Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.

The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA.

Plasma fibrinogen along with patient-reported outcome measures enhances management of polymyalgia rheumatica: a prospective study.

OBJECTIVE: We sought to prospectively examine the responsiveness of a number of patient-reported outcome (PRO) measures in polymyalgia rheumatica (PMR), as well as their relationship to the biomarkers erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma fibrinogen. METHODS: Sixty patients with PMR were divided into active (n = 25) or inactive (n = 35) disease groups based on symptoms; physician assessment; and the biomarkers ESR, CRP, and plasma fibrinogen. Groups underwent assessment at baseline and 6 weeks. Disease activity measures and relevant PRO measures were recorded. Measures of responsiveness were compared for all PRO and biomarkers. RESULTS: Visual analog scale disease activity (VASDA) and VAS quality of life (VASQOL) are more responsive to change in disease activity than VAS pain, morning stiffness, Health Assessment Questionnaire (HAQ), and PMR-activity score (AS). Analysis of PMR-AS versus VASDA, VASQOL, and HAQ showed correlation coefficients of 0.87 (p < 0.001), 0.80 (p < 0.001), and 0.68 (p < 0.001), respectively. Receiver-operating curve (ROC) analysis revealed VASDA to be more specific than either HAQ (0.95 vs 0.85; p < 0.001) or VASQOL (0.95 vs 0.93; p < 0.001) for the detection of response to treatment in active PMR. Overall, fibrinogen showed superior correlation coefficients with the various PRO than either of the standard biomarkers ESR or CRP. In addition, standardized response means for fibrinogen, ESR, and CRP were 1.63, 1.2, and 1.05, respectively, indicating that plasma fibrinogen was the most responsive biomarker for assessment of change in disease activity. CONCLUSION: VASDA and VASQOL are the most responsive PRO to changes in disease activity in PMR. In addition, plasma fibrinogen demonstrated greater responsiveness to changes in disease activity and superior correlation with the various PRO measures recorded than did the standard biomarkers ESR and CRP.

Plasma fibrinogen is an accurate marker of disease activity in patients with polymyalgia rheumatica.

OBJECTIVE: The overall aim of this study was to establish whether plasma fibrinogen was a superior biomarker of disease activity in active PMR than the standard biomarkers, ESR and CRP. METHODS: Sixty patients with PMR were divided into active (n = 25) or inactive (n = 35) disease groups based on symptoms, physician assessment and biomarkers ESR and CRP. Plasma fibrinogen was assayed. Groups underwent assessment at baseline and 6 weeks. Disease activity as per the PMR activity score (PMR-AS) was recorded at all visits. Receiver operator curves (ROCs), predictive values and likelihood ratios were calculated for all biomarkers. RESULTS: Disease activity measures improved significantly in the active group between weeks 1 and 6 (P < 0.001). There was no significant difference between the activity scores at week 6 in the active group and the inactive group. Mean fibrinogen decreased from 5.2 to 3.5 g/l (normal <4 g/l) between weeks 1 and 6 in the active group. Mean ESR and CRP decreased from 59.6 to 24.3 mm/h (normal <30 mm/h) and 45.9 to 12.66 mg/l (normal <5 mg/l), respectively. Receiver operator curve analysis revealed fibrinogen to be more specific than either ESR or CRP for the detection of response to treatment in active PMR, with an overall sensitivity and specificity of 92% and 96%, respectively. Values above the upper limit of normal for fibrinogen, CRP and ESR were associated with likelihood ratios for active disease of 20.53, 2.9 and 2.8, respectively (P < 0.001). CONCLUSION: Plasma fibrinogen is at least as useful as CRP and ESR for the diagnosis of active PMR and more specific for confirmation of response to treatment than either ESR or CRP.

The meniscus, calcification and osteoarthritis: a pathologic team.

Articular calcification correlates with osteoarthritis (OA) severity but its exact role in the disease process is unclear. In examining OA meniscal cell function, Sun and colleagues have shown recently that meniscal cells from end-stage OA subjects can generate calcium crystals and that genes involved in calcification are upregulated in OA meniscal cells. Also, this in vitro calcium deposition by OA menisci is inhibited by phosphocitrate. This study should catalyse further work examining the pathological contribution or otherwise of calcium crystals in OA. This would significantly aid the development of potential disease modifying agents in OA, which are currently unavailable.