Why are we Rheumatologists looking forward to Tofacitinib (Xeljanz) ?

Rheumatoid disease is a chronic disease predominantly involving the joints. We have come a long way as far as treatment & outcomes are concerned. We have been able to put life back into patient’s life.
However, not everyone is that lucky. We are still not able to achieve remission in each & every patient. Statistically, almost 20- 30% rheumatoid patients do not improve sufficiently with DMARDs & biologics. The retention rate of most biologics are low (retention rate is the proportion of patients continuing biologics on a long term basis). We have still not understood the rheumatoid pathogenesis completely. We have not yet located the master switch that can turn off the inflammation.

As Rheumatologists, we would like each & every patient to achieve remission & do well. That is precisely the reason why we are looking forward to further development in understanding of RA & new drugs to tame the inflammation.

Rheumatoid inflammation

Rheumatoid inflammation


In rheumatoid disease, immune cells in the synovium of the joints get activated. They secrete various chemicals called cytokines. These cytokines are absorbed in blood & circulate throughout the body. These in turn act on other immune cells; activate them. The activated immune cells start secreting more cytokines. Theses cytokines are responsible for the joint damage & other complications of Rheumatoid disease. So, our efforts are directed to block either these cytokines or the cells secreting them. This would not only reduce the chances of joint damage but also keep the inflammation in check by blocking activation of immune cells. We can block these cytokines & cells with DMARDs & biologics.

Let us consider an example to understand the rheumatoid inflammation & the mechanism of various medications. This is akin to the following plot.
Understand biologics, DMARDs & JAK inhibitors
There are 5 terrorists (cytokines ) who want to enter an island country (immune cell) to start a terrorist camp & train more terrorists (generate more cytokines). So, if they are able to enter this country, the number of terrorists will increase as also the chances of destructive activities. They can enter the country by air using multiple airlines ( Airline TNF- α, Airline IL-6, Airline B cell)

If a Rheumatologist is the police; using DMARDs is like using multiple contacts in various airlines asking them to block the entry to the terrorists. This may work if one has good contacts, but is not foolproof.

Biologics are more specific. They are like specific legal orders to specific airlines to block their entry. So if one blocks the TNF α Airline from carrying the terrorists, the island is safer. But then, this is not the only airline available. They can always take the other airlines & still manage to enter the country & succeed with their plans. The same way, a biologic works but then is not the final answer.

How about going a step further? One can also block their entry at the ports of entry. This will block the terrorists irrespective of the airline they use.
Blocking inflammation at cellular level

This is exactly where we are today.
We have taken the war against Rheumatoid to the ‘ port of entry- signal transduction’ level. Instead of blocking multiple different cytokines, we are now looking at blocking the cellular system that responds to multiple cytokines. This way, we can block the effect of multiple cytokines with a single medication & reduce activation of immune cells thus keeping the Rheumatoid inflammation under check.
Janus Kinase is an enzyme that works at the port of entry in the cell & helps the transduction of message (execution of the plot). We now have Tofacitinib (xeljanz), a Janus kinase blocker recently approved by FDA.

As we saw, this is clearly a step ahead in our battle against the Rheumatoid Disease. We would be looking how well this technological advance really translates in practice in the further blogposts.

About these ads

12 Responses to Why are we Rheumatologists looking forward to Tofacitinib (Xeljanz) ?

  1. Dr. Romesh Joshi, MD, MBA says:

    very well described!!! great work!!!

  2. Thanks Romesh!

    A humble effort from my side to simplify the recent medical developments for the readers.

  3. Dr. Romesh Joshi, MD, MBA says:

    very nice indeed!!.. we should do whatever we can from our side to make people more aware about RA, the pathogenesis n the treatment modalities available for them in whatever simple way possible….in order that they come to a well informed n a smart decision….we will carry this on in our fight against RA…not only for RA but all other AI disorders which pose a great dilemma to our patients…

  4. Priyanka Misal says:

    Rheumatoid arthritis pathogenisis and treatment is so simplifed in the article.Excellent!!!

  5. Raghuvir K Trifale says:

    Thanks ,Dr.Akerkar!!In a very simple language you have clarified the mechanism,which can be understood by a common man.One thing I could not understand,immune cells whose function is developing the rasistance or protecting the host,how come they secrete the cytokines which damage the joints.

  6. Dear Doctor, this article is brilliant, educative and informative as usual… Thanks … your articles always increase our spirit to keep continuing our fight with RA

  7. Kim says:

    Love this explanation! Thank you!
    I start Xeljanz on April 24.
    Kim

  8. After looking over a number of the articles on
    your website, I really appreciate your way of writing a
    blog. I added it to my bookmark site list and will be checking back soon.
    Please visit my website too and let me know how you feel.

  9. musingsofms says:

    This is wonderful! I have MS and my son and daughter both have RA. My son (19) started Xeljanz five months ago and it has felt like a miracle! He struggled to walk for a year and a half and is now riding a bike to/from work and can run! My daughter has only been dx for three months and is really struggling. Her RA came on much more rapidly than my son’s and has moved to all her joints within this short time. She is 16 1/2 and the doctor hasn’t considered Xeljanz for her. I think the newness of the drug might concern him. I hope Xeljanz is being studied for people under 18 because she is unable to leave the house, much less a bed or chair and that is truly heartbreaking.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Follow

Get every new post delivered to your Inbox.

Join 3,873 other followers

%d bloggers like this: