Probably the RAW article most often referenced is Blood Tests for Rheumatoid Arthritis, part 2 from over four years ago. People need answers to questions like:
My blood tests show I’m in remission, so why do I still have symptoms?
My doctor said I tested negative for RA, but could I still have it?
What is the role of blood tests in Rheumatoid Arthritis / Rheumatoid Disease?
First, there are TWO main reasons a Rheumatoid Arthritis test is important:
1) To help diagnose RA
2) To help measure RA disease activity
However, if you’ve read much of RAW, you know the test does not yet exist which can reliably do both things for every person with Rheumatoid Disease (PRD). The 2009 posts (part 2 above and Is there a blood test for Rheumatoid Arthritis? Part 1) are a primer for understanding four common tests used for PRD and their limitations. Here’s a summary:
4 common blood tests used in Rheumatoid Arthritis
1) Rheumatoid factor: the first antibody discovered to be commonly present with Rheumatoid Disease (RD), about 70% of the time. Rf is also present in many healthy people who do not develop RD. The percentage of people who show positivity for Rf increases with established disease. There are variations in the antibody that can be tested.
2) Anti-CCP or ACPA: a more recently recognized antibody commonly present with RD, and more specific to RD (so that there are fewer “false positives”). Between 70 and 90 percent of PRD are positive for ACPA.
3) Erythrocyte sedimentation rate or ESR: a test that measures the millimeters of red blood cells that fall in a test tube in one hour. ESR can be increased in pregnancy and in other conditions, including cancer, and often correlates with inflammation. The ESR is often normal in PRD.[1,2]
4) C-reactive protein or CRP: CRP is considered an acute-phase reactant because it can rise dramatically during inflammatory activity. CRP is considered a significant factor in heart disease. Several physical conditions or activities can impact CRP including smoking, diet, and obesity. The CRP is often normal in PRD.[1-4]
With the exception of a cure, a reliable RD test is the proverbial Holy Grail
With a reliable test we could rapidly diagnose RD or even what’s called pre-Rheumatoid Arthritis. We could treat with appropriate aggressiveness, and perhaps predict which treatment would work better on particular patients. In the long run, such tests would help us distinguish various subtypes of RD.[5-7]
A recent article by Ted Pincus further clarifies the roles of two kinds of tests in PRD:
1) Blood tests
2) Patient reported outcome measures (PROM)
Pincus et al. compare Rheumatoid Arthritis treatment to hypertension, diabetes, and high cholesterol, which are also incurable, but are treated to target. However, they emphasize the big difference between RD and these other disease states:
The difference is that we don’t have THE BLOOD TEST to emulate the treat to target model in RD. Look for more on biomarkers in the next post in this series.
BUT WE DO HAVE SOMETHING…
Pincus and colleagues have spent decades demonstrating that patient reported outcome measures (such as the HAQ and MDHAQ), in which the patient self reports disease status or physical function, are the most significant markers for “future quality of life and premature mortality in RA (are) not laboratory tests, radiographs, indices, or remission criteria.”
PROMs are more reliable than blood tests, but…
A recently published study in Denmark found that patient global estimate (a PROM) was significantly related to outcomes, while CRP had no relationship. But this is not new information: Wolfe concluded four years ago: “Myth 1. Normal values of ESR and CRP are meaningful in RA.” Yet, most of the time, PROMs are not used in treatment for RD, which is a shame. But the biomarkers are clues to better treatments and a cure, so we’ll talk more about those next.
NOTE: Although I’ve told Ted Pincus his work makes him a hero to patients, and his co-author Yusuf Yazici is an RPF advisor, I have one reservation with the quoted article. The introduction states that “remission is now a realistic target in RA,” however this statement needs qualification. A low percentage of patients in the field achieve remission [9,10], so remission is now a realistic target theoretically or perhaps academically, but it should not be made as an unqualified statement.
