Boletín
Electrónico de la Asociación Colombiana de Reumatología
No 9.
Apreciados
Colegas: Posterior a un receso obligado por el cambio de junta,
recibo el encargo de nuestro presidente para continuar editando
el boletín ACR, con el reto de mantener el estándar de calidad
acostumbrado, sin modificaciones por el momento del esquema y
la periodicidad. De antemano solicito la colaboración de todos
ustedes a través de su retroalimentación, sugerencias y envío
de material para publicación; para que este interesante medio
de comunicación cumpla funciones de integración a través del intercambio
de noticias. En este número se presenta en noticias el reciente
etiquetaje por parte de FDA al infliximab en relación a detección
y manejo previo de infecciones por tuberculosis subyacente u otros
oportunistas en pacientes candidatos a iniciar este tratamiento.
El informe habla por sí mismo de un tema crucial para nuestra
práctica por lo niveles endémicos de tuberculosis en nuestra población
general. La revisión por expertos nos ocupa el interesante meta-análisis
de Jonathan Adachi demostrando utilidad de la terapia de reemplazo
hormonal para prevenir fracturas no vertebrales en osteoporosis
de la postmenopausia "temprana".
Remicade
(Infliximab) Prescribing Information Updated by FDA/Drug Maker.
MALVERN,
PA -- August 15, 2001 -- Centocor, Inc. announced today that it
is updating the prescribing information for Remicade® (infliximab),
a biologic drug used in the treatment of rheumatoid arthritis
(RA) and Crohn's disease.
Developed
with the U.S. Food and Drug Administration (FDA), the revised
label instructs that patients should be evaluated for latent tuberculosis
(TB) with a tuberculin skin test in reference to current American
Thoracic Society/Centers for Disease Control and Prevention guidelines,
and that treatment for latent tuberculosis should be initiated
prior to therapy with Remicade.
In
addition, the revised label strengthens the warnings about the
risk of serious infections in general, and has drawn attention
to this important safety information through a boxed warning.
"The very mechanism of action that makes TNF-blocking agents effective
is believed to be the reason why these therapeutics may increase
the risk of infection, including the reactivation of latent tuberculosis,"
said E. William St. Clair, MD, Duke University Medical Center.
"All health care professionals should take the appropriate precautions,
including evaluating patients for latent TB with a tuberculin
skin test, prior to starting treatment with any therapy that suppresses
the immune system."
Many
of the serious infections associated with Remicade have occurred
in patients on concomitant immunosuppressive therapy that, in
addition to their Crohn's disease or rheumatoid arthritis, could
further hinder their infection-fighting capabilities.
As
of June 30, 2001, more than 170,000 patients worldwide have been
treated with Remicade in commercial experience, with 84 cases
of tuberculosis reported from post-marketing surveillance and
clinical trials of Remicade. The new label also addresses the
risk of opportunistic infections, including histoplasmosis, listeriosis
and pneumocystis.
With respect to the risk for histoplasmosis infection, the revised
labeling instructs that the benefits and risks of Remicade therapy
should be carefully considered for patients who have resided in
a region where histoplasmosis is endemic.
SOURCE:
Centocor Inc.
REVISION
POR EXPERTOS Tomado de DiseaseRef Online Journal - Volume I, Issue
40: Hormone replacement therapy and prevention of nonvertebral
fractures.
Journal
Title : Torgerson DJ, Bell-Syer SEM. Hormone replacement therapy
and prevention of nonvertebral fractures: a meta-analysis of randomized
trials. JAMA 2001;285:2891-2897 Reviewer: Jonathan D. Adachi.
OBJECTIVE:
To conduct a systematic review of all randomized trials of HRT
that have reported or collected non-vertebral fracture data but
that may not have focused on fracture prevention.
METHODS:
The MEDLINE, EMBASE, Science Citation Index and Cochrane Controlled
Trials Register databases were searched from 1997 through 2000
and a search was conducted of all systematic reviews to identify
older studies. Authors were contacted to establish whether fracture
data had been collected but not reported. Unpublished data was
sought by contacting researchers in the field. Trials were included
that randomized subjects to a minimum of 12 months of therapy.
A total of 22 of 70 studies were included in the analysis.
RESULTS:
There was a 27% reduction in non-vertebral fractures (RR, 0.73;95%
CI,0.56-0.94; P=0.02), with the greatest effect seen in women
with mean age younger than 60 years (RR, 0.67; 95% CI,0.46-0.98;
P=0.03). No significant reduction was seen in the population of
women with a mean age greater than 60 years. The reduction in
hip and wrist fractures alone was more marked (RR, 0.60;95% CI,
0.40-0.91;P=0.02) particularly for younger women younger than
60 years(RR, 0.45; 95% CI, 0.26-0.79;P=0.005).
