Willie Sutton Was Right: It’s Time to Turn to the Synovium to Drive Rheumatoid Arthritis Therapy
Bibliographic record
Abstract
Treatments for rheumatoid arthritis (RA) have come a long way in the past 20 years. Fifteen years of widespread use of methotrexate generated a paradigm shift in the management of RA; the advent of biologic response modifiers launched the next big shift. Coupled with early, aggressive therapy, these agents have made it possible to look beyond merely controlling symptoms to a treatment landscape where remission is now a reasonable possibility for nearly 50% of our patients with early disease1. At the same time, challenges remain for appropriately using available therapies. As effective as these agents are, they do not work for all patients, and despite years of searching, we still do not have systemic biomarkers that can reliably identify those patients who will respond. Combined with the tremendous costs of these drugs, this uncertainty means that RA treatment in 2016 remains an expensive, empiric proposition. We believe that it is time for the next paradigm shift, one that does not involve new therapies, but precision, targeted application of existing and future treatments. Willie Sutton was right2. And while much work remains to be done, we believe that it will soon be time to move beyond the bloodstream and look for guidance to the most critical tissue in this disease, the synovium. One needs to look no further than the world of oncology to see the path that we must begin to take in rheumatology. In just a generation, oncologists have moved from the use of broad-based chemotherapeutic agents to personalized genetic profiling that allows them in many cases to identify the specific agent or agents most likely to effectively treat the patient’s malignancy. Cancer therapy has moved from a disease-guided approach to a pathology-guided approach, then in turn to a molecular-guided approach, in which specific molecular … Address correspondence to Dr. E.M. Ruderman, 675 North St. Clair, Suite 14-100, Chicago, Illinois 60611, USA; E-mail: e-ruderman{at}northwestern.edu
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.028 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.003 | 0.004 |
| Scholarly communication | 0.007 | 0.008 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.009 | 0.023 |
| Insufficient payload (model declined to judge) | 0.022 | 0.015 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".