Polyarticular juvenile idiopathic arthritis (PJIA): an interview with Dr. Kramer, VP, Immunology and Infectious Diseases Medical Unit, Genentech

insights from industryDr. Ben KramerVice President, US Medical Affairs, Immunology and
Infectious Diseases at Genentech/Roche

Please can you give a brief introduction to Polyarticular juvenile idiopathic arthritis (PJIA)? How common is PJIA?

Polyarticular Juvenile Idiopathic Arthritis (PJIA) is a type of Juvenile Idiopathic Arthritis (JIA), a group of Rheumatoid Arthritis (RA) diseases that manifests in multiple ways in children.

These conditions all consist of joint inflammation and usually begin before the juvenile reaches the age of sixteen. If the symptoms last three months, then the disease is called chronic. PJIA, by definition, affects five or more joints and can begin at any age.

In general, JIA occurs in one in a thousand children and of that population, about 30 percent of them will have PJIA.

How does PJIA  differ from other forms of juvenile idiopathic arthritis (JIA)?

The major difference is the number of joints impacted and the fact that in Systemic Juvenile Idiopathic Arthritis (SJIA), patients experience system wide symptoms, such as fever, rash, and/or anemia. Oligoarticular Juvenile Arthritis involves fewer than five joints. This affects about half the children that have or are afflicted with arthritis.

Can you tell us about the diagnosis process?

A diagnosis can be insidious because children may not complain of pain and joint swelling may not be so obvious.

Also, there isn’t really a blood test that can be used to diagnose the condition because, unlike with adults who may have a positive rheumatoid factor blood test, in children, typically that test is negative.

Thus, it takes a really good paediatrician to notice an issue because juvenile patients are probably first going to present symptoms to their general doctor before they go to a specialist.

The typical symptoms include limping, stiffness when waking up, and it may be even more subtle, such as a reluctance to use an arm or a leg, or a reduction in activity levels. Patients may also experience some difficulty with fine motor activities. Certainly, they could also have fever, joint swelling and additional obvious symptoms, but it can be difficult to diagnose and takes a good physical and history to pick it up.

What is the reason that the rheumatoid factor blood test is often negative in children, but not in adults?

The reason is that they don’t have a certain antibody that adults would have. Why they don’t; that we’re not sure of.

How much is known about the causes of the condition?

Not a whole lot, but we do know that it’s an autoimmune phenomenon. We don’t know why a child develops this condition, and for that matter, we’re not that clear why adults do either.

It is an area of active research and Genentech is very interested in both adult and pediatric arthritides. There’s still research going on to better understand the disease process, which could lead to newer therapies. Genentech is very committed to this therapeutic area and the RA community.

If left untreated does the condition worsen over time?

Yes, it can. That’s why it’s important to diagnose and treat it. We want to control the symptoms, but even more importantly, we want to prevent joint damage and maintain function. It is really important that it gets diagnosed as early as possible and that the most effective treatment is instituted/implemented.

At what stage is PJIA usually diagnosed?

It is typically diagnosed within the first couple of months after setting in, but it depends on the presentation.

How successful are current treatments for the condition?

For PJIA, there are a number of different therapies. First line treatment usually might involve something called a non-sorbitol, anti-inflammatory drug.

If there are significant joint inflammations, a physician will progress to something called a disease modifying drug, or DMARD, which are usually drugs such as methotrexate.

If patients are not responding to methotrexate, there are biologics that will be introduced into the regimen such as our drug, Actemra (tocilizumab), which is approved to treat both PJIA and SJIA. There are also additional biologics on the market, so pediatricians can choose the medications that work for their patients. 

Since all medications may have side effects, it is important that patients be carefully monitored, usually by a pediatric rheumatologist who has a lot of experience treating these types of diseases.

Overall, are they quite successful in terms of relieving the symptoms?

Yes, I believe that overall there is a good prognosis, but of course it will vary from child to child.

What is really important is that with the introduction of biological therapy, such as Actemra, we have made significant advances in terms of the treatment and prognosis outcomes for these children, which is very positive.

