Prediction of ineffectiveness of biological drugs using machine learning and explainable AI methods: data from the Austrian Biological Registry BioReg.

OBJECTIVES: Machine learning models can support an individualized approach in the choice of bDMARDs. We developed prediction models for 5 different bDMARDs using machine learning methods based on patient data derived from the Austrian Biologics Registry (BioReg). METHODS: Data from 1397 patients and 19 variables with at least 100 treat-to-target (t2t) courses per drug were derived from the BioReg biologics registry. Different machine learning algorithms were trained to predict the risk of ineffectiveness for each bDMARD within the first 26 weeks. Cross-validation and hyperparameter optimization were applied to generate the best models. Model quality was assessed by area under the receiver operating characteristic (AUROC). Using explainable AI (XAI), risk-reducing and risk-increasing factors were extracted. RESULTS: The best models per drug achieved an AUROC score of the following: abatacept, 0.66 (95% CI, 0.54-0.78); adalimumab, 0.70 (95% CI, 0.68-0.74); certolizumab, 0.84 (95% CI, 0.79-0.89); etanercept, 0.68 (95% CI, 0.55-0.87); tocilizumab, 0.72 (95% CI, 0.69-0.77). The most risk-increasing variables were visual analytic scores (VAS) for abatacept and etanercept and co-therapy with glucocorticoids for adalimumab. Dosage was the most important variable for certolizumab and associated with a lower risk of non-response. Some variables, such as gender and rheumatoid factor (RF), showed opposite impacts depending on the bDMARD. CONCLUSION: Ineffectiveness of biological drugs could be predicted with promising accuracy. Interestingly, individual parameters were found to be associated with drug responses in different directions, indicating highly complex interactions. Machine learning can be of help in the decision-process by disentangling these relations.

The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands in Daily Clinical Routines-Its Sensitivity to Change and Preliminary Patient Relevant Variation Values: A Pilot Study.

OBJECTIVE: The SF-SACRAH was developed to assess the involvement of the hand in rheumatoid arthritis (RA) and hand osteoarthritis (HOA) patients in daily clinical routines. In this pilot study, its sensitivity to change will be assessed longitudinally, and preliminary thresholds for patient relevant changes are derived. METHODS: Ninety-nine outpatients suffering from HOA (n = 55) or RA (n = 44) completed the SF-SACRAH once initially. After approximately 3 months, patients repeated the SF-SACRAH. At both visits, patients rated their satisfaction (PATSAT) with the state of their disease (1 = very good to 5 = unsatisfactory). For assessing its sensitivity to change, SF-SACRAH changes in patients with stable, improving, or worsening conditions according to PATSAT were calculated in HOA and RA patients. The respective medians and highest values were used to estimate patient relevant variation values. SF-SACRAH changes and positive or negative PATSAT changes in HOA as well as RA patients were analyzed by applying the Kruskal-Wallis test. In RA patients, the DAS28 was also calculated. Spearman's rho was calculated to correlate SF-SACRAH changes with the EULAR response criteria. RESULTS: In HOA and RA patients, a statistically high correlation between PATSAT changes and SF-SACRAH values was revealed (p < 0.0001 in HOA and p < 0.01 in RA patients, respectively). The median changes in SF-SACRAH in patients with improving, stable, or worsening conditions according to PATSAT were HOA patients: PATSAT improving: ΔSF-SACRAH -1.6, PATSAT stable: ΔSF-SACRAH +0.8, PATSAT worsening: ΔSF-SACRAH +1.0; RA patients: PATSAT improving: ΔSF-SACRAH -0.9, PATSAT stable: ΔSF-SACRAH +0.2, PATSAT worsening: ΔSF-SACRAH +0.8. In RA patients, there is a moderate, but significant, correlation between DAS28 EULAR response criteria and SF-SACRAH changes (ΔDAS28 improving >0.6: ΔSF-SACRAH -0.4, ΔDAS28 <0.6: ΔSF-SACRAH +0.0, ΔDAS28 worsening >0.6: ΔSF-SACRAH +0.5; r = 0.433, p < 0.01). CONCLUSION: The SF-SACRAH constitutes a reliable tool for the assessment of hand impairment in patients with chronic rheumatic diseases. It proved to be sensitive to change in this short-term evaluation in both HOA and RA patients. Additionally, preliminary patient variation values for improvement (-1.60) and deterioration (+1.0) could be derived.

