“Allowing safe use of JAK inhibitors over restrictions"

Professor Ki-Jo Kim, Division of Rheumatology, Catholic University St. Vincent Hospital

“Need to classify the specific risk factors…should be prescribed according to each patient’s situation”

“Clear advantages do exist in the use of oral formulations... have concerns over unilateral restrictions that may be imposed”

Professor Ki-Jo Kim

Nowadays, safety is as important as a drug’s efficacy.

 

In particular, reaffirming the safety of drugs that require long-term administration post-approval is essential.

 

JAK inhibitors, which have entered the market as an oral option to treat various autoimmune diseases such as rheumatoid arthritis and ankylosing spondylitis, have been embroiled in controversy since last year.

 

In 2021, the US FDA had warned of increased risk of cardiovascular events and cancer on the use of Jak inhibitors, and the MFDS also issued a Dear Healthcare Professional Letter on the issue.

 

In the end, the FDA decided to include the increased risk of major heart-related events, thrombosis, and death in the black box warnings.

 

The risk is undoubtedly an issue that cannot be overlooked.

 

The risk of cardiovascular disease is a common issue that tags all treatments used for chronic diseases, but more accurate judgment on this risk is needed for JAK inhibitors as some patients do certainly benefit from its use.

 

Also, various factors including age and race need to be investigated.

 

On this, Ki-Jo Kim, Professor of Rheumatology at Catholic University St.

 

Vincent Hospital, lectured on the ‘'Management of Rheumatoid Arthritis considering Safety” at the KCR 2022 (the 42nd Korean College of Rheumatology Annual Scientific Meeting and the 16th International Symposium) that was held from the 19th to 21st.

 

Dailypharm met with Professor Kim to hear about the efficacy and safety of JAK inhibitors.

 

-Could you tell us about your lecture? When first introduced, JAK inhibitors opened a new paradigm in the treatment of rheumatoid arthritis.

 

Its safety issue had risen last year with the announcement of the Oral Surveillance study results that showed that JAK inhibitors may increase the risk of some cardiovascular disease and cancer.

 

This prompted a fierce debate in academic societies in the US, Europe, and Korea.

 

I have reviewed and reevaluated relevant data, studied how to read the results and interpret the studies that followed, and investigated whether different JAK inhibitors showed different results for the presentation.

 

-What was your conclusion? When looking into the ORAL Surveillance results in detail, data showed that the JAK inhibitors had a slightly higher risk of developing cardiovascular disease and cancer compared to TNF inhibitors.

 

But in detail, even this slight difference was limited to North American patients aged 65 or older.

 

Also, supplementary data in the paper showed that a higher proportion of North American patients in the study had a high risk of developing cardiovascular disease, due to factors such as being over 65 years of age, obesity, high blood pressure, diabetes, and various drugs intake, etc.

 

In this sense, the high-risk patients in the North American patient group may have driven such results.

 

The real-world data that followed studied all patients with rheumatoid arthritis.

 

No difference was found in these patients, and there was no difference when patients aged 50 or older that had 1 risk of cardiovascular disease were extracted and investigated as in the ORAL Surveillance study.

 

A tendency was there, but with no statistically significant difference.

 

When considering these factors, the ORAL Surveillance study data may have shown a larger difference due to its various limitations and regional variations.

 

.The FDA seems to be quite strict in monitoring the risk of cardiovascular events

 

.I understand that it is that much of a serious issue, but also suspect the decision made for JAK inhibitors had been somewhat influenced by this tendency. I agree to a certain extent

 

.Moreover, due to the recent COVID-19 pandemic and the rapid introduction of vaccines, many patients seem to have become more sensitive about safety, not only for the vaccines but for all drugs in general

 

.This may be why the FDA made such preemptive measures based on just one study result

 

.-The rising concern is that due to the issue, authorities may limit the prescription of JAK inhibitors to ‘patients that are unable to use Anti-TNF therapies.’ What is your opinion on this? It’s a shame

 

.JAK inhibitors have the advantage of being an oral formulation

 

.There is stress in receiving regular shots, especially in the case of intravenous agents

 

.There are patients who clearly show an effect when prescribed JAK inhibitors

 

.It’s not that the anti-TNF therapies are lacking in effect, it’s just about what better fits the patient

 

.Some patients who seem fine and are well controlling their inflammations but complain of pain or bad conditions were relieved of their inconveniences with JAK inhibitors

 

.All drugs have adverse reactions that are identified with the use in their respective indications

 

.We carefully examine these to select an appropriate drug for each patient

 

.I believe it is better to let the doctors in the field use their discretion for the safe use of JAK inhibitors rather than impose regulations and restrict its use to the second-line.