Stem cell clinic slapped with CBER warning

Intrathecal administration is a route of administration for drugs via an injection into the spinal canal. So before you go down the route of using the

Dr. Tobinick etanercept(Enbrel) injection, make sure they have a biologics license.

Stem cell clinic slapped with CBER warning

A chiropractor who operates a stem cell clinic has received an untitled letter from the US Food and Drug Administration (FDA) for marketing intrathecal and intravenous injection of human stem cell and tissue-based products to treat such serious conditions as Parkinson’s disease and diabetes.
 
Michael Johnson runs Optimal Health Stem Cell and Wellness Institute, also doing business as OHSTEMCELL, in Appleton, WI. On 1 October, FDA’s Center for Biologics Evaluation and Research (CBER) sent Johnson, a chiropractic neurologist, a letter that referenced information on his firm’s website, Facebook page and YouTube channel.
 
Through his business, said the letter, Johnson markets umbilical cord-derived cellular products to treat a variety of serious or life-threatening conditions. Multiple sclerosis, autism, chronic obstructive pulmonary disease, Parkinson’s disease and traumatic brain injury are among the 21 conditions cited in the CBER letter.
 
The Facebook page for Johnson’s business also markets human adipose tissue- and amniotic membrane-derived products for conditions including such autoimmune disorders as systemic lupus erythematosus and Sjogren’s disease, as well as “adrenal fatigue” and other serious conditions.
 
To support the letter’s claim that Johnson intends his products to be administered intravenously or intrathecally, CBER pointed to a quote from one of OHSTEMCELL’s Facebook posts: “INTRATHECAL INJECTIONS! We use intrathecal injections into the spine with chronic neurological patients like MS, Parkinson’s and stroke rehab patients. An intrathecal injection allows the stem cells to cross the blood-brain barrier. Having the stem cells cross the blood-brain barrier helps the neurological patient to heal faster!”
 
CBER’s letter clarifies that lawful marketing of OHSTEMCELL’s products would require that they have biologics licenses, which they do not. “Such unapproved uses raise potential significant safety concerns,” said CBER, adding that the risky routes of administration heighten the agency’s concern, since contaminated products injected intrathecally or intravenously “could cause a range of adverse events.”
 
The letter is part of CBER’s ongoing work to regulate the broader field of regenerative medicine. In a consumer-facing page on its website, FDA notes that “There is a lot of misleading information on the internet about these products, including statements about the conditions they can be used to treat.” The agency encourages reporting through its MedWatch adverse event reporting system.
 
In its warning letter, as in previous letters to stem cell clinics, CBER refers Johnson to its policy framework for human cells, tissues, or cellular or tissue-based products (HCT/Ps) as delineated in a series of four guidance documents. No stem cell products have, to date, been approved to treat any orthopedic, neurologic, cardiovascular, or pulmonary disease, or to treat many of the other conditions referred to in the CBER letter.
 
The OHSTEMCELL website calls stem cell therapy “one of the most cutting-edge and revolutionary natural therapies available,” but also asserts that “Stem cell therapy DOES NOT cure or treat any disease!” (emphasis original). The website asserts that “Stem Cells will repair and regenerate tissue and patients will show improvements for a period of up to 12-months…. Once healed, it is a permanent correction!”
 
The website also asserts that “the FDA has specific guidelines for cellular therapy and we follow these guidelines to the letter!” A typical testing and treatment course, according to the website, will cost patients between $21,000 and $30,000.
 
“Manufacturers and health care professionals who have any uncertainty regarding the regulatory status of their products are encouraged to contact FDA to obtain a recommendation or decision regarding the classification of an HCT/P,” said CBER in its letter, which requests a written response within 30 days of the letter’s receipt.

Anti-TNF and CNS Events: The Link Strengthens

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.

Anti-TNF and CNS Events: The Link Strengthens

— 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

Source Reference: Kunchok A, et al "Association between tumor necrosis factor inhibitor exposure and inflammatory central nervous system events" JAMA Neurol 2020; DOI: 10.1001/jamaneurol.2020.1162.

Secondary Source

JAMA Neurology

Source Reference: Gelfant J, Yazdany J "Risk of neuroinflammatory adverse events with tumor necrosis factor inhibitor treatment" JAMA Neurol 2020; DOI: 10.1001/jamaneurol.2020.1160.