Improving inflammatory arthritis management through tighter monitoring of patients and the use of innovative electronic tools.

Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists.

RADAI-5 and electronic monitoring tools.

Tighter monitoring of patients is regarded one of the key approaches to improve management of rheumatoid arthritis (RA). It could be demonstrated that the patient relevant disease course is not simply the linear link between two observation points, but fluctuates significantly in up to 80% of patients surveyed three times over two months, which understandably compromises quality of life. Patient self-report questionnaires such as the Rheumatoid Arthritis Disease Activity Index-Five (RADAI-5) have been shown to provide reliable information about disease activity, functionality, and other important aspects of daily life. The internal consistency of such questionnaires was shown to be significantly higher than the one of the DAS28 or the CDAI. Innovative electronic tools can be easily foreseen to constitute the media to enhance the dialogue between healthcare professionals and patients to improve disease care. These tools collect patient-recorded outcomes (PROs) data, through which physicians can monitor the course of the individual disease. Electronic versions can enable patients to receive additional medical attention between visits and provide a more detailed record of disease course over time. Applying the RADAI-5 or other questionnaires in electronic assessment tools will allow for the individual assessment of health levels, well-being, joint pain and the quality of life. Such tools will enable more frequent patient monitoring, with the potential to improve the patient's situation as well as to enhance physicians' time management, and to prioritise patients who may need further attention.

Validity of data collected in BIOREG, the Austrian register for biological treatment in rheumatology: current practice of bDMARD therapy in rheumatoid arthritis in Austria.

BACKGROUND: The purpose of the present study was to check the validity of data collected in BIOREG, the Austrian register for biological treatment in rheumatology, and to elucidate eventual differences with respect to disease activity (DA) in patients with rheumatoid arthritis (RA) on established biological DMARDs (bDMARDs) before inclusion into the register (EST) and beginners at the time point of inclusion (NEW) after 1 year of treatment. METHODS: RA patients with a complete follow-up of 1 year in BIOREG were divided into EST and NEW and compared with respect to DA, remission rates, concomitant synthetic DMARDs (csDMARDs) and glucocorticoid therapy (GC) at baseline and after 1-year follow-up. Safety concerns are listed. Descriptive statistics are applied. RESULTS: For 346 RA patients (284 EST, 62 NEW) out of 970 RA patients included into BIOREG, a full data set for a 1-year follow-up was available. No differences in DA were observed after 1 year as expressed by DAS28 or RADAI-5, and small differences as expressed by remission rates according to DAS28, RADAI-5 or Boolean criteria (namely approximately 1/2, 1/3 to 1/4 and 1/4 to 1/5 of the patients respectively). Sixty-four adverse events (AEs) were noted in 56 (20 %) of EST and 20 in 19 (31 %) of NEW patients. Malignancy occurred in four patients. After 1 year, 48 % of EST patients but only 16 % of NEW patients were on bDMARD monotherapy. CONCLUSION: Regarding DA, the date collected in BIOREG appeared to be valid. After 1 year of bDMARD therapy, all patients, whether EST or NEW, achieved a similar level of DA. AEs occurred more frequently during the early phase of bDMARD treatment. Austrian rheumatologists initiate bDMARD therapy in patients with lower disease levels than in other European countries, leading to high remission rates.

Patient-centered psoriatic arthritis (PsA) activity assessment by Stockerau Activity Score for Psoriatic Arthritis (SASPA).

