Pathway to biomarker discovery in psoriatic arthritis.

INTRODUCTION: Biomarkers may help influence long-term outcomes of psoriatic disease by improving the objective assessment of the presence and severity of psoriatic arthritis (PsA) and by guiding treatment selection. However, there are no validated biomarkers for PsA. AREAS COVERED: Beginning with a brief overview of the clinical features of PsA and concepts about biomarkers and risk prediction in medicine, this narrative review covers the recent developments in the field of PsA biomarker research including biomarkers for identifying patients with psoriasis who are at high risk for developing PsA, for PsA diagnosis, joint damage, treatment response, and disease activity. The limitations of current research and potential solutions for the near future are discussed. EXPERT OPINION: Although some progress is being made, a concerted international collaborative effort by all stakeholder - patients and advocacy organizations, clinicians, researchers, industry partners, and regulatory agencies with adequate funding ideally from a private-public partnership will be required such that robust biomarkers for this heterogeneous disease are brought to market. Use of multi-omic approaches with innovative data collection and analytic technologies is beginning and in conjunction with novel targeted therapies portend a bright future for patients with psoriatic disease.

Adaptive sampling in two-phase designs: a biomarker study for progression in arthritis.

Response-dependent two-phase designs are used increasingly often in epidemiological studies to ensure sampling strategies offer good statistical efficiency while working within resource constraints. Optimal response-dependent two-phase designs are difficult to implement, however, as they require specification of unknown parameters. We propose adaptive two-phase designs that exploit information from an internal pilot study to approximate the optimal sampling scheme for an analysis based on mean score estimating equations. The frequency properties of estimators arising from this design are assessed through simulation, and they are shown to be similar to those from optimal designs. The design procedure is then illustrated through application to a motivating biomarker study in an ongoing rheumatology research program.

Anemia, serum vitamin B12, and folic acid in patients with rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus.

OBJECTIVE: Although anemia is frequent in inflammatory rheumatic diseases, data regarding vitamin B12 status is scarce. The purpose of this study was to analyze the incidence and nature of B12 and folic acid (FA) deficiencies in a cohort of rheumatic patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE). METHODS: Levels of B12, FA, and parameters of anemia were recovered or examined in 276 outpatients. In those with recent findings of low serum B12 levels, further studies of serum homocysteine (Hcy) and urine methylmalonic acid (MMA) levels were performed. RESULTS: The incidence of anemia was high: 49%, 46%, and 35%, in RA, SLE, and PsA, respectively. Low levels of serum B12 were also frequent (24%), with almost similar occurrence in the three disease groups. Deficiency in FA was rare (<5%). Mean levels of both vitamins did not differ significantly among the three groups. No correlation between serum B12 levels and anemia was found. In the 15 patients with recently detected low B12 levels, Hcy and MMA were evaluated before and following B12 therapy. In ten of them, baseline Hcy levels were high, while MMA was increased in one patient only. Response to B12 administration, i.e., a decrease in Hcy and/or MMA levels, was noticed in four patients only, suggesting that only 26% of the low-serum-B12 patients had true B12 deficiency. CONCLUSIONS: The incidences of anemia and decreased serum B12 levels were high in these three groups of rheumatic patients. However, true tissue deficiency seems to be much rarer.

Evaluation of free and peptide bound collagen crosslink excretion in different skeletal diseases.

OBJECTIVE: To investigate urinary fractions of free and peptide forms of collagen crosslinks in patients with rheumatoid arthritis (n=50), osteoarthrosis (n=38), psoriatic arthritis (n=38) and in healthy volunteers (33 adults, 17 children). METHODS: Pyridinoline (PYD) and deoxypyridinoline (DPD) were measured by high performance liquid chromatography. RESULTS: In rheumatoid arthritis (RA) all fractions of PYD and DPD were significantly raised compared with osteoarthritis, psoriatic arthritis, and healthy controls. PYD and DPD correlated with disease activity in RA. In RA the collagen degradation resulted in primarily peptide bound forms. CONCLUSION: The correlation between total peptide bound or free collagen crosslinks in different chronic joint diseases varies; however, this variation does not allow for a reliable differentiation between inflammatory and degenerative joint diseases.

Spot urine concentrations of type I collagen cross-linked N-telopeptides and deoxypyridinoline in psoriatic arthritis.

The main objectives of this study were to investigate whether the spot urine concentrations of type I collagen cross-linked N-telopeptides (NTx) and deoxypyridinoline (Dpd) can be used to distinguish between active and suppressed disease in psoriatic arthritis (PsA) and to study the relationship between these markers of bone resorption and disease activity indices. Using enzyme-linked immunosorbent assays, concentrations of NTx and Dpd were estimated in spot urine samples from 25 patients with active disease, 10 patients with suppressed disease and 35 age- and sex-matched healthy control subjects. In patients with active disease, urine concentrations of NTx and Dpd were significantly elevated (p<0.001) compared with healthy controls and there were no significant differences (p>0.05) when compared with those with suppressed disease. In active disease, there was no significant positive correlation between urinary NTx and erythrocyte sedimentation rate (ESR) (r = 0.025, p>0.05) nor between Dpd and ESR (r = -0.208, p>0.05). In conclusion, NTx and Dpd concentrations in spot urine have no association with disease activity in patients with PsA.

Determination of tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis.

An enzyme-linked immunosorbant assay was developed to determine tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in pooled synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis. Even though basal values could be determined, the addition of synovial fluid shifted the standard curves for both tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complex to the right, because of the presence of a novel inhibitor.

[Hydroxyproline excretion in psoriasis and psoriatic arthritis]. / Hydroxyprolinausscheidung bei Psoriasis (Ps) und Arthritis psoriatica (Ap).

In the morning urine of 24 patients with psoriasis and that of 24 patients with psoriatic arthritis, we determined the excretion of hydroxyproline (mg HP/mumol crea), after preceding diet low in collagen. Surprisingly, psoriatic patients without articular involvement showed a significantly higher excretion of HP than those with psoriatic arthritis. Further differentiation revealed that there were no clear-cut correlations between the amount of HP excretion and the activity of the articular process; we proved, however, that the amount of HP excretion was definitely related to the activity of the skin eruptions in both groups of patients. We discuss whether an osteopathy pathogenetically associated with the skin disease (irrespective of synovitis in psoriatic arthritis) may possibly be responsible for these results.