Update on Biomarkers in Psoriatic Arthritis

Biomarkers in psoriatic arthritis (PsA) may serve as surrogate end points for disease outcome and can provide insights into disease susceptibility and natural history. Biomarkers could relate to diagnosis, pathogenesis, prognosis, therapeutic response, and comorbidities. The “felt need” is, however, in the development of biomarkers for the presence of PsA in patients with psoriasis, as well as that for joint damage. During the past few years, many studies related to PsA biomarkers have been conducted. These studies are reviewed here. C-reactive protein, matrix metalloproteinase-3, and circulating osteoclast precursors show promise. An international goal-directed study to determine biomarkers for joint damage in PsA is now under way through a collaborative effort of GRAPPA (the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) and OMERACT (Outcome Measures for Rheumatology Clinical Trials).     

The role of non-corticosteroid related factors in osteonecrosis (ON) in systemic lupus erythematosus: a nested case-control study of inception patients

Several factors have been associated with the development of osteonecrosis (ON) in SLE but corticosteroid (CS) therapy has been the most consistent association. We sought to determine factors that predisposed to, or protected from, the development of ON in lupus patients when cumulative oral corticosteroid doses were matched between cases and controls, thereby removing presence of corticosteroid therapy and cumulative dose as risk factors. A nested case-control study of an inception cohort of SLE patients was used to determine the clinical, laboratory and therapeutic differences between patients who developed their first ON event and patients who did not develop ON, having matched these groups for their cumulative oral corticosteroid doses. Of the 570 patients seen within the first year after diagnosis 65 (11.4%) developed ON. None of the variables examined were found to confer additional ON risk in multivariate analysis. It appears that the major factor associated with the development of ON is corticosteroid therapy. Factors which may protect a majority of patients on corticosteroids from developing ON remain to be elucidated.     

Outcome measures in psoriatic arthritis

Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor, has emerged as a more common and severe disease than previously appreciated. The disease is multifaceted. Thus the assessment of PsA requires attention to peripheral joint involvement, axial disease, dactylitis, and enthesitis, as well as the skin manifestations. In addition, the assessment of patient reported features such as patient assessment of disease activity, pain, fatigue, quality of life, and the new concept of participation are important. The assessment of damage and the assessment of tissue histology are also important outcome measures. This article summarizes these features of PsA as well as current knowledge on the instruments available for the assessment of these domains.     

The protective effect of antimalarial drugs on thrombovascular events in systemic lupus erythematosus

Objective

The antimalarial medication hydroxychloroquine has been proposed as a thromboprotective agent in systemic lupus erythematosus (SLE), but studies thus far have been limited by the possibility of confounding by indication. This study was conducted to assess whether exposure to antimalarial drugs is associated with a decrease in thrombovascular events (TEs) in patients with SLE.

Methods

The study was designed as a nested case–control study embedded in an inception cohort of patients with SLE, which allowed adjustments for possible confounding by calendar year, duration of disease, duration of observation, and severity of lupus. After controlling for the possible confounding variables in conditional logistic regression models, the use of antimalarial drugs was assessed for its effects on the development of TEs in lupus patients.

Results

Fifty‐four cases of TE were identified, and these were matched with 108 control subjects (lupus patients without TEs). Univariate analyses identified older age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01–1.07) or being older than age 50 years (OR 3.5, 95% CI 1.4–8.6) and ever having hypertension (OR 2.5, 95% CI 1.0–5.8) as being associated with an increased risk of TEs, whereas use of antimalarial drugs (OR 0.31, 95% CI 0.13–0.71) was associated with a decreased risk of TEs. Separate analyses were done for arterial and venous TEs, which yielded similar results. In multivariate analyses, use of antimalarial drugs (OR 0.32, 95% CI 0.14–0.74) and older age (OR 1.04, 95% CI 1.01–1.07) were the only 2 variables that remained significant.

Conclusion

The results from this nested case–control study demonstrate that, after accounting for the effects of disease severity, disease duration, and calendar year, antimalarial drugs were found to be thromboprotective, being associated with a 68% reduction in the risk of all TEs, with a range of risk reduction of at least 26% up to as high as 86%.

     

Improved survival in psoriatic arthritis with calendar time

OBJECTIVE: To determine whether there has been a change in mortality rates over the last 3 decades in patients with psoriatic arthritis (PsA) whose cases were followed prospectively. METHODS: Patients receiving followup care according to a standard protocol at the University of Toronto PsA Clinic between 1978 and 2004 were included. Information on patient deaths was collected prospectively. Mortality data for the general population of Ontario, Canada, stratified by 5-year age bands, sex, and calendar year from 1978 to 2004, were used to calculate the reference rates. Standardized mortality ratios (SMRs) were calculated through use of Poisson regression models for the number of observed deaths. Time trend analyses were performed through the use of 10-year "rolling-average" SMRs and followup period-specific SMRs stratified by the period of entry into clinic. RESULTS: Of 680 patients with PsA, 106 (15.6%) (55 women and 51 men) have died. Major causes of death were disease of the circulatory system, neoplasms, diseases of the respiratory system, diseases of the gastrointestinal system, injuries/poisoning, and unknown. The overall SMR for the period 1978-2004 was 1.36 (95% confidence interval 1.12, 1.64). The estimated number of life-years lost by the PsA patient cohort overall was 2.99 years (95% confidence interval 1.14, 4.77). For patients who entered the cohort during the years 1978-1986, the SMRs were 1.89, 1.83, and 1.21 for followup periods 1978-1986, 1987-1995, and 1996-2004, respectively. For patients who entered the cohort during the years 1987-1995, the SMRs were 0.55 and 0.82, while the SMR for those who entered during 1996-2004 was 0.56. CONCLUSION: The drop in SMRs in this PsA clinic population suggests that the mortality risk has improved over time. This improved survival may reflect disease severity at presentation in the earlier cohort as well as earlier diagnosis and more aggressive treatment in the more recent followup period.