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Kinase Inhibitors – A Potential Line of Treatment for RA

For anyone who knows my journey with RA, it’s no secret that I’ve been through the gamut of treatment options. The list of previous treatments reads like a who’s who of pharmaceuticals and includes the following in chronological order: sulphasalazine, methotrexate (oral), Enbrel (self-injection), Meloxicam, Salsalate, Cimzia (self-injection), Humira (self-injection), Orencia (infusion), Imuran, Leflunomide, Actemra (infusion), methotrexate (self-injection), Remicade (infusion), CellCept, and Rituxan (infusion). That’s two NSAIDs, five DMARDs, and seven biologics. The reasons for stopping these treatments varied from side effects to lack of efficacy. Rituxan infusions are the latest treatment to be cast aside. The last infusion was cancelled at the last minute by my rheumatologist due to side effects and lack of efficacy.

The latest treatment being recommended by my rheumatologist is the newer drug Xeljanz which is called an “oral biologic” (Manno, 2013).1 Xeljanz works by inhibiting a molecule called kinase. Kinases are molecules linked to a cellular pathway, called the Jak-STAT pathway, that produce inflammation-causing cytokine proteins. In RA, it’s these cytokines that ultimately cause the tissue destroying symptoms (Walker & Smith, 2005).2 Xeljanz can be used alone or with methotrexate.3

Kinase inhibitor drugs are being developed for multiple diseases including some forms of cancer, diabetes, and inflammatory diseases including rheumatoid arthritis. A book documents over 100 potential kinase inhibitor medicines (Stafford, 2009).4 In 2006 it was reported that this class of drugs had huge marketing and profit potentials (Chu).5 Xeljanz represents the first kinase inhibitor approved for the treatment of RA. I recall reading about clinical trials of this drug several years ago and now I’m going to use it.

Currently, there is one kinase inhibitor approved for RA in the United States. Xeljanz, or tofacitinib, was developed and is marketed by Pfizer. The European Medicines Agency did not approve Xeljanz because of lack of efficacy and safety (Brown, 2013).6 But other European countries along with Australia and some Arab countries approved it. Zeljanz is also being tested as a viable treatment option for other autoimmune diseases including ulcerative colitis7 and vitiligo.8

As with all medicines, there are potential side effects with Xeljanz. These include increased risk of infections, tears in the stomach or intestines, changes in blood cell counts, and lymphoma. As with most RA drugs, the immune system is impacted so attention should be paid to infections.

There are other kinase inhibitors in the development pipeline. Below is a list of some of the Kinase inhibitors currently in the development and trial pipeline. There are likely others in development but information can be difficult to find.

  • Baricitinib by Eli Lilly and Incyte – in Phase III clinical trials
  • CC-292 by Cellgene – in Phase II clinical trials
  • PLX5622 by Plexxikon – in Phase I clinical trials
  • AB494 by Abbvie – in Phase II clinical trials
  • HM71224 by Hanmi – in Phase I clinical trials

As is typical with most drug development, there are many others that failed in the clinical trial pipeline.

It remains to be seen whether Jak-STAT inhibitors as a class of drugs will become a fruitful treatment option for those with rheumatoid arthritis and other autoimmune diseases. Yet I’m encouraged by the new potential kinase inhibitor oral treatments for RA. This is good news because a large group of RA patients do not respond to other biological therapies or methotrexate (Firestein, 2003).9 Now I will try Xeljanz, pending insurance approval, to see if it works for me.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.



  • Kathy P.
    4 years ago

    Thanks for your article, Andrew. They’re always interesting and it’s nice that you cut through the technical jargon for us! I hope you have success with this one, because you’ve been through so many meds already.

    Is this one as expensive as the other biologics are? My doctor wants me to go on it and I just want to be prepared for the sticker shock.

    Will you report back and let us know how you do on it?

  • Andrew Lumpe, PhD moderator author
    4 years ago

    Thanks Kathy. I haven’t started it yet as I took it one day, had a really bad headache, was going on vacation, and decided to wait until I got back. It is as expensive as biologics which is interesting since it’s a pill. Hope it works for you.

  • Connie Rifenburg
    4 years ago

    I too have been on Xeljanz for about 6 months. I didn’t realize a side effect was the gum problem. Never mentioned it to my RA dr, but will now.

    My side effect has been like coming off Prenisone. I am agitated, hungry, depressed, and my RA dr. says this is not a known side effect. But I KNOW it is exactly like I feel after having to go up to 60+mg of prednisone and then wean off of it. I take 5 mg pred daily and have unless I have a flare. I think Xeljanz is working as far as keeping the inflamation lowered, but I don’t like these side effects.

    I’m ready to stop taking it. I was on Orencia for 3 yrs and I actually went into remission for the first time in 12 yrs. For 7 months I went off Orencia & took nothing but 5mg pred, then a flare happened, especially in my back and shoulders, and I started Xeljanz in Apr. I like the convenience of a pill twice a day, but I hate feeling enraged and hungry all the time. I want to stop Xeljanz, but RA dr. wants to wait until Dec. I might not make it – anger wise – for that long.

    I have gained 6 lbs in 2 months. That’s a lot since I have been the same weight for several yrs, even thru higher steroid doses. After coming back off the steroids, I lose the weight. But this feeling of being hungry all the time is so frustrating! I hope another pill form of biologic might come out. I like the freedom from having to go to get the infusion every month. But I don’t like the trade-off of side effects.

  • ThomasB
    4 years ago

    I have been diagnosed with RA for 17 years and have a similar list of drugs tried to yours. I have been on Xeljanz for 5 months and it is the third biologic I have tried this year. I was thrilled initially as I haven’t had any unusual side effects but appear to have been struck down with more infections than in the past, particularly respiratory and sinus infections. It appears that the Xeljanz in combination with Methotrexate (oral 10 mg a week) is doing less for me than past combinations. We added Arava (20 mg daily) back into the mix 6 weeks ago but there still wasn’t the sort of significant change we had hoped for. We have just increased the Arava to 30 mg a day (have only ever been on 20 mg daily before) for a 2 month trial. We will make a decision about the next drug to try (running out of options)at that point. I will be interested to see how you go with the Xeljanz. I live in Australia and have been getting the drug free through a Patient Familiarisation Program. It has just been approved to be added to our Pharmaceutical Benefits Scheme (subsidised by the government) so I would think that we will see more doctors starting to prescribe it. I was the first patient my Rheumatologist had tried it with. He has since put another patient on it and they have responded very well. A very different story to mine! All the best.

  • Robbi
    4 years ago

    Been on Xeljanz 5 months now. Rocky two months then seemed better and now the last month it’s not helping so much. Was on Enbrel for 10 years with much success until it just seemed to stope helping. Appt with rheumatologist end of October so we will backup and regroup. I’ve had to up prednisone to 5 mg a day after getting a 20 mg booster lady week while out of town. Good luck! Praying Xeljanz works well for you!!

  • Andrew Lumpe, PhD moderator author
    4 years ago

    Robbi, sorry it’s not working for you. 🙁 Thanks for the well wishes.

  • Veda Logan
    4 years ago

    I tried Zeljanz last year, and it does have side effects like the rest of the biologics. The one I had was an usual one – it caused a sore on the gum below my bottom front teeth. The tissue started disappearing and as a result I had to have tissue grafting to protect my teeth. I’ve been through the list of meds too, so I hope this one works for you. Right now I’m on Actemra, prednisone, Arava, and prednisone combination therapy.

  • Andrew Lumpe, PhD moderator author
    4 years ago

    Thanks for sharing your experience Veda. Always seems to be trial and error.

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