Rheumatoid Arthritis Activity Measures Research Articles

POS1455-HPR RELATIONSHIP BETWEEN PSYCHOLOGICAL FACTORS AND MEASURES OF RHEUMATOID ARTHRITIS ACTIVITY

Background:The patient-reported outcomes are important components of quantitative methods of rheumatoid arthritis (RA) activity assessment which are used to choose the appropriate drug therapy. The value of these parameters can be significantly affected not only by the inflammatory process, but also by the psychological characteristics of the patient and, in particular, by hardiness [1].Objectives:To study the relationship between psychological factors and signs of RA activity.Methods:Patients with RA who met the EULAR/ACR 2010 criteria, and observed at the V. A. Nasonova Research Institute of Rheumatology were included. Clinical examination was performed including patient global assessment (PGA), physician global assessment (PhGA), pain measurement on a visual analog scale, tender joint count (TJC), swollen joint count (SJC). The functional status was determined by HAQ, the quality of life – by SF-36 EQ-5D, the nature of pain – by painDETECT, the presence of anxiety and depression – by HADS. Patients also completed Hardiness Survey questionnaire to assess hardiness (HDS) and 3 components of the HDS – commitment (CMT), control (CT) and challenge (CLN). Disease activity was evaluated with DAS28, CDAI, and RAPID3. All patients signed informed consent to participate in the study. Analysis of the data was performed using Spearman’s rank test, Fisher exact test, qui-square and t-tests.Results:85 patients with RA were included. There were 69 women and 16 men. Mean age was 56.7±13.1 years, disease duration – 7.6±2.7 years. 72 patients were positive for rheumatoid factor, 75 – for anti-cyclic citrullinated peptide antibody. CDAI showed high activity in 15, moderate – in 37, low – in 30, and remission in 3 patients, DAS 28 – in 10, 55, 12, and 8, and RAPID3 – in 24, 25, 15, and 21, respectively. 24 patients had subclinically or clinically expressed anxiety and 15 –subclinically or clinically expressed depression (≥8 according to HADS). In 31 patients, the painDETECT questionnaire revealed possible or probable neuropathic pain. Mean HDS was 84.8±21.7, CMT – 38.9±9.2, CT – 29.4±8.6, CLN – 17.3±7.1. These values were comparable with the corresponding population data for this age group. There was a significant inverse correlation between HDS and RA activity measures, including SJC, TJC, DAS28 (p<0.05), pain, PGA, PhGA, CDAI, RAPID3, and HAQ (p<0.01). In addition, HDS and all its components positively correlated with quality of life, assessed by SF-36 and EQ-5D (p<0.01). In patients with subclinically and clinically expressed anxiety and depression, HDS, CMT, and CT were significantly lower than in patients without anxiety and depression (p<0.01), while the values of CLN in these groups did not differ significantly.Conclusion:The results of the present study suggest that low HDS may be one of the significant factors determining RA activity level because it does not allow patients to adapt adequately to a stressful situation produced by the disease.

THU0137 ASSESSING THE MULTIMORBID PROFILE (CIRS) IN RHEUMATOID ARTHRITIS. FIRST RESULTS.

Background:Objectives:To assess the presence and nature of multimorbidity in patients with rheumatoid arthritis (RA) and the impact of multimorbidity on disease activity.Methods:The investigation enrolled 117 patients (mean age, 54.8±14.8 years) with RA according to the 2010 ACR/EULAR criteria, who had been examined and treated at the V.A. Nasonova Research Institute of Rheumatology in 2018–2019. The median disease duration was 5.0 [1.5; 9.5] years; the mean DAS28 score was 5.0±1.3. Documentation and anamnesis data were analyzed with emphasis on associated diseases. The Cumulative Illness Rating Scale (CIRS) was used to assess the profile of multimorbidity.Results:The patients with RA had a high index of the spectrum of multimorbidity; concomitant diseases were detected in 96 (82%) cases.The median number of diseases in one patient was 2 [1; 4], the mean total CIRS score was 6.7±3.3; the median value was 2.5 [1; 6]. The number of concomitant diseases diagnosed before using the CIRS was significantly lower (by 48%; p<0.01) than was found in the investigation conducted.Chronic kidney disease that occurred in almost half (42.5%) of cases was most commonly undiagnosed in the cohort under study; on average, every three patients were not found to have signs of metabolic syndrome (hyperglycemia in 29%, hypercholesterolemia in 20%, obesity in 13.5%), chronic hypoxia (new-onset anemia verified in 24% of cases). In 12% of cases lung damages were not found before using the CIRS. There was a correlation of the quantitative equivalent of multimorbidity with the clinical and laboratory measures of RA activity, including the number of painful joints (r = 0.39; p<0.001), overall patient assessment (r=0.37; p=0.03), physician’s global assessment of disease activity (r = 0.37; p < 0.01), DAS28 (r = 0.42; p<0.001), CDAI (r=0.37; p<0.001), SDAI (r=0.34; p< 0.001), HAQ (r=0.34; p<0.001). The total CIRS score did not differ in patients with early- and advanced- or end-stage RA: 6.6±3.5 and 6.7±3.3, respectively (p=0.9).Conclusion:A systematic screening of multimorbidity should be carried out in all patients with RA. It is advisable to use the CIRS to estimate the prevalence of multimorbidity, its consequences and the risk factors for the development of multimorbidity in the long term.Disclosure of Interests:None declared