BACKGROUND: To investigate whether a modified Rheumatoid Arthritis Disease Activity Index-5 could be applied as a routine assessment tool for psoriatic arthritis (PsA) patients. METHODS: Ninety-seven PsA outpatients (mean age 49.78 years; age range 23-80 years; 49 male, 48 female), completed a prototype questionnaire. Tender and swollen joint counts, including enthesiopathy, physician's assessment of disease activity on a visual analog scale (MDglob), erythrocyte sedimentation rate, and patient satisfaction with disease status (PatSat: 1 = excellent to 5 = unsatisfactory) were recorded. Factorial analysis was performed and alpha, as a measure of reliability, and tau were calculated. The ultimate five-item questionnaire, calculated by (Q1 + Q2 + Q3 + Q4 + Q5)/5, was then handed over to 152 PsA outpatients (mean age 54.02 years; age range 26-80 years; 82 male, 70 female), and analyzed accordingly. RESULTS: Analyzing the internal consistency of the prototype questionnaire revealed the highest alpha value of 0.849, on deleting the question targeting disease course. Alpha for the final Stockerau Activity Score for Psoriatic Arthritis (SASPA) was 0.875, with all items contributing to the final result (item loading from 0.573 to 0.910). Kendall's tau for the relationship between SASPA scores and swollen joint count, tender joint count, and MDglob was 0.34, 0.416, and 0.392, respectively. The sensitivity of the questionnaire to change was demonstrated in patients starting treatment with a tumor necrosis factor blocker (standardized mean difference: 2.1). CONCLUSION: The SASPA questionnaire constitutes a fully patient-administered tool to monitor PsA activity. Its reliability, convergent validity, and sensitivity to change were demonstrated.

Remission in rheumatoid arthritis: a comparison of the 2 newly proposed ACR/EULAR remission criteria with the rheumatoid arthritis disease activity index-5, a patient self-report disease activity index.

OBJECTIVE: We analyzed whether a patient self-report remission criterion, such as that according to the Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5), meets the criteria of the 2011 proposed American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) definition of remission. METHODS: The 2 approaches of the ACR/EULAR proposal [Boolean- and Simplified Disease Activity Index (SDAI)-based] as well as the RADAI-5 were used to assess whether patients with RA are in remission. Sensitivity, specificity, positive and negative predictive values (PPV, NPV), and kappa analyses were performed to illustrate the relationship among the different approaches defining remission at a group level. RESULTS: In total, 705 patients' assessments were included. Eighty-nine patients were classified as being in remission according to the Boolean-based and 169 according to the SDAI-based definition of the ACR/EULAR proposals, and 154 according to the RADAI-5. Sixty-eight assessments were classified as being in remission according to all 3 definitions. In the case of RADAI-5 remission, sensitivity was 78%, specificity 86%, PPV 45%, and NPV 96%, indicating remission according to the Boolean-based definition; and 60%, 92%, 66%, and 90%, respectively, indicating remission according to the SDAI-based definition. In the case of remission according to the SDAI-based ACR/EULAR definition, sensitivity was 52%, specificity 100%, PPV 98%, and NPV 87%, also indicating remission according to the Boolean definition; while according to the Boolean definition the values were 98%, 87%, 52%, and 100%, respectively. Kappa statistics showed fair to good agreement for all 3 definitions. CONCLUSION: Nearly twice as many assessments were classified as being in remission using the SDAI-based or the RADAI-5 definitions when compared to the Boolean-based definition. Remission according to the RADAI-5 also was highly specific for both ACR/EULAR criteria. Sensitivity for the RADAI-5 criterion was even better for the Boolean-based definition than that for the SDAI-based definition.

[Prophylaxis and therapy of the glucocorticoid-induced osteoporosis - a review of recent guidelines]. / Prophylaxe und Therapie der Glukokortikoid-induzierten Osteoporose - rezente Leitlinien im Überblick.