CONCLUSIONS.
this meta-analysis of randomized controlled trials of HRT noted
a statistically significant reduction in nonvertebral fractures.
Commentary:
For
many years hormone replacement therapy (HRT) has been the mainstay
of therapy for the prevention and treatment of postmenopausal
osteoporosis despite the lack of evidence for fracture efficacy
from randomized, double-blind, placebo controlled trials. The
support for HRT was derived initially from epidemiologic and observational
studies that demonstrated fracture efficacy to various degrees1,2.
This was further supported from randomized trials that showed
significant improvements in bone mineral density (BMD)3,4. HRT
was the treatment of choice as it was one of the few therapies
available that could potentially prevent fractures1,2,5. Subsequently,
many well designed trials of alendronate6-8, raloxifene9,10, risedronate11-13
and calcitonin14 were being conducted that went on to demonstrate
reductions in both vertebral and non-vertebral fractures with
corresponding benefits in BMD. Due to this new high quality data,
the demand for more compelling evidence for the use of HRT in
the treatment of osteoporosis was required. Indeed, the FDA has
only approved HRT for the prevention and not the treatment of
osteoporosis.
Torgerson
and Bell-Syer set out to provide non-vertebral fracture evidence
in support of HRT through a meta-analysis of all of the randomized
trials of HRT15. They have conducted a thorough search of the
literature looking for fracture data. They demonstrated a 27%
reduction in non-vertebral fractures, with the greatest effect
seen in women with mean age younger than 60 years. No significant
reduction was seen in the population of women with a mean age
greater than 60 years. The reduction in hip and wrist fractures
was more marked particularly for younger women.
This
study is not without limitations. It should be noted that many
of the trials were not designed to look at fractures as a primary
endpoint and therefore many fractures may not have been reported
as they might not have been looked for. Note is made of the fact
that a significant reduction in fractures was not demonstrated
in the older age group. In part this may be explained by the fact
that most of these patients did not have osteoporosis and therefore
the population studied were at low risk for fracture. As a result
the meta-analysis may have lacked the power to demonstrate a reduction
in non-vertebral fracture. Note should be made of the fact that
many of the bisphosphonate trials showed similar negative results
in populations that were not at high risk for fracturing8,13.
Grady and Cummmings in their critique of this study point
out that many of the trials were of questionable quality16. In
particular they commented on the significant difference in the
dropout rate in the largest trial that included younger women.
In this study, there was a 3-fold greater loss to follow-up in
the estrogen groups (31%) compared to only 10% in the comparison
groups. As a result many of the fractures occurring in the estrogen
group may have been missed. Grady and Cummings also argue that
the difference seen in the effect of estrogen on fractures by
age is probably not valid as the differences based on age disappear
when only high quality studies are included in the analysis16.
Despite these limitations Torgerson and Bell-Syer have contributed
to the literature by demonstrating significant reductions in non-vertebral
fractures and in particular significant reductions in hip and
wrist fractures with HRT. The real question for clinicians and
patients alike is whether this evidence is compelling enough,
given the current controversies about the risks and benefits of
HRT, for more women to seriously consider it for the treatment
of osteoporosis. Having then considered HRT, long-term acceptance
and adherence may still be a problem for those considering HRT
as a therapy for the treatment of osteoporosis.
Referencias
disponibles en DiseaseRef Online Journal - Volume I, Issue 40.
Sitios
recomendados:
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a www.rheumatologylinx.com y reciba diariamente en su correo noticias
provenientes de las más recientes publicaciones en las diversas
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DE REUMATOLOGIA se encuentra en adelantada fase de construcción
y muy pronto disponible en la dirección: www.asoreuma.org.
Eventos
y Conferencias:
Del
26 al 30 Agosto en Edmonton Canadá se realizará el congreso ILAR
2001: The 20th Congress of the International League of Associations
for Rheumatology. Todo sobre este interesante evento consúltelo
en www.ilar.org.
Otras sociedades científicas nacionales que organizan eventos
en fechas próximas son:
La
Asociación Colombiana de Medicina Interna (ACMI) los días 28 y
29 de Septiembre en el Hotel Casa Dann Carlton de Bogotá celebra
el XVIII CURSO DE POSTGRADO ACMI ACP, "Imágenes en Medicina Interna".
La Asociación Colombiana de Osteología y Metabolismo Mineral (ACOMM)
el I Congreso Colombiano de Osteoporosis durante los días 25 y
26 de Octubre en la Casa Dann Carlton de la ciudad de Bogotá.
Espero sugerencias, comentarios y el material informativo que
quieran ver publicado para el próximo número. Con aprecio y consideración
les saludo.
Mauricio
Abello Banfi.
Editor del Boletín Electrónico
