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Abstract
Background This investigation aimed to determine whether patients presenting to a psoriatic arthritis (PsA) clinic early in the course of the disease had less severe disease at presentation, and whether disease duration at presentation predicts progression of joint damage.
Methods Patients followed prospectively in a specialised clinic were divided into those first seen within 2 years of diagnosis (group 1) and those seen with more than 2 years of disease (group 2). The groups were compared with regard to demographics and disease characteristics at presentation. A multivariate analysis using a negative binomial model was conducted to determine whether patients with early disease had less progression of joint damage.
Results 436 patients were identified in group 1 and 641 patients in group 2. Patients in group 2 were older, had longer duration of psoriasis and PsA, more joint damage and were less likely to be treated with disease-modifying antirheumatic drugs, but had similar level of education and degree of psoriasis severity. After adjusting for age, sex, education level, clinical joint damage at first visit and treatment, group 2 had significantly greater rate of clinical damage progression compared with group 1.
Conclusions Disease progression is more marked in patients presenting with established disease of more than 2 years' duration. These results suggest that patients with PsA should be treated earlier in the course of their disease.
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Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease associated with psoriasis and is often seronegative for rheumatoid factor.1 Over the past few decades it has become clear that the disease is more common and more severe than previously appreciated.2 PsA causes deformities and joint damage leading to impaired quality of life and function and is associated with an increased mortality risk.3 4 The majority of the studies reporting on outcome in patients with PsA include patients with longstanding disease. The one study of early PsA that included patients within 5 months of onset of symptoms identified 27% of the patients to have erosive disease at presentation to the early arthritis clinic, suggesting that the disease may be aggressive at an early stage.5 Indeed, 47% of these patients were found to have erosive disease within 2 years of follow-up despite the fact that the majority had been treated with disease-modifying antirheumatic drugs (DMARD). These patients were not compared with patients presenting later in the course of their disease. Therefore, it remains to be determined whether early diagnosis and treatment would alter the course of the disease.
The aims of the current investigation were to determine whether patients presenting to a PsA clinic early in the course of their disease had less severe disease at presentation, and whether disease duration at presentation predicts the progression of joint damage.
Patients and methods
Setting
The University of Toronto PsA Clinic was established in 1978 to study the course and prognosis of patients with this disease. Patients have been enrolled in the clinic if they have an inflammatory arthritis associated with psoriasis, with 99% fulfilling the classification of PsA criteria.1 6 Patients with PsA have been followed prospectively in this specialised clinic for 32 years.7 Patients are assessed at 6–12-month intervals according to a standard protocol, which includes a complete history, general physical examination, detailed musculoskeletal examination and skin and nail assessment. The musculoskeletal examination includes an assessment of actively inflamed joints measured by joint line tenderness or stress pain and/or effusions, an assessment of clinical damage based on the presence of restriction of movement of more than 20% of the range not attributed to the presence of effusion, deformities, fused or flail joints and joints that had undergone surgical replacement. Laboratory tests including routine haematology and biochemistry, serology for rheumatoid factor and anti-nuclear factor are carried out. Radiographic evaluations are performed at 2-year intervals and include radiographs of hands, feet, total spine and pelvis. Radiographs of the peripheral joints are scored according to a modification of the Steinbrocker method.8
Patient selection
Patients were divided into those first seen within 2 years of diagnosis (group 1) and those seen with more than 2 years of disease (group 2). The two groups were compared with regard to demographics and disease characteristics at presentation to clinic and progression of joint damage.
Assessment of joint damage progression: the outcome measure was an increase in the number of clinically damaged joints. This is assessed clinically based on the presence of joint deformities defined as a limitation of movement of more than 20% of the range that is not related to a joint effusion, the presence of flexion contractures, fused or flail joints, or evidence of surgery in a particular joint. This method has proved reliable and has been used as an outcome measure in previous studies.9 We have also demonstrated that there is a strong relationship between clinical and radiological damage. In this study we used the rate of clinical damage progression as the outcome measure.10 The study has been approved by the Research Ethics Board of the University Health Network.