Several international guidelines for treatment and prophylaxis of glucocorticoid-induced osteoporosis (GIO) have been published. Consistent with the development of new therapeutic agents, a different approach to treatment can be recognized depending on the year of publication. Also, new insights for the postmenopausal osteoporosis leave their marks on recent guidelines. The working committee on Osteology of the Austrian Society for Rheumatology and Rehabilitation (ÖGR) sifted through actual guidelines and recent literature on the topic to develop recommendations for the prophylaxis and treatment of the GIO.

The use of tumour necrosis factor alpha-blockers in daily routine. An Austrian consensus project.

To define relevant disease parameters and their respective limits indicating the initiation of TNF-alpha-blockers in individual patients. Subsequently, to analyze retrospectively patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), who started TNF-alpha inhibition in 2006. Points to consider, regarded relevant for individual treatment decisions as well as their assessment methods, were ascertained by experts' consensus applying the Delphi technique. Subsequently, these parameters' thresholds with respect to the initiation of a TNF-alpha-blocker were identified. Thereafter, the rheumatologists representing 12 centres all over Austria agreed to retrospectively analyze their patients started on a TNF-alpha-blocker in 2006. Experts' opinion regarding disease parameters relevant to initiate TNF-alpha-blockers in RA patients only slightly differed from those applied in clinical trials, but the parameters' threshold values were considerably lower. For PsA patients, some differences and for AS patients, considerable differences between experts' opinion and clinical studies appeared, which held also true for decisive parameters' means and thresholds. Six hundred and fifty patients, started on TNF-blockers in 2006, could be analyzed retrospectively, 408 RA patients (53.3 years mean, 340 females), 93 PsA patients (48.9 years mean, 59 males) and 149 AS patients AS (42.2 years mean, 108 males), representing approximately 25% of all Austrian patients initiated on a TNF-blocker in this respective year. Far more individualized, patient-oriented treatment approaches, at least in part, are applied in daily routine compared with those derived from clinical trials or recommendations from investigative rheumatologists.

A comparison of patient questionnaires and composite indexes in routine care of rheumatoid arthritis patients.

OBJECTIVE: To evaluate the agreement between the Routine Assessment of Patient Index Data 3 (RAPID-3) and a modified version of the Rheumatoid Arthritis Disease Activity Index (RADAI-5), as well as the Disease Activity Score including a 28 joint count (DAS28-ESR) and the Clinical Disease Activity Index (CDAI) in daily routine. METHODS: One hundred and twenty-eight rheumatoid arthritis (RA) out-patients completed the RADAI-5 and the RAPID-3. Simultaneously, the DAS28-ESR and the CDAI were applied. Cronbach's Alpha as a measure for reliability was calculated and factorial analysis was performed. For agreement analysis, Kendall's Tau was calculated. RESULTS: Time to score the questionnaires was 25seconds. The median RADAI-5 was 2.8 (0-9.2), the median RAPID-3 3.3 (0-8.6), the median DAS28-ESR 2.95 (0.43-6.24), and the median CDAI 5.6 (0-37.5). Cronbach's Alpha for the RADAI-5 was 0.906 and 0.871 for the RAPID-3, however, only 0.165 for the DAS28-ESR and 0.210 for the CDAI, respectively. Factorial analysis revealed that both questionnaires and the DAS28-ESR, but not the CDAI, constitute mono-dimensional instruments. Tau for the agreement between the RADAI-5 and the RAPID-3 appeared to be 0.587 (p<0.001), and to be 0.582 (p<0.001) between the DAS28-ESR and the CDAI, while it was lower for the relationship between the questionnaires and the composite indexes. CONCLUSION: Reliability of the RAPID-3 and RADAI-5 was significantly higher than of the indexes. The questionnaires as well as the indexes proved to be in highly moderate agreement, while agreement between the questionnaires and the indexes appeared to be lower.

