Maria I. Alba

Clinically important changes in individual and composite measures of rheumatoid arthritis activity: thresholds applicable in clinical trials.

Objective Thresholds of minimal clinically important improvement (MCII) are needed to plan and interpret clinical trials. We estimated MCIIs for the rheumatoid arthritis (RA) activity measures of patient global assessment, pain score, Health Assessment Questionnaire Disability Index (HAQ), Disease Activity Score-28 (DAS28), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Methods In this prospective longitudinal study, we studied 250 patients who had active RA. Disease activity measures were collected before and either 1 month (for patients treated with prednisone) or 4 months (for patients treated with disease modifying medications or biologics) after treatment escalation. Patient judgments of improvement in arthritis status were related to prospectively assessed changes in the measures. MCIIs were changes that had a specificity of 0.80 for improvement based on receiver operating characteristic curve analysis. We used bootstrapping to provide estimates with predictive validity. Results At baseline, the mean (±SD) DAS28-ESR (erythrocyte sedimentation rate) was 6.16±1.2 and mean SDAI was 38.6±14.8. Improvement in overall arthritis status was reported by 167 patients (66.8%). Patients were consistent in their ratings of improvement versus no change or worsening, with receiver operating characteristic curve areas ≥0.74. MCIIs with a specificity for improvement of 0.80 were: patient global assessment −18, pain score −20, HAQ −0.375, DAS28-ESR −1.2, DAS28-CRP (C-reactive protein) −1.0, SDAI −13, and CDAI −12. Conclusions MCIIs for individual core set measures were larger than previous estimates. Reporting the proportion of patients who meet these MCII thresholds can improve the interpretation of clinical trials in RA.

Domain-specific transition questions demonstrated higher validity than global transition questions as anchors for clinically important improvement

OBJECTIVES Estimates of minimal clinically important differences in health measures may be affected by the anchor used. We examined if domain-specific transition questions had higher construct validity than global health transition questions as anchors for measures in a given domain. STUDY DESIGN AND SETTING In a prospective study of 249 patients with rheumatoid arthritis, we examined changes in pain, physical function, joint swelling, stiffness, fatigue, and depression with treatment. We related these changes to a domain-specific transition question, global arthritis transition question, and the Short Form-36 (SF-36) health transition item. RESULTS Changes in all six clinical measures were more highly correlated with the domain-specific transition questions than with the global arthritis question and SF-36 transition question. Discrimination between patients who improved or not was also better using domain-specific questions. Estimates of minimal clinically important improvement (MCII) differed with the anchor when these were based on mean changes. MCII estimates from receiver operating characteristic curve analysis were not influenced by the choice of anchor when anchors had high agreement. CONCLUSION Domain-specific transition questions had higher construct validity as anchors for determining clinically important differences in health measures focused on a single domain than either global disease or general health transition questions.

Dependence of the minimal clinically important improvement on the baseline value is a consequence of floor and ceiling effects and not different expectations by patients

OBJECTIVE Estimates of minimal clinically important improvements (MCIIs) are larger among patients with higher values at baseline, suggesting that these patients require larger changes to appreciate improvements. We examined if baseline dependency of MCIIs was associated with specific patients across three measures, or was owing to floor and ceiling effects. STUDY DESIGN AND SETTING We prospectively examined 250 outpatients with active rheumatoid arthritis (RA). We used an anchor-based approach to estimate MCIIs for three measures of RA activity (patient global assessment, swollen joint count, and walking time). We examined if the same patients constituted the baseline subgroups with high MCIIs across measures. RESULTS The MCIIs were greater for those with higher baseline values of all three measures. At the ceiling, there was little opportunity to improve, and judgments were unrelated to measured changes. At midrange, improvements were balanced by worsenings, including some judged as improvements. At the floor, improvements were not similarly balanced. Patients in subgroups with high MCII for patient global assessment were not also predominantly in subgroups with high MCII for the swollen joint count or walking time, and vice versa. CONCLUSION Variation in MCII by baseline values is because of floor and ceiling effects rather than expectations of particular patients.

Brief Report: Rheumatoid Arthritis Response Criteria and Patient‐Reported Improvement in Arthritis Activity: Is an American College of Rheumatology Twenty Percent Response Meaningful to Patients?

