Looking forward to the future, RA treatment has entered the era of precise targeting

*For medical professionals only

On the road of exploring the treatment of RA, small molecule JAK inhibitors have been at the forefront
.

Rheumatology and immunology is an important branch of modern medicine, although it has a history of hundreds of years of development in the world, but it is the youngest professional discipline
in China's domestic science.
In recent years, under the promotion of discipline associations and the unremitting efforts of experts and scholars, China's rheumatology and immunology profession has grown from small to large, from weak to strong, and has achieved remarkable results and embarked on the fast track
of high-quality development.

Nevertheless, in the face of a large number of patients in China, the task of prevention and treatment of rheumatic immune diseases is still extremely arduous
.
As one of the third major killers threatening human health, this type of disease has a high incidence, high disability rate, and low awareness ^{rate [1]}, and there are still many clinical conditions that need to be improved
.

A hundred boats compete for the current, and those who strive first
.
As benchmarks of the discipline, Professor Mu Rong and Professor Zhao Jinxia of Peking University Third Hospital have made outstanding contributions
to the continuous improvement of the clinical research level and medical diagnosis and treatment of rheumatology and immune diseases in China day after day.
In this issue, let's talk to two professors and work with them to imagine the future of rheumatology and immunology and explore the latest drug treatment processes
.

Based on clinical practice, looking forward to the future prospects of the department

The Department of Rheumatology and Immunology of the Third Hospital of Beijing Medical University, established in October 2006, as a discipline leader, when asked why he decided to become a rheumatologist in the first place, both professors said that this was an accidental and inevitable result
.
Professor Zhao Jinxia said, "When I graduated from my bachelor's degree, I wanted to continue to study internal medicine, and rheumatology and immunology, as an emerging discipline, can fully reflect the clinical thinking
of internal medicine doctors.
After another five years of study, I gained a deeper understanding
of rheumatic diseases.
Therefore, after graduation, I came to the Third Hospital of Beijing Medical University by chance to continue to engage in this specialty
.
In the past ten years, I have also witnessed the growth of the department, of course, the more I work, the more I like it.
"
Professor Mu Rong chose this major because of his interest at the beginning, "At that time, when I was an intern, the first department I rotated was endocrinology and rheumatology and immunology, which I thought was very interesting, so I chose this department
at that time.
Of course, at that time, it was a period of rapid development of immunology, and after decades of clinical rheumatology diagnosis and treatment and discipline development, we are more convinced that the profession is very promising.
"

The existence and development of the Department of Rheumatology and Immunology is the embodiment
of the comprehensive strength of the hospital.
All this is inseparable from the usual clinical diagnosis and treatment work, but also inseparable from scientific research and innovation
.
Regarding how to balance clinical and scientific research, Professor Zhao put forward his own views, "If you want to be a good doctor, you must walk on two legs of clinical and scientific research at the same time
.
These two works are not completely separated, we must find problems in the clinic, and then use scientific research thinking and means to solve problems, and then promote clinical development
.
For example, in the clinical encounter of special cases that are difficult to diagnose, we can explore diagnosis and treatment methods
by consulting the literature.
If you want to introduce new treatment options to patients, you can use case series studies or even more rigorous RCTs
.
Clinical and scientific research are themselves balanced, if you only focus on clinical and do not do scientific research, then it is difficult for medicine to progress
.
”

The rheumatology and immunology department has grown vigorously along the way, which is the result
of the perseverance and long-term accumulation of the department team.
The construction of departments should take clinical as the foundation, scientific research as the driving force, and talents as the core
.
For the future development of rheumatology and immunology and department planning, Professor Mu has his own expectations, "The diagnosis and treatment level of the entire rheumatology field has been greatly improved, and many new studies will appear
every year.
We should take discipline construction as the starting point to drive the high-quality development of
departments.
First of all, in the diagnosis and treatment of common diseases and difficult rare diseases, it is necessary to be more standardized, and at the same time, drive the surrounding hospitals together to prevent and diagnose rheumatic diseases, and treat rheumatic diseases, as well as the follow-up rehabilitation and return of patients to society, forming a generalizable medical model
.
In addition, it is also hoped that the doctors with relatively high seniority in the department can have their own deep cultivation in scientific research, and can study the more difficult or urgent problems within the scope of the discipline at present, and promote the further development
of the discipline.
”

Ready to go, RA therapy has entered the era of targeting

Rheumatoid arthritis (RA), the most common disease of the rheumatic immune system, mainly affects the joints and has a persistent high degree of inflammation
.
According to the 2018 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis, the incidence of RA in China is about 0.
42^{% [2]}, and this data has been rising
in recent years.

