Impact of disease outcomes on the Assessment of SpondyloArthritis International Society Health Index (ASAS HI): a Bayesian network analysis of the DESIR cohort.

OBJECTIVE: The objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) in patients with axial spondyloarthritis (axSpA). METHODS: Cross-sectional data collected at month 72 of the Devenir des Spondylarthropathies Indifferénciées Récentes cohort was analysed. Combining prior knowledge and observed data, probabilistic Bayesian network modelling was used to study how the interplay of different disease outcomes affects the ASAS HI, which measures disease-specific overall functioning and health. Disease outcomes comprised, among others, the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) and the Bath AS Functional Index (BASFI). RESULTS: Data of 384 patients were analysed. The obtained structure suggests that ASAS HI is determined by both patient-reported physical function (BASFI) and disease activity (ASDAS). The parameters of the structural model show that an increase of ASDAS or BASFI by 1 unit corresponds to an increase of ASAS HI by 0.70 or 1.25 units, respectively. Moreover, the model suggests that disease activity has an indirect impact on ASAS HI via BASFI. No relationship between spinal mobility or structural damage and ASAS HI was found. CONCLUSIONS: This is the first structural model developed to better understand the construct and the interplay between clinically relevant outcomes related to ASAS HI in axSpA patients. It shows that disease activity and physical function have a strong impact on ASAS HI, confirming it to be a valid construct of overall functioning and health in axSpA patients.

Clinimetric Validation of the Assessment of Spondyloarthritis International Society Health Index in Patients With Radiographic Axial Spondyloarthritis in Ixekizumab Trials.

OBJECTIVE: To assess test-retest reliability, construct validity, known groups discrimination, and responsiveness of the Assessment of the SpondyloArthritis international Society Health Index (ASAS HI) to evaluate functioning, disability, and health in patients with radiographic axial spondyloarthritis (r-axSpA). METHODS: Data were generated from 2 randomized, placebo-controlled, active-controlled phase III ixekizumab studies (COAST-V, N = 341; COAST-W, N = 316). Assessments included the following: test-retest reliability (ie, intraclass correlation coefficients [ICCs] between ASAS HI scores at screening and baseline), construct validity (ie, Spearman correlation with standard r-axSpA outcome measures), known groups discrimination (ie, 1-way ANOVA comparing the ASAS HI with different disease activity categories, measured by the Ankylosing Spondylitis Disease Activity Score [ASDAS]), and responsiveness (ie, Spearman correlation between changes in the ASAS HI and changes in the Bath Ankylosing Spondylitis Functional Index [BASFI], the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], the ASDAS, and the Patient Global Assessment [PtGA] as well as ANOVA comparing changes in the ASAS HI with various responder categories). RESULTS: The ICC for test-retest reliability was 0.78 for COAST-V and 0.76 for COAST-W, indicating adequate agreement. Moderate-to-large correlations (r = 0.40-0.61) were observed between the ASAS HI and the BASDAI. Statistically significant differences (all P < 0.001) between mean ASAS HI scores were observed for subgroups based on ASDAS-defined disease activity categories at baseline and week 16. Moderate-to-large correlations existed between changes in the ASAS HI and the BASFI, BASDAI, ASDAS, and PtGA from baseline to week 16. The ASAS HI differentiated statistically (P < 0.001) between ASAS, BASDAI, and ASDAS response groups. CONCLUSION: The ASAS HI demonstrated reliability, construct validity, known groups discrimination, and responsiveness in adults with r-axSpA in 2 clinical trials.

Measuring quality of life of patients with axial spondyloarthritis for economic evaluation.