TNF Inhibitor Use for Rheumatic Diseases Tied to Incident Neuroinflammatory Events

Be careful out there if you are being treated with Enbrel (etanercept) by

Dr. Edward Tobinick.

TNF Inhibitor Use for Rheumatic Diseases Tied to Incident Neuroinflammatory Events

-Risk only seen in patients with psoriatic arthritis and ankylosing spondylitis

by Zeena Nackerdien PhD, CME Writer, MedPage Today 2020-04-07

Study Authors: Tine Iskov Kopp, Bénédicte Delcoigne, et al.
Target Audience and Goal Statement: Rheumatologists
The goal of this study was to determine if use of tumor necrosis factor (TNF) inhibitors was associated with an increased risk of neuroinflammatory events among patients with rheumatic diseases.
Question Addressed:

• Did patients with rheumatic diseases experience a higher risk of neuroinflammatory events when treated with TNF inhibitors?

Study Synopsis and Perspective:
TNF inhibitors are among the most effective agents for reducing inflammation associated with several rheumatic diseases. The availability of such effective therapeutic options enables rheumatologists to use a multifaceted approach to achieve disease control. According to Jain and Singh, this includes starting aggressive treatment early in the course of inflammatory arthritides, tailoring therapies to disease response that slows radiographic damage to joints and minimizes structural joint damage and disability, providing better symptom control and quality of life to patients, and switching therapy when the response is not adequate.

Action Points

• Patients with psoriatic arthritis and ankylosing spondylitis -- but not rheumatoid arthritis -- who were treated with tumor necrosis factor (TNF) inhibitors were at increased risk for developing neuroinflammatory events, according to a large prospective Danish and Swedish cohort study.
• Understand that the underlying biological mechanism needs to be further explored to characterize the mechanism of action and to enable identification of susceptible patients.

However, small studies have suggested that treatment with TNF inhibitors may be associated with risk of neuroinflammatory disorders, including multiple sclerosis (MS), inflammatory neuropathies, and optic neuritis. For example, TNF may play an important role in the pathogenesis of MS. Randomized clinical trials involving TNF inhibitor-treated patients with MS have also shown unfavorable results, such as disease exacerbations.
Psoriatic arthritis (PsA) patients have been reported to be at elevated risk for MS, even without treatment with TNF inhibitors, while an inverse correlation has been suggested for rheumatoid arthritis (RA) and MS. There was clearly a need to assess whether MS-related disorders may be adverse events following treatment with TNF inhibitors for arthritic diseases.
According to a large prospective cohort study conducted in Denmark and Sweden, patients with PsA or ankylosing spondylitis (AS) who were exposed to TNF inhibitors had a 50% greater risk for any neuroinflammatory event compared with unexposed patients (hazard ratio [HR] 1.50, 95% CI 1.07-2.11). And among Danish patients with AS or PsA who used TNF inhibitors, the risk increased 3.4-fold (HR 3.41, 95% CI 1.30-8.96), said Tine Iskov Kopp, PhD, of the department of neurology at Rigshospitalet Glostrup in Denmark, and colleagues.
However, there was no significantly increased risk for patients with RA, with hazard ratios of 0.97 (95% CI 0.72-1.33) in Sweden and 1.45 (95% CI 0.74-2.81) in Denmark, they reported in Annals of the Rheumatic Diseases.
"This information will be important for risk communication and evaluation in clinical practice, even though the absolute risk is low," they noted.
Of the 175,520 patients with RA, PsA, or AS identified from national registers in Denmark (Danish DANBIO register) and Sweden (Swedish Rheumatology Quality Register) from 2000 to 2017, 43,909 were treated with TNF inhibitors at any time during follow-up.
Median follow-up time varied from 2.7 years for non-exposed PsA and AS patients in DANBIO to 7.4 years among RA patients exposed to TNF inhibitors in both cohorts. The most commonly used TNF inhibitors were adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol.
Neuroinflammatory events were classified as MS, other demyelinating diseases such as optic neuritis, or polyneuropathy events. Adjusted models included age, gender, and year of inclusion in the cohorts.
For AS and PsA, crude incidence rates of all neuroinflammatory events in each country (per 1,000 person-years) were 0.59 (Sweden) and 0.87 (Denmark) in TNF inhibitor-exposed patients versus 0.40 (Sweden) and 0.19 (Denmark) in unexposed patients.
Time to any event among exposed patients was 3.8 years in the Swedish group and 3.1 years in the Danish group, and patient ages at the time of the event were 43 and 46 years, respectively.
Compared with unexposed patients, risks for neuroinflammatory events in exposed patients were the greatest for demyelinating diseases of the central nervous system and optic neuritis: a 1.65-fold and a threefold increase in the Swedish and Danish cohorts, respectively. The Swedish cohort had a significant 1.65-fold increased risk for MS. There was only a 1.13-fold increase in risk for inflammatory polyneuropathies.
"The risk estimates obtained from the 'on-drug' analysis among PsA and AS patients were lower than in the main analysis which may suggest that demyelinating events develop after longer exposure time, and even after the treatment has been discontinued," the researchers wrote.
Nevertheless, they added the caveat that "the time to event varied across cohorts, thus making it difficult to confirm the nature of any temporal association between exposure and outcome."
Other study limitations included confounding by indication.
Source Reference: Annals of the Rheumatic Diseases 2020; DOI: 10.1136/annrheumdis-2019-216693
Study Highlights and Explanation of Findings:
Some of the study strengths listed by the authors included the use of high-quality population-based rheumatic disease registers with long follow-up times, increased statistical power gained by using data from two countries, and the agreement between results from the two countries (despite slightly different definitions of TNF inhibitor-naive comparative cohorts in the two countries).
Both Etminan et al. and Bernatsky et al. used U.S. health claims databases and a nested case-control design to also assess the risk of different neuroinflammatory events after treatment with TNF inhibitors for arthritis patients. Etminan et al. found a more than twofold increased risk of peripheral neuropathy among arthritis patients (RA, PsA, and AS) with a past use of TNF inhibitors compared with arthritis patients not exposed to this treatment, while Bernatsky et al. found a non-significant 31% increased risk of demyelinating events following TNF inhibitor exposure among RA patients compared with non-exposed RA patients.
However, Kopp and team stated that "both studies had relatively short mean follow-up times (1.9 and 2.3 person-years, respectively) and the claims-based databases used were unrepresentative (based on unemployed and older individuals)."
By contrast, their study had a longer follow-up time and demonstrated that the pattern of risks for developing a

