Category Archives: Rheumatology

Autoimmune disease research community gets boost from AMP RA/SLE study results

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Data from the Phase I study of collaborative industry partnership AMP are now available, meaning scientists can benefit from access to important research about Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Datasets characterising individual cells in rheumatoid arthritis and systemic lupus erythematosus disease tissue from the Accelerating Medicines Partnership for Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Phase I study are now available to the research community. Scientists from across the biomedical research community can access the AMP RA/SLE datasets to explore important research questions about these autoimmune conditions.

Commenting on what they hope to achieve from the research programme, National Institutes of Health Director Francis S. Collins, M.D, Ph.D said:

“This pioneering programme seeks to speed the development of new ways to combat a range of devastating diseases that affect millions of people.”

“AMP RA/SLE is entering an exciting phase as experts around the world will begin to mine this invaluable biomedical resource in search of tomorrow’s cures.”

This study used state-of-the-art technologies to analyse individual cells from the lining of the joints in people with rheumatoid arthritis (RA) and the kidneys from people with lupus from research cohorts whose clinical characteristics were well-studied. Other research tools tend to examine signals from across populations of cells, and as such may miss important factors coming from only a few individual cells. By focusing on single cells, researchers can tease out the contributions of specific pathways inside these cells that may play a role in disease, providing a new approach to understanding autoimmunity.

Autoimmune diseases with similar characteristics

RA and lupus are autoimmune diseases that can last a lifetime, cause significant disability, greatly reduce quality of life and are associated with increased risk of early death. These disorders share similar flaws in immune function and regulation, leading to inflammation that damages tissues. People with these conditions need more and better treatments, as some fail to respond to existing therapies.

The newly released information holds clues for potential research targets that may lead to future treatment options. Availability of the data expands the search for genes, proteins, biological pathways and other factors that influence these conditions. Researchers mining the data can seek to identify treatment targets to develop medicines for diseases of interest. The data also has potential implications for precision medicine, as AMP RA/SLE researchers identify differences in the pathways active in the tissue of different patients.

Power of collaboration

The AMP RA/SLE programme is one of three AMP projects launched in 2014 as part of an unprecedented public-private partnership to identify promising biological targets for potential therapeutics and reduce the time and cost of developing them. The NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases, alongside the National Institute of Allergy and Infectious Diseases (NIAID), manages the AMP RA/SLE programme. The Foundation for the National Institutes of Health (FNIH) manages the partnership between the NIH and the external partners, which include participating members from industry (AbbVie, Bristol-Myers Squibb, Merck & Co. Inc., Pfizer Inc., Sanofi, and Takeda Pharmaceuticals International Inc.) and non-profit partners (Arthritis Foundation, Lupus Foundation of America, Lupus Research Alliance, and Rheumatology Research Foundation). Within the context of the partnership, industry and non-profit partners are also actively involved in sharing resources and expertise.

“No single organisation has the resources to take on the challenges facing the rheumatoid arthritis and lupus communities,” said Maria C. Freire, Ph.D., president and executive director of the FNIH. “AMP brings together government, pharmaceutical and not-for-profit expertise to collaboratively move therapies forward for these autoimmune diseases.”

The AMP RA/SLE investigators are currently conducting Phase II studies that include a larger cohort of patients with RA and lupus.

The Phase I data are freely available through the NIAID-sponsored Immunology Database and Analysis Portal Genomic data are also being submitted to be made available through the NIH’s database of Genotypes and Phenotypes


Psoriasis drug found to reduce aortic vascular inflammation

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An antibody used to treat the skin disease psoriasis is also effective at reducing aortic inflammation, a key marker of future risk of major cardiovascular events.

An antibody used to treat the skin disease psoriasis is also effective at reducing aortic inflammation, a key marker of future risk of major cardiovascular events.

Researchers from the Perelman School of Medicine at the University of Pennsylvania, in collaboration with the National Heart, Lung, and Blood Institute, led a randomised, double-blind, placebo-controlled study and found patients who took the drug ustekinumab had a 19 percent improvement in aortic inflammation, as measured and confirmed by imaging, when compared to the placebo group. Dr Joel M. Gelfand, a Professor of Dermatology and Epidemiology at Penn and the study’s first author.