What research is currently being carried out into PJIA?

At Genentech, we have a very strong interest in this area and there is a lot of active research being carried out. In general, people are trying to better understand the autoimmune disease process and why it occurs.

We are also trying to look for new therapies that could be even more advantageous than what is currently available.

Another important area of research, both for children and adults, is the identification of biomarkers, whether they are protein or genetic signatures. These may indicate a patient’s vulnerability to getting the disease, their prognosis during treatment, or their response to a particular therapy. Genentech is committed to this area of research.

Can you tell me about Genentech’s Rheumatoid Arthritis franchise and your commitment to patients in this space?

As you know, we currently have two products - Actemra and Rituxan.

Rituxan is an anti CD20 molecule, which is a monoclonal antibody that binds to a protein on an immune cell that actually makes antibodies.

In both Rheumatoid and Juvenile Arthritis, immune cells make antibodies which cause the inflammation that occurs in joints. Rituxan is a biologic which acts on those antibodies to prevent the inflammation.

Rituxan received FDA approval for RA in February 2006 and is currently indicated in combination with methotrexate (MTX) in adult patients with moderately-to-severely active RA who have had inadequate response to one or more anti-tumor necrosis factor (TNF) therapies.

We continue to conduct clinical research with Rituxan. In fact, we just finished a study last year showing that administering Rituxan with a shorter infusion rate is still safe and effective. This data was presented at the 2013 American College of Rheumatology annual meeting, and have submitted a supplemental Biologics License Application (sBLA) to the FDA for a shorter infusion time for in adult RA patients.

As mentioned previously, Actemra is a biologic that is approved for PJIA and for adult RA, at several different lines of therapy, including for adults after they have failed or only partially responded to drugs like methotrexate. Actemra binds to the receptor for a protein called IL-6, which has been found in high concentrations in joints that are actively inflamed with RA. It has been on the market since 2010 and we are proud that Actemra has been approved for multiple indications over the past four years, offering a variety of patients treatment options.

Actemra is available both intravenously and subcutaneously, meaning by injection. We think that it is important because having different formulations gives consumers the flexibility to choose a treatment that fits their needs. It’s important that patients work with their health care providers to make decisions about what is the right treatment or formulation for them.

Where can readers find more information?

There are a couple of websites that I think would be helpful for patients.

RheumatoidArthritis.com is a website where patients and health care providers can find information.

What is unique about RheumatoidArthritis.com is the fact that it’s an educational website designed by Genentech to provide useful and up to date information, in many different forms including articles, videos and online tools - the content on the website is created by those who either work in the arthritis area or patients that have it.

For example, RAise Your Voice is a series of videos which feature key players from the RA community including rheumatologists, patients, advocacy groups, and RA bloggers who communicate relevant information about the disease to patients and caregivers.

Genentech continuously updates the website and we are excited to share that we are in the process of working with well known RA patient bloggers to add additional inspiration content later this year.

We think that RheumatoidArthritis.com is a valuable resource for patients, caregivers and their healthcare providers.

Certainly, the American College of Rheumatology has a website with a lot of useful information that is available to patients. There are definitely a number of different sources that patients can find on the internet that can really enhance their understanding of their disease and their treatment options.

At Genentech, we are truly committed to the RA community. We continue to dedicate ourselves to providing multiple treatments options for those suffering from the disease and to performing research that will advance the field of RA management in general.

About Dr. Kramer

Ben Kramer, MD, is the Vice President, US Medical Affairs, Immunology and Infectious Diseases at Genentech/Roche. After nearly 20 years in the pharmaceutical industry, he has significant leadership experience both in global clinical development and global medical affairs in respiratory, urology and immunology.

Dr. Kramer earned his undergraduate degree at Brandeis University and his medical degree at New York Medical College. He is board certified in allergy and immunology, as well as internal medicine. Throughout the course of his career, Dr. Kramer has frequently presented new data at medical meetings and is well published in his field.

April Cashin-Garbutt

Written by

April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.


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