Reply
Authors: Yoshie Sanayama, Kei Ikeda, Mieko Yamagata, Shunsuke Furuta, Osamu Ohara, Hiroshi Nakajima
Journal: Arthritis & Rheumatology (2014)

We appreciate Dr. Yazici's interest in our study. He raises concerns about the small sample size and the inadequate or missing control groups in our study and, based on recent articles, implies that finding useful biomarkers might be difficult for common diseases. We respect Dr. Yazici's opinion and completely agree that our study, as discussed in our article, would have allowed for more accurate interpretation had it included a larger sample size. We also agree that the presence of control groups of patients receiving other antirheumatic treatments would demonstrate the specificity of those candidate biomarkers for TCZ. In fact, we have been conducting an additional study that includes patients treated with methotrexate and other biologic agents. We believe that data-sharing among studies that use exploratory technology or have limited resources is a crucial part of scientifically sound methodology for advances in medicine. Even when a study has limitations due to budget or feasibility issues and the final impact of the study is uncertain, early disclosure of the data in the form of publication, as long as the methods and results are clarified, allows for mutual appraisal and the maximal use of technology, resources, and expertise among the research community. The final impact of a study should be determined as a part of a body of evidence together with the results of other studies; sharing data at an early stage should catalyze and shorten the research process. We also thank Dr. Yazici for sharing interesting articles that highlight the difficulty of identifying useful biomarkers (1-3). Two of these articles, however, actually support the starting point of our study that using genetic markers (1) or a limited set of serum biomarkers selected based on the putative mechanisms (3) is not likely to result in identification of a novel, clinically useful predictor and that analyzing expression levels of genome-wide transcripts would hold greater promise. We read with particular interest the article by Smolen et al, which suggests that personalized medicine for RA may be impossible (2). However, we interpret the same data they base their argument on from a different angle. Conventional composite measures of RA can reflect not only inflammation, but also mechanical and psychosocial factors. We speculate that patients who do not respond to multiple biologic agents are those with minimal inflammation and that identifying this population through use of biomarkers may be possible and will be clinically useful. We also expect that direct comparison of expression levels of genome-wide transcripts between different antirheumatic agents in our above-mentioned study may result in identification of specific predictive biomarkers. We completely agree with Dr. Yazici that the real clinical applicability of any measures should be tested as physicians treat one patient at a time, not groups of patients. In fact, not infrequently, we encounter RA patients whose composite measures, which have been validated in groups of patients, do not accurately reflect real inflammatory activity in the individual patient. Thus, the quest for biomarkers should not end until we find one that better reflects the pathophysiology and improves the clinical outcome of individual patients.