Physician Global Disease Activity Research Articles

Construct validity of PROMIS pain interference, fatigue, and physical function as patient-reported outcomes in adults with idiopathic inflammatory myopathies: An international study from the OMERACT myositis working group

BackgroundValidated patient-reported outcome measures to assess disease impact in patients with adult idiopathic inflammatory myopathies (IIMs) are needed. The objective of this study was to assess the construct validity of PROMIS Pain Interference, Fatigue, and Physical Function measures in comparison with core disease activity measures. MethodsAdults with IIM, excluding inclusion body myositis, from OMERACT Myositis Working Group (MWG) clinic sites completed PROMIS Short Form v1.0—Pain Interference 6a, PROMIS Short Form v1.0—Fatigue 7a, and PROMIS Short Form v2.0—Physical Function 8b measures. Core disease activity measures including patient and physician global disease activity assessments, manual muscle testing, serum creatine kinase activity, and Health Assessment Questionnaire Disability Index (HAQ-DI) were simultaneously assessed. To evaluate construct validity, a priori hypotheses for the expected correlations between PROMIS measures, age, and core disease measures were determined by >70 % agreement among MWG members and were compared against observed Pearson's correlations. Internal consistency of items and floor or ceiling effects for the PROMIS measures were also assessed. Subgroup analysis according to IIM subtype (dermatomyositis vs. non-dermatomyositis IIM) was performed. Results135 adults with IIM from 5 countries across North America, Europe, Asia, and Australia were included. For construct validity, a priori hypotheses were confirmed for 5 of 6 (83 %) PROMIS Pain Interference, 4 of 5 (80 %) PROMIS Fatigue, and 3 of 4 (75 %) PROMIS Physical Function correlations. Internal consistency was high for each PROMIS measure (Cronbach's alpha >0.9). Ceiling effects were observed only for PROMIS Pain Interference, with low/no pain in 29 % of patients. Subgroup analysis between dermatomyositis (n = 65) and non-dermatomyositis (n = 70) subtypes demonstrated similar correlations between PROMIS measures and disease activity measures. ConclusionsPROMIS Short Form v1.0—Pain Interference 6a, PROMIS Short Form v1.0—Fatigue 7a, and PROMIS Short Form v2.0—Physical Function 8b measures demonstrate strong construct validity when compared to core disease activity measures in IIM, with consistent results across IIM subtypes. These findings support the use of these selected PROMIS measures to assess core domains of interest for measuring life impact in IIMs.

Responsiveness and meaningful thresholds of PROMIS pain interference, fatigue, and physical function forms in adults with idiopathic inflammatory myopathies: Report from the OMERACT Myositis Working Group

BackgroundA series of qualitative studies conducted by the OMERACT Myositis Working Group identified pain interference, fatigue, and physical function as highly important life impact domains for adults with idiopathic inflammatory myositis (IIM). In this study, our goal was to assess the responsiveness and minimal important difference of PROMIS pain interference (6a), fatigue (7a), and physical function (8b). MethodsAdults with IIM from USA, Netherlands, Korea, Sweden, and Australia with two "clinical" visits were enrolled in this prospective study. Anchor questions on a Likert scale were collected at baseline, and manual muscle testing (MMT), physician and patient reported global disease activity, and PROMIS instruments were collected at both visits. Responsiveness was assessed with i) ANOVA, ii) paired t-test, effect size and standardized response mean, and iii) Pearson correlation. Minimal important difference (MID), minimal important change (MIC) and minimal detectable change (MDC) values were calculated. Results114 patients with IIM (median age 60, 60 % female) completed both visits. Changes in PROMIS instruments were significantly different among anchor categories. Patients who reported improvement had a significant improvement in their PROMIS scores with at least medium effect size, while patients who reported worsening and stability did not show a significant change with weak effect size. PROMIS instruments had weak to moderate correlations with MMT, patient and physician global disease activity. MID was approximately 2–3 points for Pain Interference and 3–4 points for Fatigue and Physical Functionforms based on the method used. MIC was approximately 4–5 for improvement of all the instruments, while MDC was 1.7–2 points for Pain Interference and Physical Function and 3.2–3.9 for Fatigue. ConclusionThis study provides evidence towards the responsiveness of the PROMIS instruments in a large international prospective cohort of adults with IIM supporting their use as PROMs in adult myositis.