Immediate resolution of stroke pain after treatment by Edward Tobinick, M.D., February 12, 2020.

Anyone who puts supposed scientific research results on YouTube instead of a valid and vetted research journal is not to be trusted. My opinion only but google Dr. Edward Tobinick reviews.  And read this:

Another Lawsuit To Suppress Legitimate Criticism – This Time SBM

The YouTube here:

Immediate resolution of stroke pain after treatment by Edward Tobinick, M.D., February 12, 2020.

Pfizer knew drug may prevent Alzheimer's. Why didn't it tell us?

Because acknowledging it would have resulted in vast pressure to do the trial. It is much cheaper to not release the report. The company doesn't care about anyone's health, profit is the only concern. 

Pfizer knew drug may prevent Alzheimer's. Why didn't it tell us?

By Christopher Rowland

June 5, 2019 — 1.08pm

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A team of researchers inside Pfizer made a startling find in 2015: The company's blockbuster rheumatoid arthritis therapy Enbrel, a powerful anti-inflammatory drug, appeared to reduce the risk of Alzheimer's disease by 64 per cent.
The results were from an analysis of hundreds of thousands of insurance claims. Verifying that the drug would actually have that effect in people would require a costly clinical trial - and after several years of internal discussion, Pfizer opted against further investigation and chose not to make the data public, the company confirmed.

Alzheimer's cause plaques between nerve cells in the brain.

Researchers in the company's division of inflammation and immunology urged Pfizer to conduct a clinical trial on thousands of patients, which they estimated would cost $US80 million, to see if the signal contained in the data was real, according to an internal company document obtained by The Washington Post.

"Enbrel could potentially safely prevent, treat and slow progression of Alzheimer's disease,'' said the document, a PowerPoint slide show prepared for review by an internal Pfizer committee in February 2018.

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Hope for Alzheimer's treatment as older patients' memories return

The company said it decided during its three years of internal reviews that Enbrel did not show promise for Alzheimer's prevention because the drug does not directly reach brain tissue. It deemed the likelihood of a successful clinical trial to be low. A synopsis of its statistical findings prepared for outside publication, it says, did not meet its "rigorous scientific standards".
Science was the sole determining factor against moving forward, company spokesman Ed Harnaga said.

