The Convergence of Clinical Research and Clinical Care Peter E Lipsky

EDITORIAL

www.nature.com/clinicalpractice/rheum The convergence of clinical research and clinical care Peter E Lipsky

A striking change in the field of rheumatology The data for fundamental questions about human patho- has been highlighted by the approval of another derived from physiology to be addressed for the first time. biologic agent, abatacept, for the treatment of What role does tumor necrosis factor play in rheumatoid arthritis, and by the ongoing clinical … clinical rheumatoid arthritis? Is interleukin-1 an essen- trials of a variety of biologic therapies in other encounters tial mediator of rheumatoid inflammation? diseases, including systemic lupus erythe ma- could … point What is the role of T cells or B cells in rheuma- tosus (SLE, discussed in the Review by the way to toid arthritis or in SLE? Can patients in whom D Isenberg and A Rahman in this issue of Nature more effective a specific cytokine or cell is dominant be Clinical Practice Rheumatology). Until recently, prospectively recognized? nearly all therapeutic interventions in rheumatic application of This has completely changed the scien- diseases, such as rheumatoid arthritis and SLE, biologic agents tific basis of rheumatology and, in a subtle were empiric. We had insufficient information and greater but potentially profound way, the practice about either the pathogenesis of the diseases or benefit for the of rheumatology. Clinical care has become the mechanism of action of the medicines to gain potentially synonymous with clinical research much insight into disease processes from the patients because every time a clinician administers a results of therapeutic interventions. The causes biologic drug, he or she is asking whether the and precise pathogeneses of diseases such as precise target of the biologic treatment has a rheumatoid arthritis and SLE still elude us, and role in disease pathogenesis in that patient. the salient mechanism of action of drugs such as The data derived from all of these clinical gold salts, hydroxychloroquine, methotrexate, encounters could potentially provide essential and cyclophosphamide in these diseases is also information on the physiologic basis of various unknown. As a result, laborious pragmatic clin- rheumatic diseases that could point the way to ical trials have been necessary to develop regi- more effective application of biologic agents mens that optimized the clinical benefit and and greater benefit for the patients. The chal- minimized toxicity. These trials were largely built lenge is to develop a means to collect and on previous clinical observations, rather than on collate this information. physiologic or pharmacologic insight. Evidence In this issue of Nature Clinical Practice from the trials could therefore tell us about the Rheumatology, T Pincus discusses the need for clinical impact of a particular agent in a specific “practice-based evidence” to complement infor- disease, but could not reveal much about how mation from clinical trials. This, he feels, could the disease process was influenced and how this be done in academic practices and in promi- resulted in the clinical benefit. nent clinical practices and might supplement All of this changed with the introduction of the data obtained from traditional formulaic biologic drugs. For the first time, we had highly controlled clinical trials, to give a more complete PE Lipsky is specific agents that each targeted a particular the Editor-in- and balanced view on the likely clinical impact molecule. The newly available biologic treat- Chief of Nature of new therapeutics. Although it is laudable, ments are not merely expensive disease- Clinical Practice maybe this approach does not go far enough. modifyin g antirheumatic drugs, but are Rheumatology. Perhaps the goal should be to consider a way to precisely targeted therapies that neutralize a mine data in a more broad clinical arena, so that particular molecule or cell. Although the Competing interests as much information as is practically possible The author declared he has primary questions for clinicians remained, no competing interests. can be collected and analyzed to permit a full “Does it work?” and “Is it safe?”, the applica- understanding of the impact of targeted therapy www.nature.com/clinicalpractice tion of biologic agents afforded the opportunity doi:10.1038/ncprheum0138 of rheumatic disease.

MARCH 2006 VOL 2 NO 3 NATURE CLINICAL PRACTICE RHEUMATOLOGY 113