Long-term follow-up of children with chronic non-bacterial osteomyelitis—assessment of disease activity, risk factors, and outcome

IntroductionChronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone-disease of unknown origin. The National Pediatric Rheumatologic Database (NPRD) collects long-term data of children and adolescents with rheumatic diseases including CNO.ObjectiveTo assess characteristics, courses, and outcomes of CNO with onset in childhood and adolescence and to identify outcome predictors.MethodsFrom 2015 to 2021 patients with a confirmed diagnosis of CNO, who were registered in the NPRD during their first year of disease and at least one follow-up visit, were included in this analysis and observed for up to 4 years.ResultsFour hundred patients with recent diagnosis of CNO were enrolled in the NRPD during the study period. After 4 years, patient data documentation was sufficient to be analyzed in 81 patients. A significant decline of clinical and radiological lesions is reported: at inclusion in the registry, the mean number of clinical lesions was 2.0 and 3.0 MRI lesions per patient. A significant decrease of manifestations during 4 years of follow-up (mean clinical lesions 0.5, p < 0.001; mean MRI lesions 0.9 (p < 0.001)) was documented. A significant improvement of physician global disease activity (PGDA), patient-reported overall well-being, and childhood health assessment questionnaire (C-HAQ) was documented. Therapeutically, an increase of disease-modifying anti-rheumatic drugs over the years can be stated, while bisphosphonates rather seem to be considered as a therapeutic DMARD option in the first years of disease. Only 5–7% of the patients had a severe disease course as defined by a PGDA > = 4. Predictors associated with a severe disease course include the site of inflammation (pelvis, lower extremity, clavicle), increased erythrocyte sedimentation rate, and multifocal disease at first documentation. The previously published composite PedCNO disease activity score was analyzed revealing a PedCNO70 in 55% of the patients at 4YFU.ConclusionAn improvement of physician global disease activity (PGDA), patient reported overall well-being and imaging-defined disease activity measures was documented, suggesting that inactivity of CNO disease can be reached. PedCNO score and especially PGDA, MRI-defined lesions and in a number of patients also the C-HAQ seem to be reliable parameters for describing disease activity. The identification of risk factors at the beginning of the disease might influence treatment decision in the future.

Consumer-based activity trackers in evaluation of physical activity in myositis patients.

Inflammatory myopathies are characterized by muscle weakness that limits the activities of daily living. Daily step count is an accepted metric of physical activity. Wearable technologies such as Fitbit® enable tracking of daily step counts. We assessed the psychometric properties of Fitbit® and compared the accuracy of Fitbit® step counts to ActiGraph®. This was a pilot, proof of concept, prospective observational study with four visits at 0, 1, 3 and 6months in PM, DM, necrotizing myopathy (NM) or anti-synthetase syndrome (AS) subjects. Six core set measures (manual muscle testing, physician global disease activity, patient global disease activity, and extra-muscular disease activity, HAQ-Disability Index and creatine kinase), three functional tests (six-min walk, timed up-and-go, sit-to-stand tests) and SF-36 physical function-10 (PF10) were collected at each visit. Patients wore waist-worn Fitbit® One and ActiGraph® T3X-BT concurrently for 7 days/month for 6months. Twenty-four (10 DM, 8 PM/NM, 6 AS) patients (17 females/7 males; 91% Caucasian) were enrolled. Test-retest reliability of daily steps was strong in 1-month follow-up (ICC 0.89). Daily steps and peak 1-min cadence showed moderate-strong correlations with physician global disease activity, patient global disease activity, HAQ-Disability Index, SF-36 PF10 and all three functional tests. Fitbit® and ActiGraph® step counts demonstrated good agreement and strong correlation (ICC 0.96). Fitbit® daily steps and peak 1-min cadence are reliable and valid measures of physical activity in a cohort of myositis patients. This pilot data suggests that Fitbit® has a potential for use in clinical practice and trials to monitor physical activity in myositis patients, but larger studies are needed for further validation.

