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.

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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.

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