The rheumatoid arthritis disease activity index-5 in daily use. Proposal for disease activity categories.

OBJECTIVE: To establish thresholds for rheumatoid arthritis (RA) activity categories according to the RA Disease Activity Index-5 (RADAI-5). METHODS: Three hundred ninety-two patients with RA were categorized according to Disease Activity Score 28-joint count (DAS28), Clinical Disease Activity Index (CDAI), and their satisfaction (PATSAT) with disease status. These measures built the basis for the calculation of disease activity limits for the RADAI-5. Patient assessments simultaneously meeting the identical DAS28, CDAI, and PATSAT categories were taken as the references to establish the thresholds for the respective RADAI-5 categories by calculating the third quartile of the corresponding RADAI-5 values. Subsequently, these new thresholds were applied to all assessments. RESULTS: Seven hundred fifty-eight assessments in 392 patients (2 assessments median/patient) could be obtained, most patients having mild to moderate disease according to DAS28 and CDAI. Calculating the third quartile, the RADAI-5 thresholds were as follows: 0.0-1.4 for a remission-like state, 1.6-3.0 for mild disease activity, 3.2-5.4 for moderate, and 5.6-10.0 for high disease activity. Categorization according to the RADAI-5 showed a normal distribution, while DAS28 and CDAI were somewhat shifted to the left. DAS28 and CDAI levels, as well as tender and swollen joint counts and physician's global assessment and erythrocyte sedimentation rate, proved to be highly significantly different within the different RADAI-5 categories (Kruskal-Wallis test p < 0.001). CONCLUSION: RADAI-5 thresholds for RA activity could be elaborated. Patient self-report questionnaires may substitute composite disease activity scores and may contribute significantly to improving documentation in routine patient care.

A comparison of the modified score for the assessment of chronic rheumatoid affections of the hands and the australian/canadian osteoarthritis hand index in hand osteoarthritis patients.

Objectives. To compare the modified score for the assessment and quantification of chronic rheumatoid affections of the hands (M-SACRAH) with the Australian/Canadian osteoarthritis hand index (AUSCAN) in hand osteoarthritis (HOA). Both are self-administered patient questionnaires, being designed to assess functional status, stiffness, and pain in affected patients, despite some differences in format, compass and arrangement of questions. Methods. 66 HOA patients (51 females), attending the outpatient clinic, were included. Patients completed the AUSCAN (15 visual analogue scales) (VAS) and the M-SACRAH (12 VAS). Results. AUSCAN-pain amounted to a mean of 41.9 (+/-2.9 SEM), AUSCAN-stiffness to 53.1 (3.7) and AUSCAN function to 42.6 (3.2). M-SACRAH-function amounted to 25.4 (2.4), M-SACRAH-stiffness to 42.6 (3.0), and M-SACRAH-pain to 43.7 (3.1). The total mean M-SACRAH was 37.2 (2.4) (all P's < .0001). The three respective domains of the two scores correlated significantly: pain: r = 0.73, stiffness: r = 0.75, and function: r = 0.76 (all P's < .0001). The four identical items in both scores also correlated significantly. No significant gender specific differences were observed. Conclusion. Despite a different scope of items, a significant high correlation of these two scores evaluating HOA patients could be demonstrated. We conclude that both scores are equivalently valuable for the assessment of health status in these patients.

Patient-centered rheumatoid arthritis disease activity assessment by a modified RADAI.