Reliability, validity and responsiveness of physical activity monitors in patients with inflammatory myopathy

Idiopathic inflammatory myopathies (IIMs) cause proximal muscle weakness, which affects the ability to carry out the activities of daily living. Wearable physical activity monitors (PAMs) objectively assess continuous activity and potentially have clinical usefulness in the assessment of IIMs. We examined the psychometric characteristics for PAM outcomes in IIMs. Adult IIM patients were prospectively evaluated (at baseline, 3 months and 6 months) in an observational study. A waist-worn PAM (ActiGraph GT3X-BT) assessed average step counts/minute, peak 1-minute cadence, and vector magnitude/minute. Validated myositis core set measures (CSMs) including manual muscle testing (MMT), physician global disease activity (MD global), patient global disease activity (Pt global), extramuscular disease activity (Ex-muscular global), HAQ-DI (HAQ disability index), muscle enzymes, and patient-reported physical function were evaluated. Test-retest reliability, construct validity, and responsiveness were determined for PAM measures and CSMs, using Pearson correlations and other appropriate analyses. A total of 50 adult IIM patients enrolled [mean (s.d.) age, 53.6 (14.6); 60% female, 94% Caucasian]. PAM measures showed strong test-retest reliability, moderate-to-strong correlations at baseline with MD global (r = -0.37 to -0.48), Pt global (r=-0.43 to -0.61), HAQ-DI (r = -0.47 to -0.59) and MMT (r = 0.37-0.52), and strong discriminant validity for categorical MMT and HAQ-DI. Longitudinal associations with MD global (r=-0.38 to -0.44), MMT (r = 0.50-0.57), HAQ-DI (r = -0.45 to -0.55) and functional tests (r = 0.30-0.65) were moderate to strong. PAM measures were responsive to MMT improvement ≥10% and moderate-to-major improvement on ACR/EULAR myositis response criteria. Peak 1-minute cadence had the largest effect size and standardized response means. PAM measures showed promising construct validity, reliability, and longitudinal responsiveness; especially peak 1-minute cadence. PAMs are able to provide valid outcome measures for future use in IIM clinical trials.

Soluble IL-2 Receptor in Dermatomyositis: Its Associations with Skin Ulcers and Disease Activity.

Objective To investigate the role of soluble interleukin-2R (sIL-2R) in idiopathic inflammatory myopathies (IIM). Methods Serum sIL-2R levels were measured in 74 dermatomyositis (DM), 16 immune-mediated necrotizing myopathy (IMNM), 24 rheumatoid arthritis (RA), 20 systemic lupus erythematosus (SLE), and 20 healthy controls (HCs) by chemiluminescent immunometric assay. Clinical features and laboratory data were collected from electronic medical record. Disease activity was evaluated by using physician global disease activity and myositis disease activity assessment visual analog scale (MYOACT) on admission. 20 DM patients were followed. Serum sIL-2R levels were analyzed and compared with clinical features, laboratory data, and measures of disease activity. Results Serum sIL-2R levels were significantly higher in DM patients than in IMNM patients and HCs (648.8 ± 433.1 U/ml vs. 352.3 ± 126.0 U/ml and 648.8 ± 433.1 U/ml vs. 285.8 ± 101.9 U/ml, respectively; all P < 0.001), while there was no significant difference between IMNM and HCs. There were also no significant differences of sIL-2R levels in DM, SLE, and RA. Importantly, serum sIL-2R levels were significantly higher in treatment-naïve or active DM patients than those that are not (1100.9 ± 550.4 U/ml vs. 615.6 ± 330.4 U/ml, P = 0.006; 808.8 ± 421.6 U/ml vs. 339.8 ± 103.4 U/ml, P < 0.001). DM patients with skin ulcers had significantly higher sIL-2R levels than those without (889.3 ± 509.9 U/ml vs. 640.0 ± 368.7 U/ml, P = 0.023). Cross-sectional analysis in DM showed that sIL-2R levels positively correlated with CK, ESR, CRP, ferritin, physician VAS, and MYOACT scores (rho = 0.278, rho = 0.474, rho = 0.469, rho = 0.454, r = 0.646, and r = 0.600, respectively; all P < 0.05), negatively correlated with T cell counts and MMT8 scores (r = −0.380, P = 0.002; rho = −0.394, P = 0.001). Follow-up study showed that changes in sIL-2R levels after treatment correlated with changes in physician VAS and MYOACT scores (r = 0.823 and r = 0.695, respectively; all P < 0.01). Conclusion Serum sIL-2R levels were elevated in DM but not in IMNM. Serum sIL-2R could act as a disease activity marker and be associated with ulcerative skin lesions in DM.

