DAS28 best reflects the physician's clinical judgment of response to infliximab therapy in rheumatoid arthritis patients: validation of the DAS28 score in patients under infliximab treatment

Abstract

This study is based on an expanded access program in which 511 patients suffering from active refractory rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab (3 mg/kg+methotrexate (MTX)) at weeks 0, 2, 6 and every 8 weeks thereafter. At week 22, 474 patients were still in follow-up, of whom 102 (21.5%), who were not optimally responding to treatment, received a dose increase from week 30 onward. We aimed to build a model to discriminate the decision to give a dose increase. This decision was based on the treating rheumatologist's clinical judgment and therefore can be considered as a clinical measure of insufficient response. Different single and composite measures at weeks 0, 6, 14 and 22, and their differences over time were taken into account for the model building. Ranking of the continuous variables based on areas under the curve of receiver-operating characteristic (ROC) curve analysis, displayed the momentary DAS28 (Disease Activity Score including a 28-joint count) as the most important discriminating variable. Subsequently, we proved that the response scores and the changes over time were less important than the momentary evaluations to discriminate the physician's decision. The final model we thus obtained was a model with only slightly better discriminative characteristics than the DAS28. Finally, we fitted a discriminant function using the single variables of the DAS28. This displayed similar scores and coefficients as the DAS28. In conclusion, we evaluated different variables and models to discriminate the treating rheumatologist's decision to increase the dose of infliximab (+MTX), which indicates an insufficient response to infliximab at 3 mg/kg in patients with RA. We proved that the momentary DAS28 score correlates best with this decision and demonstrated the robustness of the score and the coefficients of the DAS28 in a cohort of RA patients under infliximab therapy.

Figure 1

Plot of the mean scores over time. Act, activity; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; SJC, swollen joint count; TJC, tender joint count; pt, patient; Phys, physician; SQRT, variable normalized by taking the squared root; ln, variable normalized by taking the natural logarithm; VAS, visual analogue scale.

Figure 2

Validation of the DAS28 score and coefficients (see text). ESR, erythrocyte sedimentation rate; VAS, visual analogue scale.

Figure 3

ROC curve analysis of the DAS28 at week 22 (plotting the 1-specificity versus the sensitivity). Also the accuracy, PPV and NPV are plotted. PPV, positive predictive value (predictive value to give a dose increase as a measure of insufficient response); NPV, negative predictive value (predictive value to continue on the current dose as a measure of good response).