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Background/Aims Ixekizumab (IXE), a monoclonal antibody that selectively targets interleukin IL-17A, has shown efficacy in patients with radiographic axial spondyloarthritis (r-axSpA). Spinal pain, in particular spinal pain at night (SP-N), is a major contributor to the patient burden of r-axSpA.To assess SP-N improvement in patients up to week (W) 52 and to determine the association of SP-N improvement in patients treated with IXE with other patient-reported outcomes (PROs) at W16 and with reaching ASDAS LDA at W52. Methods The Phase III COAST-V (NCT02696785) trial investigated the efficacy of IXE in 341 patients with r-axSpA and were biological disease-modifying anti-rheumatic drug (bDMARD)-naïve. Patients were randomised to IXE every 2W (IXEQ2W), IXE every 4W (IXEQ4W), adalimumab (ADA) or placebo (PBO) up to W16. Only approved dose IXEQ4W data are presented here. SP-N was measured at each visit using a numeric rating scale (NRS) (0-10). A clinically relevant improvement in SP-N was defined as > 2 point improvement from baseline. Differences in baseline variables between those achieving versus not achieving >2 improvement in SP-N were tested using Fisher’s exact test (binary variables) and analysis of variance (ANOVA; continuous variables). Associations of SP-N improvement with PROs (BASFI, Fatigue Severity NRS, Jenkins Sleep Evaluation Questionnaire (JSEQ), SF-36 PCS) at W16, and ASDAS LDA at W52 were tested using analysis of covariance (ANCOVA; continuous variables) and logistic regression (binary variables). Missing values were imputed using non-responder imputation (NRI), and modified baseline observation carried forward. Results A greater proportion of patients achieved >2 improvement in SP-N with IXE treatment compared to PBO at W16 (63.0% vs. 32.2%, p 2 improvement in SP-N (63%) at W16 were younger, more frequently positive for HLA-B27 and had higher disease activity at baseline compared to those that did not achieve >2 improvement. Achieving >2 improvement in SP-N was associated with improvement in PROs including BASFI, Fatigue Severity, JSEQ and SF-36 PCS at W16 and with achieving ASDAS2 improvement in SP-N. Conclusion IXE improved SP-N for patients with r-axSpA not previously treated with bDMARDs. Improvements in SP-N were associated with improvements in disease activity, function, fatigue, and quality of life. Disclosure S. Ramiro: Consultancies; S. Ramiro has served as a speaker and/or consultant for: AbbVie, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and UCB Pharma. Grants/research support; S. Ramiro has received grant and/or research support from: AbbVie, Galapagos NV, Novartis, Pfizer, and UCB Pharma. C. Lukas: Consultancies; C. Lukas has served as a speaker and/or consultant for: AbbVie, Amgen, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly and Company, Galapagos NV, Merck Sharp & Dohme, Novartis, Pfizer, Roche. Grants/research support; C. Lukas has received grant and/or research support from: Eli Lilly and Company, Novartis, Pfizer, and Roche. M. Nissen: Consultancies; M. J. Nissen has served as a speaker and/or consultant for: AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, and Pfizer. Y. Schymura: Shareholder/stock ownership; Y. Schymura is a shareholder and employee of: Eli Lilly and Company. K. Ng: Shareholder/stock ownership; K. Ng is a shareholder and employee of: Eli Lilly and Company. A. Bradley: Shareholder/stock ownership; A. Bradley was an employee of: Eli Lilly and Company at the time of the study. G. Doridot: Shareholder/stock ownership; G. Doridot is a shareholder and employee of: Eli Lilly and Company. S. Liu-Leage: Shareholder/stock ownership; S. Liu-Leage is a shareholder and employee of: Eli Lilly and Company. A. Chan: Consultancies; A. Chan has served as a speaker and/or consultant for: AbbVie, Amgen, Biogen, Celgene, Eli Lilly and Company, Janssen, Novartis, and UCB Pharma. C. Wei: Grants/research support; J. C.-C. Wei has received consulting fees and/or grant and/or research support from: AbbVie, Bristol Myers Squibb, Celgene, Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Biopharm, and UCB Pharma.

