Upatinib, the first targeted new drug for psoriatic arthritis, is here!

As one of the hottest targets in the field of immune diseases in the world in recent years, from the beginning of 2022, JAK1 inhibitors represented by AbbVie Upatinib will be launched in China at an accelerated pace, which is a good way to enter the field of rheumatic immune diseases.
ready
.
Recently, AbbVie announced that its innovative immunotherapy drug Refu® (upatinib sustained-release tablets) has been approved for the third indication in China for the treatment of ineffective or intolerable one or more DMARDs.
Active psoriatic arthritis (PsA) in adult patients
.
It is reported that upatinib extended-release tablet is an oral selective JAK1 inhibitor with a recommended dose of 15 mg once a day
.
This is the first and currently the only targeted therapy approved for the treatment of PsA in China, marking China's official entry into a new era of targeted therapy for PsA
.
It is worth noting that, from February 2022 to the present, in just two months, Upatinib has been approved for three consecutive indications in China, and the speed has attracted widespread attention in the industry
.
So—— Why does Upatinib have such an efficient approval speed in my country? What is the current status of PsA diagnosis and treatment in my country? What are the benefits of Upatinib for PsA patients who have been "underserved and underserved" for many years? As an "iteratively updated" targeted immunosuppressant, what are the advantages of JAK1 inhibitors represented by upatinib? What kind of clinical data is behind it? What is the future prospect? .
.
.
In response to the above questions, Sina Pharma specially interviewed Professor Liu Yi from the Department of Rheumatology and Immunology, West China Hospital of Sichuan University, the principal investigator of the domestic PsA Phase III study of Upatinib, to find out the answers one by one
.
01 The real needs of patients behind the efficient approval are the key "Behind the two indications of RA and PsA that Upatinib has been approved in China, it is based on the good response of global clinical data, and it is also the reason why patients in my country have suffered from the disease for many years.
The urgent need of 'lack of doctors and few medicines'; it is also a manifestation of the increasing attention paid to rheumatic immune diseases by my country's regulatory authorities
.
Talking about the speed at which Upatinib has been effectively approved in China, Professor Liu Yi said
.
The data show that PsA is a heterogeneous, systemic inflammatory disease that can affect multiple bodies including joints and skin.
sites, such as peripheral arthritis, enthesitis, skin lesions, dactylitis, midshaft involvement, fingernails, etc.
1
These inflammations caused by the immune system can cause joint pain, swelling, and stiffness in patients, and even It causes irreversible joint damage, resulting in joint deformation and disability, which seriously affects the quality of life of patients2
.
According to statistics, about 30% of psoriasis patients suffer from PsA3,4
.
Professor Liu Yi introduced that for a long time in China, PsA The treatment predicament is mainly reflected in two aspects: "low diagnosis rate" and "lack of doctors and medicines"
.
The diagnosis rate is low - the launch of upatinib to promote the standardized treatment of PsA "It is precisely because of the diverse clinical manifestations of PsA that the clinical misdiagnosis rate is relatively high.
In addition, the incidence of the disease is hidden, and many doctors do not pay enough attention to it, so the diagnosis rate of PsA in China is not high, especially some patients with joint symptoms first and then psoriasis are almost always missed
.
Clinically, although PsA is a joint disease, it is often treated as a 'comorbidity' of psoriasis, and the dermatology department also 'represents' some of the functions of the rheumatology department.
"
In this regard, Professor Liu Yi affirmed: "Upatinib is now on the market as a 'new weapon' in the field of rheumatic immune disease treatment, which will help increase doctors' attention to PsA, thereby promoting standardized treatment of PsA and improving patient prognosis
.
At the same time, he pointed out that in the future, rheumatology should not only become the "main battlefield" in the treatment stage of PsA, but also play a greater role in early diagnosis, which requires rheumatologists to further improve the awareness and ability of differential diagnosis of PsA.

.
In addition, he specially reminded: "The manifestations of skin lesions in patients with PsA are often very hidden, such as in the perineum, scalp and other parts, it is difficult to diagnose if you are not careful, so when the clinical indicators are negative for rheumatoid factor and negative for CCP, it is like When it is destructive arthritis, clinicians should realize that it may be related to PsA as soon as possible, so that the diagnosis rate of PsA will be greatly increased
.
” Lack of medicines and drugs – upatinib is listed to fill the gap of PsA targeted therapy in Liu Yi According to the professor, before the launch of Upatinib, there was a long-term lack of innovative therapies in the clinical treatment of PsA in China, and the treatment needs of patients were far from being met.
Disability, severe damage to the joints of many patients, and the emergence of "telescope" hands have long been medical helplessness
.
It is reported that the previous treatment methods for PsA mainly fall into the following categories5: 1) Dermatological symptomatic drugs: mainly used locally for skin lesions, which can relieve skin lesions, but cannot solve the fundamental problem of the disease from the mechanism
.
2) Traditional therapy of rheumatology and immunology: traditional immunosuppressants such as methotrexate, azathioprine, etc.
These drugs have a certain effect on peripheral arthritis and dactylitis, but have no obvious effect on other joint diseases such as axial type.
However, the intensity of action and curative effect are insufficient, and it is easy to relapse, so the clinical application has limitations
.
3) Biological agents: including tumor necrosis factor (TNF-α) inhibitors, interleukin antagonists, etc.
There are many types, which are one of the effective means for the treatment of PsA.
The preparation has a good effect on skin lesions, but there is no biological preparation that can comprehensively deal with the clinical symptoms of PsA
.
At present, biological agents are occasionally used clinically, but these biological agents have not been approved for the treatment of PsA in China
.
As the first targeted therapy approved for the treatment of PsA in China, upatinib will greatly fill the gap in targeted therapy in this disease
.
It is reported that the approval of upatinib is based on the data support of a global phase 3 clinical study selec-PsA 1, in which Chinese patients are also involved.