To examine the association of the American College of Rheumatology (ACR) response criteria (20% improvement [ACR20], ACR50, and ACR70) and the European League Against Rheumatism (EULAR) response criteria with patient‐reported improvement in rheumatoid arthritis (RA) activity.

Standards of comparison and discordance in rheumatoid arthritis global assessments between patients and clinicians

Patient‐physician discordance in health status ratings may arise because patients use temporal comparisons (comparing their current status with their previous status), while clinicians use social comparisons (comparing this patients status to that of other patients, or to the full range of disease severity possible) to guide their assessments. We compared discordance between patients with rheumatoid arthritis (RA) and clinicians, using either the conventional patient global assessment (PGA) or a rating scale with 5 anchors describing different health states. We hypothesized that discordance would be smaller with the rating scale because clinicians likely used similar social comparisons when making global assessments.

Origins of Discordant Responses among 3 Rheumatoid Arthritis Improvement Criteria

Objective. We examined agreement between the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), and Simplified Disease Activity Index (SDAI) response criteria in rheumatoid arthritis (RA) and tested whether discordant responses were associated with patients’ baseline characteristics or changes in RA activity encapsulated by the different criteria. Methods. In a prospective longitudinal study, we examined responses of 243 patients with active RA to escalation of antirheumatic treatment. We computed agreement between pairs of response criteria using κ coefficients and identified patient characteristics associated with unique responses to individual criteria. Results. We found that 110 patients (45.3%) had an ACR 20% improvement (ACR20) response, 135 (55.5%) had a EULAR moderate/good response, and 83 (34.1%) had an SDAI50 response. Agreement was moderate to good (ACR20/EULAR κ 0.57; ACR20/SDAI50 κ 0.64; EULAR/SDAI50 κ 0.59). All who had SDAI50 response also had a EULAR response. Patient characteristics at baseline generally did not distinguish those who responded to both, 1, or neither criterion. Discordance was most often because of improvements in the erythrocyte sedimentation rate or C-reactive protein level among EULAR and SDAI50 responders, which were not as common among ACR20 responders. Based on receiver-operating characteristic curves, SDAI35 response had a better balance of sensitivity and specificity relative to ACR20 and EULAR moderate/good responses than SDAI50. Conclusion. Discordant responses to RA improvement criteria are most often because of differences in responses of acute-phase reactants. SDAI35 response had higher sensitivity for improvement, as reflected by other response criteria, than SDAI50 response.

Minimal Clinically Important Improvement of Routine Assessment of Patient Index Data 3 in Rheumatoid Arthritis

Objective. To estimate minimal clinically important improvement (MCII) of RAPID-3 (Routine Assessment of Patient Index Data 3) in rheumatoid arthritis (RA). Methods. RAPID-3 was computed before and after treatment escalation in a prospective study of adults with active RA. Patient judgment of improvement was used as the standard for a receiver-operating characteristic curve, from which MCII was estimated. Results. Mean RAPID-3 improved from 16.3 to 11.1 between visits. MCII was −3.8 based on simultaneously optimized sensitivity and specificity, −3.5 using the 0.80 specificity criterion, and −4.1 using the Youden index. Conclusion. RAPID-3 improvement of 3.8/30 units appears clinically meaningful.

RHEUMATOID ARTHRITIS RESPONSE CRITERIA AND PATIENT-REPORTED IMPROVEMENT IN ARTHRITIS ACTIVITY: Is an ACR20 Response Meaningful to Patients?

To examine the association of the American College of Rheumatology (ACR) response criteria (20% improvement [ACR20], ACR50, and ACR70) and the European League Against Rheumatism (EULAR) response criteria with patient‐reported improvement in rheumatoid arthritis (RA) activity.

Brief Report: Rheumatoid Arthritis Response Criteria and Patient-Reported Improvement in Arthritis Activity: Is an American College of Rheumatology Twenty Percent Response Meaningful to Patients?: RA Response Criteria and Patient-Perceived Improvement

To examine the association of the American College of Rheumatology (ACR) response criteria (20% improvement [ACR20], ACR50, and ACR70) and the European League Against Rheumatism (EULAR) response criteria with patient‐reported improvement in rheumatoid arthritis (RA) activity.