Objectives To systematically review the psychometric properties of outcome measurement instruments used in ANCA-associated vasculitis (AAV). Methods Medline, EMBASE, Cochrane, Scopus and Web of Science were searched from inception to 14 July 2020 for validation studies of instruments used in AAV. Following the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) and OMERACT frameworks, different psychometric properties (validity, reliability, responsiveness and feasibility) were summarized. Risk of bias was assessed according to the COSMIN checklist. Results From 2505 articles identified, 32 met the predefined selection criteria, providing information on 22 instruments assessing disease activity (n = 7), damage (n = 2), activity and damage (n = 1), health-related quality of life (HRQoL; n = 9) and function (n = 3). Most of the instruments were tested in AAV as a group or in granulomatosis with polyangiitis only. The BVAS, any version, the Vasculitis Damage Index (VDI) and the AAV-Patient-Reported Outcome (AAV-PRO) have been more extensively validated than the other instruments. BVAS for Wegener Granulomatosis (BVAS/WG) has been shown to be valid for measuring disease activity [correlation with Physician global assessment (r = 0.90)], reliability (inter-observer intraclass correlation coefficient = 0.97), responsiveness and feasibility. For damage, VDI was shown to be moderately valid (correlations with BVAS version 3 at 6 months r = 0.14, BVAS/WG at 1 year r = 0.40 and 5 years r = 0.20), and feasible. For HRQoL, AAV-PRO demonstrated validity (correlations of the six AAV-PRO domains with EQ-5D-5L: −0.78 to −0.55; discrimination between active disease and remission, P Conclusion Among the 22 outcome measurement instruments used for AAV, BVAS (any version), VDI and AAV-PRO had the strongest psychometric properties.

Objectives The aim of this study was to investigate the association between individual-level and country-level socio-economic (SE) factors and health outcomes across SpA phenotypes. Methods Patients with axial SpA (axSpA), peripheral SpA (pSpA) or PsA from the ASAS-perSpA study (in 23 countries) were included. The effect of individual-level (age, gender, education and marital status) and country-level [e.g. Gross Domestic Product (GDP)] SE factors on health outcomes [Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.1, ASDAS, BASFI, fatigue and the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI)] was assessed in mixed-effects models adjusted for potential confounders. Interactions between SE factors and disease phenotype were tested. A mediation analysis was conducted to explore whether the impact of country-level SE factors on ASDAS was mediated through biologic/targeted synthetic (b/ts) DMARD uptake. Results In total, 4185 patients (61% males, mean age 45) were included (65% axSpA, 25% PsA, 10% pSpA). Female gender [β= 0.14 (95% CI: 0.06, 0.23)], lower educational level [β = 0.35 (0.25, 0.45)) and single marital status [β = 0.09 (0.01, 0.17)] were associated with higher ASDAS. Living in lower GDP countries was also associated with higher ASDAS [β = 0.39 (0.16, 0.63)], and 7% of this association was mediated by b/tsDMARD uptake. Higher BASFI was similarly associated with female gender, lower education and living alone, without the effect of country-level SE factors. Female gender and lower educational level were associated with worse ASAS-HI, while more fatigue was associated with female gender and higher country-level SE factors [lower GDP, β = −0.46 (−0.89 to −0.04)]. No differences across disease phenotypes were found. Conclusions Our study shows country-driven variations in health outcomes in SpA, independently influenced by individual-level and country-level SE factors and without differences across disease phenotypes.