OBJECTIVES: To estimate the relationship between EQ5D (three levels, UK version) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) for use in the economic evaluation of health technologies for people with axial spondyloarthritis (axSpA). To compare against the relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). METHODS: An electronic, prospective, Portuguese, nationwide, rheumatic disease register (Reuma.pt) provided data on 1140 patients (5483 observations) with a confirmed diagnosis of axSpA. We estimated models of EQ5D as a function of ASDAS, alone or in combination with measures of functional impairment, using bespoke mixture models which reflect the complex distributional features of EQ5D. The SPondyloArthritis Caught Early cohort provided data from 344 patients (1405 observations) in four European countries and was used for validation. A previously published model of BASDAI/Bath Ankylosing Spondylitis Functional Index (BASFI) was also used to generate predicted EQ5D scores and model performance compared. RESULTS: A non-linear relationship exists between EQ5D from ASDAS. The final model included ASDAS, ASDAS squared, age and age squared and demonstrated close fit in both datasets except where data were sparse for patients with very high levels of disease activity (ASDAS >4). This finding held in the validation dataset. Models that included BASFI improved model fit. The ASDAS based models fit the data marginally less well than models using BASDAI. CONCLUSIONS: Mapping models linking ASDAS to EQ5D allow results from clinical studies to be used in economic evaluation of health technologies with confidence. There is some loss of information compared with BASDAI but this has only a marginal impact.

Determinants of the Physician Global Assessment of Disease Activity and Influence of Contextual Factors in Early Axial Spondyloarthritis.

OBJECTIVE: To investigate determinants of the physician global assessment (PhGA) of disease activity and the influence of the contextual factors on this relationship in patients with early axial spondyloarthritis (SpA). METHODS: Five-year data of DESIR, a cohort of early axial SpA, were analyzed. Univariable generalized estimating equations (GEEs) were used to investigate contributory explanatory effects of various potential determinants of PhGA. Effect modification by contextual factors (age, sex, and educational level) was tested, and if significant, models were stratified. Autoregressive GEE models (i.e., models adjusted for PhGA at the previous time point) were used to confirm a longitudinal relationship. RESULTS: A total of 708 patients were included. Higher Bath Ankylosing Spondylitis Disease Activity Index individual questions, swollen joint count in 28 joints (SJC28), tender joint count in 53 joints, Maastricht Ankylosing Spondylitis Enthesitis Score, C-reactive protein (CRP) level, and Bath Ankylosing Spondylitis Metrology Index score were associated with a higher PhGA. Sex and age were effect modifiers of SJC28; the contributory effect of SJC28 was largest in the younger male stratum (ß = 1.07 [95% confidence interval (95% CI) 0.71, 1.43]), and the smallest in the older female stratum (ß = 0.13 [95% CI 0.04, 0.22]). Autoregressive GEE models revealed the same determinants as having a longitudinal association with PhGA and the same pattern of effect modification. CONCLUSION: Patients' subjective symptoms, peripheral arthritis and enthesitis, higher CRP level, and impaired spinal mobility contribute to explaining PhGA in patients with early axial SpA, irrespective of sex and age. Intriguingly, physicians consider the presence of swollen joints as more important in males than in females.

Age at onset in axial spondyloarthritis around the world: data from the Assessment in SpondyloArthritis international Society Peripheral Involvement in Spondyloarthritis study.

OBJECTIVE: Age at onset is useful in identifying chronic back patients at an increased risk of axial SpA (axSpA). However, the majority of data on which the criterion of age at onset <45 years is based originates from Europe. Therefore it is unknown if this criterion applies in other parts of the world. We aimed to assess the age at onset of axSpA and its relationship with HLA-B27 and gender across the world. METHODS: Analyses were applied to patients from 24 countries across the world with an axSpA diagnosis and known age at onset of axial complaints. Cumulative probability plots were used to display the cumulative distribution of age at onset of axial symptoms. Linear regression models were built to assess the effect of HLA-B27 and gender on age at onset of axial symptoms. RESULTS: Of 2579 axSpA patients, 92% had an age at onset of axial symptoms <45 years, with only small variations across the geographical regions [Asia, n = 574 (94%); Europe and North America, n = 988 (92%); Latin America, n = 246 (89%); Middle East and North Africa, n = 771 (91%)]. Age at onset of axial symptoms was consistently lower in HLA-B27-positive patients {median 25 years [interquartile range (IQR) 19-32] vs 31 [IQR 22-39]} and male patients [median 25 years (IQR 19-33) vs 28 (IQR 21-37)], but in multivariable models an additional statistically significant effect of male gender independent of HLA-B27 was only found in Asia. CONCLUSION: Around the world, the great majority of axSpA patients had an age at onset of axial disease of <45 years, with HLA-B27 and male gender associated with earlier disease onset.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

