Connect with us

Health

New Data Reveal Molecular Drivers of Thyroid Eye Disease (TED) May Remain Activated In Patients with – PharmiWeb.com

Published

 on


— Oral presentation at AAO 2022 suggests IGF-1 and its related pathways are extensively upregulated throughout all stages of TED —

DUBLIN–(BUSINESS WIRE)–Horizon Therapeutics plc (Nasdaq: HZNP) today announced the presentation of new data defining molecular patterns in TED and further implicating the role of insulin-like growth factor-1 (IGF-1) in patients with low CAS. These data were presented during the American Academy of Ophthalmology Annual Meeting (AAO 2022), Sept. 30 – Oct. 3 in Chicago.

Genius Dog 336 x 280 - Animated

TED is a progressive and potentially vision-threatening rare autoimmune disease, which has been historically characterized as biphasic: acute, which is traditionally believed to be patients with high CAS and earlier in their TED journey; and chronic, traditionally believed to be patients with low CAS and later in the course of their disease.1 This analysis reveals that in patients with both high and low CAS, there is clear activation of IGF-1 and related pathways, as well as the extracellular matrix (ECM) organization, a structural network that supports cellular processes.2

“By demonstrating that disease activity remains in patients with low CAS, this analysis may help explain why many patients who have lived with Thyroid Eye Disease for several years are still struggling with challenging symptoms that can be debilitating,” said Shoaib Ugradar, M.D., The Jules Stein Eye Institute at University of California, Los Angeles (UCLA). “It is important for physicians to be aware of the continued activation of IGF-1 throughout the course of the disease and its potential impact on treatment decisions.”

The study analyzed genome ribonucleic acid (RNA) sequencing and pathway analysis in orbital tissue from patients with a CAS of ≥ 3 and patients with a CAS ≤ 2, as well as five control subjects. Though high CAS patients are often distinguished by activation of immune system pathways, which remain largely unaffected in low CAS patients, IGF-1 and its related pathways were found to be upregulated in both stages of disease. Additional analysis suggests that IGF-1 activity plays a central role in linking immune and ECM pathways in people with TED.2

The upregulation of IGF-1 found in low CAS patients with extended disease duration is further supported by a growing body of evidence that outlines the impact of TED on people who have lived with it for several years.3 One assessment published in the journal Ophthalmology and Therapy in 2021 found that disease burden continues well into the chronic phase, affecting daily lives with appearance and persistent visual changes, increasing risk for anxiety and depression.4

“This study, which represents one of the first molecular analyses of the continuum of Thyroid Eye Disease, confirms this challenging disease may not simply subside after a few years of obvious symptoms,” said Jeffrey W. Sherman, M.D., FACP, executive vice president, chief medical officer, Horizon. “We are committed to pioneering research like this to better understand drivers of the evolution of this disease in order to better support patients living with Thyroid Eye Disease across the course of their lifetimes.”

About Thyroid Eye Disease (TED)

TED is a serious, progressive and potentially vision-threatening rare autoimmune disease.1 TED often occurs in people living with Graves’ disease, but is a distinct disease that is caused by autoantibodies activating an IGF-1R-mediated signaling complex on cells within the retro-orbital space.5,6 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness. Early signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis; pressure and/or pain behind the eyes; and diplopia.7,8

About Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

References

  1. Barrio-Barrio J, et al. Graves’ Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:249125.
  2. Ugradar S, et al. Whole Genome Transcriptome Comparison of Acute and Chronic Thyroid Eye Disease: Emergence of a Molecular Signature. Oral presentation at: American Academy of Ophthalmology (AAO); 2022 Sept. 30- Oct. 1; Chicago, IL.
  3. Wang Y, et al. Inflammatory and non-inflammatory thyroid eye disease: comparison of disease signs, symptoms and quality of life in US patients. Endo Practice. 2022;28(9):842-846.
  4. Cockerham KP, et al. Quality of Life in Patients with Chronic Thyroid Eye Disease in the United States. Ophthalmol Ther. 2021;10(4):975-987.
  5. Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257.
  6. Pritchard J, et al. Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor 1 Receptor Pathway. J Immunol. 2003;170:6348-6354.
  7. Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves’ Orbitopathy. Eur J Endocrinol. 2021;185:G43-G67.
  8. McKeag D, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves’ Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007;91:455-458.