Time course of changes in the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis during therapy with an interleukin-6 receptor inhibitor

Objective : to investigate the impact of therapy with the interleukin-6 receptor inhibitor tocilizumab (TCZ) on the time course of changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with rheumatoid arthritis (RA) during a 12-month follow-up period. Subjects and methods . 31 RA patients (26 women and 5 men) with an inadequate response and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included. Their median age was 54 [45; 61] years; the disease duration – 110 [62; 168] months; DAS28 – 6.2 [5.1; 7.1]; SDAI – 35.0 [23.9; 51.0], and CDAI – 30.0 [21.0; 42.0]. All the patients were seropositive for rheumatoid factor (RF), 84% – for anti-cyclic citrulinated peptide (anti-CCP) antibodies. Extra-articular manifestations were found in 54% of patients. Patients with chronic heart failure were not included. The RA patients were found to have a high frequency of traditional risk factors for cardiovascular diseases (CVD): hypertension (75%), dyslipidemia (61%), smoking (17%), overweight (61%), a family history of CVD (36%) , and hypodynamia (68%). Coronary heart disease was diagnosed in 11% of patients. The inefficacy of three or more NSAIDs was noted in 45% of cases; intolerance to previous therapy with NSAIDs was observed in 55%. The patients received TCZ at a dose of 8 mg/kg every 4 weeks: 39% received TCZ alone; 61% – in combination with methotrexate (MTX), the MTX median dose was 20 [18; 25] mg/week. The level of NT-proBNP was measured before and 12 months after TCZ therapy. Results and discussion . After 12 months of treatment with TCZ 54% of patients had disease remission (DAS28 <2.6), 46% – low disease activity (DAS28 <3.2). Median DAS28 value decreased from 6.2 [5.1; 7.1] to 2.7 [1.5; 3.3] (p<0.01), erythrocyte sedimentation rate (ESR) – from 38 [24; 54] to 8 [4; 16] mm/h (p<0.01), C-reactive protein (CRP) – from 27 [10; 49] to 0.5 [0.2; 0.7] mg/L (p<0.01) and NT-proBNP – from 75.8 [43.0; 100.7] to 37.8 [25.1; 78.5] pg/l (p=0.01), although the frequency of its increased values (≥100 pg/ml) remained unchanged (13%). There was a correlation of ΔNT-proBNP with ΔESR (r=0.43; p<0.05) and with ΔCRP (r=0.46; p<0.05). No association was found between ΔNT-proBNP, RA activity measures, RF, and anti-CCP. The level of NT-proBNP in patients treated with TCZ alone and in combination with MTX did not differ considerably. Conclusion . After 12 months of treatment to suppress RA activity, there was a decrease in NT-proBNP levels when TCZ was used alone and in combination with MTX. The lower concentration of NT-proBNP was associated with a reduction in acute phase measures (CRP and ESR). Control of RA activity results in the reduced damaging effect of inflammation on the myocardium.

Translating Treatment Effects Between Rheumatoid Arthritis Activity Measures and American College of Rheumatology Responses in Direct Comparison Trials.

