ARTHRITIS & RHEUMATISMVol. 52, No. 11, November 2005, pp 3333–3336DOI 10.1002/art.21410© 2005, American College of Rheumatology

COMMENTARY

The Need for New Classification Criteria forRheumatoid Arthritis

Daniel Aletaha,1 Ferdinand C. Breedveld,2 and Josef S. Smolen3

Over the past decade, there has been breathtak-ing progress in the evolution of both basic research andclinical insights into rheumatoid arthritis (RA): newinsights into pathophysiology, new measures to deter-mine outcome, new therapeutic strategies, and newtherapeutic compounds have emerged (1–13). In paral-lel, the recognition that RA needs to be diagnosed earlyand treated promptly with disease-modifying antirheu-matic drugs (DMARDs) to most successfully interferewith the disease process and its progression to majordamage and disability has become a new paradigm(14–20). This paradigm, combined with novel treatmentoptions, has translated into improved prognosis forpatients, with significant success with respect to im-provement of global disease activity, retardation of jointdamage, prevention of disability, and reduction in mor-tality (21). Nevertheless, in many patients, disease activ-ity and progression cannot be reduced to a clinicallymeaningful extent once RA is established, and in manywho experience significant improvement, there is resid-ual activity (22). While remissions are rare in establisheddisease, remission is the ultimate aim of therapeuticintervention, and the improvements achievable todayhave put this goal on the agenda.

Interference with the disease process may beeasier in the very early stages of the disease. In fact, mostrecent evidence obtained in early-arthritis clinics indi-cates that very early DMARD treatment, i.e., institutedwithin 3 months of symptom onset, may be highly

effective in leading to remission and preventing majorradiographic progression (23–25). This suggests the ex-istence of a “therapeutic window of opportunity.” How-ever, as much as scientists working in early-arthritisclinics attempt to establish a correct diagnosis of RA,they usually do so based on subtle findings due to lack ofappropriate criteria even though, as noted above,prompt diagnosis has prognostic implications given thegreater likelihood of progressive joint destruction anddisability in patients who are not treated early.

The currently widely used 1987 RA classificationcriteria of the American College of Rheumatology(ACR; formerly, the American Rheumatism Associa-tion) (26) were developed using patients with estab-lished RA (mean disease duration close to 8 years) andhad a sensitivity of 91% and a specificity of 89%. Amongthe 7 components of these criteria, 1 is a radiologiccriterion that is met only rarely in early disease; amongpatients with very early arthritis (symptom duration �3months [median 8 weeks]) who all developed RA,erosions were found in only 13% (27), whereas jointerosions are present in 50–70% of RA patients 2 yearsafter onset (28). Another component of the 1987 criteriais serologic in nature, i.e., rheumatoid factor (RF), whichalso is seen less frequently in early than in establisheddisease (29). Among the 5 clinical components of thecriteria set, rheumatoid nodules are very rare in earlyRA. Thus, only 4 of the 7 components of the ACRcriteria set are clinical and joint related and may there-fore have a reasonable probability of being fulfilled inearly RA. Moreover, 1 of these remaining 4 clinicalcriteria relates to involvement of at least 3 joint areaswhereas RA frequently initially presents as a mono- oroligoarticular disease, further reducing the diagnosticpotential of these criteria in early RA.

Not surprisingly, therefore, the sensitivity of theACR classification criteria in early RA ranges from 40 to60% and the specificity is no better than 80–90%(15,27,30–33). Patients with many non-RA arthritides,

1Daniel Aletaha, MD: Medical University of Vienna, Vienna,Austria, and National Institute of Arthritis and Musculoskeletal SkinDiseases, NIH, Bethesda, Maryland; 2Ferdinand C. Breedveld, MD:University Hospital Leiden, Leiden, The Netherlands; 3Josef S.Smolen, MD: Medical University of Vienna and Lainz Hospital,Vienna, Austria.

Address correspondence and reprint requests to DanielAletaha, MD, Division of Rheumatology, Department of InternalMedicine III, University of Vienna, Vienna General Hospital, Wae-hringer Guertel 18-20, A-1090 Vienna, Austria. E-mail: josef.smolen@wienkav.at.

Submitted for publication March 29, 2005; accepted in revisedform August 9, 2005.

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such as systemic lupus erythematosus, polymyositis, orviral arthritides, may fulfill the 1987 criteria, which donot list a series of exclusions. Taken together, these dataindicate that the usefulness of the ACR criteria in earlyRA is low.

The 1958 criteria (34) contained 11 components,2 of which were histologic in nature and 1 of whichrequired synovial fluid analysis. Like the 1987 criteria,they also included radiographic changes, rheumatoidnodules, and RF as components. The remaining 5 wererelated to signs and symptoms of joint involvement; 2 ofthose even allowed a finding of pain or swelling in asingle joint. Interestingly, in various studies (35) thesensitivity and specificity of the 1958 criteria were verysimilar to or even higher than those of the 1987 criteria.The 1958 criteria were subsequently modified in Romein 1961 (36,37), at which time the 2 histologic compo-nents and the synovial fluid analyses were omitted,leaving a set of 8 criteria. A patient was considered tohave definite RA if 5 of the 8 (or 11) components of thecriteria set were met. In addition, a series of exclusioncriteria were added, mainly relating to other defineddisorders. Moreover, with these older criteria, a patientwould be classified as having probable RA if 3 or 4 of thecomponents were met and the exclusion criteria werefulfilled.

