The changes in rheumatoid arthritis (RA) treatment, while of unquestioned benefit to patients, nevertheless come with a price for our specialty, and they could have a profound impact on our prospects for the future. Change is essential in a multitude of areas: the design of clinical trials; the development of new outcome measures, including reliable and relevant definitions of remission; the organization of practice; workforce projections; the structure of training programs; the finances of academic rheumatology; and the establishment of new priorities for the research. And that, friends, is just the tip of iceberg.
RA remains a disease as puzzling as it can be destructive. Indeed, the underlying pathogenesis is intricately complicated given the complex interplay of the genetics and the environment. As studies on genetics of autoimmunity show, a plethora of genetic variants can predispose to disease. The manner in which these polymorphisms can be sorted at the individual level is seemingly infinite. With an immense barrage of environmental triggers impacting on this genetic substrate, it is likely that each patient with RA is unique. Although revealing this genetic and environmental puzzle is feasible with today’s technology, finding all of the pieces may seem less pressing in the face of therapy that is ever increasing in effectiveness.
Reference to rheumatic fever may be informative. How many of you ever really used the Jones criteria in a real-life patient situation and, for that matter, ever saw a patient with bona fide rheumatic fever? Not surprisingly, research on this disease has dwindled not because it is uninteresting but because antibiotics have made rheumatic fever a rarity in the Western world. Unless Streptococcus stages a comeback, rheumatic fever is likely to remain history, although those criteria will always show up on exams.
Further complicating the research agenda in RA is the likelihood that, as more is learned about the immune system, the list of potential targets for new treatments will grow. The path to take ideas from the bench to the bedside has become increasingly well trodden, and investigators will have to determine which of many new targets is really worth shooting at, especially given the competition with existing agents. As one of my colleagues said to me recently, “The RA market is crowded.”