Evaluation of a clinical pharmacogenetics model to predict methotrexate response in patients with rheumatoid arthritis.

Variability of response to treatment hinders successful management of rheumatoid arthritis (RA). Consequently, a clinical pharmacogenetics model for predicting response to methotrexate (CP-MTX) has been previously proposed that includes four clinical variables (disease activity, sex, the presence of rheumatoid factor and smoking status) and four SNPs (rs2236225, rs17602729, rs1127354, and rs2372536) in genes of the folate pathway. It showed good performance, but failed to attract attention, likely, in relation with lack of clear clinical benefit. Here, we have revised the value of the CP-MTX model directly addressing its clinical benefit by focusing on the expected benefit-cost of the predictions. In addition, our study included a much larger number of RA patients (n = 720) in MTX monotherapy than previous studies. Benefit of CP-MTX prediction was defined as the patients that would have received combination therapy as first treatment because they were correctly predicted as non-responders to MTX monotherapy. In contrast, cost of CP-MTX prediction was defined as the responder patients that were wrongly predicted as non-responders. Application of CP-MTX predictions to our patients showed a good benefit-cost relationship, with half of the 66.7% non-responders to MTX monotherapy rightly directed to alternative treatments (a benefit of 33.3%) at the cost of 8.5% wrongly predicted non-responders. These benefits-costs were consistent with reanalysis of the previously published studies. Therefore, predictions of CP-MTX showed a good benefit-cost relationship for informing MTX prescription.

Ultrasonographic assessment of enthesitis in HLA-B27 positive patients with rheumatoid arthritis, a matched case-only study.

INTRODUCTION: HLA-B27 has a modifier effect on the phenotype of multiple diseases, both associated and non-associated with it. Among these effects, an increased frequency of clinical enthesitis in patients with Rheumatoid Arthritis (RA) has been reported but never explored again. We aimed to replicate this study with a sensitive and quantitative assessment of enthesitis by using standardized ultrasonography (US). METHODS: The Madrid Sonography Enthesitis Index (MASEI) was applied to the US assessment of 41 HLA-B27 positive and 41 matched HLA-B27 negative patients with longstanding RA. Clinical characteristics including explorations aimed to evaluate spondyloarthrtitis and laboratory tests were also done. RESULTS: A significant degree of abnormalities in the entheses of the patients with RA were found, but the MASEI values, and each of its components including the Doppler signal, were similar in HLA-B27 positive and negative patients. An increase of the MASEI scores with age was identified. Differences in two clinical features were found: a lower prevalence of rheumatoid factor and a more common story of low back pain in the HLA-B27 positive patients than in the negative. The latter was accompanied by radiographic sacroiliitis in two HLA-B27 positive patients. No other differences were detected. CONCLUSION: We have found that HLA-B27 positive patients with RA do not have more enthesitis as assessed with US than the patients lacking this HLA allele. However, HLA-B27 could be shaping the RA phenotype towards RF seronegativity and axial involvement.