Darts, Magic Bullets, Remission

Darts, Magic Bullets, Remission

Treating RA often resembles a game of darts. Hitting close to the bullseye would be a moderately effective medication with tolerable side-effects: the pain and inflammation are significantly reduced though they occur on occasion, and side effects are tolerable. A sure hit would be a medication that is totally effective, eliminating disease flares and pain, and having no side effects. Such a bullseye would be a magic bullet really, able to cut through a crowd of innocent bystanders striking only the perpetrator of the crime.*

Complete Remission?

Remission is a word that takes on almost mystical properties in my mind, as its definition is vague in common parlance. Is it a significant reduction in the disease to the point of life carrying on as it used to? A total elimination of symptoms and the disappearance of this monstrosity that rears its ugly head to torment? Ambiguity is likewise present in medical terms. The American College of Rheumatology set out Preliminary Criteria for the Clinical Remission of Rheumatoid Arthritis in 1981, stating that, "Although there is general agreement that complete remission of disease activity may occur in RA, either spontaneously or under the influence of medications, the characteristics of this state of remission have never been defined."1 They followed with gloomy news: "The term 'complete remission' implies the total absence of all articular and extraarticular inflammations and immunologic activity related to RA. Although this state may be achieved occasionally, remission is more likely to be incomplete, even under the influence of potent drugs and after long periods of freedom from symptoms." So set out the American College of Rheumatology to define remission by compiling all scientific evidence at the time. Here is what they decided on in 1981:

To be deemed in complete clinical remission (as differentiated from partial remission), five of the following six criteria had to be met for the duration of at least two consecutive months:

  1. Morning stiffness < 15 min
  2. No fatigue
  3. No joint pain
  4. No joint tenderness or pain on motion
  5. No soft tissue swelling in joints or tendon sheaths
  6. Normal ESR. (Erythrocyte Sedimentation Rate detected in blood test)

According to a review of the research by Vivian P. Bykerk and Elena M. Massorotti in the Oxford Journal of Rheumatology (2012, V.51), "Few patients met these criteria, limiting the widespread use of the remission criteria, especially in the pre-biologic era, when fewer long-lasting treatments were available."2

Remission Criteria

An update to the ACR/EULAR remission criteria in 2011 for clinical trials accounts for the many changes in testing, treatment options, and growth of knowledge in the last thirty years:

The Boolean-based definition

At any time point, a patient must satisfy all of the following:

Tender Joint Count ≤ 1
Swollen Joint Count ≤ 1
C-Reactive Protein ≤ 1 mg/dl
Patient Global Assessment ≤ 1 (on a 0-10 scale)

The Index-based definition

Simplified Disease Activity Index score of ≤ 3

The simplified disease activity index score is calculated with "the simple sum of the tender joint count (using 28 joints), swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale), and C-reactive protein level (mg/dl).3

As is generally the case in trying to establish precise terminology for referenced biological states, these new definitions are the subject of some debate: "Particularly, it remains to be determined if this remission target is too stringent, without appreciable gain in other elements important to patients, including elimination of fatigue, quality of life, long-term function and physical deformity," note Bykerk and Massarotti. "Whether or not these criteria will stand the test of time will be based on how achievable they are for all patients and whether or not they reflect other measures of good outcome." The opposite question can also be asked: Are the criteria stringent enough? "Patients can have one tender and one swollen joint and be defined as being in remission."4

Clearly, the question of remission is not straightforward and is complicated by numerous different factors. Yet, a definition has great utility in drug research and clinical trials, and is, according to my doctor, the goal of my treatment.

Even for those who do go into remission, many do not stay there.

"Using the DAS-based definition of remission [Disease Activity Score], at most only 15% of patients have been able to achieve sustained drug-free remission in two large observational cohort studies."5 In our own survey of RA in America in 2015, of the near 3100 respondents, 63% had never gone into remission, 20% had previously been in remission due to medication but the disease is once again active, 8% have completely gone into remission due to medication, 7% went into remission without treatments though it is active again, and 1% had RA go into remission on its own.6 The R word is a tricky one.

Being treated for Rheumatoid Arthritis often feels like I am afloat in a capricious ocean of health and wellness, pulled this way and that by fluctuating tides. I still hope for a magic bullet that will halt this disease and restore my old life. A few darts have landed close to the mark, allowing me a quality of life not possible without treatment. Yet, my doctor wants a bullseye. I do too.

We will keep trying.

* The term "magic bullet" in the treatment of illness is attributed to Nobel Laureate Dr. Paul Ehrlich, who created the first treatment of syphilis, called Salvarsan, in 1910. This spurned the the emergence of chemotherapeutic agents in medicine, with "magic bullet" referring to the delivery of a toxin to a targeted pathological cell while sparing all others. For excellent reading on the earliest development of pharmaceuticals, including Ehrlich's discoveries, I would recommend "The Demon Under the Microscope" by  Thomas Hager.

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