Xeljanz

Anyone heard of this new drug ?

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Yes, I ran across this one (Xeljanz) when doing research on Ruxolitinib and other drugs ending in "nib", which represents a large class of Janus Kinase Inhibitors. Here are some brief abstracts:

Emerging clinical research has demonstrated the integral role of Janus kinase (JAK) proteins in the pathogenesis of psoriasis. As of 2010, two new oral JAK inhibitor drugs, ruxolitinib and tofacitinib (formerly called tasocitinib), have shown rapid and promising efficacy in Phase I/II trials with patients showing significant skin clearing within one week of beginning treatment. Ruxolitinib has completed Phase II clinical trials supplied as a topical cream.

Tofacitinib (trade name Xeljanz, formerly tasocitinib, CP-690550) is a drug discovered and developed by Pfizer. It is currently approved for the treatment of rheumatoid arthritis (RA) in the United States and is being studied for treatment of psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection.

It is an inhibitor of the enzyme janus kinase 3 (JAK3), which means that it interferes with the JAK-STAT signaling pathway, which transmits extracellular information into the cell nucleus, influencing DNA transcription.

Recently it has been shown in a murine model of established arthritis that tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. This efficacy in this disease model correlated with the inhibition of both JAK1 and 3 signaling pathways, suggesting that tofacitinib may exert therapeutic benefit via pathways that are not exclusive to inhibition of JAK3

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http://www.fda.gov/downloads/Drugs/DrugSafety/UCM330702.pdf

This is a serious med. after reading the above warnings from the FDA I think only you can make the decision to try the drug.

I always like to do research on any drug. There are many others on the same drug for more online info. On this drug.

Let us know what you decide ...

Good luck.

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I am in week 4 of a topical trial. It seems to have dramatically cleared up some really annoying facial lesions, cleared a few small spots on the body and gradually chipping away at the really ugly (now less ugly) plaques on the body. OTOH, it could be the placebo since I've never used Cetaphil before and the "ointment" seems to have same "feel" to it (but the staff thinks otherwise).

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One way of approaching any medical condition is to view the pathology
as too much of something or too little of something else.

Maybe psoriasis, in some cases, is too little of SOCS: suppressors
of cytokine signaling. Therefore suppressing the JAK-STAT pathway
through the use of Tofacitinib or Ruxolitinib would be a safe and effective
way to restore the balance.

But on the other hand, the JAK-STAT pathway could be normal with another
pathway as the culprit.

See wiki article:

http://en.wikipedia.org/wiki/JAK-STAT_signaling_pathway

What's needed is a cellular assay of the normal amount of SOCS in normal
tissue versus the measurement in individuals with psoriasis. In other words,
match the drug with the biochemistry of the cell.

Within the next few years biochemical assays as well as a genomic analysis
will be the norm before prescribing any medication. This will ensure a proper
match-up and prevent adverse reactions.

The whole biomedical field is on a verge of progress similar to the computer
revolution of the 1980s. New advances will eradicate cancer, inflammatory
conditions, and even............, increase our life spans to age 200 and beyond.

Of course, you could also choose to become a follower of Ray Kurzweil and
join the Singularity movement...................., i.e., half human/half robot and live
forever.

In conclusion: never give up hope. New advances in science and medicine
are moving not only exponentially, but as an exponent of an exponent. Also
known as a second order derivative for those interested in math.

Remember, math and science go hand in hand, mathematics being described
as expressing the elegance of the beautiful nature of science.

And for those interested in going into the field of medical research, study both
math and physics. Those 2 fields serve as the basis for everything in the entire
Cosmos.

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I am trying to patiently await the revolution of information you speak of. YAY SCIENCE! But I just can't wait. It is all going to come together. The real question is, "When?" Crossing my fingers!

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I would temper that optimism.

"It is an inhibitor of the enzyme janus kinase 3 (JAK3), which means that it interferes with the JAK-STAT signaling pathway, which transmits extracellular information into the cell nucleus, influencing DNA transcription."

But when you interfere with the JAK-STAT signaling pathway, what else are you interfering with ? Perhaps the ability for the immune system to fight off cancers ? Don't think it is all a "bed of roses" when it comes to the use of so-called "biologics" to fight off psoriasis. Yes, many of us do not have a choice, but anything which messes with the immune system also messes with the immune system's ability to fight off other disease processes.

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Yes, you are correct. Immunosuppression could depress the immune system such that cancer and
opportunistic pathogens can do great harm.

There is another approach called Immune Modulation, one type of which involves the use of PDE 4 Inhibitors
which could be as safe as caffeine.

In fact caffeine, as well as theobromine (found in chocolate), theophylline (found in tea) and other methylated
xanthines are all nonspecific PDE Inhibitors.

And for those of us with mild to moderate psoriasis, immune modulators may be the best and safest choice.
Several PDE 4 Inhibitors are being developed by different pharmaceutical companies. Currently, Apremilast
is in the final stage of testing and should soon be available at your pharmacy. And the best part, it's in pill
form (2x daily).

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It does appear the warning labels for the Oral form of Xeljanz suggest the same kind of compromised-immune system issue typical of the other "biologics" (I have tried Enbrel and wound up with a serious infection soon after...). What is fascinating is it's possible use as a topical and an alternative to steroid creams. Earlier clinical trials suggested it was effective on psoriasis plaques and that more serious trials were warranted.

Now if it does prove effective, what happens at the end of the trial ? Is there a "rebound" effect post-treatment ? Do I go cold turkey or are there expectations of continued treatments post-study ? Guess I should have asked before starting... I did not have great expectations (either of efficacy or continuation) and had the time to say what the heck.

If a clinical trial drug proves to be effective, are patients generally allowed to continue the drug (for free?) post-study until FDA approval ?

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