Direct comparison trials in rheumatoid arthritis (RA) increasingly use changes in continuous disease activity measures as endpoints. However, the between-arm differences in these scores that are clinically meaningful are uncertain. To aid interpretation of clinical trials that use the Disease Activity Score in 28 joints (DAS28) or Simplified Disease Activity Index (SDAI) as endpoints, we developed statistical equivalences between changes in these measures and American College of Rheumatology (ACR) responses. For superiority trials, we computed the minimal detectable difference in DAS28 changes and SDAI changes that correspond to the ACR criteria for 20% improvement (ACR20) and 50% improvement (ACR50) responses at the same type I and type II errors and same sample size. For noninferiority trials, we computed noninferiority margins that were statistically equivalent across measures. Standard deviations of the changes in the DAS28 and SDAI from a recent observational study were used as the basis of calculations in our examples. In the base scenario with type 1 error 0.05 and power 0.80, a trial with 300 subjects per arm would detect a 0.31-point difference in mean DAS28 change scores and 3.71-point difference in mean SDAI change scores as statistically equivalent to an absolute difference of 11% in ACR20 between treatment arms. We developed a web-based utility that provides equivalent differences among these measures for customized sample sizes, error rates, and standard deviations of the DAS28 and SDAI between-arm differences. The DAS28 and SDAI responses can be related to statistically equivalent changes in ACR responses, which can aid the interpretation of trials that use these measures.

Assessing the multimorbid profile (CIRS) in rheumatoid arthritis. First results

Objective : to assess the presence and nature of multimorbidity in patients with rheumatoid arthritis (RA) and the impact of multimorbidity on disease activity. Patients and methods . The investigation enrolled 117 patients (mean age, 54.8+14.8years) with RA according to the 2010 ACR/EULAR criteria, who had been examined and treated at the V.A. Nasonova Research Institute of Rheumatology in 2018—2019. The median disease duration was 5.0 [1.5; 9.5] years; the mean DAS28 score was 5.0+1.3. Documentation and anamnesis data were analyzed with emphasis on associated diseases. The Cumulative Illness Rating Scale (CIRS) was used to assess the profile of multimorbidity. Results and discussion . The patients with RA had a high index of the spectrum of multimorbidity; comorbidity was detected in 96 (82%) cases. The median number of diseases in one patient was 2 [1; 4], the mean total CIRS score was 6.7+3.3; the median value was 2.5 [1; 6]. The number of comorbidities diagnosed before using the CIRS was significantly fewer (by 48%; p<0.01) than was found in the investigation conducted. Chronic kidney disease that occurred in almost half (42.5%) of cases was most commonly undiagnosed in the cohort under study; on average, every three patients were not found to have signs of metabolic syndrome (hyperglycemia in 29% and obesity in 13.5%) and chronic hypoxia (new-onset anemia verified in 24% of cases). There was a correlation of the quantitative equivalent of multimorbidity with the clinical and laboratory measures of RA activity, including the number of painful joints (r = 0.39; p<0.001), overall patient assessment (r=0.37; p=0.03), physician's global assessment of disease activity (r = 0.37; p < 0.01), DAS28 (r = 0.42; p<0.001), CDAI (r=0.37; p<0.001), SDAI (r=0.34; p< 0.001), HAQ (r=0.34;p<0.001). The total CIRSscore did not differ in patients with early- and advanced- or end-stage RA: 6.6+3.5 and 6.7+3.3, respectively (p=0.9). Conclusion . A systematic screening of multimorbidity should be carried out in all patients with RA. It is advisable to use the CIRS to estimate the prevalence of multimorbidity and its consequences.

Relationship of epigenetic variability of miR-124 to extracellular matrix remodelling and age-related MMP-3 expression in rheumatoid arthritis

The aim of study was to examine relation among miR-124 and serum levels of selected cytokines and chemokines, MMP-3, production of auto-antibodies, and factors describing clinical activity (DAS28) and radiographic progression in rheumatoid arthritis (RA). A total of 80 RA patients according to the ACR classification criteria, and 32 control subjects were recruited into study. The measurements of miR-124 and U-6 expression, CRP, anti-CCP, rheumatoid factors (RFs), radiographs of both hands with calculation of total sharp score (TSS), DAS28 and cytokines, chemokines and MMP levels in serum were obtained from all RA patients. miR-124 was down-regulated in RA patients compared to controls (7-fold decrease). The miR-124 expression correlated to MMP-3 levels (p < 0.001), which were in multivariate analysis associated to age of RA onset. Higher levels were detected in younger subjects. No relation of miR-124 expression to measures of RA activity (DAS28 score; TSS), auto-antibodies (anti-CCP, RF, RF IgG, RF IgA, RF IgM), acute inflammatory markers (CRP, IL-6), and other cytokine and chemokines (IL-13, IL-15, IL-8, TNF-α, MCP-1, RANTES) was observed. In conclusion, we present a down-regulation of miR-124 in RA patients and its correlation to MMP-3 levels, which associated to age of RA onset.

