Early Aggressive Biologic Treatment in Pediatric Rheumatology

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• Precision Medicine Future
• Treat to Target Concept
• Risks of Chronic Inflammation
• Corticosteroid Sparing Goal
• Flipping the Treatment Pyramid
• Long-Term Societal Benefits
• Full Transcript

Precision Medicine Future

Dr. Randy Cron, MD, identifies precision medicine as the future of pediatric rheumatology. This approach involves knowing which patients should receive which specific medications. Dr. Randy Cron, MD, explains this strategy is crucial for all medicine, both adult and pediatric specialties.

Precision medicine aims to tailor treatment plans to individual patient profiles. This personalized care improves outcomes and minimizes unnecessary side effects.

Treat to Target Concept

A central concept in modern rheumatology is 'treat to target'. Dr. Randy Cron, MD, describes this process. The physician makes a diagnosis and sets a treatment goal with the patient and family.

The ultimate goal is often inactive disease or clinical remission. Dr. Randy Cron, MD, notes that while cures are not yet common for many rheumatic diseases, prolonged remission is an achievable objective. The strategy involves escalating treatment aggressively if the initial therapy does not reach the target.

Risks of Chronic Inflammation

Dr. Randy Cron, MD, emphasizes the severe consequences of untreated chronic inflammation in children. He states that the potential side effects of biologic agents are far outweighed by the damage from ongoing inflammation.

Chronic inflammation can disrupt a child's growth, leading to significant problems. These issues include joint destruction, leg length discrepancies, and micrognathia (a small jaw). Dr. Cron also notes that inflammation is harmful to overall health, affecting the heart and brain.

Corticosteroid Sparing Goal

A major goal in pediatric rheumatology is to spare patients from long-term corticosteroid use. Dr. Randy Cron, MD, explains that while steroids are life-saving, they have a huge list of side effects.

Using effective biologic therapies helps control inflammation without relying on chronic steroids. This strategy minimizes the risk of steroid-related complications like osteoporosis and weight gain. Dr. Anton Titov, MD, discusses these treatment trade-offs with experts like Dr. Cron.

Flipping the Treatment Pyramid

Dr. Randy Cron, MD, describes a historic shift in treatment philosophy. The old pyramid approach started with mild drugs like NSAIDs (e.g., ibuprofen) and slowly escalated.

This method often allowed damage to accrue over a year or two. The new paradigm flips this pyramid upside down. For very sick patients, treatment may begin immediately with a potent TNF inhibitor, sometimes combined with methotrexate.

This aggressive early intervention aims to achieve rapid remission. The goal is to use the most effective drugs with the best benefit-to-side-effect ratio first.

Long-Term Societal Benefits

Dr. Randy Cron, MD, addresses the economic considerations of advanced biologic therapies. He acknowledges that these medications are expensive compared to traditional drugs, which can create hurdles with insurance providers.

However, Dr. Cron argues that these treatments provide significant long-term benefits to society. By preventing chronic damage and disability, they ultimately save money. This cost-benefit analysis is a critical part of the conversation about modern rheumatologic care.

Full Transcript

Dr. Anton Titov, MD: Professor Cron, what is the future in pediatric rheumatology in general, and in cytokine syndrome treatment in particular?

Dr. Randy Cron, MD: I think you mentioned precision medicine, and knowing which patients to give which meds is the future, not just for pediatric rheumatology, probably for all aspects of medicine, adult and pediatric. But it's definitely true in pediatric rheumatology.

There is this concept in rheumatology of "treat to target." So you have a patient, you make a diagnosis, you sit with the patient and the family if it's a pediatric case. You say, what's the goal, and often that goal is inactive disease or remission.

We can't cure many of our diseases at this point, although that will ultimately be the long term goal of all this. I don't know when that will be for some of our diseases.

I've kind of seen a glimpse of that with some of our more aggressive approaches to treating lupus that I hadn't seen in the past, and that may be on the horizon.

But for arthritis, at least we are not able to cure kids of the disease. But we can get them into prolonged remission, sometimes off of meds. So that's the ultimate goal.

And so "treat to target" concept is the following. You try something and if you're not there, then you keep getting more aggressive, because for the most part, particularly with the biologic agents, the side effects are outweighed. The potential for side effects by the medicines are far outweighed by the chronic inflammation and the damage.

And as a kid you're growing. And so it can actually affect your growth in a lot of bad ways, particularly destructive things around the joints, or having one leg longer than the other, or the jaw, which is a commonly involved joint. You can get a small jaw, or micrognathia, and all these have long-term consequences.

In adults, we know better than in kids. But chronic undertreated inflammation is bad for your body in general, whether it's your heart or your brain. Inflammation is not a good thing.

And if we can keep it under check, and not have a ton of side effects from the medicines we're using to do that, we are able to spare corticosteroids which have a huge laundry list of side effects.

It is always a goal, particularly in rheumatology, kids and adults. Because steroids have so many side effects. They are life-saving drugs, and we completely rely on them a lot of the time.

But chronically, they're not great drugs to be on, particularly at substantial doses.

So yeah, I mean, the future just keeps looking better and better for us. We just have to be smarter about which patients should get which drug, the timing of that, how aggressive to be.

There used to be what was called a pyramid approach to treating chronic rheumatic diseases, both adults and kids. You would start out with something like Motrin, ibuprofen, for example, a non steroidal anti-inflammatory drug.

For the most part, you worry about a ton of side effects, but again, it chronically can bother your kidneys, your liver, your gut, for example. And you would start there and the kid wasn't much better in three months.

So then you would add what we call a disease-modifying antirheumatic drug, because the non-steroidal anti-inflammatory drugs don't disease-modify something, for example, like low dose methotrexate.

And you would try that for a while, and they get a little bit better, maybe, but they weren't good enough. And then you raise the dose of that and see how they're doing, a year or two into the disease. They're still not doing great, and you've accrued a lot of damage along the way.

But now, we're trying to flip that pyramid upside down. So if you're sick enough, maybe at diagnosis, we're going to start a TNF inhibitor, maybe in conjunction with methotrexate, for example.

Maybe we try to take the methotrexate away over a year or two, if we can get them into remission. So using what works best with the least side effects.

And that's not always popular with third-party payers, because they tend to be expensive medicines compared to their other drugs. But in terms of long-term benefit to society, they definitely save money.

But we still kind of struggle with that. But flipping the pyramid so that we're using the drugs with the highest benefit, the side effects ratio that makes the most sense.