The Role of 25-Hydroxyvitamin D as a Predictor of Clinical and Radiological Outcomes in Early Onset Rheumatoid Arthritis.

The aims of this study were to compare the levels of 25-hydroxyvitamin D (25(OH)D) in patients with early-onset rheumatoid arthritis (EORA) versus a healthy control group and to assess the association of 25(OH)D deficiency and the BsmI polymorphism of the vitamin D receptor gene with clinical, radiological, and laboratory parameters. Early-onset RA Colombian patients were enrolled in a 3-year follow-up study. Vitamin D deficiency was diagnosed for 25(OH)D levels of less than 20 ng/mL. Pearson and Spearman correlation coefficients were used to assess data. Seventy patients and 70 matched healthy subjects were included. 25-Hydroxyvitamin D was lower in the EORA group (27.13 [SD, 13.4] ng/mL vs. 33.74 [SD, 16.7] ng/mL; P = 0.01); 31.4% of EORA patients were vitamin D deficient. Remission was higher in subjects without 25(OH)D deficiency (22.7% vs. 47.9%; P = 0.04). Patients with 25(OH)D deficiency at baseline had higher Health Assessment Questionnaire and Physician Global Disease Activity Assessment scores, fatigue levels, erythrocyte sedimentation rate, and morning stiffness after 3 years. At disease onset, only a relationship between 25(OH)D deficiency with fatigue and morning stiffness was found. Neither radiographic progression nor Sharp van der-Heidje score was associated to hypovitaminosis D after 36-month follow-up. The bb genotype was less frequent in patients with vitamin D deficiency (0% vs. 16.6%; P = 0.04). Patients with BB-Bb genotype had lower 25(OH)D and a propensity to more severe disease. Our data provide further support for a role of vitamin D as a clinical biomarker for RA. Baseline 25(OH)D could have potential as a predictor of disease severity in EORA.

Assessment of Global Disease Activity in Rheumatoid Arthritis by Patients and Physicians: Differences Across Countries in the METEOR Database.

The aim of the study was to compare the differences between patient global disease activity (PtGDA) and physician global disease activity (PhGDA) score within and across 13 countries in the METEOR (Measurement of Efficacy of Treatment in the "Era of Outcome" in Rheumatology) database. Data from METEOR were used to compare PtGDA and PhGDA, scored independently on a 100-mm visual analog scale from 0 (best possible) until 100 (worst possible), in 23,117 visits in 5709 anonymized patients during the period between 2008 and 2012. Linear mixed models were used to model mean differences between PtGDA and PhGDA in 13 countries (Brazil, Czech Republic, France, Ireland, Italy, Latvia, Mexico, the Netherlands, Pakistan, Portugal, Spain, United Kingdom, and the United States), adjusted for differences in Disease Activity Score in 28 joints (DAS28). Generalized estimating equations were used to model differences (>20 mm) between PtGDA and PhGDA score as the outcome and countries as determinants, adjusted for DAS28. Mean difference between PtGDA and PhGDA scores varied by country, from -2 mm (physician scores higher) in Mexico to +14 mm (patient scores higher) in Brazil. "Country" was a significant determinant of the difference between PtGDA and PhGDA scores, independent of differences in DAS28. With the Netherlands as reference, PtGDA and PhGDA scores for individual patients differ significantly in almost all (n = 10) countries, with the exception of France and Spain. Differences between patients' and physicians' assessment of GDA vary across the countries. Influence of country must be taken into account when interpreting discordances between the patient's and the physician's assessment of GDA in rheumatoid arthritis.

