The Food and Drug Administration (FDA) requires not only fulfillment of the ACR criteria but also evidence of arrest of radiographic changes and for clinical remission to be present for more than six months.21 These criteria combine clinical and structural remission, which may not be the initial therapeutic aim for rheumatologists and, by using the ACR criteria for clinical remission (“five-of-six” requirement), may also be misleading in some cases.
Therefore, defining remission by composite scores may be more valuable in clinical practice and possibly also in clinical trials. Categories for remission have been clearly defined for the DAS28, SDAI, and CDAI. 9,15 (See Table 1, at right.) The SDAI and CDAI remission criteria (≤3.3 and ≤2.8)—by virtue of their subcomponents—do not allow for the presence of more than one tender and one swollen, or two tender or two swollen joints. In fact, the vast majority of the patients in SDAI or CDAI remission have no tender or swollen joint.20
DAS28 remission differs somewhat from SDAI and CDAI remission. Up to 16 swollen joints (or up to eight tender joints) can be present in DAS28 remission (<2.6), and one or more residual swollen joints can be found in 25% or more of the patients.15,20,22-25 The DAS28 remission state may mean low disease activity or a state near remission for a large proportion of patients, leaving room for potential treatment increase given current therapeutic aims. Considering that a majority of rheumatologists would not consider more than one swollen and/or two tender joints acceptable for defining remission, trial reports of up to 40% of patients in remission represent an exaggeration of the term remission, since the DAS28 was used in these definitions.4,26-28 While this difference may appear semantic, it may, in fact, be meaningful as depicted in Figure 1 (see p. 16) where one can see a subtle difference in residual HAQ levels between DAS28 and SDAI remission, which comprises the medians and the 75th percentiles.
Defining remission is especially important if reduction of a therapeutic modality is being considered; this decision may be made differently in a patient with no (or at best one residual) swollen or tender joints when compared, for example, to a patient with five or more residual active joints. In defining remission it is important to consider the scores used, their components, and their construction to avoid potential treatment withdrawal in patients with residual activity. In our clinic, we usually aim therapy toward remission and employ the CDAI criteria, which makes immediate decisions possible and does not require waiting for any laboratory test. C-reactive protein levels can be used for confirmatory purposes or to calculate the SDAI.
Sustained Remission
Even if you achieve remission at one point in time, you should not feel satisfied with the treatment outcome. Yo-yo effects, where a state of remission is followed by states of low to even high disease activity, are common.29 The goal should be sustained remission, achievable in a considerable number of patients in clinical practice with today’s therapies (up to 20%, even when using stringent SDAI/CDAI criteria), a tremendous advance over previous decades.20
Consider Patient and Physician Perspectives
Several studies show that physicians evaluate swollen joint counts more stringently than tender joint counts or pain, while the reverse is true when patients assess their disease.4,22,30,31 This can be seen by the differences observed when comparing patients’ and physicians’ global assessments of disease activity, which are often disparate.4,22,32 On the other hand, variables primarily valued by patients (such as tender joints) relate to different outcomes than those mostly valued by physicians (such as swollen joints): Tender joint counts in the short and long term correlate best with functional impairment, while swollen joint counts over time are predominantly associated with increasing joint damage.3 Consequently, judging the disease state as “very good” by virtue of the absence of pain and tender joints would translate into a propensity for joint destruction in residual swollen joints. On the other hand, judging the disease state as “very good” due to the absence of swollen joints—despite the presence of residual tender joints—would neglect the respective functional consequences.
