Rheumatoid Arthritis: From Damage Control to Taking Control

Living with RA once meant documenting failure. Until one discovery led researchers down an uncharted path.

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A Difficult Disease with Difficult Choices

Picking the right songs for a knuckle replacement surgery isn’t easy. Do you choose a punk rock song so the heavy drum and bass will cancel out the noise? Or a soothing melody to help you forget the fact that, at 18 years old, your joint damage is so great that it warrants this type of procedure?

These were the questions facing Lori Anne, a teenager living with rheumatoid arthritis (RA) in South Carolina, U.S.A., as she rifled through her CD collection one day in the 1990s; the kinds of questions a teenager should never have to contemplate.

And that’s why, an ocean away in Ludwigshafen, Germany, and hundreds of miles away in Massachusetts, U.S.A., scientists were on a path to changing the treatment paradigm for RA – a disease that could transform a healthy, active girl to a patient feeling three times her age, choosing songs to play as they replaced her decimated joints.
 

Then: Few Treatment Options

The history of rheumatoid arthritis starts long before Lori Anne and her CD collection.

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When Lori Anne was diagnosed with RA in the 1980s, practicing rheumatologists like Dr. Stefan Simianer were accustomed to seeing patients hospitalized.

“You had all the records of those patients at your hands; you’d have a big bag with X-rays in it, and you could see over the years how those patients systematically deteriorated, how their X-rays got worse and worse,” says Simianer, now vice president, international R&D and general manager, Ludwigshafen, Germany, AbbVie. “Basically, this was a document of failure … Rheumatology was quite demanding for physicians because there was really not much help you could offer.”

Lori Anne utilized available treatments, which allowed her to get out of bed and go to school. But she was still exhausted, unable to play tennis or basketball, which she’d once loved, and her body showed the effects of the disease. Upon returning to her small, private school, she noticed a teacher quickly turning away.

“She was crying, she was so upset. I had lost so much weight because I really didn’t eat,” Lori Anne says. “That’s how drastic it was and how quickly it happened.”
 

A Simple Research Question that Would Change RA

Meanwhile, at what would later become AbbVie’s research center in Germany, scientists were studying a protein in the body called Tumor Necrosis Factor alpha, or TNFα. In acute conditions like septic shock, TNFα levels were extremely high; the body was sending extra TNFα to fight the infection.

What they were surprised to learn was that the protein was also prevalent in people with RA. These people didn't have infections, so why were their levels of TNFα so high?

The research team had already developed a TNF antibody that worked in septic shock, but they quickly discovered it couldn’t be used for a chronic condition like RA, as long-term use triggered antibodies that made the drug ineffective. So, the scientists started down a new – and completely uncharted – path, working with research colleagues in Massachusetts.

Jochen Salfeld, vice president, global biologics discovery and distinguished research fellow, AbbVie, who led the Massachusetts team at the time, explains:

For Jochen Salfeld and his team, setting high expectations meant the potential to help many people with autoimmune diseases.

Innovation Beyond the Medicine

Salfeld and his team weren’t the only innovators studying TNF-alpha inhibitors by the time their fully human anti-TNF antibody entered clinical studies in the ‘90s. Top scientists around the world were studying this new group of medicines called biologics, made from living cells, which became available to people living with RA.

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Tumor Necrosis Factor (TNF) antibodies work by attaching to the TNF protein in the body, which is over produced in conditions like RA and can lead to inflammation. Attaching the TNF antibody to TNF helps reduce the effects of excess TNF in the body.4

Innovation isn’t only about drug discovery, however.

“We did not want to develop ‘just’ a medicine, but a best-in-class therapeutic that would change patients’ lives,” Salfeld says. “We were very interested in not just treating the disease, but coming up with a convenient delivery system for the patient as well."

As a therapeutic antibody, not the type of therapeutic suitable for oral dosing, medicine would need to be given by injection. “Convenience would of course mean that patients could administer the medicine to themselves, rather than spend hours some place receiving an infusion,” Salfeld says.

“Our team did a study with arthritis patients in different countries and gave them options for a pre-filled syringe type of device … They’d give you feedback, ‘this is working’, or ‘this is the best of the three’ or ‘make this and this change.’ The pre-filled syringes we ended up launching with were actually designed for patients by patients.”
 

RA Today and Tomorrow

Nowadays, due to advances in the field of rheumatology, including the availability of biologic medicines, Lori Anne is thriving as a wife, mother and principal – at the very school where, years ago, a teacher had been brought to tears by a teenage Lori Anne’s declining health.

Lori Anne, high school
Lori Anne with son, present day

“So much has changed (in RA) over the last 15 to 20 years – from our understanding of the disease process to the development of new and advanced medications, to how the arthritis community receives and uses health information,” says Andrea Kane, medical editor, Arthritis Today, a publication of the Arthritis Foundation. “Thanks to the improved treatments available, many people with RA not only talk about being able to lead so-called normal and active lives but also about achieving remission.”

“That said, the road to remission isn’t easy and not everyone gets to travel on it,” Kane says. “Even for those who do, it’s still peppered with potholes, such as periodic flares, nagging fatigue and progressive joint damage.”

That’s why scientists like Salfeld keep searching for new ways to treat autoimmune diseases like RA.

“Everybody has a life plan and suddenly you find out you have an autoimmune disease. Autoimmune diseases are chronic diseases; it’s very difficult to understand upon initial diagnosis that this is actually going to be with me all my life. It’s not going to be going away in two weeks,” Salfeld says. “One thing that all of us at AbbVie think about how can we build on past experience? How can we treat more patients and impact the disease even further?”

Ultimately, its patient stories like Lori Anne’s that make the long journey of drug discovery and development worthwhile.

“For patients, the idea that they can take control of their disease has a tremendous impact – because it’s no longer the disease controlling me, I can now together with my physician control the disease,” he says. “That really is for me why I come to work, why all of us come to work.”

Along with many of our partners like the Arthritis Foundation, AbbVie is committed to advancing understanding and awareness about rheumatoid arthritis, and to furthering research that seeks to improve the lives of those living with and impacted by this disease.

Learn more about our work to bring relief to patients living with immune-mediated inflammatory conditions.

References:

  1. Entezami, BS, Fox, David, et. al. Historical Perspective on the Etiology of Rheumatoid Arthritis. Hand Clin. 2011 Feb; 27(1): 1-10. Accessed: February 27, 2018. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119866/
  2. Sokka, Tuulikki, Envalds, Minja, Pincus, Theodore. Treatment of rheumatoid arthritis: a global perspective on the use of antirheumatic drugs. Mod Rheumatol. 2008 Jun; 18(3): 228-239. Accessed: February 27, 2018: Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668379/
  3. Monaco, Claudia, Nanchahal, Jagdeep, et. al. Anti-TNF therapy: past, present and future. International Immunology. 2014 Nov; 27(1): 55-62. Accessed: March 1, 2018. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279876/
  4. How HUMIRA Works. Accessed: March 1, 2018. Available at: https://www.humira.com/rheumatoid-arthritis/how-humira-works-for-ra
 

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Jillian Griffin
Email: jillian.griffin@abbvie.com
Call: +1 224-545-4122
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