Pfizer said it opted against publication of its data because of its doubts about the results. It said publishing the information might have led outside scientists down an invalid pathway.

Pfizer's deliberations, which previously have not been disclosed, offer a rare window into the frustrating search for Alzheimer's treatments inside one of the world's largest drug companies. Despite billions spent on research, Alzheimer's remains a stubbornly prevalent disease with no effective prevention or treatment.

Science

To fight dementia, government takes a moonshot ... on a pill

Some outside scientists disagree with Pfizer's assessment that studying Enbrel's potential in Alzheimer's prevention is a scientific dead end. Rather, they say, it could hold important clues to combating the disease and slowing cognitive decline in its earliest stages.
Pfizer did share the data privately with at least one prominent scientist, but outside researchers believe Pfizer also should at least have published its data, making the findings broadly available to researchers.

"Of course they should. Why not?'' said Rudolph Tanzi, a leading Alzheimer's researcher and professor at Harvard Medical School and Massachusetts General Hospital.

"It would benefit the scientific community to have that data out there,'' said Keenan Walker, an assistant professor of medicine at Johns Hopkins who is studying how inflammation contributes to Alzheimer's. "Whether it was positive data or negative data, it gives us more information to make better informed decisions.''

Internal discussions about possible new uses of drugs are common in pharmaceutical companies. In this case, Pfizer's deliberations show how decisions made by industry executives - who are ultimately accountable to shareholders - can have an impact well beyond corporate board rooms.
As its Enbrel deliberations ended early last year, Pfizer was getting out of Alzheimer's research. It announced in January 2018 that it would be shutting down its neurology division, where Alzheimer's treatments were explored, and laying off 300 employees.

The company says it was not worth pursuing the results.Credit:AP

Drug companies often are criticised for extending the patent life of a drug - and winning new profits - by merely tweaking a drug's molecule or changing the method of delivery into the body. But it is a "heavy lift'' for a company to win regulatory approval to use a drug for a completely different disease, said Robert Field, a professor of law and health care management at Drexel University.

"Our patent laws do not provide the appropriate incentives,'' Field said. Drug therapy for early Alzheimer's "would be a godsend for American patients, so we should be doing everything we can as a country to encourage development of treatments. It's frustrating that there may be a missed opportunity.''

As Enbrel's life cycle winds down, Pfizer has introduced a new rheumatoid arthritis drug, Xeljanz, that works differently from Enbrel. Pfizer is putting its marketing muscle behind the new treatment. While Enbrel revenue is shrinking, Xeljanz revenue is growing. The Xeljanz patent expires in 2025 in the United States and 2028 in Europe, according to Pfizer's public disclosures. The drug is on track to make Pfizer billions more each year for the foreseeable future.
Drug companies frequently have been pilloried for not fully disclosing negative side effects of their drugs. What happens when the opposite is the case? What obligation does a company have to spread potentially beneficial information about a drug, especially when the benefits in question could improve the outlook for treating Alzheimer's, a disease that afflicts at least 500,000 new US patients per year?

A medical ethics expert argued that Pfizer has a responsibility to publicise positive findings, although it is not as strong as an imperative to disclose negative findings.

"Having acquired the knowledge, refusing to disclose it to those who might act upon it hides a potential benefit, and thereby wrongs and probably harms those at risk of developing Alzheimer's by impeding research,'' said Bobbie Farsides, professor of clinical and biomedical ethics at Brighton and Sussex Medical School in London.

Drug companies decided not to pursue Enbrel for Alzheimer's

Enbrel(etanercept) is the drug that Dr. Tobinick(19 posts) seems to have never even entertained trying to get his uses of etanercept  for stroke tested in a clinical trial. Here is an analysis of Dr. Tobinick's use of Enbrel for whatever. Enbrel for Stroke and Alzheimer’s   Drug companies decided not to pursue Enbrel for Alzheimer's CHICAGO, June 5, 2019 — “Any science that has promise for Alzheimer’s disease and other dementias and is not genuinely pursued, or shared with the research community, does a disservice to the millions of individuals facing the disease today and in the future. Alzheimer's is a personally devastating and fatal disease, the sixth leading cause of death in the United States, with the number of people impacted by the disease increasing daily. No stone should be left unturned. The expectation of the Alzheimer’s Association and our millions of constituents is that every possible path is pursued thoroughly and aggressively with people living with the disease as a priority.” — Maria C. Carrillo, Ph.D., chief science officer, Alzheimer’s Association

