The term "inflammatory arthritis" refers to a number of conditions where there is obvious inflammation of the joint. Sometimes the diagnosis is known... an example would be a patient with classic rheumatoid arthritis (RA). Unfortunately, the diagnosis is not always apparent. We know inflammation exists but we don't have an exact label.
Dr. Joe Markenson recently had an interview with Medscape, so I thought I'd try to break it down so you, the reader, would understand some of the exciting things going on.
Dr. Markenson said, "What's new is that we keep learning about new pathways and new inflammatory mediators, as well as new ways to stop inflammation. Some of the molecules developed to block these new pathways have unacceptable side effects."
He adds, "Nonetheless, we are learning a lot about inflammation: what causes it and how to stop the process. These are pretty exciting times. A lot of new things are coming up, but even going back to old therapies, such as methotrexate, it seems that patients do well for a finite amount of time. Previous studies have shown, for example, that when studying the older oral disease-modifying antirheumatic drugs (DMARDs) over a 5-year period, only about 70% of patients with RA who started are still taking methotrexate (the best drug) That's the good news. The bad news is that about 30% of these patients do not respond adequately to methotrexate."
He also mentioned that a similar study done in Sweden, about 3 years ago, with tumor necrosis factor (TNF) inhibitors (anti-TNF drugs), showed the same thing.
Apparently, patients who drop their treatment aren't dropping out because of treatment side effects; they stop taking their medication because of loss of efficacy.
Much research being conducted on treatments is not only looking at new mechanisms, but is also looking at new methods of delivery. The problem is that blocking certain pathways that inhibit inflammation also are the same pathways required for other normal body functions so, as Dr. Markenson says, "... you end up with a lot of toxicities because the effects spread among various pathways."
He used the example of the new oral JAK drugs to illustrate this point.
The good news, though, is that more recent research with some of the newer oral kinase inhibitors "show some very promising results with less toxicity and very good efficacy."
A different set of compounds has targeted another pathway... The IL-6 pathway has received much attention over the last couple of years. And one of the IL-6 inhibitors, Actemra, has applied for FDA approval.
Dr. Markenson states, "Early on, a few patients do not respond to therapy (10%-20%), but what is worrisome is [that] in those who do respond well, it's not always long lasting. You get out to the 5-year mark, ask how many patients are still on your medication, and find that 7 out of 10 are still on."
When RA patients are started on treatment, one of three things can occur.
The first is that the drug doesn't work right from the start. That's called a "primary failure."
The other two things occur in patients who respond to the treatment. This second group can have two things develop. They may go on to discontinue therapy for two reasons: side effects or lack of efficacy.
What is being found is that with RA, only about 70% of patients started on a biologic drug are still on it five years later.
Dr Markenson adds, "In an illness that lasts 20-30 years, it's a challenge to continue to provide effective therapy for people who are failures."
The longer we use biologic drugs, the more we, as rheumatologists, realize that not every one responds... and that even the responders eventually can lose their responsiveness. Thus the need for newer therapies.