In view of the fact that RA is a chronic progressive disease, the goals of clinical treatment are mainly to control disease symptoms, slow disease progression, reduce disability rate, and improve prognosis ^[3].

The treatment principle of "early diagnosis, early treatment" ^[2] has always been advocated
by rheumatologists.
With the in-depth research on this disease and the advent of innovative drugs, RA treatment strategies have been continuously optimized, and clinical remission has become an achievable treatment goal
for RA patients.

The 2018 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis pointed out that once RA patients are diagnosed, csDMARDs should be started as soon as possible, and methotrexate alone and as an "anchor drug" for combination therapy is recommended ^[2].

。 In the past decade, biologics DMARDs (bDMARDs) targeting anti-tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6), as well as targeted synthetic DMARDs (tsDMARDs), such as Janus kinase (JAK) inhibitors and other small molecule drugs, have promoted RA therapy into the targeted era with the
advantages of precision treatment and rapid onset.

"In the absence of these targeted drugs, RA treatment was mainly based on csDMARDs, but this only worked
for some patients.
In addition, some patients may have a lack of treatment due to drug intolerance or slow onset
.
Previously, about half of the patients in the clinic, even if we took all the drugs, their symptoms would continue to worsen until they became disabled
.
As targeted drugs increasingly enter the clinic, we can see that it works significantly faster
than past drugs.
Professor Mu expressed great recognition of the efficacy of targeted drugs, "Each targeted drug also has its own characteristics, which can be treated for different groups of people, and should be selected
according to the patient's own clinical characteristics and drug response.
" Therefore, I also hope that there will be some biomarkers in the clinic in the future that can help us better judge how to choose which targeted drugs, so as to achieve real precision treatment
.
All in all, the emergence of these innovative drugs can make the rate of patient compliance higher
and higher.
So I believe that as we diagnose patients earlier and earlier, delay treatment less and less, coupled with rational medication, almost all patients can achieve true clinical remission
.
Then everyone's fear of RA, especially the fear of patients
, should no longer exist.
”

From traditional drugs to targeted era, the treatment of RA is constantly changing
.
In the past, patients often thought that RA was an "immortal cancer" and treatment was difficult, but the advent of new drugs has enhanced patients' confidence
in treatment.
From Professor Mu's words, we can know that targeted drugs have become a "sharp weapon" in the hands of rheumatologists to fight RA, and it will usher in a new round of development opportunities in the future and make more contributions
to the treatment of RA.

Clinical testimonials, JAK inhibitors help patients "target" the future

As new immune pathways continue to be discovered, new drug targets are constantly being explored, and biologics and targeted drugs are also updated
.
Small molecule drug JAK inhibitors inhibit JAK phosphorylation, thereby preventing STAT phosphorylation, blocking the synthesis and secretion of a variety of inflammatory factors, and exerting anti-inflammatory and immunomodulatory effects ^[4].

Professor Zhao further added to the mechanism of the drug, "JAK inhibitors can selectively inhibit JAK kinase, block the JAK/STAT pathway, and then block the progression of RA from the source ^[5].

In contrast to TNF-a inhibitors, which target only one cytokine, JAK inhibitors, which can block the action
of many cytokines at the same time.
Compared with traditional DMARDs, the efficacy is also significantly better
.
”

At the same time, Professor Zhao introduced to us the case of RA with remarkable effect after the clinical application of JAK inhibitors, a male patient in his fifties, whose condition lasted for decades and could not be cured for a long time, still experienced joint deformity and hormone-related adverse reactions
after experiencing methotrexate intolerance, leflunomide plus low-dose hormone shock control symptoms.
Fortunately, biologics entered the national medical insurance catalog, reducing their financial burden, so the patient continued to use traditional DMARDs, added TNF-a inhibitors, and finally achieved hormonal reduction
.
After that, TNF-a inhibitors had secondary failures, and JAK inhibitors were switched, although complete remission was not achieved temporarily, but the disease activity remained low
.

It can be said that this patient is the epitome of countless RA patients in the clinic, and countless patients in the past have endured huge physical pain and heavy financial burdens
in the face of incurable diseases.
The emergence of innovative drugs has alleviated their condition and even given them hope
for a cure.
We also expect that with the advancement of medicine, more new drugs and new regimens will shine in the treatment of RA patients
.