FDA Approves Etanercept Biosimilar

You will notice nothing here on uses for stroke. There wouldn't be, Dr. Tobinick(19 posts) seems to have never even entertained trying to get his uses of etanercept tested in a clinical trial.
Curious about etanercept? I've written 27 posts on it.
http://www.medpagetoday.com/Rheumatology/Arthritis/59963?
The FDA today approved Erelzi, a biosimilar to etanercept (Enbrel), for all the indications included in the labeling of the reference product, according to manufacturer Sandoz.
The injectable medication can be used for these conditions:

• Moderate to severe rheumatoid arthritis, alone or in combination with methotrexate
• Moderate to severe polyarticular juvenile idiopathic arthritis in patients ages 2 years and older
• Active psoriatic arthritis, including as a combination therapy with methotrexate for patients with an inadequate response to methotrexate monotherapy
• Active ankylosing spondylitis
• Moderate to severe plaque psoriasis in adults

In its separate news release, the FDA advised healthcare professionals to review the biosimilar product's prescribing information for details about its use. Included are the same boxed warnings about risks of serious infections and certain hematologic malignancies also carried on etanercept's label.
"The biosimilar pathway is an important mechanism to improve access to treatment for patients with rheumatic and autoimmune diseases," Janet Woodcock, MD, director of the agency's Center for Drug Evaluation and Research, said in the news release.
"We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product," she said.
In July, the FDA Arthritis Advisory Committee unanimously recommended approval of the biosimilar. It had been evaluated in four pharmacokinetic studies that included 216 healthy volunteers and in a clinical study of 531 patients with chronic plaque psoriasis that confirmed "efficacy and safety similarity."
Pharmacodynamic and immunogenicity data also were reviewed during the approval process.
The FDA also stated that Erelzi is a biosimilar, not an interchangeable product. The designation of interchangeable indicates that it's safe to switch between the reference and biosimilar products.
A biosimilar to infliximab (Remicade) known as Inflectra, also has been approved, but has faced difficulties in reaching the marketplace because of patent disputes. In addition, a biosimilar to adalimumab (Humira) has demonstrated clinical equivalence in a phase III study.
An application for the biosimilar also is under review by the European Medicines Agency.
Sandoz is a Novartis company.

The Comparative Safety of TNF Inhibitors in Rheumatoid Arthritis - A Meta-Analysis Update of 44 Randomized Controlled Trials

TNF - tumor necrosis factor is the action that Dr. Edward Tobinick  claims is the main problem with recovery from stroke. He uses Etanercept and injects it into the neck in a patented way. This may give your doctor some more information on risks of using this.
http://www.amjmed.com/article/S0002-9343%2814%2900488-4/abstract?rss=yes

Tzeyu L. Michaud, MHA

,

Young Hee Rho, MD, PhD, MPH

,

Tatyana Shamliyan, MD, MS

,

Karen M. Kuntz, ScD

,

Hyon K. Choi, MD, DrPH

Received: November 18, 2013; Received in revised form: May 22, 2014; Accepted: June 9, 2014; Published Online: June 17, 2014

DOI: http://dx.doi.org/10.1016/j.amjmed.2014.06.012

Publication stage: In Press Accepted Manuscript

• Abstract
• Full Text
• Images
• References
• Supplemental Materials

Highlights

• •Adalimumab, certolizumab pegol, and infliximab are associated with a higher risk of serious infection, which appears to contribute to higher rates of discontinuation.
• •In contrast, etanercept showed a lower rate of discontinuation with a tendency towards a lower rate of serious infection.
• •These comparative safety findings should inform clinical and policy decision making in the management of rheumatoid arthritis.

Abstract

Objective

To evaluate and update the safety data from randomized controlled trials of TNF inhibitors (TNFis) in patients treated for rheumatoid arthritis.

Methods

A systematic literature search was conducted from 1990 through May 2013. All studies included were randomized, double blind, controlled trials of patients with rheumatoid arthritis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The serious adverse events and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs).