BACKGROUND: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research. DESIGN: Prospective, multicenter, multinational, cross-sectional study. METHODS AND ANALYSES: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information. ETHICS: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885.

Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies.

OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. We evaluated radiographic progression in tofacitinib-treated patients with RA for up to 3 years in two pooled long-term extension (LTE) studies (ORAL Sequel; A3921041) (primary analysis), and for up to 5 years using data integrated from one phase (P)2 (A3921068), two P3 (ORAL Start; ORAL Scan) and two LTE studies (exploratory analysis). METHODS: In LTE studies, patients received tofacitinib 5 mg twice daily (BID) or 10 mg BID as monotherapy or with conventional synthetic (cs)DMARDs. Radiographic outcomes up to 3 years: least squares mean (LSM) change from baseline in van der Heijde modified Total Sharp Score (ΔmTSS), erosion score (ΔES) and joint space narrowing (ΔJSN) score; proportion of patients with no radiographic progression (ΔmTSS ≤0.5); proportion of patients with no new erosions (ΔES ≤0.5). ΔmTSS was evaluated for up to 5 years in an exploratory analysis. RESULTS: For all tofacitinib-treated patients with radiographic data available at LTE month 36 (n = 414), LSM ΔmTSS was 1.14, LSM ΔES was 0.66, LSM ΔJSN was 0.74, and 74.3% and 86.2% of patients showed no radiographic progression and no new erosions, respectively. Similar values were observed regardless of tofacitinib dose, or whether patients received tofacitinib as monotherapy or with csDMARDs. In an exploratory analysis of integrated P2/P3/LTE studies, LSM ΔmTSS was 3.34 at month 60 (n = 269). CONCLUSION: Limited progression of structural damage was observed in tofacitinib-treated patients up to 5 years, with similar results for tofacitinib used as monotherapy or combination therapy up to 3 years. TRIAL REGISTRATION: ClinicalTrials.gov (http://clinicaltrials.gov): NCT01164579; NCT01039688; NCT00847613; NCT00413699; NCT00661661.

Revisiting the use of remission criteria for rheumatoid arthritis by excluding patient global assessment: an individual meta-analysis of 5792 patients.