 

Contacts

Investors:
Tina Ventura
Senior Vice President, Chief Investor Relations Officer

Investor-relations@horizontherapeutics.com

U.S. Media:
Rachel Vann
Senior Director, Product Communications

media@horizontherapeutics.com

Ireland Media:
Gordon MRM

Ray Gordon

ray@gordonmrm.ie

Adblock test (Why?)



Source link

Continue Reading

Health

Toronto-based infectious disease expert seeing more older patients with flu in hospital

Published

 on


An infectious diseases physician in Toronto is reporting an increase in the number of older patients he is seeing with seasonal influenza.

Dr. Isaac Bogoch at Toronto General Hospital noted this year’s flu season started early and escalated quickly.

Genius Dog 336 x 280 - Animated

According to the Public Health Agency of Canada, children under five are still making up the largest age bracket of flu patients in hospital. However, rates among seniors (aged 65 and up) are on the rise.

Bogoch expects the number of flu cases to keep increasing. The season usually peaks in January.

To track the number of flu cases in Durham Region this season, click here.

 

Source link

Continue Reading

Health

Breakthrough Infections More Likely in Infliximab Treated IBD Patients Than Those Treated With Vedolizumab

Published

 on

Patients with inflammatory bowel disease (IBD) treated with infliximab who were vaccinated against SARS-CoV-2 were more likely to have a breakthrough infection than patients treated with vedolizumab, but the benefits of the vaccine are still superior.

A team, led by Zhigang Liu, PhD, Department of Metabolism, Digestion and Reproduction, Imperial College London, determined how infliximab and vedolizumab affect vaccine-induced neutralizing antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants.

The Treatments

Anti-TNF drugs, including infliximab, are linked to attenuated antibody responses following SARS-CoV-2 vaccination. The variants included in the analysis have the ability to evade host immunity and with emerging sublineages are currently the dominating variants causing the current waves of infection.

In the prospective, multicenter, observation, CLARITY IBD cohort study, the investigators looked at the effect of infliximab and vedolizumab on SARS-CoV-2 infections and vaccinations in patients with IBD.

Genius Dog 336 x 280 - Animated

The study included patients aged 5 years or older with an IBD diagnosis that were treated with infliximab or vedolizumab for 6 weeks or longer in infusion units at 92 hospitals in the UK. Each participant had uninterrupted biological therapy since recruitment and were not previously diagnosed with a SARS-CoV-2 infection.

Outcomes

The investigators sought primary outcomes of neutralizing antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 following 3 doses of a SARS-CoV-2 vaccine.

The team also investigated the risk of breakthrough infections in relation to neutralizing antibody titers using Cox proportional hazard models.

There were 7224 patients with IBD recruited to the study between September 22 and December 23, 2020. Of this group, 1288 had no previous SARS-CoV-2 infections after 3 doses of the vaccine that were established on either infliximab (n = 871) or vedolizumab (n = 417). The median age of the patient population was 46.1 years.

Following 3 doses of SARS-CoV-2 vaccine, 50% neutralizing titers were significantly lower in the infliximab group compared to patients treated with vedolizumab against wild-type (geometric mean, 2062; 95% CI, 1720–2473 vs geometric mean, 3440; 95% CI, 2939–4026; P <0.0001), BA.1 (geographic mean, 107.3; 95% CI, 86.40–133.2 vs geographic mean, 648.9; 95% CI, 523.5–804.5; P <0.0001), and BA.4/5 (geographic mean, 40.63; 95% CI, 31.99–51.60] vs geographic mean, 223.0; 95% CI, 183.1–271.4; P <0.0001) variants.