Results

Forty-four randomized controlled trials involving 11,700 subjects receiving TNFis and 5,901 subjects receiving placebo and/or traditional disease-modifying anti-rheumatic drugs (DMARDs) were included. TNFi treatment as a group was associated with a higher risk of serious infection (OR, 1.42; 95% CI, 1.13-1.78) and treatment discontinuation due to adverse events (OR, 1.23; 95% CI, 1.06-1.43) compared with placebo and/or traditional DMARD treatments. Specifically, patients on adalimumab, certolizumab pegol, and infliximab had an increased risk of serious infection (OR, 1.69, 1.98, and 1.63) and showed an increased risk of discontinuation due to adverse events (OR, 1.38, 1.67 and 2.04). In contrast, patients on etanercept had a decreased risk of discontinuation due to adverse events (OR, 0.72; 95% CI, 0.55-0.93). Although ORs for malignancy varied across the different TNFis, none reached a statistical significance.

Conclusion

These meta-analysis updates of the comparative safety of TNFis suggest a higher risk of serious infection associated with adalimumab, certolizumab pegol, and infliximab, which appears to contribute to higher rates of discontinuation. In contrast, etanercept use showed a lower rate of discontinuation. These data may help guide clinical comparative decision making in the management of rheumatoid arthritis.

RheumReports: Swollen Ears and Enbrel

Be careful out there if you are planning on using Etanercept with Dr. Tobinick.  
http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/47774?

Dr. Edward Tobinick - of etanercept (Enbrel) fame suing a blogger

Dr. Tobinick could easily solve all these problems of his by writing up proof of his clinical research but he goes down the dubious route of suing critics. In my opinion a sign of desperation when truth and facts are not on your side.
I never would have gone down this route anyway, there never was anything other than anecdotes for this as a stroke treatment.

Case docket here:
http://dockets.justia.com/docket/florida/flsdce/9:2014cv80781/443251
Dr. Gorski writing about it here;
http://www.sciencebasedmedicine.org/another-lawsuit-to-suppress-legitimate-criticism-this-time-sbm/

Methods for treatment of brain injury utilizing biologics

Ok, the stupidity of patenting drug delivery is here for all to see. This is the guy that is trying to push Enbrel/etanercept as a stroke treatment.  He now has included nasal delivery and delivery thru the skin in the patent. This patent needs to be invalidated. The only drug delivery he doesn't try to patent is intravenous and oral.  A great stroke association would object to this.
Stupid, stupid, stupid. 
http://www.freepatentsonline.com/y2013/0224197.html
A method of using biologics to treat chronic brain injury or spasticity due to stroke, trauma and other causes. Preferred embodiments include perispinal, parenteral, transepidermal or intranasal use of TNF antagonists. The TNF antagonists include TNF receptor fusion proteins, TNF monoclonal antibodies (mAbs), humanized TNF mAbs, fully human TNF mAbs, chimeric TNF mAbs, domain TNF antibodies, mAB fragments, anti-TNF nanobodies, dominant negative TNF constructs and TNF inhibitory single chain antibody fragments. One of the preferred embodiments of this invention is the perispinal administration of etanercept for treatment of mammals following stroke. The use of Trendelenburg positioning, catheters, pumps, or depot formulations are included.

Jeri Rowe: Shot offers hope in stroke recovery

Well, the PR is working for etanercept. With no clinical trials this is masterful magical thinking.
This here seems to be the only study referenced in PubMed and its only observational;

Selective TNF inhibition for chronic stroke and traumatic brain injury: an observational study involving 629 consecutive patients treated with perispinal etanercept

If the idea is to get Enbrel into the brain why do it this way?
Why not have your doctor try the nasal to brain route. I have 13 posts on it with this one being the most interesting.
http://www.oc1dean.blogspot.com/2013/04/uw-spinoff-impel-neuropharma-passes-key.html
It bypasses the danger of the needle and the patent. 

Jeri Rowe: Shot offers hope in stroke recovery 

Disciplinary Action against Edward Lewish Tobinick, M.D.

In case you were interested in the etanercept/Enbrel injections. Be careful out there.
http://www.casewatch.org/board/med/tobinick/accusation.shtml

A sceptical analysis of Enbrel for Stroke and Alzheimer’s

By  Steven Novella  of Science Based Medicine.If you are considering etanercept or Enbrel at all you need to completely read this. I won't be doing this.
http://www.sciencebasedmedicine.org/index.php/enbrel-for-stroke-and-alzheimers/
A couple of sentences from the post, read it all at the link.
The claims of Tobinick, however, are not in the gray area – they are leaps and bounds ahead of the evidence. Further, the conditions he claims to treat are not clearly immune-mediated diseases. 
Stroke researchers are also very familiar with what is known as the “cheerleader effect.” Take any patient with chronic deficits, give them any intervention and then encourage them to function better, and they will function better.