Biologic predictors of clinical improvement in rituximab-treated refractory myositis.

BackgroundTo examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies (autoAbs) as predictors of disease improvement in refractory myositis patients treated with rituximab.MethodsIn the RIM Trial, all subjects received rituximab on 2 consecutive weeks. Using start of treatment as baseline, serum samples (n = 177) were analyzed at baseline and after rituximab with multiplexed sandwich immunoassays to quantify type-1 IFN-regulated and other pro-inflammatory chemokines and cytokines. Biomarker scores were generated for the following pathways: type-1 IFN-inducible (IFNCK), innate, Th1, Th2, Th17 and regulatory cytokines. Myositis autoAbs (anti-synthetase n = 28, TIF-γ n = 19, Mi-2 n = 25, SRP n = 21, MJ n = 18, non-MAA n = 24, unidentified autoantibody n = 9, and no autoantibodies n = 33) determined by immunoprecipitation at baseline, were correlated with outcome measures. Kruskal-Wallis rank sum tests were used for comparisons.ResultsThe mean (SD) values for muscle disease and physician global disease activity VAS scores (0–100 mm) were 46 (22) and 49 (19). IFNCK scores (median values) were higher at baseline in subjects with anti-synthetase (43), TIF1-γ (31) and Mi-2 (30) compared with other autoAb groups (p < 0.001). At 16 weeks after rituximab, anti-synthetase and Mi-2 autoAb positive subjects and non-MAA had a greater improvement in IFNCK scores (− 6.7, − 6.1 and −7.2, p < .001). Both IFNCK high scores (>30) and autoAb group (Mi-2, non-MAA, and undefined autoantibody) demonstrated the greatest clinical improvement based on muscle VAS (muscle-interaction p = 0.075).ConclusionBiomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab.

THU0444 Assessment of Global Disease Activity in RA by Patients and Physicians: Cultural Differences across Countries in the Meteor Database

BackgroundDissonant perceptions of disease activity between rheumatoid arthritis (RA) patients and their rheumatologists may influence treatment decisions. The discordance between patient's and physician's global disease activity assessment (PtGDA and PhGDA,...

SAT0465 The Myositis Disease Activity Assessment Tool and the Printo Criteria for Clinically Inactive Disease Applied after Long-Term Follow-Up in Juvenile Onset Dermatomyositis.

BackgroundThere is limited knowledge about persistent disease activity and frequency of inactive disease in Juvenile Dermatomyositis (JDM) patients after long-term follow-up.ObjectivesTo apply the Myositis Disease Activity Assessment Tool (MDAAT) and...

SAT0197 B Cell Activating Factor (BAFF) Correlate with Disease Activity and Antibody Levels in Anti-Pm-Scl Positive Patients with Idiopathic Inflammatory Myopathies

BackgroundIncreased serum levels of B cell activating factor (BAFF) have been detected in patients with idiopathic inflammatory myopathies (IIM) [1], which in anti-Jo-1 positive patients correlate with serum autoantibody concentration....

Responsiveness of disease activity indices ESSPRI and ESSDAI in patients with primary Sjögren's syndrome treated with rituximab

ObjectiveTo evaluate the responsiveness of the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in patients with primary Sjögren's syndrome (pSS) treated with...

The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study

IntroductionThe aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).MethodsThis is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.ResultsAfter three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician's global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.ConclusionsThree years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures.

Development of a preliminary composite disease activity index in psoriatic arthritis

ObjectivesTo develop a preliminary composite psoriatic disease activity index (CPDAI) for psoriasis and psoriatic arthritis.MethodsFive domains were assessed and specific instruments were employed for each domain to determine the extent...