OBJECTIVES: To determine the impact of excluding patient global assessment (PGA) from the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission criteria, on prediction of radiographic and functional outcome of rheumatoid arthritis (RA). METHODS: Meta-analyses using individual patient data from randomised controlled trials testing the efficacy of biological agents on radiographic and functional outcomes at ≥2 years. Remission states were defined by 4 variants of the ACR/EULAR Boolean definition: (i) tender and swollen 28-joint counts (TJC28/SJC28), C reactive protein (CRP, mg/dL) and PGA (0-10=worst) all ≤1 (4V-remission); (ii) the same, except PGA >1 (4V-near-remission); (iii) 3V-remission (i and ii combined; similar to 4V, but without PGA); (iv) non-remission (TJC28 >1 and/or SJC28 >1 and/or CRP >1). The most stringent class achieved at 6 or 12 months was considered. Good radiographic (GRO) and functional outcome (GFO) were defined as no worsening (ie, change in modified total Sharp score (ΔmTSS) ≤0.5 units and ≤0.0 Health Assessment Questionnaire-Disability Index points, respectively, during the second year). The pooled probabilities of GRO and GFO for the different definitions of remission were estimated and compared. RESULTS: Individual patient data (n=5792) from 11 trials were analysed. 4V-remission was achieved by 23% of patients and 4V-near-remission by 19%. The probability of GRO in the 4V-near-remission group was numerically, but non-significantly, lower than that in the 4V-remission (78 vs 81%) and significantly higher than that for non-remission (72%; difference=6%, 95% CI 2% to 10%). Applying 3V-remission could have prevented therapy escalation in 19% of all participants, at the cost of an additional 6.1%, 4.0% and 0.7% of patients having ΔmTSS >0.0, >0.5 and >5 units over 2 years, respectively. The probability of GFO (assessed in 8 trials) in 4V-near-remission (67%, 95% CI 63% to 71%) was significantly lower than in 4V-remission (78%, 74% to 81%) and similar to non-remission (69%, 66% to 72%). CONCLUSION: 4V-near-remission and 3V-remission have similar validity as the original 4V-remission definition in predicting GRO, despite expected worse prediction of GFO, while potentially reducing the risk of overtreatment. This supports further exploration of 3V-remission as the target for immunosuppressive therapy complemented by patient-oriented targets.

Development and validation of an alternative ankylosing spondylitis disease activity score when patient global assessment is unavailable.

OBJECTIVE: To develop an alternative Ankylosing Spondylitis Disease Activity Score (ASDAS) to be used in research settings in axial SpA (axSpA) when Patient Global Assessment (PGA) is unavailable in databases. METHODS: Longitudinal data from four axSpA cohorts and two randomized controlled trials were combined. Observations were randomly split in a development (N = 1026) and a validation cohort (N = 1059). Substitutes of PGA by BASDAI total score, single or combined individual BASDAI questions, and a constant value, were established in the development cohort. Conversion factors for each substitute were defined by Generalized Estimating Equations, obtaining seven 'alternative' formulae. Validation was performed in the validation cohort according to the OMERACT filter, taking into consideration: (i) truth (agreement with original-ASDAS in the continuous score, by intraclass correlation coefficient and in disease activity states, by weighted kappa); (ii) discrimination [standardized mean difference of ASDAS scores between high/low disease activity states defined by external anchors, e.g. Patient Acceptable Symptom State; agreement (kappa) in the percentage of patients reaching ASDAS improvement criteria according to alternative vs original formulae]; and (iii) feasibility. RESULTS: Comparing various options, alternative-ASDAS using BASDAI total as PGA replacement proved to be: truthful (intraclass correlation coefficient = 0.98, kappa = 0.90), discriminative [ASDAS scores between Patient Acceptable Symptom State no/yes: standardized mean difference = 1.37 (original-ASDAS standardized mean difference = 1.43); agreement with original-ASDAS in major improvement/clinically important improvement criteria: kappa = 0.93/0.88] and feasible (BASDAI total often available, as questions required for the ASDAS; conversion coefficient ≈ 1). CONCLUSION: Alternative-ASDAS using BASDAI total score as PGA replacement is the most truthful, discriminative and feasible instrument.

Determinants of the patient global assessment of well-being in early axial spondyloarthritis: 5-year longitudinal data from the DESIR cohort.

OBJECTIVES: To investigate the determinants of patient well-being over time, and the influence of age, gender and education in patients with early axial spondyloarthritis (axSpA). METHODS: Five-year data from DESIR, a cohort of early axSpA, were analysed. The outcome was the BAS-G over 5 years. Generalized estimating equations (GEE) were used to test the relationship between potential explanatory variables from five outcome domains (disease activity, physical function, spinal mobility, structural damage and axial inflammation) and BAS-G over time. Longitudinal relationships were analysed using an autoregressive GEE model. Age, gender and educational level were tested as effect modifiers or confounders. RESULTS: A total of 708 patients were included. Higher BASDAI questions on fatigue [ß (95% CI): 0.17 (0.13, 0.22)], back pain [0.51 (0.46, 0.56)], peripheral joint pain [0.08 (0.04, 0.12)] and severity of morning stiffness [0.08 (0.03-0.13)], and higher BASFI [0.14 (0.08, 0.19)] were associated with a higher BAS-G. In the autoregressive model, the same variables except for morning stiffness were associated with a worsening in BAS-G. Age, gender and educational level were neither effect modifiers nor confounders. CONCLUSION: A higher level of back pain is associated with a worsening of patient well-being, as are, though to a lesser extent, higher levels of fatigue, peripheral joint pain and physical disability. Age, gender and educational level do not have an impact on these relationships.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update.