Etanercept(Enbrel) and IBMs' Watson

This is from a technology site so take what they are saying with a grain of salt. Video training on how to apply it. Still seems more like a puff piece.
Patented by Amgen.
http://www.hpcwire.com/hpcwire/2013-03-26/ibm_s_watson_making_diagnosis_and_treatment_recommendations.html
According to an article in the March 2013 edition of Atlantic magazine titled “The Robot Will See You Now," IBM’s super computer Watson has teamed up with Memorial Sloan/Kettering Hospital to make diagnosis and treatment recommendations. IBM Watson has been programmed with 600,000 pieces of medical evidence from over two million pages of medical text as well as the entire English version of Wikipedia all stored in 15 terabytes of RAM (15 trillion bytes of memory). This is roughly equivalent to the information contained on a bookshelf that is 19 miles long.

“Computer-driven, evidence-based advice like that provided by IBM’s Watson gives validity to the off label use of prescription drugs” states Rolando Rodriguez, M.D., Neurosurgeon at Neurological Wellness Center. “The perispinal administration of the drug etanercept (Enbrel) to patients diagnosed with Alzheimer’s, stroke or traumatic brain injury (TBI) has the potential to enable a significant recovery in memory, mood, speech and physical function,” stated Dr. Rodriguez. “Doctors and nurses are drowning in information with new research popping up daily. They often don’t know what to do and are guessing as well as they can,” said Samuel Nussbaum, WellPoint’s Chief Medical Officer.

A general consensus is emerging among healthcare professionals that to effectively address the many problems in the present healthcare system in America will require a fundamental redesign, a transformation in which existing modalities are replaced by new care delivery paradigms. The expansion of computer medical decision support systems like that provided by IBM's Watson has emerged as one of the areas where there is broad support among the medical community. The proliferation of biomedical information will continue to accelerate taxing the cognitive abilities of physicians as they struggle with the weight of new research findings, clinical guidelines, and recommendations of best practices. Computerized medical decision support systems certainly have the potential to produce better outcomes, increase productivity, lower costs and reduce the occurrence of adverse events.

Perispinal injections of the drug Enbrel are an excellent example. “The medical research is clear: a single injection has the potential to produce a life-changing recovery in persons afflicted with stroke or traumatic brain injury with little to no risk to health, yet the procedure is only slowly starting to gain traction with mainstream medicine,” states Dr. Rodriguez. IBM’s Watson has the potential to be a major game changer in the field of medicine. When physicians’ diagnoses and treatment decisions are evaluated with computer-assisted 20/20 hindsight WellPoint’s Samuel Nussbaum said that “health care professionals make accurate treatment decisions in lung cancer cases only 50% of the time.” “The dictates of a capitalistic healthcare system preclude a drug like Enbrel from ever gaining FDA approval for the treatment of stroke or TBI. The estimated cost for repurposing Enbrel for treating stroke and TBI is $100 million. Considering just one to eight doses are required for the complete treatment, I can be confident this drug will never be approved for stroke or TBI” said Augusto Ramirez, M.D., of Neurological Wellness Center. Neurological Wellness Center offers a complete two-hour course on Alzheimer's treatment, stroke treatment and traumatic brain injury treatment covering all aspects of perispinal injection technique at their center in Managua Nicaragua.

For many, flying to Managua Nicaragua to receive this personalized training is an enormous expense and inconvenience. To overcome this problem, Neurological Wellness Center, under the direction of Augusto Ramirez, M.D., created Perispinal Enbrel Step-By-Step Instructional Video and accompanying e-book.

Neurological Wellness Center’s perispinal Enbrel is profoundly effective as an Alzheimer’s treatment, stroke treatment and TBI treatment. The complete treatment recommendation: for stroke is one 25mg injection of Enbrel every four days for a total of four doses over 16 days; for TBI is one 25mg injection of Enbrel every four days for a total of eight doses. This compares with Amgen/Pfizer’s FDA-approved dose schedule for moderate plaque psoriasis of 50mg twice weekly for three months followed by 50mg weekly for life. The Neurological Wellness Center’s maximum recommended dose for Alzheimer’s disease is 25mg/week for life.