Polysymptomatic Distress in Patients With Rheumatoid Arthritis: Understanding Disproportionate Response and Its Spectrum

Fibromyalgia (FM) in rheumatoid arthritis (RA) can cause consternation because symptoms are seen to be out of proportion to physician and laboratory assessments, and composite RA activity scores such as the 28 joint Disease Activity Score, Clinical Disease Activity Index, and Routine Assessment of Patient Index Data 3 (RAPID-3) can yield apparently "wrong" results. We explored the effect of polysymptomatic distress (PSD), a measure of fibromyalgianess and a quantity derived from the American College of Rheumatology 2010 FM diagnostic criteria, to explain the relationship of patient to physician variables. We obtained PSD scores on 300 RA patients prior to ordinary clinical care, and assessed the associations of PSD with tender and swollen joints, physician global estimate of RA activity, pain, Health Assessment Questionnaire score, and composite RA activity measures during routine clinic assessments. PSD scores greater than the sample mean (8.8) were associated with increased patient symptoms regardless of the presence or absence of FM, while scores below the mean were associated with better patient outcomes. PSD scores predicted all patient outcomes and less strongly predicted physician outcomes. The discrepancy between patient and physician measures was greatest at low levels of physician-estimated disease activity. PSD rather than FM diagnosis more usefully identifies and predicts disproportionate responses. Just as there are patients who lean disproportionately toward greater severity, there are also patients who disproportionately report milder symptoms. Composite measures used to assess RA are flawed, as they confound RA inflammation and patient distress, and more consideration should be given to disaggregated assessments. PSD also appears to be influenced weakly by RA disease activity.

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

ObjectiveThresholds 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...

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

ObjectiveEstimates 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 SettingWe 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. ResultsThe 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. ConclusionVariation in MCII by baseline values is because of floor and ceiling effects rather than expectations of particular patients.

Relation of IL‐6, IL‐13 and IL‐15 gene polymorphisms to the rheumatoid factors, anti‐CCP and other measures of rheumatoid arthritis activity

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL-6, IL-13 and IL-15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti-CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL-6, IL-13 and IL-15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL-15 -267C/T polymorphism. A higher prevalence of heterozygote variants of IL-15 polymorphisms (14035A/T and -267C/T) in the RF IgG- and RF IgA-negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL-15 with circulating level of IL-15 (14035A/T and 367G/A) and with total RF and Ig-specific RFs (-267C/T) was found. The relation of IL-15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL-13 polymorphism -1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL-15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL-15 levels in circulation to RFs.

AB0404 Rheumatoid arthritis: What are the predictors of rheumatologists’ “usual care” management?

BackgroundTreat to target strategy trials have been shown to improve patient outcomes in the research setting. However, a general goal in exploring targeted therapy in rheumatoid arthritis (RA) will continue...

THU0003 Correlation of MIR-124 to Extracellular Matrix Protein MMP-3 in Patients with Rheumatoid Arthritis

BackgroundMicroRNAs (miRNAs) are a 21 to 25 nucleotide long, small non-coding RNAs that post-transcriptionally regulate the expression of target genes, and thus modulate biological processes including cell differentiation, proliferation, apoptosis...

Measures of Rheumatoid Arthritis Disease Activity in Australian Clinical Practice

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

Comparison of the Construct Validity and Sensitivity to Change of the Visual Analog Scale and a Modified Rating Scale as Measures of Patient Global Assessment in Rheumatoid Arthritis