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial.

BACKGROUND: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. METHODS: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. DISCUSSION: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. TRIAL REGISTRATION: Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018).

Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis.

Objectives: To compare the clinical characteristics, burden of disease (eg, disease activity, function, quality of life), treatment modalities and treatment effect in patients with radiographic and non-radiographic axial Spondyloarthritis (r-axSpA and nr-axSpA). Methods: A systematic literature review (2009-2018) was performed using the participants, intervention, comparator and outcomes methodology. Studies reporting outcomes (clinical presentation, burden of disease, treatment modalities and treatment effect) of both r-axSpA and nr-axSpA were included. A pooled analysis was performed (standardised means difference and relative risk for continuous and binary variables, respectively) and random or fixed effects methods were used depending on the heterogeneity of the studies. Results: 60 studies out of 787 references were included. Pooled analysis showed that, compared with patients with nr-axSpA, patients with r-axSpA were more frequently men (69.6% vs 53.6%), smokers (37.7% vs 31.1%) and had higher mean disease duration (8.6 vs 5.0 years) and longer time to diagnosis (6.1 vs 4.2 years). Peripheral manifestations were more prevalent in nr-axSpA, while uveitis and structural damage on MRI of the sacroiliac joints were more prevalent in r-axSpA. C-reactive protein and the Bath Ankylosing Spondylitis Mobility Index were higher in r-axSpA, while Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index and Ankylosing Spondylitis Quality of Life were similar in both groups. No significant differences were found with regard to treatment effect. Conclusions: Patients with r-axSpA and nr-axSpA share a similar clinical presentation except for peripheral involvement, which is more prevalent among nr-axSpA. Except for a more impaired mobility in r-axSpA, both groups showed a comparable burden of disease, treatment modalities and treatment effect.

Development of one general and six country-specific algorithms to assess societal health utilities based on ASAS HI.

Objective: Health utilities represent preference values that persons attach to health states. This study aims to develop one general and six country-specific algorithms to calculate societal preference values for health of patients with spondyloarthritis (SpA), as assessed by the disease-specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). Methods: A survey was performed in random population samples from six European countries. In a best-worst choice experiment, subjects were asked to indicate repeatedly which of 4 random aspects of the 17-item ASAS HI was were most and least important. Bayesian analysis provided the relative importance of each of the 17 items. To rescale the relative importance scores on the absolute utility scale between 0 and 1, participants additionally completed two lead time trade-off experiments, one for 'severe SpA' and one for 'best health' without SpA. Six country-specific algorithms and one general algorithm were derived. The general algorithm was tested in 199 patients with axial SpA (axSpA). Results: 3039 subjects, mean age 47 years (SD 15) and 52% female completed the experiments. The population's health utility value for SpA varied between - 0.24 for 'worst' SpA (country range -0.35 to 0.03), and 0.88 for 'best' health (country range 0.81 to 0.90). Among 199 patients with axSpA, the mean utility was 0.36 (SD 0.30, range -0.24 to 0.88) and discriminated well between patients having high (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4) or low (BASDAI < 4) disease activity (0.18 (SD 0.24) vs 0.51(SD 0.27), p<0.01). Conclusion: One general and six country-specific algorithms are available to convert scores from the ASAS HI into disease-specific societal utility values.