OBJECTIVE: To evaluate the psychometric properties and validity of a modified version of the Rheumatoid Arthritis Disease Activity Index (RADAI) without joint counts in order to facilitate rapid and easy RA activity assessment in daily routine. METHODS: One hundred sixty-nine outpatients with RA completed the original RADAI and the modified RADAI-5. Simultaneously, the Disease Activity Score-28-erythrocyte sedimentation rate (DAS28-ESR) and C-reactive protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI) and Clinical DAI (CDAI) were applied. Cronbach's alpha, as a measure for internal consistency, and Spearman's rho, to evaluate the linear relationship of the different disease activity scales, were calculated. Rho was determined for the RADAI-5 and the core set measures to assess convergent validity. For agreement analysis, kappa statistics were calculated. An attempt was made to estimate the modified questionnaire's sensitivity to change. RESULTS: Means for the RADAI and the RADAI-5 were 2.8 (range 0.0-9.12) and 3.07 (0-10), respectively. Other means were as follows: DAS28-ESR 3.51 (0.28-6.67), DAS28-CRP 3.19 (1.12-5.83), CDAI 11.53 (0.0-44.6), and SDAI 12.36 (0.1-44.9). Cronbach's alpha was highest for the RADAI-5 (0.917) and lowest for the DAS28-CRP (0.510). The RADAI-5 was highly significantly correlated (all p < 0.0001) to all other instruments. However, kappa was < 0.65 for the relation of the RADAI-5 and all other scores except the RADAI. Changes of the RADAI-5, DAS28-ESR, and CDAI were significantly correlated (p < 0.001). CONCLUSION: The RADAI-5, refraining from joint counts, was shown to be capable of measuring RA activity. Reliability and convergent validity could be proven.

Disease activity score-28 values differ considerably depending on patient's pain perception and sex.

OBJECTIVE: To determine if the Disease Activity Index including a 28-joint count (DAS28) is equally applicable for the total population with rheumatoid arthritis (RA). METHODS: Five hundred fifty-seven outpatients with RA [432 women, 125 men; median age 64 yrs (range 0-85), median disease duration 48 mo (range 2-548)] were enrolled consecutively into this cross-sectional study. DAS28, physician's global assessment of disease activity, patient's assessment of pain on visual analog scale, C-reactive protein (mg/dl), rheumatoid factor (RF), and disease duration were recorded. t-tests were applied for all comparisons of DAS28 values. Linear regression analysis was performed for each confounding factor. RESULTS: The mean DAS28 in female patients was 3.66 +/- 0.57 SEM, and in males 3.01 +/- 1.12 (p < 0.001). DAS values in patients with early RA (< 37 mo) were significantly higher than in patients with advanced RA (3.62 +/- 0.67 vs 3.37 +/- 0.81, respectively; p < 0.017). Regression analysis revealed a highly significant relationship between DAS28 score and patient's pain rating (r = 0.592, p < 0.0001). Pain exerted the greatest influence on the DAS28 (p < 0.0001), while of the other factors only age (p < 0.008 for females, p < 0.007 for males) was also significantly correlated with the DAS28 values. CONCLUSION: DAS28 values differ considerably depending primarily on the patient's pain perception and gender and to a lesser degree on patient's age, whereas results for disease duration and RF were inconclusive.

The polymyalgia rheumatica activity score in daily use: proposal for a definition of remission.

OBJECTIVE: To confirm the reliability and applicability of the Polymyalgia Rheumatica Disease Activity Score (PMR-AS), and to establish a threshold for remission. METHODS: First, 78 patients with PMR (50 women/28 men, mean age 65.97 years) were enrolled in a cross-sectional evaluation. The PMR-AS, patient's satisfaction with disease status (PATSAT; range 1-5), erythrocyte sedimentation rate (ESR; first hour), and a visual analog scale of patients' general health assessment (VAS patient global; range 0-100) were recorded. Subsequently, another 39 PMR patients (24 women/15 men, mean age 68.12 years) were followed longitudinally. Relationships between the PMR-AS, PATSAT, ESR, and VAS patient global were analyzed by the Kruskal-Wallis test, Spearman's rank correlation, and kappa statistics. PMR-AS values in patients with a PATSAT score of 1 and a VAS patient global <10 formed the basis to establish a remission threshold. RESULTS: PMR-AS values were significantly related to PATSAT (P < 0.001), VAS patient global (P < 0.001), and ESR (P < 0.01). PATSAT and VAS patient global were reasonably different (kappa = 0.226). The median PMR-AS score in patients with PATSAT score 1 and VAS patient global <10 was 0.7 (range 0-3.3), and the respective 75th percentile was 1.3. To enhance applicability, a range from 0 to 1.5 was proposed to define remission in PMR. The median ESR in these patients was 10 mm/hour (range 3-28), indicating external validity. CONCLUSION: We demonstrated the reliability, validity, and applicability of the PMR-AS in daily routine. Moreover, we proposed a remission threshold (0-1.5) founded on patient-dependent parameters.