Patient global assessment (PGA) is commonly measured using a visual analog scale (VAS). The VAS asks patients to integrate many dimensions of rheumatoid arthritis (RA) activity, yet its scope is poorly defined and its endpoints are vague. We investigated whether a modified Rating Scale that used marker states and more defined endpoints would provide a more valid measure of PGA. In our prospective longitudinal study, 164 patients with active RA rated their global arthritis activity using the VAS and Rating Scale before and after treatment. To compare construct validity, we correlated each score with 2 reference measures of RA activity, the 28-joint count Disease Activity Score (DAS28) and the physician global assessment, and examined how each measure was associated with different aspects of RA activity, including pain, functioning, and depressive symptoms, in multivariate regression analyses. We also examined sensitivity to change. Both measures were correlated with the DAS28 (r = 0.39 for VAS; r = 0.35 for Rating Scale) and physician global assessment (r = 0.41 for VAS; r = 0.26 for Rating Scale) at the baseline visit. Pain and depressive symptoms had the strongest association with the VAS, while functional limitations and depressive symptoms had the strongest association with the Rating Scale. Residual analysis showed no differences in heterogeneity of patients' ratings. VAS was more sensitive to change than the Rating Scale (standardized response means of 0.55 and 0.45). As measures of PGA, the VAS and Rating Scale had comparable construct validity, but differed in which aspects of arthritis activity influenced scores. VAS was more sensitive to change.

An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status

This prospective open-label pilot study evaluated the effectiveness and safety of adalimumab and the relationship to antibodies against infliximab (IFX) in adult patients with active rheumatoid arthritis (RA) who had been treated previously with IFX and experienced treatment failure owing to lack or loss of response or intolerance. Patients self-administered adalimumab 40 mg subcutaneously every other week for 16 weeks, followed by maintenance therapy for up to Week 56. Measures of effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, 28-joint Disease Activity Score, and the Health Assessment Questionnaire Disability Index. Serum IFX concentrations, human antichimeric antibody against IFX (HACA), adalimumab serum concentrations, antiadalimumab antibody, and safety also were assessed. Of the 41 enrolled patients, 37 completed 16 weeks and 30 completed 56 weeks of treatment. Patients experienced clinically meaningful improvements in all measures of RA activity, with greater response rates observed for patients who had experienced loss of initial response to or intolerance of IFX. At Week 16, 46% of patients achieved an ACR20 and 28% achieved an ACR50; 61% achieved an at least moderate and 17% achieved a good EULAR response. Clinical benefit was maintained through Week 56 in all effectiveness parameters. Baseline HACA status did not significantly impact effectiveness. No new safety signals were observed; neither former IFX intolerance status nor baseline HACA status had a clinically relevant impact on adverse event frequency or severity. Adalimumab was effective and well-tolerated in patients with RA who previously failed IFX therapy, irrespective of reason for discontinuation and of HACA status.

Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

Assessing the relative sensitivity to change of rheumatoid arthritis activity measures: Is the type of treatment an important third variable?

Observational studies and meta-analyses of controlled clinical trials have been used to identify which measures of rheumatoid arthritis activity are most sensitive to change. These analyses often pool studies of different drugs, although it is not known if arthritis activity measures are differentially responsive to different drugs. In meta-analyses, estimates of the relative sensitivity to change of different measures may also be confounded by differences in drug efficacy, if studies of different drugs contribute different measures to the meta-analysis. To determine if the type of treatment acts as an important effect modifier or confounder in studies of the relative sensitivity to change of arthritis activity measures, we computed effect sizes for four measures (weighted tender joint count, grip strength, duration of morning stiffness, and erythrocyte sedimentation rate) used in each of 16 trials of five different disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, cyclosporin A, intramuscular gold, and D-penicillamine) in rheumatoid arthritis. In a complete factorial analysis of variance, effect sizes differed significantly among drugs ( p = 0.0006), but differed only marginally among measures ( p = 0.08). No interaction was detectable between drugs and measures. These results suggested that effect modification by drugs was not present, but that pooled estimates of the sensitivity to change of different measures may be confounded in meta-analyses, if trials of more efficacious drugs contribute different measures than trials of less efficacious drugs. In a similar analysis of 26 trials of nine nonsteroidal anti-inflammatory drugs, we found significant differences in effect sizes among measures ( p < 0.0001), but no differences among drugs ( p = 0.96), and no interaction between drugs and measures. This study suggests that pooled analyses of the relative sensitivity to change of arthritis activity measures based on trials of different disease-modifying drugs may be confounded by drug effects, but confounding by drug effects is unlikely if these meta-analyses are based on trials of different nonsteroidal anti-inflammatory drugs. Although the power of these analyses to detect small interaction effects was limited, effect modification by drugs was not observed, indicating that the measures we examined were not strongly differentially responsive to different drugs.