Disability progression in multiple sclerosis is slower than previously reported

To investigate disease progression and risk factors in a large geographically based population with multiple sclerosis (MS), using two different inception points--clinical onset and date of birth. The authors reviewed a database of subjects with definite MS and symptom onset prior to July 1988. The main outcome was sustained progression to Expanded Disability Status Scale (EDSS) 6 (requires a cane), using the date of birth and date of MS onset as inception points in separate analyses. Risk factors examined were sex, relapsing vs primary progressive course, onset age, and onset symptoms. The study included 2,837 patients, followed prospectively for 22,723 patient years. The median time to EDSS 6 was 27.9 years, 15 years after onset; only 21% reached EDSS 6, and by age 50, 28% required a cane. Men progressed 38% more quickly than women from onset (p < 0.0005), yet both required canes at similar ages: 58.8 years for men and 60.1 for women (p = 0.082). A younger onset age predicted a slower progression, but those older at onset were consistently older when reaching EDSS 6. A primary progressive course predicted a more rapid progression from both onset (p < 0.0005) and birth (hazard ratio = 2.7 [95% CI: 2.2 to 3.3]). No onset symptom consistently predicted progression. Disability progression in multiple sclerosis (MS) accrued more slowly than found in earlier longitudinal studies. The authors also challenged two fundamental concepts in MS, demonstrating that neither male sex nor older onset age was associated with worse disease outcome.

Decreased aerobic capacity in children with juvenile dermatomyositis

To determine whether patients with juvenile dermatomyositis (DM) have limited aerobic capacity compared with healthy controls. Fourteen juvenile DM patients with inactive to moderately active, stable disease (age range 7-17 years) and 14 age- and sex-matched controls performed a maximal exercise test using a cycle ergometer. Oxygen uptake and power were measured at peak exercise (VO(2peak) and W(peak), respectively) and at anaerobic threshold (AT and W(AT)). Juvenile DM disease activity and damage were also assessed. Patients with juvenile DM had significantly reduced VO(2peak) (19.6 ml O(2)/kg/minute in juvenile DM versus 31.1 ml O(2)/kg/minute in controls), peak heart rate (166 versus 184 beats per minute), W(peak) (1.6 versus 2.7 watts/kg), AT (11.1 versus 18.0 ml O(2)/kg/minute) and W(AT) (0.6 versus 1.4 watts/kg), compared to controls (P <or= 0.05 for each). Aerobic exercise parameters correlated with physician global disease activity and damage, T1-weighted magnetic resonance imaging, and Childhood Myositis Assessment Scale scores (r(s) = 0.58 - 0.82, P <or= 0.05). Patients with juvenile DM with a range of disease activity have a decreased aerobic and work capacity compared to healthy children. Aerobic exercise limitation in juvenile DM correlates best with measures of disease damage (global damage assessment, T1-weighted magnetic resonance imaging, and disease duration). Aerobic exercise testing may be valuable in the assessment of physical endurance, and aerobic training may be indicated as part of the therapeutic regimen in myositis patients with inactive to moderately active, stable disease.

3 Evaluation of early rheumatoid arthritis disease activity and outcome

In rheumatoid arthritis nowadays a more aggressive treatment strategy is followed based on early consistent use of second-line agents frequently given in combination. This approach requires an accurate monitoring of the disease activity to follow the course of the disease and to evaluate therapeutic interventions. International consensus is reached over a core set of disease activity variables, including: a 28-joint count for tenderness and swelling, an acute phase reactant, patient's pain and global disease activity, physician's global disease activity, functional disability and radiographs. Guidelines for measurement techniques need to be further specified. Indices of disease activity are developed to improve the unambiguous interpretation of disease activity and comparability of trial results. These measures can be divided in measures for current disease activity and improvement criteria. Further validation will be necessary to adapt finally a uniform measurement technique. The usefulness of self-administered joint counts needs to be studied further.