The Disease Activity Score in 28 joints in rheumatoid arthritis and psoriatic arthritis patients.

OBJECTIVE: To assess the factorial structure of the Disease Activity Score including a 28-joint count (DAS28) if applied in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: DAS28 values from 85 consecutive PsA outpatients and 2 RA patient cohorts comprising 85 patients each were compared. The first RA cohort (RA1) consisted of age- and sex-matched patients seen during the same period as the patients with PsA. The first 85 RA outpatients from September 2003 were included in the second cohort (RA2). Item weighting, factor loading, and internal consistency were assessed by factor analysis, principal component analysis, and calculation of Cronbach's alpha. RESULTS: The mean +/- SD DAS28 scores of patients in the PsA, RA1, and RA2 cohorts were 3.2 +/- 1.31, 3.21 +/- 1.45, and 3.79 +/- 1.44, respectively. A significant difference between the PsA and RA2 cohorts was found for DAS28 (P = 0.0063), swollen joint count (P = 0.007), and patient's global assessment (P < 0.001), but not for erythrocyte sedimentation rate. Internal consistency of the DAS28 in patients with PsA was considerably lower, item weighting showed remarkable differences, and factor analysis revealed that the DAS28 constitutes a bidimensional instrument in patients with PsA, whereas in both RA cohorts it appeared to be monodimensional. CONCLUSION: With respect to its statistical properties, the DAS28 proved to be considerably different in PsA compared with RA. Therefore its application for disease activity assessment in patients with PsA cannot be recommended without a formal validation procedure.

A meta-analysis of controlled clinical studies with diacerein in the treatment of osteoarthritis.

BACKGROUND: This systematic meta-analysis on randomized controlled trials with diacerein was performed to provide an evidence-based assessment of its symptomatic efficacy in the treatment of osteoarthritis. METHODS: Electronic databases were searched for randomized controlled trials with diacerein. A manual review of the literature, abstracts, and posters was also conducted. Unpublished final reports were obtained from the manufacturer. Only studies performed in knee and/or hip osteoarthritis were chosen for review. Study inclusion, quality scoring, and data extraction were performed by 2 reviewers independently. Objectives for analysis comprised pain, function, escape medication use, global efficacy, and safety ratings by patients and investigators. Specific study periods, such as the active treatment period and the treatment-free follow-up period (when present), were analyzed. Statistical analyses were based on the intention-to-treat principle as far as possible, and acknowledged tests were used for data analysis. RESULTS: A total of 23 studies were identified, 19 of which were included. Diacerein was significantly superior to placebo during the active treatment phase (Glass score, 1.50 [95% confidence interval, 0.80-2.20]). Both diacerein and nonsteroidal anti-inflammatory drugs (NSAIDs) were similarly efficacious during the treatment period; however, diacerein, but not NSAIDs, showed a carryover effect, persisting up to 3 months after treatment, with a significant analgesic-sparing effect during the follow-up period (Glass score, 2.06 [95% confidence interval, 0.66-3.46]). Tolerability assessment revealed no differences between diacerein and NSAIDs, although the latter showed more severe events. CONCLUSION: This systematic meta-analysis provides evidence for the symptomatic efficacy of diacerein in the treatment of knee and hip osteoarthritis, with reasonable tolerability.