.
The study head-to-head compared the efficacy, safety, and tolerability of upatinib with the TNF-α inhibitor adalimumab in patients with PsA
.
Findings 6: Upatinib also significantly improved clinical measures of remission
.
At week 12, upatinib 15 mg was as effective as adalimumab in terms of ACR20 response rates (meeting the American College of Rheumatology criteria for improvement, where patients achieved a 20% disease remission)
.
Improvements with upatinib persisted over time, with durable efficacy and simultaneous improvement in multiple clinical symptoms
.
At week 24, the ACR20, ACR50 and ACR70 response rates of 15mg upatinib were significantly higher than those of adalimumab; at week 56, the ACR50, ACR70 response rates, pain, HAQ-DI, PtGA, SF-36, and improvement in self-assessment of psoriasis symptoms were significantly better than adalimumab
.
In this study, the safety profile of patients with active PsA who received upadatinib 15 mg was consistent with that observed in patients with rheumatoid arthritis
.
It is worth mentioning that the head-to-head comparison between upatinib and the TNF-α inhibitor adalimumab has been full of attention in the industry
.
Regarding the difference between the two, Professor Liu Yi explained: "As a class of receptor tyrosine kinases, JAK is a more 'upstream' target than TNF-α, and inhibiting JAK can block TNF-α and other inflammatory factors at the same time.
, such as interleukin 17, interleukin 6, etc.
, so the inhibition range of JAK targets is wider
.
” From the clinical data of the Chinese subgroup, he said: “Upatinib has demonstrated clinical effectiveness in the treatment of the Chinese population.
It is great to see meaningful relief for many patients suffering from the signs and symptoms of psoriatic arthritis, which, combined with the convenience of oral medication, is expected to be a key drug in the treatment of PsA
.
He also expressed his concern about the availability of upatinib after the launch of the drug in the future.
In his opinion, the most important thing for patients in drug selection is "safety" and "effectiveness".
After the emergence of "safe" and "effective" innovative treatment methods, it is hoped that through the efforts of all parties, more patients will have access to drugs and medicines that can be cured
.
02 PsA indications are only the "tip of the iceberg" JAK1 inhibitors have broad prospects.
The approval of the new indication for PsA in China is not only a groundbreaking breakthrough in the field of PsA treatment in China, but also an important proof that JAK1 inhibitors are showing their potential in the field of rheumatic immune diseases
.
Four family members, JAK1, JAK2, JAK3, and TYK2, were found, which are involved in the regulation of various immune balance and physiological functions in the human body
.
Based on the inhibitory activity of different JAK family members, JAK inhibitors can be divided into the first generation pan-JAK Inhibitors and second-generation selective JAK inhibitors
.
Regarding the current industry's strong concern about the "safety" of JAK inhibitors, Professor Liu Yi said, "Although the current JAK inhibitors have encountered some challenges in the development process, In recent years, it has had more and more clinical breakthroughs
.
I think JAK inhibitors are far safer than other targeted biologics for rheumatic immune diseases in the past
.
He added: "In clinical practice, the application of JAK inhibitors is also more and more extensive.
JAK inhibitors are a direct inhibition, the effect is very mild, so there are relatively few clinical side effects
.
Upatinib, as a second-generation selective JAK1 inhibitor, has proven its safety and efficacy in Phase III clinical studies, and is still advancing to Phase IV extension studies.
I have no doubt that it has a good effect.
safety
.
Regarding the clinical application prospects of JAK inhibitors, he said: "The JAK-STAT pathway is one of the few immunomodulatory pathways that has been proven, and the inhibition of JAK can have a 'comprehensive coverage' effect on many inflammatory factors.
JAK inhibitors are expected to be widely used in the field of rheumatic immune diseases
.
"In the JAK family, JAK1 is widely found in various tissues and cells in the body, and is closely related to the activation of inflammatory factors such as IL-6 and IFN.

As a new second-generation selective JAK1 inhibitor, in addition to the existing three indications of psoriatic arthritis, rheumatoid arthritis, and atopic dermatitis, upatinib is rapidly developing radiology at home and abroad.
Negative axial spondyloarthritis, ankylosing spondylitis and other phase III studies related to rheumatic immune diseases will have more extensive clinical applications in the future
.