Statistical analysis
Descriptive statistics were used to describe the demographic and clinical features. A multivariate analysis using a negative binomial model was conducted to determine whether patients with early disease had less progression of joint damage.11 The outcome variable was the count of the number of progressing joints based on clinical damage assessments, and the variables entered in the model were age, sex, group (1 and 2), count of the number of joints with clinical damage at the first visit, non-steroidal anti-inflammatory drug (NSAID) use at first visit, DMARD use at first visit, treatment with biological agents at first visit, treatment with NSAID after the first visit, treatment with DMARD after the first visit, and treatment with biological agents after the first visit. The calendar effect, based on the decade of entry into the clinic was also included in the model.
Results
Of the 1077 patients registered in the PsA clinic database, 436 patients were identified in group 1 (within 2 years of diagnosis) and 641 patients in group 2 (disease duration greater than 2 years). Demographic and disease characteristics at first visit are shown in table 1. Patients with early disease were older at the diagnosis of psoriasis and PsA but younger at the first visit to the clinic than patients with longer disease duration. By definition, they had shorter disease duration at presentation. However, they had a similar number of actively inflamed joints and psoriasis activity. While both groups had a similar frequency of isolated axial disease, more of the patients with a late presentation had both peripheral and axial disease, whereas peripheral presentation was more common among the patients presenting early. Clinical and radiological damage was higher among patients presenting later than those presenting within 2 years of diagnosis. Patients with longstanding disease were more likely to have been treated with DMARD and biological agents than those presenting early. The level of education, which may be viewed as a surrogate for economic status, was not different between the two groups. The results of multivariate regression analysis on predictors for progression of clinical joint damage are shown in table 2. After adjusting for age, sex, level of education, calendar time of entry into clinic, clinical joint damage at first visit and treatment, Group 2 has a significantly higher rate of clinical damage progression compared to Group 1. There was a clear dose/exposure–response relationship with respect to the duration of disease, which was shown by fitting a similar model to that above but instead stratifying the duration of disease at the first visit into six groups (table 3)
Demographic and disease characteristics of study subjects at first visit
Results of multivariate analysis on predictors for progression of clinical joint damage in patients with PsA
Stratification by duration of disease at clinic entry
Discussion
While in the past PsA was considered a mild disease, recent evidence attests to its severity. Until 2000 there were no treatments that led to a reduction in progression of joint damage.12 However, with the advent of antitumour necrosis factor agents, it is now possible to arrest the progression of damage in these patients.13,–,16 As it has been shown that the degree of inflammation predicts the progression of both clinical and radiological damage, both as a global feature17 and in the individual joint,18 it now behoves clinicians and patients to obtain appropriate therapy in a timely fashion to prevent joint damage progression.
However, most studies to date in PsA have been performed on patients with longstanding disease. The mean disease duration in most trials is greater than 7 years. To date, there is no published randomised controlled trial on the use of proper therapy in early PsA, with less than 1 or 2 years' duration. This information is crucial if we are to obtain appropriate treatment for patients with early disease, because many jurisdictions require the presence of an erosion before making an anti-tumour necrosis factor agent available on a drug benefit programme. Because of a lack of randomised controlled trials, we set out to determine whether patients who present to a specialised clinic early fare better that those who present later in their course.
This study demonstrates that patients who present within 2 years of diagnosis, while presenting with a similar degree of inflammation, have less severe disease at presentation than those presenting later in their course. Patients who presented later in the course were more likely to have used DMARD and biological agents than patients who presented earlier in their course. Importantly, the rate of disease progression is more marked in those patients presenting with established disease of greater than 2 years' duration.
We used clinical damage to determine the progression of damage rather than radiological damage in this study because this measure is obtained at each protocol visit, whereas radiographs are obtained at 2-year intervals. We have previously shown that there is a relationship between clinical and radiological damage.10 We have also shown that similar features predict the progression of clinical and radiological damage.17
As joint damage is predictive of both functional limitation and mortality in patients with PsA,19 20 it is important to prevent the progression of joint damage in order to prevent this untoward outcome.
These results suggest that patients with PsA should be treated earlier in the course of their disease in order to prevent the progression of damage and disability and increase survival.
References
Footnotes
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Ethics approval This study was conducted with the approval of the Research Ethics Board of the University Health Network.
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Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.
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