Most important clinical advancements: Let us celebrate the seemingly endless number of drugs approved or in the pipeline that are effective for rheumatoid arthritis. Do you remember when methotrexate was the only "new drug" for RA and the end of the line of reasonable choices? Now we can add to that a long list of effective therapies, including penicillamine, azathioprine, cyclophosphamide, and yes, even chlorambucil for RA! Some were beginning to believe that RA was just unsolvable. I break out in a cold sweat just thinking about it. TNF-inhibitors were just the beginning!
The approval of belimumab as a modestly effective agent for lupus. Not a gangbuster, to be sure, but isn’t it great that a well-designed clinical trial has actually shown a drug to work in lupus.
Another major advance has been approval of new drugs with others in the pipeline for managing gout. Suddenly, gout is hot again.
We can add to the treatment successes several drugs that are at least partially effective for pulmonary hypertension.
And the #1 advance, by far, are findings from the RAVE trial demonstrating that rituximab is as effective as cyclophosphamide for inducing remission in ANCA-positive vasculitis. This is truly a game changer, and a pleasant surprise to many of us.
Biggest disappointments:
• TNF inhibitors failed to work in Wegener’s (WGET)
• The lack of a viable alternative beyond TNF-inhibitors for psoriatic arthritis.
• The ongoing lack of a clear-cut steroid-sparing agent in temporal arteritis.
• The colchicine fiasco.
• Despite the fact that we now have effective old and new treatment for gout, this straightforward disease continues to be mismanaged.
• Scleroderma. Need I say more?
• And the No. 1 disappointment: Rituximab failed to work in lupus (Explorer and Lunar). I still have trouble believing it, as do many rheumatologists.
Biggest potential yet to be realized: Where are the small molecule remittive agents, including the Janus-associated kinase (JAK) inhibitors? Soon?
Biggest challenge: How can we continue to provide timely and excellent rheumatologic care in what seems to be an increasingly hostile economic environment on almost all levels: the workplace, private insurance, the state and federal governments, etc. Now that we have all these great drugs, with more on the way, how can we afford to continue paying for them as a society?
One I’m skeptical about: Will we see development of a remittive agent for osteoarthritis? First of all, I’m not sure if it’s possible to stop the old "wear-and-tear" arthritis. Second, I’m still not convinced it’s all that inflammatory. And, if we did find a therapeutic that altered the natural progression of OA, at what age would "patients" have to start taking it and who would pay for it? If such a drug were developed, it would be the closest thing yet to a fountain of youth. And if it were a biologic, it would surely break the U.S. health care system bank! I have a vision of class warfare about who would be eligible for such a drug.
Oh well, maybe I’m wrong. It wouldn’t be the first time. In fact, I hope to check back with you in 10 years with my native knees still in place, running in the REF 5Ks at the ACR, taking my inexpensive, small-molecule OA pill once a day. Ah, life is good!
Christopher M. Burns, M.D.
Dartmouth University in Lebanon, N.H.