
5
Journal Article
Recenzirano
Purpose of Review
The present paper establishes a narrative and analytical review of diffuse alveolar hemorrhage (DAH) in ANCA-associated vasculitis, systemic lupus erythematosus, and ...antiphospholipid syndrome.
Recent Findings
Recent studies found a frequent association between DAH and infections and systemic lupus erythematosus and its associated factors. Biological therapies like rituximab have demonstrated benefit mainly in patients with ANCA-associated vasculitis.
Summary
Main clinical manifestations of diffuse alveolar hemorrhage in these three diseases include dyspnea, pulmonary infiltrates, cough, and hypoxemia. The presence of hemorrhagic bronchoalveolar lavage, hemosiderin containing macrophages, or an increase of carbon monoxide diffusing capacity have been described in some series as helpful findings for the diagnosis. Hemoptysis has been seen mainly in systemic lupus erythematosus. The cornerstone of therapy includes glucocorticoids and cyclophosphamide, and recent findings in ANCA-associated vasculitis suggest the similar benefit of rituximab. Future evaluations and systematic reviews will help to define the real benefit for therapies that appeared to be controversial at the moment.
Background
Hospitalizations due to systemic lupus erythematosus (SLE) incur substantial resource use. Hospitalization trends provide a key benchmark of the disease burden. However, there is little ...long-term data in Mexico. Therefore, we evaluated Mexican hospitalization trends for SLE during 2000–2019.
Methods
Hospitalization trends of SLE were studied using data from 2000 to 2019 releases of the National Dynamic Cubes of the General Direction of Health Information, which provides data on hospitalization discharges in Mexico. Patients aged ≥15 years hospitalized during the study period with a principal discharge diagnosis of SLE (ICD-10 code M32) were included.
Results
From 2000 to 2019, there were 17,081 hospitalizations for SLE, of which 87.6% were in females and 87% in subjects aged 15–44 years. From 2000 to 2019, the age-standardized hospitalization rate for patients with SLE increased from 0.38 per 100,000 persons to 0.65 per 100,000 persons with an average annual percentage change (APC) of 2.9% (95% CI 6.2–63.2). Although there was a significant uptrend from 2000 through 2011, there was a significant decline from 2011 to 2019 (APC: −4.8%, 95% CI −7.0% to −2.5%). Similar trends were identified in subjects aged 15–44 years and in both sexes. The length of stay and inpatient mortality decreased between 2000–2009 and 2010–2019.
Conclusions
Although there was a substantial increase in SLE hospitalizations in 2000–2019, in 2011–2019, a decreased trend was reported in younger patients and in females and males. The length of stay was also reduced.
Patients with diffuse connective tissue diseases frequently develop interstitial lung disease, which carries a worse prognosis and shortens survival. High-resolution computed tomography is the ...first-choice test, and is competitive with histopathology, however, the cost and radiation may limit its use, particularly for screening. Lung ultrasound is a rapid, accessible, reproducible, and inexpensive study that is useful for diagnosis of interstitial lung disease. Furthermore, extensive training is not required to identify the alterations associated with these lung diseases. B lines and pleural irregularities compose the ultrasonographic interstitial syndrome, although, it must be kept in mind that it is not specific, and it is necessary to rule out haemodynamic, cardiovascular, and infectious abnormalities. This review highlights the elevated prevalence of this lung condition in the main rheumatological diseases, with emphasis on the usefulness of pulmonary ultrasound.
Las enfermedades difusas del tejido conectivo con frecuencia desarrollan enfermedad pulmonar intersticial, lo que conlleva peor pronóstico y acorta la supervivencia. La tomografía axial computarizada de alta resolución es la prueba diagnóstica de elección, ya que ésta, es muy competitiva con la histopatología; sin embargo, el costo y la radiación pueden limitar su empleo, particularmente como escrutinio. El ultrasonido pulmonar, estudio rápido, de acceso fácil, reproducible y de menor costo resulta muy atractivo para determinar la existencia de enfermedad pulmonar intersticial. Adicionalmente, se requiere de poca experiencia para determinar las alteraciones correlacionables con estos padecimientos pulmonares. Las líneas B y las irregularidades pleurales conforman el denominado síndrome intersticial ultrasonográfico, aunque debemos tener en mente que no es específico y estamos obligados a considerar anormalidades hemodinámicas, cardiovasculares e infecciosas. En esta revisión, exponemos la alta prevalencia de esta patología pulmonar en los principales padecimientos reumatológicos, con énfasis en la utilidad del ultrasonido pulmonar, su facilidad de realización y alto desempeño diagnóstico.
We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis ...and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (TREG, Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for TREG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.
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