Ustekinumab, sold under the name Stelara, is approved by the US Food and Drug Administration to treat psoriasis, psoriatic arthritis, and Crohn’s Disease. Researchers wanted to know if the benefits of the drug go beyond clearing the skin.

“The type of inflammation we see in psoriasis is similar to what we see in atherosclerosis – a type of heart disease that involves the build-up of fats, cholesterol, and inflammatory cells in the artery walls,” Dr Gelfand said. “Since ustekinumab blocks the specific pathways involved in both skin and cardiovascular inflammation, we wanted to test whether it can improve aortic vascular inflammation.”

Psoriasis patients were randomly divided into two groups, with 21 patients in the placebo group and 22 patients receiving the treatment. The primary outcome was aortic inflammation, as measured by 18-FDG-PET/CT scans – an imaging technique that reveals inflammation in the aorta. The imaging was performed before treatment and at 12 weeks. The treatment group saw a 6.6 percent decrease in aortic inflammation, while the placebo group saw a 12 percent increase, meaning the drug is responsible for a 19 percent improvement relative to untreated patients. As expected, ustekinumab also resulted in a dramatic improvement in skin inflammation as well, with 77 percent of treated patients achieving a 75 percent or better improvement in psoriasis activity, compared to just 10.5 percent in the placebo group. Both findings were highly statistically significant (p?0.001).

The results are consistent with a previous, smaller uncontrolled trial of ustekinumab, but they are in direct contrast to two large trials using a different drug called adalimumab, which is sold as Humira.

“This is the first placebo-controlled trial of a biologic drug to show a benefit in aortic inflammation, a key marker of cardiovascular disease,” Dr Gelfand said. “The effect is similar to what we would expect if we put the patient on a statin.”

Dr Gelfand, who conducted the study in collaboration with Dr Nehal N. Mehta, Chief of the Section of Inflammation and Cardiometabolic Diseases at the National Heart, Lung, and Blood Institute, confirmed their results by having a second, separate lab independently evaluate imaging data.

“This study represents a promise that this treatment may reduce the risk of heart attack and stroke in the future. It’s an encouraging finding,” Dr Gelfand said.

The trial is ongoing, and Dr Gelfand says his team will evaluate these patients at a longer follow up to see if the effects are sustainable and if patients continue to improve.


Two new approvals for Janssen’s Simponi Aria

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US regulators have expanded the scope of Janssen Biotech’s Simponi Aria to include the treatment of adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS).

According to the firm, the decision means that the drug – a 30-minute intravenous formulation of golimumab – is now the only fully-human anti-TNF-alpha infused therapy now approved for these conditions and rheumatoid arthritis.

Approval follows clinical trials involving more than 600 patients, in which a higher proportion of patients demonstrated significant improvement in the signs and symptoms of PsA and AS in the groups receiving treatment with Simponi Aria compared with those receiving placebo.

In the GO-VIBRANT (PsA) trial, 75 percent of patients receiving the drug, versus 22 percent of patients receiving placebo, achieved at least a 20 percent improvement in the American College of Rheumatology (ACR20) response at week 14, while treatment with Simponi Aria also resulted in the inhibition of the progression of structural joint damage and improvement in physical function associated with PsA at week 24.

In the GO-ALIVE (AS) study, 73 percent of patients in the treatment arm compared with 26 percent of patients receiving placebo achieved at least a 20 percent improvement in the Assessment of Spondyloarthritis International Society criteria (ASAS20) at week 16.

Arthur Kavanaugh, professor of Medicine at the University of California San Diego, and Chair of the GO-VIBRANT steering committee, highlighted the need for new treatment options for patients with PsA, and said the approval of IV golimumab “brings an important new treatment option to patients, especially those who prefer IV administration, and offers one with a 30-minute infusion time”.

Atul Deodhar, professor of Medicine at the Oregon Health & Science University in Portland, and Chair of the GO-ALIVE steering committee, also emphasised the limited treatment options for patients with ankylosing spondylitis, and so the approval of Simponi Aria “provides a welcomed new option”.


