Rheumatoid arthritis, with a worldwide prevalence of about 1%, remains a major cause of chronic pain and disability and depression. Ironically, (current) patients and their rheumatologists are fortunate this prevalence number is so high, as it gives incentive to pharmaceutical and biotech enterprises to continue to explore treatments. The recent ACR meeting in Philadelphia showcased some interesting research, and below is a peek at what is happening in the world of rheumatoid arthritis treatment.
The Janus Kinases (JAKs) is a family of enzymes discovered in 1988. Some of these enzymes located in cells can play a role in the control of biochemicals which are involved with diseases, including rheumatoid arthritis.
JAK inhibitors continue to draw much attention from investigators in the never-ending search for better drugs for a terrible disease. These oral drugs interfere with the events occurring on a cellular level which make daily life so miserable for rheumatoid arthritis patients. Thus far, the studies show that JAK inhibitors have the potency of the biologic agents such as Humira and Enbrel, but they are obviously more attractive in that they are oral-a plus for those of us who hate needles; in addition, oral drugs are generally significantly less expensive.
The JAK inhibitor named by the manufacturer (Pfizer) CP-690,550 has not been associated with the infections that can be seen with the injectable biologic agents, and there have thus far been no reports of malignancies/lymphomas with this drug. There have been reports of significant anemia, and increases in LDL-the so-called "bad" cholesterol. Large clinical studies should give us more of a sense as to where JAK inhibition will fit into the treatment plan for the rheumatoid arthritis patient.
Some other interesting drugs, a little farther up the pipeline:
1. GSK315234 is a monoclonal antibody which attacks human Oncostatin M (OSM). OSM is a member of the interleukin (IL)-6 family, and is present in the inflamed joints and blood of rheumatoid arthritis patients. OSM can be thought of as an agent which contributes to the severity of joint inflammation. The study presented at this year's ACR meeting had the goal of confirming the safety and tolerability in healthy people; and, indeed, it was well-tolerated. Now, we all must wait for the study of its effectiveness in rheumatoid arthritis patients. I think we should all be interested.
2. LX2931 is an oral drug which inhibits sphingosine-1-phosphate (S1P) lyase. This allows for more S1P, and reduces inflammation in mice and rats. The study of this drug just presented at the ACR meetinng showed its safety in humans already on methotrexate. Studies on the effectiveness of LX2931 in reducing the inflammation of rheumatoid arthritis will be coming soon.
3. ARG098 is a monoclonal antibody which targets molecules on the surface of certain cells involved in producing the inflammation seen in rheumatoid arthritis. In this case, ARG098 was injected into the knees of rheumatoid arthritis patients, resulting in overall improvement of pain of the knee. It appears safe, and resulted in less pain and swelling. It is a new concept, but may prove helpful as both an add-on drug, or even as a first-line drug.
I apologize for the numeric and alphabet soups I have splashed you all with today. I hope you were wearing your bibs. But the future is there, and so it is here, whether you think it is exciting or not. There were a number of other new compounds and molecules presented at the meeting, including a few thus far only tested in rats and mice. They all have the potential for success, failure, or a combination of the two. And so it remains important to keep the eyes on the prize, as it might be here sooner than you think.
