Objectives The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on selfreported data and radiographic... Show moreObjectives The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on selfreported data and radiographic features. Methods The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. Results In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0–15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. Conclusions International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology. Show less
Almayali, A.A.H.; Boers, M.; Hartman, L.; Opris, D.; Bos, R.; Kok, M.R.; ... ; Wee, M.M. ter 2023
Objective The randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2... Show moreObjective The randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2 years in patients aged 65+ years with rheumatoid arthritis (RA). Here, we studied disease activity, flares and possible adrenal insufficiency after blinded withdrawal of study medication.Methods Per protocol, patients successfully completing the 2-year trial period linearly tapered and stopped blinded study medication in 3 months. We compared changes in disease activity after taper between treatment groups (one-sided testing). Secondary outcomes (two-sided tests) comprised disease flares (DAS28 (Disease Activity Score 28 joints) increase >0.6, open-label glucocorticoids or disease-modifying antirheumatic drug (DMARD) increase/switch after week 4 of tapering) and symptoms/signs of adrenal insufficiency. In a subset of patients from 3 Dutch centres, cortisol and ACTH were measured in spot serum samples after tapering.Results 191 patients were eligible; 36 met treatment-related flare criteria and were only included in the flare analysis. Mean (SD) DAS28 change at follow-up: 0.2 (1.0) in the prednisolone group (n=76) vs 0.0 (1.2) in placebo (n=79). Adjusted for baseline, the between-group difference in DAS28 increase was 0.16 (95% confidence limit –0.06, p=0.12). Flares occurred in 45% of prednisolone patients compared with 33% in placebo, relative risk (RR) 1.37 (95% CI 0.95 to 1.98; p=0.12). We found no evidence for adrenal insufficiency.Conclusions Tapering prednisolone moderately increases disease activity to the levels of the placebo group (mean still at low disease activity levels) and numerically increases the risk of flare without evidence for adrenal insufficiency. This suggests that withdrawal of low-dose prednisolone is feasible and safe after 2 years of administration. Show less
Hartman, L.; Silva, J.A.P. da; Buttgereit, F.; Cutolo, M.; Opris-Belinski, D.; Szekanecz, Z.; ... ; Boers, M. 2022
Objective: To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or... Show moreObjective: To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. Methods: In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients >= 65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. Results: A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12-15%, area under the curve 0.67-0.69). Conclusion: Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. Show less
Boers, M.; Hartman, L.; Opris-Belinski, D.; Bos, R.; Kok, M.R.; Silva, J.A.P. da; ... ; GLORIA Trial Consortium 2022
Background: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. Methods: The GLORIA (Glucocorticoid LOw-dose in... Show moreBackground: Low-dose glucocorticoid (GC) therapy is widely used in rheumatoid arthritis (RA) but the balance of benefit and harm is still unclear. Methods: The GLORIA (Glucocorticoid LOw-dose in Rheumatoid Arthritis) pragmatic double-blind randomised trial compared 2 years of prednisolone, 5 mg/day, to placebo in patients aged 65+ with active RA. We allowed all cotreatments except long-term open label GC and minimised exclusion criteria, tailored to seniors. Benefit outcomes included disease activity (disease activity score; DAS28, coprimary) and joint damage (Sharp/van der Heijde, secondary). The other coprimary outcome was harm, expressed as the proportion of patients with >= 1 adverse event (AE) of special interest. Such events comprised serious events, GC-specific events and those causing study discontinuation. Longitudinal models analysed the data, with one-sided testing and 95% confidence limits (95% CL). Results: We randomised 451 patients with established RA and mean 2.1 comorbidities, age 72, disease duration 11 years and DAS28 4.5. 79% were on disease-modifying treatment, including 14% on biologics. 63% prednisolone versus 61% placebo patients completed the trial. Discontinuations were for AE (both, 14%), active disease (3 vs 4%) and for other (including covid pandemic-related disease) reasons (19 vs 21%); mean time in study was 19 months. Disease activity was 0.37 points lower on prednisolone (95% CL 0.23, p<0.0001); joint damage progression was 1.7 points lower (95% CL 0.7, p=0.003). 60% versus 49% of patients experienced the harm outcome, adjusted relative risk 1.24 (95% CL 1.04, p=0.02), with the largest contrast in (mostly non-severe) infections. Other GC-specific events were rare. Conclusion: Add-on low-dose prednisolone has beneficial long-term effects in senior patients with established RA, with a trade-off of 24% increase in patients with mostly non-severe AE; this suggests a favourable balance of benefit and harm. Show less
Objectives: In Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic... Show moreObjectives: In Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA. Methods: Multidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested. Results: The experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good. Conclusion: Radiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria sets. Show less
Nagy, G.; Roodenrijs, N.M.T.; Welsing, P.M.J.; Kedves, M.; Hamar, A.; Goes, M.C. van der; ... ; Laar, J.M. van 2021
Objective To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA).... Show moreObjective To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). Methods An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. Results Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). Conclusions These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research. Show less
Nagy, G.; Roodenrijs, N.M.T.; Welsing, P.M.J.; Kedves, M.; Hamar, A.; Goes, M.C. van der; ... ; Laar, J.M. van 2021
Background Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be... Show moreBackground Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking.Objective The Task Force in charge of the "Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step.Methods The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting).Results The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of >= 2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient.Conclusions The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research. Show less
Najm, A.; Nikiphorou, E.; Kostine, M.; Richez, C.; Pauling, J.D.; Finckh, A.; ... ; Berenbaum, F. 2019
Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these... Show moreSince publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1-3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4-8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence. Show less
Roodenrijs, N.M.T.; Hair, M.J.H. de; Goes, M.C. van der; Jacobs, J.W.G.; Welsing, P.M.J.; Heijde, D. van der; ... ; EULAR Recommendations 2018