Sanofi’s Kevzara will be funded for NHS use

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Some patients with rheumatoid arthritis living in England and Wales should get ‘routine’ NHS access to Sanofi’s Kevzara after cost regulators issued draft guidelines deeming the drug cost effective.

The National Institute for Health and Care Excellence is backing use of Kevzara (sarilumab) with methotrexate as an option for treating severe active rheumatoid arthritis in adults whose disease has responded inadequately to intensive therapy with a combination of conventional disease-modifying antirheumatic drugs (DMARDs).

It’s also being recommended for adults with severe RA who have had an inadequate response to, or who cannot have other DMARDs, including at least one biological DMARD, and who cannot have rituximab.

The draft guidance also back use of Kevzara with methotrexate as an option for adults with severe active RA when their disease has responded inadequately to rituximab and at least one biological DMARD, and as monotherapy for those who can’t take methotrexate.

Sanofi has agreed a patient access scheme that will reduce the cost of the drug to the NHS, but the details are confidential.

Rheumatoid arthritis is a chronic inflammatory autoimmune disease that attacks the tissues of the joints, causing inflammation, pain, and eventually joint damage and disability, which affects around 450,000 people in the UK, of whom around 15 percent have the severe form of the disease.

As many patient fail to respond adequately to existing therapies or experience loss of response over time new treatment options are urgently needed.

“Over the years, we have made great progress in the diagnosis and management of RA, yet many patients still do not achieve symptom control despite the treatment choices available. NICE’s recommendation of sarilumab is good news for people with RA and their specialists as it potentially adds another treatment option,” said Professor Ernest Choy, consultant Rheumatologist, University of Cardiff.

“Rheumatoid arthritis is an unpredictable chronic disease. It strikes at any age, often during working life. It causes severe pain and comorbidities, which can have a huge impact on all aspects of their daily life including psychological wellbeing.”

Kevzara is a human monoclonal antibody that binds to the interleukin-6 receptor (IL-6R), and has been shown to inhibit IL-6R mediated signalling. In excess and over time, IL-6 can contribute to the inflammation associated with RA.

The drug’s approval in Europe in June was based on results from seven Phase III trials in the global SARIL-RA clinical development programme of more than 3,300 adults with moderately to severely active RA who have had an inadequate response or intolerance to one or more biologic or non-biologic DMARDs, which showed that the drug induced statistically significant, clinically-meaningful improvements in patients.

Improvement in signs and symptoms of RA at 24 weeks, as measured by the American College of Rheumatology score of 20 percent improvement (ACR20), were: 61 percent in the sarilumab 200mg group; 56 percent in the sarilumab 150mg group; and 34 percent in the placebo group, all in combination with DMARD therapy.


Humira Approved for Paediatric use

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The European Commission says the drug can be used on children to treat chronic non-infectious anterior uveitis.

Biopharmaceutical company AbbVie has secured approval of humira, which is more commonly known as adalimumab, for the treatment of chronic non-infectious anterior uveitis in children.

The approval allows the drug to be used on those over the age of two who have had “an inadequate response to or are intolerant to conventional therapy,” the company confirmed.

Approval was sought and secured based on the results of the SYCAMORE clinical trial, AbbVie said. The study found that adalimumab, combined with methotrexate, significantly delayed the time to treatment failure when compared to methotrexate with a placebo in children with JIA-associated uveitis.

Principle investigator on the study, Professor Athimalaipet Ramanan, highlighted: “Paediatric uveitis is a debilitating and potentially blinding condition…these results demonstrate adalimumab has the potential to help many children who have failed standard treatments to preserve their eyesight from the ocular complications associated with chronic non-infectious anterior uveitis.”

The approval means adalimumab is the only approved biological treatment option for this purpose in those aged two and over across the EU.

UK medical director of AbbVie, Alice Butler, said: “This approval marks an important milestone for paediatric uveitis patients who, up until this point, had no licensed biologic treatment options for them.

“The label expansion for adalimumab is a further step in AbbVie’s dedication to addressing the unmet needs for both adult and paediatric patients living with serious immune-mediated inflammatory diseases.”