Breakthrough infections more frequently occurred in patients treated with infliximab (n = 119; 13.7%; 95% CI, 11.5–16.2) than in those treated with vedolizumab (n = 29; 7.0%; 95% CI, 4.8–10.0; P = 0.00040).

The Cox proportional hazard models show time to breakthrough infection after the third vaccine dose in the infliximab group was associated with a higher hazard risk than treatment with vedolizumab (HR, 1.71; 95% CI, 1.08-2.71; P = 0.022).

There was also higher neutralizing antibody titers against BA.4/5 with a lower hazard risk in the group with a breakthrough infection and a longer time to breakthrough infection (HR, 0.87; 95% CI, 0.79-0.95; P = 0.0028).

“Our findings underline the importance of continued SARS-CoV-2 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies,” the authors wrote.

The study, “Neutralizing antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicenter cohort study,” was published online in The Lancet Gastroenterology & Hepatology.

Source link

Continue Reading

Health

Flu shot uptake in children ‘too low,’ P.E.I. CPHO says

Published

 on

With flu cases on the rise in the province, P.E.I.’s Chief Public Health Officer is urging parents to get their young children a flu shot.

Currently, just 19 per cent of children under the age of 10 have gotten a vaccine.

“I do think that’s too low,” said Dr. Heather Morrison, the province’s chief public health officer. “On the other hand, we’ve had great uptake of our high dose influenza for those who are 65 years of age and up.”

Morrison said there are some clinics on the weekend in Charlottetown through public health nursing and appointments are available “to really help those who may not be able to come during the week.”

Genius Dog 336 x 280 - Animated

By Dec. 3 there have been 155 lab-confirmed cases, according to a P.E.I. government website. The median age of cases to date is 14 years old. The site says there was “widespread flu activity” last week on P.E.I. with flu activity “above expected levels for this time of year.”

‘They are getting better now’

Without vaccines, children four and under are most at risk of being hospitalized, Morrison said. That’s exactly what happened to Island resident Shidhin Philip’s youngest son, Adam, who was less than a month old when he was hospitalized with influenza and RSV.

Shidhin Philip’s youngest child, Adam, at the QEH when he was sick with RSV and influenza at less than a month old. (Submitted by Shidhin Philip)

“We were really scared,” said Philip. “But we know we took him to the hospital at the right time, so that was a good decision.”

On Wednesday, Philip brought two of his older children to the children’s clinic in Sherwood to get their flu shot.

“They all had the flu, the sore throat, running nose, they had fever, they were throwing up. They were absent from school for two weeks,” Philip said. “They are getting better now, I don’t want to get it back again. So I took the appointment for the flu shot today.”

A man in a puffy green jacket wraps his arms around his two daughters, who stand on either side of him.
Shidhin Philip and two of his four children, Angel and Anna, outside a vaccination clinic in Charlottetown. (Steve Bruce/CBC)

But he says having vaccines available at public schools would make it easier for busy parents to get their children vaccinated.

“They can send the paper home, we can sign the consent,” he said. “Instead of making an appointment or waiting [a] long time, you know, it can finish in one day.”

Morrison says there are some logistical issues with making the vaccine available in schools, but it is something the province is potentially looking into for future years.

“It’s something that we certainly would be very open to having that conversation with education, public health, nursing, Health P.E.I,” she said. “It has been something that has been discussed over the years.”

In the meantime, she encourages parents to make an appointment and hopes strong messaging, combined with the recent spike in flu cases, will motivate parents to book their kids’ shots.

“Children are at school, and activities, we’re all busy,” she said. “But if we can get it now, get our children vaccinated, ourselves vaccinated, it will protect us in time for the holidays.”

Visit P.E.I.’s weekly influenza summary and flu vaccination clinics websites for more information.

Source link

Continue Reading

Trending