Construct validity and responsiveness of ASAS Health Index assessed in two longitudinal studies of tumour necrosis factor alpha inhibitor initiation and dose reduction in patients with axial spondyloarthritis.

The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a novel questionnaire of global functioning for patients with axial spondyloarthritis (SpA). The objective was to assess the construct validity, discriminatory ability and responsiveness of ASAS HI in relation to patient-reported outcome measures (PROMs), MRI and radiography. Data from two longitudinal studies with tumour necrosis factor inhibitor (TNFi) initiation (novel MRI And biomarkers in Golimumab-treated patients with axial spondyloarthritis (MANGO): n=45) respectively tapering (Dose adjustment of Biological treatment in patients with SpA (DOBIS): n=106) were used. Analyses included a wide panel of PROMs, MRI and radiography scores of the spine and sacroiliac joints (SIJs). In the MANGO study, 30 (68%) patients were clinical responders at week 16. In the DOBIS study, 105 (99%) patients flared after mean (SD; min-max) 31 (17; 2.7-81) weeks. After initiation of TNF inhibitor in MANGO, ASAS HI significantly decreased from baseline to week 4, 16 and 52. In DOBIS, ASAS significantly increased from baseline to the flare visit and significantly decreased from the flare visit to week 96. In multivariate regression models, ASAS HI was independently associated with Spondyloarthritis Research Consortium of Canada MRI SIJ Inflammation score, Canada-Denmark MRI Spine Inflammation score, EuroQol, Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Disease Activity Index and Patient Global. Patients stratified according to ASAS HI health status groups (good, moderate, poor) at baseline and change categories (absolute and percentage change) from baseline to week 16/flare showed good discriminatory ability for almost all outcome variables (p≤0.001). ASAS HI had a large responsiveness in MANGO (standardised response mean (SRM)=-1.3, effect size (ES)=-1.7) and moderate responsiveness in DOBIS (SRM=0.7, ES=0.6). ASAS HI showed good construct validity, discriminatory ability and responsiveness. ClinicalTrials.gov: NCT02011386.

Lorincz M ，Østergaard M ，Wetterslev M ，Sørensen IJ ，Madsen OR ，Christiansen SN ，Hetland ML ，Bakkegaard M ，Klarlund M ，Duer A ，Boesen M ，Gosvig KK ，Pedersen SJ ... -  《-》

Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor alpha inhibitors.

Pedersen SJ ，Sørensen IJ ，Hermann KG ，Madsen OR ，Tvede N ，Hansen MS ，Thamsborg G ，Andersen LS ，Majgaard O ，Loft AG ，Erlendsson J ，Asmussen K ，Johansen JS ，Jurik AG ，Møller J ，Hasselquist M ，Mikkelsen D ，Skjødt T ，Hansen A ，Ostergaard M ... -  《-》

Measurement properties of the ASAS Health Index: results of a global study in patients with axial and peripheral spondyloarthritis.

To evaluate construct validity, interpretability, reliability and responsiveness as well as determination of cut-off points for good and poor health within the original English version and the 18 translations of the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI) in 23 countries worldwide in patients with spondyloarthritis (SpA). A representative sample of patients with SpA fulfilling the ASAS classification criteria for axial (axSpA) or peripheral SpA was used. The construct validity of the ASAS HI was tested using Spearman correlation with several standard health outcomes for axSpA. Test-retest reliability was assessed by intraclass correlation coefficients (ICCs) in patients with stable disease (interval 4-7 days). In patients who required an escalation of therapy because of high disease activity, responsiveness was tested after 2-24weeks using standardised response mean (SRM). Among the 1548 patients, 64.9% were men, with a mean (SD) age 42.0 (13.4) years. Construct validity ranged from low (age: 0.10) to high (Bath AnkylosingSpondylitisFunctioning Index: 0.71). Internal consistency was high (Cronbach's α of 0.93). The reliability among 578 patients was good (ICC=0.87 (95% CI 0.84 to 0.89)). Responsiveness among 246 patients was moderate-large (SRM=-0.44 for non-steroidal anti-inflammatory drugs, -0.69 for conventional synthetic disease-modifying antirheumatic drug and -0.85 for tumour necrosis factor inhibitor). The smallest detectable change was 3.0. Values ≤5.0 have balanced specificity to distinguish good health as opposed to moderate health, and values ≥12.0 are specific to represent poor health as opposed to moderate health. The ASAS HI proved to be valid, reliable and responsive. It can be used to evaluate the impact of SpA and its treatment on functioning and health. Furthermore, comparison of disease impact between populations is possible.

Kiltz U ，van der Heijde D ，Boonen A ，Akkoc N ，Bautista-Molano W ，Burgos-Vargas R ，Wei JC ，Chiowchanwisawakit P ，Dougados M ，Duruoz MT ，Elzorkany BK ，Gaydukova I ，Gensler LS ，Gilio M ，Grazio S ，Gu J ，Inman RD ，Kim TJ ，Navarro-Compan V ，Marzo-Ortega H ，Ozgocmen S ，Pimentel Dos Santos F ，Schirmer M ，Stebbings S ，Van den Bosch FE ，van Tubergen A ，Braun J ... -  《-》

A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis.

Axial spondyloarthritis (SpA) is a chronic inflammatory disease characterized by back pain and stiffness. The objective of this study was to determine whether golimumab is superior to placebo in patients with nonradiographic axial SpA. This phase III, double-blind, randomized, placebo-controlled trial was performed to evaluate subcutaneous golimumab (50 mg) versus placebo in patients ages ≥18 years to ≤45 years who had active nonradiographic axial SpA according to the Assessment of SpondyloArthritis international Society (ASAS) criteria for ≤5 years since diagnosis, high disease activity, and an inadequate response to or intolerance of nonsteroidal antiinflammatory drugs. Patients were randomized 1:1 to receive golimumab or placebo subcutaneously every 4 weeks. The primary end point was 20% improvement according to the ASAS criteria (ASAS20) at week 16. Key secondary end points were an ASAS40 response, ASAS partial remission, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and change in the Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) index for sacroiliac (SI) joint inflammation (SPARCC score). Of the 198 patients randomized, 197 were treated (97 received golimumab, and 100 received placebo). The mean age of the patients was 31 years, and 57.1% were male. At baseline, the mean ± SD BASDAI was 6.5 ± 1.5, the mean ± SD ASDAS was 3.5 ± 0.9, and the mean ± SD SPARCC score was 11.3 ± 14.0. The primary end point, an ASAS20 response, was achieved by significantly more patients in the golimumab group compared with the placebo group (71.1% versus 40.0%; P < 0.0001). An ASAS40 response was also achieved by significantly more patients in the golimumab group compared with the placebo group (56.7% versus 23.0%; P < 0.0001). The incidence of adverse events did not differ meaningfully between groups. Patients with active nonradiographic axial SpA treated with golimumab had significantly greater improvement in symptoms compared with patients treated with placebo. Golimumab was well tolerated and had a favorable risk/benefit profile.

Sieper J ，van der Heijde D ，Dougados M ，Maksymowych WP ，Scott BB ，Boice JA ，Berd Y ，Bergman G ，Curtis S ，Tzontcheva A ，Huyck S ，Weng HH ... -  《-》

The European Portuguese version of the ASAS Health Index for Patients with Spondyloarthritis: Measurement properties.

Rodrigues-Manica S ，Cruz E ，Ramiro S ，Sousa S ，Aguiar R ，Sepriano A ，Machado P ，Branco J ，Kiltz U ，Pimentel-Santos F ... -  《-》