Objectives To investigate the impact of clinical and socioeconomic factors on work disability (WD) in early axial spondyloarthritis (axSpA). Methods Patients from the DESIR cohort with a clinical diagnosis of axSpA were studied over 5 years. Time to WD and potential baseline and time-varying predictors were explored, with a focus on socioeconomic (including ethnicity, education, job-type, marital/parental status) and clinical (including disease activity, function, mobility) factors. Univariable analyses, collinearity and interaction tests guided subsequent multivariable time-varying Cox survival analyses. Results From 704 patients eligible for this study, the estimated incidence of WD among those identified as at risk (n = 663, 94%), and across the five years of DESIR, was 0.05 (95% CI 0.03, 0.06) per 1000 person-days. Significant differences in baseline socioeconomic factors, including lower educational status and clinical measures, including worse disease activity, were seen in patients developing WD over follow-up, compared with those who never did. In the main multivariable model, educational status was no longer predictive of WD, whereas the AS disease activity score (ASDAS) and the BASFI were significantly and independently associated with a higher hazard of WD [HR (95%CI) 1.79 (1.27, 2.54) and 1.42 (1.22, 1.65), respectively]. Conclusion WD was an infrequent event in this early axSpA cohort. Nevertheless, clinical factors were among the strongest predictors of WD, over socioeconomic factors, with worse disease activity and function independently associated with a higher hazard of WD. Disease severity remains a strong predictor of adverse work outcome even in early disease, despite substantial advances in therapeutic strategies in axSpA.

ObjectivesTo investigate the frequency and order of impairment of spinal mobility measures (SMMs) and their cross-sectional and longitudinal usefulness in early axial spondyloarthritis.MethodsSMMs measurements of patients from the DESIR (5-year data) and SPACE (2.6 (1.9) years of follow-up) cohorts were analysed. Cross-sectional (group level) and longitudinal (individual level) analyses were performed comparing SMMs to pre-defined cut-offs derived from healthy individuals. Subgroup analyses were used to study patient and disease characteristics potentially influencing spinal mobility. Reliability was analysed using intraclass correlation coefficients and the smallest detectable change.ResultsIn 328 DESIR and 148 SPACE patients, lateral spinal flexion (LSF) and mSchober were the most impaired SMMs. If both (LSF and mSchober) were measured, 84% (DESIR) and 74% (SPACE) of the patients with impairment in ≥1 SMM would be captured. LSF and Bath AS Metrology Index best discriminated between subgroups of patients (higher impairment in patients ever treated with biologics, with higher disease activity and presence of baseline syndesmophytes): e.g. 31% of LSF impairment in patients with Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 in ≥2/3 visits vs 49% in those with ASDS ≥ 2.1. A high variability in SMMs within the same patient over time was observed, even when restricting the analysis to patients with low disease activity. Reliability of SMMs was ‘fair’ to ‘good’ (inter-reader intraclass correlation coefficients (2, 1): 0.55–0.84; intrareader intraclass correlation coefficients (2, 1): 0.49–0.72). Smallest detectable changes were in general high, e.g. 5.1 cm for LSF.ConclusionCross-sectional use of SMMs, at the group level, is informative in patients with early axial spondyloarthritis. However, the high variation of SMMs over time impairs their use, at the individual patient level.

Objective To develop algorithms for calculating the Rheumatic Diseases Comorbidity Index (RDCI), Charlson-Deyo Index (CDI) and Functional Comorbidity Index (FCI) from the Medical Dictionary for Regulatory Activities (MedDRA), and to assess how these MedDRA-derived indices predict clinical outcomes, utility and health resource utilization (HRU). Methods Two independent researchers linked the preferred terms of the MedDRA classification into the conditions included in the RDCI, the CDI and the FCI. Next, using data from the Norwegian Register-DMARD study (a register of patients with inflammatory joint diseases treated with DMARDs), the explanatory value of these indices was studied in models adjusted for age, gender and DAS28. Model fit statistics were compared in generalized estimating equation (prediction of outcome over time) models using as outcomes: modified HAQ, HAQ, physical and mental component summary of SF-36, SF6D and non-RA related HRU. Results Among 4126 patients with RA [72% female, mean (s.d.) age 56 (14) years], median (interquartile range) of RDCI at baseline was 0.0 (1.0) [range 0-6], CDI 0.0 (0.0) [0-7] and FCI 0.0 (1.0) [0-6]. All the comorbidity indices were associated with each outcome, and differences in their performance were moderate. The RDCI and FCI performed better on clinical outcomes: modified HAQ and HAQ, hospitalization, physical and mental component summary, and SF6D. Any non-RA related HRU was best predicted by RDCI followed by CDI. Conclusion An algorithm is now available to compute three commonly used comorbidity indices from MedDRA classification. Indices performed comparably well in predicting a variety of outcomes, with the CDI performing slightly worse when predicting outcomes reflecting functioning and health.