The drug Enbrel is available now. Enbrel received FDA approval in 1998. Its safety profile is well understood. For Enbrel to effectively treat Alzheimer’s, stroke and TBI, it must be administered to the back of the neck precisely between the cervical vertebrae C-5 and C-6. (I wouldn't allow just any doctor to inject me at this location)This perispinal injection allows Enbrel to enter the brain by lymph drainage assisted by gravity. Fortunately for the millions of people now afflicted with Alzheimer’s, stroke and TBI, a video is now available online detailing in step-by-step fashion how to administer a perispinal injection of Enbrel,” said Dr. Rolando Rodrigues.

Psoriasis Drugs May Curb Heart Disease Risk

Remember the unproven  miracle drug etanercept from a year and a half ago? It supposedly reduced the TNF, tumor necrosis factor, just like this drug does. So contact your researcher  and have them see if reducing TNF actually helps in stroke rehab and then if this drug might help. No one else is going to push this so you have to. 

Psoriasis Drugs May Curb Heart Disease Risk

Treating psoriasis patients with biologic drugs that inhibit tumor necrosis factor (TNF) may cut risk of heart attack compared with other treatments, observational results suggested.
TNF-treated patients were half as likely to have a myocardial infarction (MI) as those treated with topical drugs after adjustment for other factors, Jashin J. Wu, MD, of the Kaiser Permanente Los Angeles Medical Center, and colleagues found in a retrospective cohort study.
Oral drugs and phototherapy were also significantly better than topical treatment in terms of MI risk, though rates tended to be even lower with the TNF inhibitors, the researchers reported online in the Archives of Dermatology.
"It seems that controlling psoriasis with aggressive therapy and, thus, lowering inflammation leads to a reduction in MI risk," they wrote.
As a systemic inflammatory disease, psoriasis is linked to many cardiovascular risks, from obesity and atherosclerosis to type 2 diabetes, stroke, MI, and cardiac death.
The same is true in rheumatoid arthritis, but a large observational study linked TNF blockers to reduced cardiovascular events in that disease.
To evaluate the effect in psoriasis, Wu's group retrospectively analyzed the Kaiser Permanente Southern California health plan databases.
Among the 8,845 members with multiple diagnostic claims codes for psoriasis or psoriatic arthritis and no history of MI at baseline:

• 19% took a TNF inhibitor for at least 2 months
• 24% were TNF-inhibitor naive and received other systemic agents, like methotrexate, or phototherapy
• 57% received none of the above and were classified as treated only topically

During a mean 4.3 years of follow-up, MI incidence was 3.05 per 1,000 patient-years in the anti-TNF-treated group compared with 3.85 in those on oral drugs or phototherapy and 6.73 in those on topical drugs.
That translated to an unadjusted 55% lower risk of MI with the TNF inhibitors and 43% lower risk with oral drugs or phototherapy compared with topical agents (both P less than 0 data-blogger-escaped-.001=".001" data-blogger-escaped-p="p" greater than TNF blockers were associated with 21% lower MI risk compared with other systemic drugs or phototherapy in that analysis, though the difference wasn't statistically significant.
In an age-stratified analysis, both treatments appeared more protective against MI in older adults. Compared with topical agents, the hazard ratios were:

• Among patients age ≤60, 0.46 with TNF inhibitors (95% CI 0.25 to 0.88) and a nonsignificant 0.60 with oral therapy and phototherapy
• Among patients age >60, 0.32 with TNF inhibitors (95% CI 0.14 to 0.73) and 0.35 with oral agents or phototherapy (95% CI 0.21 to 0.59)

"One reason for this is that older patients are more likely to have type 2 diabetes mellitus, and the benefits of TNF inhibitor use may be mediated through improving risk of type 2 diabetes," the researchers noted.
Alternatively, older patients may be less likely to get a TNF inhibitor because of lower coverage of prescription benefits through Medicare for these costly drugs, or because of recent history of cancer as a contraindication for TNF inhibitor therapy, they added.
The study didn't compare the individual TNF blockers -- infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira) -- used in psoriasis.
The study was limited by lack of data on psoriasis severity, which could have been a confounding factor if severe cases were more likely to receive no systemic therapy.
Other limitations were lack of adjustment for over-the-counter medications like nonsteroidal anti-inflammatory drugs and for duration and dosing of drugs analyzed in the study (statins, beta-blockers, or methotrexate).