Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response.

OBJECTIVE: The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects. Here, we conducted a comparative proteomics study in attempt to identify a predictive theranostic signature of non-response in patients with rheumatoid arthritis treated by etanercept/methotrexate combination. METHODS: A serum sample was collected prior to treatment exposure from a cohort of 22 patients with active RA. A proteomic "label free" approach was then designed to quantitate protein biomarkers using mass spectrometry. To verify these results, a relative quantification followed by an absolute quantification of interesting protein candidates were performed on a second cohort. The criterion of judgment was the response to etanercept/methotrexate combination according to the EULAR criteria assessed at 6 months of treatment. RESULTS: These investigations led to the identification of a set of 12 biomarkers with capacity to predict treatment response. A targeted quantitative analysis allowed to confirm the potential of 7 proteins from the latter combination on a new cohort of 16 patients. Two highly discriminating proteins, PROS and CO7, were further evaluated by ELISA on this second cohort. By combining the concentration threshold of each protein associated to a right classification (responders vs non-responders), the sensitivity and specificity reached 88.9 % and 100 %, respectively. CONCLUSION: Prior to methotrexate/etanercept treatment, abundance of several sera proteins, notably PROS and CO7, were associated to response status of RA patients 6 month after treatment initiation.

Use of glucocorticoids in rheumatoid arthritis - pratical modalities of glucocorticoid therapy: recommendations for clinical practice based on data from the literature and expert opinion.

OBJECTIVE: To develop recommendations about the use of glucocorticoids in patients with established rheumatoid arthritis (RA) managed in everyday practice, using the evidence-based approach and expert opinion. METHODS: A three-step procedure was used: a scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; a systematic literature review was conducted by searching the Medline and Embase databases and the abstracts of meetings held by the Société Française de Rhumatologie (SFR), American College of Rheumatology (ACR), and European League Against Rheumatism (EULAR); and recommendations were developed and validated by a panel of experts based on the data from the literature review and on their experience. For each recommendation, the level of evidence and extent of agreement among experts were determined. RESULTS: The five questions pertained to the use of glucocorticoids in RA patients: role for intravenous glucocorticoid bolus therapy, role for intraarticular injections, and practical modalities of glucocorticoid administration and discontinuation. From the literature search, 93 articles were selected based on their titles and abstracts. Of these, 50 were selected for the literature review. Eight recommendations about the use of glucocorticoid therapy in everyday practice in patients with established RA were validated by a vote among all participating experts: bolus glucocorticoid therapy should be reserved for highly selected situations; triamcinolone hexacetonide is the preferred glucocorticoid for intraarticular therapy, and the joint should be rested for about 24h after the injection; for oral glucocorticoid therapy, agents with a short half-life taken once daily should be preferred; and when discontinuing glucocorticoid therapy, the patient and usual physician should be informed of the risk of adrenal insufficiency.

Safety of infliximab used in combination with leflunomide or azathioprine in daily clinical practice.

OBJECTIVE: To investigate the safety of infliximab (INF) combination therapy with leflunomide (LEF) or azathioprine (AZA) in patients with rheumatoid arthritis (RA). METHOD: A standardized questionnaire on the use of INF in combination with LEF or AZA was mailed to hospital physicians and collected over a 2 month period. Adverse events (AE) and the reasons for withdrawal of combination therapy were analyzed. RESULTS: Data on 225 patients with RA were collected retrospectively. INF was used in combination with LEF in 171 patients and with AZA in 54. The duration of INF exposure was similar in both groups (mean 8.8 mo). AE were reported in 75 patients (33.3%), 60 LEF/INF (35%) and 15 AZA/INF combinations (27.8%) (p=nonsignificant). No unexpected AE were observed. The main AE were infections (6.2%), cytopenia (5.8%), hepatotoxicity (5.8%), reactions to infusion (5.3%), and skin reactions (4%). At the time the questionnaires were sent out, 161 patients were continuing combination therapies. The main reasons for drug withdrawal were AE (53 patients, 23.5%), inefficacy (10 patients, 4%), and one temporary discontinuation for surgery. CONCLUSION: Our study suggests that INF used in combination with LEF or AZA could be an alternative to methotrexate/INF combinations.