Objective The aim of this study was to assess if any of the different types of radiographic damage [true joint space narrowing (JSN), (sub)luxation and erosions] are preferentially related to disability in patients with RA. Methods Longitudinal data from 167 RA patients from the European Research on Incapacitating Diseases and Social Support study over 10 years were analysed to investigate the relationship between the three types of radiographic damage and disability [grip strength, HAQ and the dexterity scale in the Arthritis Impact Measurement Scales (AIMS)]. A longitudinal analysis including separate models per type of damage and joint group and combined models including all information was conducted. Results All types of damage were inversely related to grip strength in the analysis of separate models, but only true JSN independently remained statistically significant in the combined analysis [β = -0.087 (95% CI -0.151, -0.022)]. Neither JSN, (sub)luxation nor erosions were associated with HAQ score, while erosions were associated with AIMS dexterity only in the analysis of separate models. After stratifying for hand joint group, erosions at MCP joints [β = -0.288 (95% CI -0.556, -0.019)] and true JSN at the wrist [β = -0.132 (95% CI -0.234, -0.030)] were significantly related to grip strength. Erosions at the PIP [β = 0.017 (95% CI 0.005, 0.028)] and MCP joints [β = 0.114 (95% CI 0.010, 0.217)] was the only type of damage associated with HAQ and AIMS dexterity, respectively. Conclusion All types of radiographically visible joint damage interfere with important aspects of physical functions. True JSN is most closely related to hand function.

Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008–09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. Results. A total of 49 242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice. Conclusions. Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice.

Objective To evaluate the intima-media thickness (IMT) of arteries involved in GCA for determining cut-off values. Methods Forty newly diagnosed GCA patients in a fast-track GCA clinic and 40 age- and sex-matched controls were included. IMT measurement was performed at or within 24 h after diagnosis. The common superficial temporal arteries with their frontal and parietal branches and the facial arteries were bilaterally examined with a 10-22 MHz probe and the axillary artery with a 6-18 MHz probe. Receiver operating characteristics analysis was performed for estimating cut-off values. Results The mean age was 72 years (s.d. 9) and 68% were females. In the control group, IMT was 0.23 mm (s.d. 0.04), 0.19 mm (s.d. 0.03), 0.20 mm (s.d. 0.03), 0.24 mm (s.d. 0.05) and 0.59 mm (s.d. 0.10) for the common superficial temporal arteries, the frontal and parietal branches, the facial arteries and the axillary arteries, respectively. In vasculitic segments of GCA patients, IMT was 0.65 mm (s.d. 0.18), 0.54 mm (s.d. 0.18), 0.50 mm (s.d. 0.17), 0.53 mm (s.d. 0.16) and 1.7 mm (s.d. 0.41), respectively. Cut-off values are 0.42, 0.34, 0.29, 0.37 and 1.0 mm, respectively, with 100% sensitivities and specificities for common superficial temporal arteries, for frontal branches and for axillary arteries and sensitivities of 97.2 and 87.5% and specificities of 98.7 and 98.8% for parietal branches and facial arteries, respectively. The intraclass correlation coefficient was between 0.87 and 0.98. Conclusion IMT measurement can correctly distinguish vasculitic from normal arteries in suspected GCA.

In 2015, both the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and the EULAR presented updated recommendations on the management of PsA [1, 2]. New therapies, assessments and increasing evidence on comorbidities required substantial revision of treatment strategies. This editorial provides comments on the key barriers faced and how these were addressed. The challenges focus around the remit of the recommendations, the scope of the literature review and assessment of the available data.

Objective. To explore whether age, gender or education influence the time until initiation of the first bDMARD in patients with RA. Methods. Data from the Norwegian Register of DMARDs collected between 2000 and 2012 were used. Only DMARD-na 57 years) and became more pronounced by the end of the decade. Conclusions. Less educated and older patients have disadvantages with regard to access to costly treatments, even in a country with highly developed welfare like Norway. Females had lower access in the beginning of the 2000s, but access had improved by the end of the decade.