If you are thinking of doing the (INR - Institute of Neurological Recovery)Dr. Tobinick etanercept(Enbrel) injection you need to know of this risk. But I know nothing since I'm not medically trained, don't listen to me, make your own decision based on all factors.
Etanercept is a tumor
necrosis factor (TNF) blocker that is used in adults to prevent joint
damage caused by rheumatoid arthritis, psoriatic arthritis, or
ankylosing spondylitis.
— Three-fold higher risk of inflammatory CNS adverse events in autoimmune diseases treated with TNF inhibitors
by
Nancy Walsh,
Contributing Writer, MedPage Today
May 18, 2020
Patients with autoimmune diseases who were treated
with tumor necrosis factor (TNF) inhibitors had an increased risk of
developing inflammatory central nervous system (CNS) adverse events, a
nested case-control study found.
Among patients with diseases such as rheumatoid arthritis (RA),
psoriasis, and ulcerative colitis who were exposed to TNF inhibitors,
there was a three-fold increased risk of any inflammatory CNS event in
the study's primary analysis, with an adjusted odds ratio of 3.01 (95%
CI 1.55-5.82,
P=0.001), according to Andrew McKeon, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.
And
the risk was almost five-fold higher among the subgroup of patients
with RA specifically, with an adjusted OR of 4.82 (95% CI 1.62-14.36,
P=0.005), the researchers reported in
JAMA Neurology.
A link between TNF inhibitors and
demyelinating CNS events(not good, this is the multiple sclerosis problem) has been
suspected since shortly after those agents became available more than 20
years ago. These events included multiple sclerosis (MS), optic
neuritis, transverse myelitis, and neuromyelitis optica spectrum
disorder. In
a Spanish registry, there have been 740 reports of demyelinating events, 254 of which were MS, and 358 cases of optic neuritis.
There also have been reports of inflammatory nondemyelinating CNS
events such as neurosarcoidosis and CNS vasculitis, although less is
known about these events.
To explore these potential associations in a large population, McKeon
and colleagues examined the electronic health record system of the Mayo
Clinic's three locations (Rochester; Scottsdale, Arizona; and
Jacksonville, Florida) for the years 2003 to 2019.
The study population included more than 32,000 patients who had been
diagnosed with RA, psoriasis, psoriatic arthritis, ankylosing
spondylitis, Crohn's disease, or ulcerative colitis, and who had been
treated with any disease-modifying therapy. They identified 106 patients
who developed CNS events, matching them with 106 controls who had the
same autoimmune diseases but without CNS events.
Two-thirds
of the patients were women. Median age was 36 at the onset of the
autoimmune disease for patients and 35 for controls, and median disease
duration was 12 years for patients and 13 years for controls. The most
common diagnosis was RA in 45%.
Inflammatory demyelinating events developed in 56 patients, with most
being MS, and inflammatory nondemyelinating events such as aseptic
meningitis, CNS vasculitis, and idiopathic leptomeningitis were reported
in 50.
Among the 106 patients who developed CNS events, 60% had been exposed
to any of the available TNF inhibitors, which were etanercept (Enbrel),
infliximab (Remicade), adalimumab (Humira), golimumab (Simponi), and
certolizumab pegol (Cimzia). Among the control group, 40% had received
anti-TNF treatment.
Among the patients who had demyelinating events, 70% had anti-TNF
exposure compared with 50% of controls, while of those who had
nondemyelinating events, 50% of patients were exposed compared with 28%
of controls.
When the analysis was stratified according to the type of CNS event, similar results were seen as in the primary analysis:
- Inflammatory demyelinating CNS events: adjusted OR 3.09 (95% CI 1.19-8.04, P=0.02)
- Inflammatory nondemyelinating CNS events: adjusted OR 2.97 (95% CI 1.15-7.65, P=0.02)
Unlike
the RA subgroup, a pooled analysis of patients with ankylosing
spondylitis, psoriasis, psoriatic arthritis, Crohn's disease, and
ulcerative colitis found no significant risk of inflammatory CNS events
(OR 2.13, 95% CI 0.90-5.05,
P=0.09).
In 90% of patients who developed the neurologic symptoms, anti-TNF
exposure took place within 1 year of the symptom onset, suggesting a
temporal association, the researchers noted.
"We hypothesized that TNF inhibitors may further dysregulate already
aberrant immune responses, triggering inflammatory CNS events in
patients with certain autoimmune diseases," they wrote.
The TNF cytokine has multiple functions ranging from immune
regulation to inhibition of tumor cells and defense against pathogens.
"Proposed mechanisms for the paradoxical development of inflammatory CNS
events in association with TNF inhibitor exposure include immune
dysregulation from the inhibition of apoptosis of autoreactive T cells,
which may then enter the CNS and cause demyelination," they explained.
They also emphasized that the TNF inhibitors are highly effective
therapies for these diseases, and the CNS events are uncommon, and also
acknowledged that their study does not imply causality.
"Further
research is needed to explore whether this association indicates de
novo inflammation or exacerbation of already aberrant inflammatory
pathways," they concluded.
In an accompanying editorial, Jeffrey M. Gelfand, MD, and Jinoos
Yazdany, MD, of the University of California San Francisco cautioned
that "the effect size reported in the study should be interpreted with
some caution," because the analysis did not adjust for severity of
underlying disease. "It is plausible that individuals with more severe
autoimmune diseases were both more likely to receive biological agents
such as TNF inhibitors and more prone to develop neuroinflammatory
events," the editorialists wrote.
"The next steps should include population-based observational studies that control for disease severity," they wrote.
Last Updated May 18, 2020
Disclosures
The study was funded by the National Center for Advancing Translational Sciences.
The
authors disclosed relevant relationships with Biogen, Pfizer,
Genentech, AbbVie, Sanofi-Genzyme, Alexion, Viela Bio, Union Chimique
Belge, Astellas, Griffols, Autoimmune Encephalitis Alliance,
Chugai/Roche, Mitsubishi Tanabe, Novartis, Caladrius, Brainstorm
Therapeutics, Roivant, Euroimmun, and Medimmune.
Primary Source
JAMA Neurology
Secondary Source
JAMA Neurology
Open Access
Peer-Reviewed
