Rheumatoid Arthritis #2: Advances of Drug Treatment

Doctor's Insight.

Hello and welcome to Doctor's Insight.

Rheumatoid arthritis, or RA, is a disease that destroys a person's own joints due to a malfunction of the immune system.

Until about 20 years ago, RA was mainly treated with pain relievers.

It was difficult to stop the deformity caused by joint destruction, and the disease was said to be incurable.

It is said that 1 in every 100 people in Europe and the U.S. suffers from rheumatoid arthritis, and the number continues to increase each year.

In Japan, the patient's onset age peaks in the 40s, and 80% of patients are women.

Moreover, the cause of the disease is not clearly known, and anyone can be affected by RA.

However, the advent of a particular class of drugs has revolutionized the way doctors think about treatment.

They are "biological anti-rheumatic drugs," often referred to as "biologics."

How have biologics changed the treatment of rheumatoid arthritis?

Today, we will introduce the latest on drug treatment.

Today's expert is Dr. Kaneko Yuko from Keio University.

She is committed to providing tailored treatment that suits the patient's lifestyle.

Dr. Kaneko, thank you for joining us again today.

It's great to be here.

Drug treatment for rheumatoid arthritis seems to have evolved a great deal.

Considerable progress has been made over the past 20 years.

As a result, we can now aim to achieve remission.

In other words, living your daily life without being interfered by the disease.

Remission... that's different from being cured.

Cure implies that the disease goes away and treatment is no longer necessary.

Remission means that the disease is still there, but you can live almost a normal life with treatment, but there is a risk of recurrence if treatment is stopped.

So achieving remission is the goal for treating RA?

Exactly.

More specifically, the goal is to reduce swelling and pain, and to prevent the progression of joint damage and joint deformity.

These are the primary treatment goals not only in Japan but throughout the world.

Achieving remission has been the goal of RA treatment, and good results were made over the past 20 years.

In Japan, a survey was conducted on more than 5,000 patients.

This graph shows the percentage of people in remission.

In 2001, only 8% of people were in remission, who had recovered to the point where they had no impairment in their daily lives.

However, the remission rate has improved over the years and now stands at 61%.

This is due to the evolution of therapeutic drugs.

What kind of drugs were used in the past?

More than 20 years ago, steroids and painkillers were used on patients.

However, these drugs only alleviated the symptoms and did not treat rheumatoid arthritis itself.

And then, new drugs were developed.

That's right.

Oral medicine known as anti-rheumatic drug became available.

Among them, methotrexate became widely used, because of its high efficacy in suppressing the immune function at a relatively low cost.

1 out of every 3 patients are reported to be in remission and 1 in 2 improved symptoms with methotrexate.

Oh, wow. It's great that some people have gone into remission with this drug.

But that still means that 2 out of 3 people are not in remission.

You're right.

And then, "biologics" were developed.

This dramatically changed the treatment of rheumatoid arthritis.

How is methotrexate different from biologics?

There is a type of vitamin in our body called folic acid which is important for immune cell activation.

Methotrexate is a drug that blocks folic acid.

In other words, it reduces inflammation by decreasing the activity of immune cells.

On the other hand, biologics bind to proteins called cytokines secreted by immune cells that cause inflammation in rheumatoid arthritis.

This image shows biologics binding to cytokines and blocking their effects.

This is how they reduce inflammation.

How effective are biologic drugs?

Some have reported that the pain had stopped as early as several days after starting the treatment.

A survey conducted in Japan found that 90% of those who used biologics felt that the treatment was effective.

90%. That's really amazing.

So, do all people diagnosed with rheumatoid arthritis now use biologics?

No, not necessarily.

Methotrexate is still the first-line therapy for people with rheumatoid arthritis.

If a patient is diagnosed with severe rheumatoid arthritis and has a high risk of progressing to joint destruction, biologics may be used immediately.

But because of the high cost of biologics, it is standard to start treatment with methotrexate first.

There are currently 8 types of biologics available, including intravenous and injection under the skin.

The time interval between injections varies depending on the drug.

For example, some subcutaneous injections are given once a week, while some IVs are required only once every two months.

There are many different types of biologics.

How do you know which of the 8 types will work for a patient?

It's hard to determine which biologic is right for the person before the patient tries it.

So what physicians do is find out about the patient's lifestyle and choose a biologic that would be easy to stick with.

While IVs require a hospital visit, patients can perform subcutaneous injections on their own at home after learning the injection method.

I can say the injection of biologics is very easy.

Having more options is one of the advancements of rheumatoid arthritis treatment.

That's really great to hear.

Once you find the right match, does the patient continue using it?

Yes, the basic rule is to continue that treatment.

In that case, it would lead to worries about medical costs, right?

Currently, it is standard to combine methotrexate and biologics, but if the treatment is found to be highly effective,

they could lower the cost by reducing methotrexate, or increasing the interval between biologics.

In addition, biologics called "biosimilars" have recently become available, and patients may have the option of using them.

Biosimilar is a biologic drug created by a pharma company which is similar to an existing drug of a different manufacturer whose patent has expired.

Since biosimilars require less cost for development compared to new drugs, they are more affordable.

It is similar to the idea of generic drugs.

Biosimilars do not contain identical ingredients with the original ones, but they are shown to have comparable efficacy and side effects.

Both methotrexate and biologics have side effects because of their effects of suppressing the immune system.

In particular, pregnant women and the elderly should be careful.

Also, methotrexate should not be used before or after pregnancy and while breastfeeding.

Methotrexate and biologics are said to increase the risk of interstitial pneumonia and herpes zoster, so it's important to discuss this with your physician when starting treatment.

There really are a wide range of options.

Now, what happens if none of them work?

Are there any other options?

In such cases, we consider using oral medication called "JAK inhibitors," that came out in recent years.

JAK inhibitors suppress immunity and inflammation by interfering with the enzyme that activates immune cells, thus helps to reduce the symptoms.

The efficacy is said to be equal or slightly better than biological agents, and now, there are 5 types of JAK inhibitors available here in Japan.

However, the fact is, they cost as much or more than biologics.

That's why they are not being used as a first-line therapy.

I see.

But looking back at the time, when all we could do was to suppress the pain, there has been great advancements in treating rheumatoid arthritis.

Doctor Kaneko, how would you wrap up today's topic?

Drugs are ever-improving, and I believe more and more patients will be able to achieve remission in the future.

That's why I want to encourage early diagnosis and early treatment for rheumatoid arthritis.

Dr. Kaneko, thank you so much for being on our show.

Thank you.