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The clinical utility of a rule for predicting rheumatoid arthritis in patients with early undifferentiated arthritisComment on the article by van der Helm-van Mil et al.

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Vol. 60, No. 3, March 2009, pp 905–906
© 2009, American College of Rheumatology
ACPAs in an additional 3 patients. Therefore, in our small
cohort, the prediction rule is less sensitive than ACPA status
alone in identifying UA patients who will have developed RA
at ⱖ1 year (8 of 15 versus 11 of 15).
Interestingly, van der Helm-van Mil et al showed
through the construction of ROC curves that the diagnostic
performance of their prediction rule was superior to that of
autoantibody status considered in isolation. We suggest that
this is attributable to its excellent NPV among ACPA-negative
UA patients, the group in which prognostic markers are most
needed. Of the 41 ACPA-negative UA patients in our cohort,
22 (54%) could be assigned prediction scores of ⱕ6 at inception, none of whom had progressed to RA at ⱖ1 year. This of
course leaves a significant subset of UA patients for whom
neither prediction score nor ACPA status can accurately
predict outcome, and 21% (4 of 19) of this subset developed
RA in our cohort.
Among our patients, the well-conceived prediction rule
proposed by van der Helm-van Mil et al is most valuable as a
negative predictor of RA among ACPA-negative UA patients.
However, additional biomarkers are needed for appropriate
diagnosis and prognosis among these patients, many of whom
present at an early arthritis clinic with a challenging set of
DOI 10.1002/art.24348
The clinical utility of a rule for predicting rheumatoid
arthritis in patients with early undifferentiated
arthritis: comment on the article by
van der Helm-van Mil et al
To the Editor:
We read with great interest the excellent article by van
der Helm-van Mil et al, which provided convincing validation
of a much-needed prediction rule for disease outcome in
patients with recent-onset undifferentiated arthritis (UA) (1),
and we have 2 observations.
First, the definition of early UA deserves comment. In
our own practice, a patient is said to have UA when, in a
consulting rheumatologist’s opinion, “an inflammatory arthritis is suspected, with RA remaining a possibility, but established classification criteria for any rheumatologic condition
are not fulfilled.” This is akin to the description of “undifferentiated polyarthritis” given by Wolfe et al, which states that it
is not explicitly required that objectively observed joint inflammation be present, providing there is a history of inflammatory arthritis, especially in the presence of increased levels
of inflammation markers (2). Among our own cohort of 53
patients with UA defined in this way (median symptom
duration 14 weeks; followup ⱖ1 year), 18 (34%) would have
been excluded if the 1958 “probable RA” criteria (3) favored
by researchers in Leiden, The Netherlands, had been employed. In fact, the UA of 2 of these patients subsequently
evolved into rheumatoid arthritis (RA), as defined by the
American College of Rheumatology (formerly, the American
Rheumatism Association) in its revised criteria (4). Consensus
is certainly required in this area, but encouragingly, the
prediction rule proposed by van der Helm-van Mil et al
performed well in our UA cohort (positive predictive value
[PPV] of a score ⱖ8 100%; negative predictive value [NPV] of
a score ⱕ6 100%), as confirmed by the construction of a
receiver operating characteristic (ROC) curve (area under the
curve 0.88; SEM 0.048).
The second observation relates to the specific subset of
UA patients in which a prediction rule of this kind is likely to
be of most value. A previous study by other authors from the
Leiden group demonstrated that the presence of circulating
autoantibodies to citrullinated peptides (ACPAs) accurately
predicted progression to RA among UA patients (PPV 93%
over 3 years) (5). Given the heavy weighting (2 of a possible 13
points) attributed to ACPA status in the scoring system
proposed by van der Helm-van Mil et al (1), one might
anticipate that a “high-risk” score of ⱖ8 would simply identify
ACPA-positive individuals whose progression to RA is already
very likely. This is borne out in our own cohort. Of the 15 UA
patients whose disease progressed to RA at ⱖ1 year, all 8 of
those assigned “high-risk” prediction scores of ⱖ8 were ACPA
positive. Furthermore, among the remaining 7 patients (in
whom the assigned prediction score of 6–⬍8 was unhelpful),
progression to RA was accurately predicted by the presence of
Dr. Pratt’s work was supported by a clinical research fellowship from the
Arthritis Research Campaign.
A. G. Pratt, BSc, MRCP
J. D. Isaacs, BSc, PhD, FRCP
Newcastle University
and The Freeman Hospital
Newcastle-upon-Tyne, UK
G. Wilson, RN, DipHE
The Freeman Hospital
Newcastle-upon-Tyne, UK
1. Van der Helm-van Mil AH, Detert J, le Cessie S, Filer A, Bastian
H, Burmester GR, et al. Validation of a prediction rule for disease
outcome in patients with recent-onset undifferentiated arthritis:
moving toward individualized treatment decision-making. Arthritis
Rheum 2008;58:2241–7.
2. Wolfe F, Ross K, Hawley DJ, Roberts FK, Cathey MA. The
prognosis of rheumatoid arthritis and undifferentiated polyarthritis
syndrome in the clinic: a study of 1141 patients. J Rheumatol
3. Ropes MW, Bennett GA, Cobb S, Jacox R, Jessar RA. 1958
Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum
Dis 1958;9:175–6.
4. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF,
Cooper NS, et al. The American Rheumatism Association 1987
revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24.
5. Van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, de Jong BA,
Breedveld FC, Verweij CL, et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study.
Arthritis Rheum 2004;50:709–15.
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