What is needed at the present time, however, is aset of criteria that are useful for the stage of the diseaseat which physicians most frequently need the help ofcriteria, namely, very early in its course, when thedecision to initiate a clinically beneficial but potentiallyharmful therapy must be made. Such criteria have neverbeen elaborated consensually for early arthritis. Theywould have important implications regarding therapy,and inaccurate classification could therefore lead toundertreatment or overtreatment aside from simplymisinforming the patient and other clinicians. Thisimplies that these criteria should have prognosticimplications—to ultimately prevent the occurrence of anunfavorable outcome by increasing the likelihood ofappropriate early intervention. Initial attempts usingprospectively studied patient populations have beenmade (32,33), but they need further validation in differ-ent cohorts of patients with very early arthritis followedup prospectively.

Prognostication in early arthritis relates primarilyto persistence of disease and also to the propensity ofpersistent disease to cause joint damage. The latter is themore serious sequela of joint inflammation requiring themost intensive therapeutic intervention, although persis-tent inflammation even in the absence of a major

destructive component is also associated with disability.While the presence of radiologic changes is associatedwith an unfavorable prognosis (38–42), these changesare rare in the very early stages of disease that developsinto (destructive) RA (27,28,43). However, new imagingmodalities have entered the field, such as sonographyand magnetic resonance imaging, which allow discern-ment of soft tissue changes with more accuracy thanclinical examination and might be useful for early detec-tion of erosions (44).

Like radiologic abnormalities, RF is one of thecomponents of both the 1958 (1961) and the 1987criteria for RA. And like the former abnormalities, RFhas been regarded as a poor prognostic marker(17,42,45). Significant evidence has accumulated indicat-ing that the mere presence of RF has only limitedsensitivity and specificity in early RA. However, use of acutoff value of 50 IU/ml greatly increases specificitywhile only mildly reducing sensitivity (46–48). Anotherrecently recognized addition to the spectrum of autoan-tibodies in RA is the group of antibodies directed atcitrullinated peptides, which have a similar sensitivity toand somewhat higher specificity than RF (33,47,49).Given that these autoantibodies, as well as high-titer RF,are associated with both persistence and destructivenessof RA (33,43,47,49), it might be worthwhile to considerthem as an addition to future diagnostic or classificationcriteria for (early) RA. Whether the association of theshared epitope with RA is independent or is related tothe presence of autoantibodies is still a matter of debate(45,50–52).

Although there has been so much activity andprogress in RA research and management since 1987—not only the development of novel therapeutic agentsand strategies making remission a realistic therapeuticgoal, but also the establishment of new disease activitycriteria (5,7,9,53,54) and the advances in serology andimaging mentioned above (55)—disease criteria havenot changed. Would it not be timely to reevaluate theclassification (or, as they were called in 1958, diagnostic)criteria for RA? To assess the usefulness of a set ofcriteria for persistent and/or destructive arthritis thatmight better address the issues arising during very earlystages of joint inflammation? To examine if we havesufficient knowledge to distinguish such very early RApopulations among patients with very early arthritis? Toperform thorough evaluations and subsequent valida-tions in prospectively collected patient cohorts?

Thus, new criteria will ideally need to shift fromclassifying established RA to classifying a subtype ofearly arthritis that is projected to become persistent and

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erosive (rheumatoid) disease. This persistence of symp-toms is an explicit part of the current ACR criteria, andnew criteria will have to replace this requirement ofalready present persistence with reliable prediction ofpersistence. However, it will be necessary to criticallyassess whether sufficient evidence for prognostic mark-ers already exists (and which ones these would be) orwhether this needs to be part of a future research agendafostered by developing preliminary criteria based oncurrent insights. What one would call such criteria andwhether one would include the term “rheumatoid” areof secondary importance.

Such criteria would not be meant to define a newsubset of the disease but rather to help to identifypersistent (and likely erosive) arthritis as early as possi-ble, allowing it to be distinguished from other forms ofearly arthritides. The utility of new criteria for very earlyRA could be manifold: first, they would provide theclinician with tools to improve patient care in accor-dance with the treatment paradigm changes of recentyears; second, they could allow the study of variousgroups of patients fulfilling different components of thecriteria to further analyze the heterogeneity and conse-quently possible underlying pathways of RA; and third,the ultimate therapeutic goal, i.e., curing RA or prevent-ing the development of erosive (or persistent) disease,could be tested better by attempting to reach this goal inpatients who fulfill the criteria.

It would, in fact, be timely for the EuropeanLeague Against Rheumatism (EULAR) and the ACR toact in liaison to revise the criteria for RA—the ACRwith its long-term history of developing criteria andEULAR with its long-term devotion to the study of earlyarthritis. It is also timely to provide rheumatologistsworldwide with a scheme that would allow them toescape the current difficulty in classifying RA early, or,better, to subclassify patients with any type of earlyinflammatory joint disease according to prognosis. Suchnew criteria might materialize within a few years andconstitute a good basis for the celebration of the 20thanniversary of the 1987 (or the 50th anniversary of the1958) criteria that have served rheumatologists well fordecades but whose era has come to an end.

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