EDITORIALS |
Psoriatic arthritis is a joint-damaging disease—a call for action!
1Department of Medicine, University of Otago Wellington, New Zealand and 2Academic Section of Musculoskeletal Medicine and Rehabilitation, University of Leeds, UK.
Correspondence to: W.J. Taylor, Department of Medicine, University of Otago Wellington, New Zealand. E-mail: will.taylor{at}otago.ac.nz
In this issue of the journal, Morgan and colleagues [1] present data from the Norfolk Arthritis Register (NOAR) that confirm psoriasis–associated inflammatory arthritis is associated with similar 5-yr outcomes to inflammatory arthritis without psoriasis. The importance of this finding is that it was derived from observing an inception cohort. NOAR represents a possibly unique resource for observing the natural history of inflammatory arthritis. Prognostic studies that commence observation later in the history of the disease (commonly after presentation to secondary or tertiary referral centres) have many potential biases that confound simple interpretation. The most pertinent bias is that less severe disease or disease that appears to remit quickly may never be observed. When comparing the outcome of one disease with another, such comparisons may be difficult to interpret when the extent of referral bias may be different for the different diseases. Thus, the most robust means of determining natural history remains an inception cohort study.
That this approach leads to similar conclusions to studies conducted in specialist clinics greatly strengthens the concept that psoriatic arthritis (PsA) is not a benign disease [2]. In absolute terms, of the NOAR cohort, 36.7% of patients with psoriasis had radiographic erosions compared with 33.8% of patients without psoriasis after 5 yrs. This compares with 47% of PsA patients in an early synovitis clinic after 2 yrs [3].
Another difficulty with studying PsA that Morgan and colleagues have neatly sidestepped is the issue of case definition. The authors are careful not to classify their cohort as actually having PsA or not—the groups are only labelled as polyarthritis with or without psoriasis. From an epidemiological point of view this may be correct but it is increasingly difficult to deny the differences between cases of arthritis with psoriasis and those without. These distinctions are seen in immunohistochemistry [4], genetics [5] and imaging [6]. There may be a tendency to assume that diseases with similar outcomes are similar diseases, but this is flawed logic, and is dependent upon how ‘outcome’ is conceptualized. Diseases as different as diabetes mellitus and chronic obstructive airways disease may have similar outcomes in terms of disability or quality of life; and groups of patients with the same disease may have different outcomes, depending upon the severity of their disease. Thus, it is important to separate cases of PsA from, for example, rheumatoid arthritis (RA) and newly developed classification criteria will help both in established and early disease [7]. The importance of finding lesions of typical psoriasis cannot be over-emphasized, yet the study by Morgan et al. [4] only examined ‘available’ skin surfaces and did not enquire about past history (both likely to lead to false negatives). Thus, finding psoriasis in 9.5% of their cohort was surprising and leads to speculation that other dermatoses (such as seborrhoea and eczema) were being diagnosed as psoriasis.
One problem that was successfully addressed in One Morgan et al. study [1] was to take out the ‘true’ RA patients contaminating the psoriasis cohort, using rheumatoid factor (RF) positivity as a marker of potential RA. By comparing only RF-negative patients, the likelihood of RA contaminating the psoriasis group was probably much reduced. Misclassification may occur the other way, probably only to a small extent, whereby some patients with ‘true’ PsA may not yet have developed psoriasis. In any case, if classification criteria for PsA were actually used in this study it is unlikely that the results would be much different since most criteria rely strongly upon the presence of psoriasis and the absence of RF. For example, the presence of psoriasis and absence of RF is sufficient for classification as PsA by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria [7].
Functional status is known to be strongly related to joint inflammation in RA [8], but increasingly related to joint damage in late RA [9]. This provides a strong mechanistic need for therapies to prevent future joint damage since it is probable that functional status will also be improved by such therapies. Is the same relationship between joint damage and functional status true of PsA? There is very little data to address this question. Studies from Toronto form a major source of information concerning the longitudinal follow-up of people with PsA. In one of these studies, of patients seen for the first time between 1978 and 1982 and followed for at least 5 yrs, the percentage of patients with five or more radiologically damaged joints increased from 19 to 41%, but the percentage of patients in ARA functional class III or IV increased from 12 to only 13% (essentially unchanged) [10]. There was very poor correlation between radiographic damage and the revised and expanded version of the Arthritis Impact Measurement Scales (AIMS2) in another study of patients with a mean disease duration of 15 yrs [11].
Despite the paucity of this kind of data, there is more direct evidence from randomized trials that effective therapy for PsA reduces both radiographic damage and improves physical functioning. However, it is still prudent to note that improvement in one of these domains cannot be assumed to be associated with improvements in the other domain. Studies of adalimumab [12] and etanercept [13] show changes in HAQ scores in the order of 50–60% improvement and also radiographic improvement, whereas in the study of infliximab [14] and leflunomide [15], HAQ scores improved but radiographic scores were not described. The question might be raised, ‘Is it always necessary for successful treatment of PsA, that drugs which influence radiographic progression be used?’ From the patient perspective, at least judged by the HAQ, the answer might be ‘no’.
An additional clue from the study by Morgan et al. [1], that the relationship between joint damage and disability may not be the same in PsA as in RA, could lie with the difference in the severity of radiographic damage scores in those with radiographic erosions. Patients with psoriasis and radiographic erosions had a median Larsen score of 13 compared with 28 in those without psoriasis. In other words, although patients with psoriasis were as likely to have some degree of radiographic damage, the severity of the damage was less. The HAQ scores in patients with erosive disease were not reported separately but it would be of interest to determine whether the relationship between HAQ and radiographic damage was different for people with and without psoriasis in patients with erosive disease. It may be the case that disability does not mirror peripheral radiographic damage scores as closely in PsA as in RA.
Nonetheless, given that (i) PsA is associated with structural joint damage to a similar extent as other forms of inflammatory arthritis (mainly RA); and (ii) joint damage can be prevented with certain kinds of therapy, it is possible that a successful treatment paradigm for PsA ought to be similar to RA. That is, early assessment of patients in specialist clinics, commencement of drugs that have disease-modifying properties (retard radiographic progression) early in the presentation [16] and regular adjustment of therapy to promote remission of inflammatory disease activity (treatment-to-target strategy) [17]. All this sounds quite plausible, but the evidence that such a paradigm actually works in PsA is remarkably slim. There are no reported trials of treatment for early disease. The only agents for which there is evidence of radiographic benefit are anti-TNF drugs [12]. There are no valid definitions for remission of inflammatory activity in PsA and no trials that test treatment strategy (rather than individual drugs) for PsA. There is much that can be done now for the patient with PsA who is in the clinic, but there is also much to be done by carefully designed studies that may help answer some of these questions.
Disclosure statement: The authors have declared no conflicts of interest.
References
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