- 14-3-3eta can work in low CRP patients: 14-3-3eta Marker in Rheumatoid Arthritis Patients with Low CRP
- A new antibody test: New Blood Test for Rheumatoid Arthritis: 14-3-3eta
- A combination of 12 markers in one test: The Vectra DA test
- A new type of anti-CCP test: 4 Benefits of a New ACPA Rheumatoid Arthritis Test
- Only CRP+ patients are in most trials: All I Want for Christmas Is My CRP
- Weight of Patient Reported Outcome Measures on Diagnosis & Treatment of RA
- The HAQ’s, the RAPID’s & the Rest: 3 Reasons It’s a Moot Point
The posts that started the discussion: WHAT ARE THESE TESTS WORTH?
1 Sokka T, Pincus T. Erythrocyte sedimentation rate, C-Reactive protein, or rheumatoid factor are normal at presentation in 35%–45% of patients with rheumatoid arthritis seen between 1980 and 2004: Analyses from Finland and the United States. 2009 May [cited 2013 Oct 16];36(7):1387-1390. Available from: http://jrheum.org/content/36/7/1387.abstract
2 Wolfe F. The many myths of erythrocyte sedimentation rate and C-reactive protein. J Rheumatol [Internet]. 2009 Aug [cited 2013 Oct 16];36(8):1568-1569. Available from: http://jrheum.org/content/36/8/1568.full
3 Linde L, Sørensen J, Østergaard M, Hetland ML. Gain in quality-adjusted life-years in patients with rheumatoid arthritis during 1 year of biological therapy: A prospective study in clinical practice. J Rheumatol [Internet]. 2013 Jul 1 [cited Oct 16];40(9):1479-1486. Available from: http://www.jrheum.org/content/40/9/1479.full
4 Teitel AD. C-reactive protein. Medline Plus – National Institutes of Health [Internet]. 2013 Mar 22 [cited 2013 Oct 16]. Available from: http://www.nlm.nih.gov/medlineplus/ency/article/003356.htm
5 Chen DY, Chen YM, Chen HH, Hsieh CW, Lin CC, Lan JL. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-a therapy. Arthritis Res Ther [Internet]. 2011 [cited 2031 Oct 16];13(4):126. Available from: http://arthritis-research.com/content/13/4/R126
6 West R. Fundamental studies of rheumatoid arthritis genetics & genomics. Rheumatoid Arthritis Warrior [Internet]. 2011 Jul 11 [cited 2013 Oct 16]. Available from: https://www.rawarrior.com/fundamental-studies-of-rheumatoid-arthritis-genetics-genomics/
7 Young K. Evidenced-based medicine or easy-bake oven: Tension between evidence and reality. Rheumatoid Arthritis Warrior [Internet]. 2011 Aug 5 [cited 2013 Oct 16]. Available from: https://www.rawarrior.com/evidenced-based-medicine-or-easy-bake-oven-tension-between-evidence-reality/
8 Pincus T, Castrejón I, Yazici Y. Documenting the Value of Care for Rheumatoid Arthritis, Analogous to Hypertension, Diabetes, and Hyperlipidemia: Is Control of Individual Patient Self-Report Measures of Global Estimate and Physical Function More Valuable Than Laboratory Tests, Radiographs, Indices, or Remission Criteria? J Rheumatol [Internet]. 2013 Sep [cited 2013 Oct 16];40(9):1469-1474. Available from: http://www.jrheum.org/content/40/9/1469.full?
9 Prince FHM, Bykerk VP, Shadick NA, Lu B, Cui J, Frits M, Iannaccone CK, Weinblatt ME, Solomon DH. Sustained rheumatoid arthritis remission is uncommon in clinical practice. Arthritis Res Ther [Internet]. 2012 Mar 19 [cited 2013 Oct 16];14(2):R68. Available from: http://arthritis-research.com/content/pdf/ar3785.pdf
10 Young K. Sustained rheumatoid arthritis remission is rare. Rheumatoid Arthritis Warrior [Internet]. 2012 Mar 30 [cited Oct 16]. Available from: https://www.rawarrior.com/sustained-rheumatoid-arthritis-remission-is-rare/