Comparative Efficacy of Advanced Therapies in the Treatment of Radiographic Axial Spondyloarthritis or Ankylosing Spondylitis as Evaluated by the ASDAS Low Disease Activity Criteria.

INTRODUCTION: With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations. METHODS: A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS. Clinical efficacy was considered by the Ankylosing Spondylitis Disease Activity Score low disease activity (ASDAS LDA) criteria, defined as ASDAS score less than 2.1, among approved therapies. Comparative efficacy in the TNFi-naïve population was assessed utilizing network meta-analysis, while comparative efficacy in the TNFi-IR population was assessed utilizing matching-adjusted indirect comparison. Odds ratios were calculated, from which absolute rates and numbers needed to treat were calculated. Safety in the form of trial-reported and placebo-adjusted rates of discontinuation due to adverse events (AEs) was reviewed. RESULTS: Among the TNFi-naïve population, the estimated ASDAS LDA rate between week 12 and 16 was highest for patients treated with upadacitinib (52.8%) and lowest for patients treated with placebo (11.6%). Among the TNFi-IR population, the estimated ASDAS LDA rate was 41.3% for patients treated with upadacitinib and 17.5% for patients treated with ixekizumab. The trial-reported and placebo-adjusted rates of discontinuation due to AEs were generally low across included advanced therapies. CONCLUSIONS: Relative to other assessed therapies, upadacitinib demonstrated greater clinical efficacy per ASDAS LDA in the treatment of active AS in both TNFi-naïve and TNFi-IR populations. Head-to-head and real-world data comparisons are warranted to both validate these findings and aid medical decision makers.

BASDAI versus ASDAS in evaluating axial involvement in patients with psoriatic arthritis: a pooled analysis of two phase 3 studies.

Objective: In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA. Methods: Patients with active PsA in DISCOVER-1 and DISCOVER-2 (ClinicalTrials.gov: NCT03162796 and NCT03158285, respectively) with or without axPsA but with available baseline BASDAI information were analysed; those with investigator-identified axial symptoms and imaging-confirmed sacroiliitis comprised the axPsA cohort. Correlations between BASDAI/ASDAS and clinical variables were assessed with Pearson's coefficient (r). Longitudinal effects of enthesitis (Leeds Enthesitis Index [LEI]), swollen joint count and presence versus absence of axPsA on BASDAI/ASDAS (normalized 0-10 scale) were analysed with mixed models for repeated measures. Results: At baseline in the axPsA (n = 312) and non-axPsA (n = 124) cohorts, BASDAI scores showed no or weak correlation with swollen joint count (0.18-0.20), tender joint count (0.12-0.29), LEI (-0.04 to 0.24) and physician global assessment (0.35-0.43); moderate correlation with fatigue (both -0.56); and strong correlation with patient global assessment of disease activity (0.62-0.69) and patient-reported pain (0.66-0.70). Similar correlations were observed for ASDAS. Axial involvement versus non-involvement was associated with higher BASDAI scores and ASDAS (all ß ≥ 0.5), without differences between instruments; longitudinal associations between swollen joint count (ß ≤ 0.06)/LEI (ß ≤ 0.19) and BASDAI/ASDAS were clinically unimportant. Conclusion: BASDAI and ASDAS performed similarly in patients with active PsA and axial involvement, independent of peripheral disease involvement, supporting their performance in assessing axial disease activity. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03162796 and NCT03158285.

Comparison of Ankylosing Spondylitis Disease Activity Score and Bath Ankylosing Spondylitis Disease Activity Index tools in assessment of axial spondyloarthritis activity.

Axial spondyloarthritis (axSpA) is an inflammatory joint disease, in which the dominant symptom is inflammatory back pain. It affects approximately 1% of the population, with a higher incidence in males. Spinal pain associated with spondyloarthritis is referred to as inflammatory back pain. In clinical practice, it is extremely important to be able to assess the activity of inflammatory back diseases and to select appropriate treatment and monitor the therapy. Currently, two main tools are used for assessment of the activity of axial spondyloarthritis: BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and ASDAS (Ankylosing Spondylitis Disease Activity Score). The BASDAI is a tool used for years for assessment of disease activity, determining eligibility for treatment, and making decisions about continuation of therapy. Since BASDAI depends entirely on patient self-assessment, it is considered less objective than the ASDAS index. In turn, the latter includes not only answers to questions provided by the patient but also a parameter of inflammation such as erythrocyte sedimentation rate or C-reactive protein (CRP). Additionally, increasing numbers of studies report advantages of the ASDAS index over BASDAI. Moreover, as indicated by ASAS/EULAR (Assessment in Spondyloarthritis International Society/European Alliance of Associations for Rheumatology) 2022, ASDAS, especially ASDAS-CRP is the preferred tool for assessment of the activity of axSpA, whereas BASDAI is used only when the evaluation of the ASDAS is not possible. This paper presents the definition and symptoms of axSpA and reviews the latest research on ASDAS and BASDAI, with emphasis on the objectivity of the ASDAS assessment also presenting the doubts and limitations concerning this tool.

To be or not to B27 positive: implications for the phenotypes of axial spondyloarthritis outcomes. Data from a large multiracial cohort from the Brazilian Registry of Spondyloarthritis.

BACKGROUND: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). METHODS: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. RESULTS: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. CONCLUSIONS: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

The activity of psoriatic arthritis with axial involvement correlates with the PsAID12.

OBJECTIVE: To determine the impact of the disease in patients with PsA in daily clinical practice and to evaluate its relationship with its axial activity. METHODS: A cross-sectional study was conducted in consecutive patients attended from January 2021 to December 2021 who met the CASPAR criteria, with clinical of inflammatory back pain and positive axial imaging, with or without peripheral involvement. Demographic, clinical, analytical data, HAQ index, PsAID12 and activity index (BASDAI and ASDAS-PCR) were also collected. Patients were divided into two groups, those with high impact and those with low impact according to PsAID results. Continuous variables are shown as median (Q1-Q3) and categorical variables as percentages and frequencies. RESULTS: Of the 269 patients evaluated with PsA, 72 patients with axial involvement were included, 40 men (55.6%), with a median age of 54.1 years and disease duration of 7 years. 28.3% of the patients were obese and serum CRP level was 0.45 mg/dl (0.08-1.10). BASDAI was 4.2 (2.0-6.2) and ASDAS-PCR was 2.4 (1.5-3.2), which translates into 39.6% of patients in low activity or remission. The median PsAID total score was 3.9 (1.6-5.4), evaluated in 61 patients. The patients who achieved a PsAID12 ≤ 4 were 63%, mostly men and with lower CRP levels than PsAID ≥ 4 patients. In addition, low impact measured by the PsAID12 was associated with low results in BASDAI and ASDAS-PCR. CONCLUSIONS: Axial involvement reflected lower impact of the disease measured by PsAID12 and it is correlated with low activity measured by BASDAI and ASDAS-PCR.

La actividad de la artritis psoriásica con afectación axial se correlaciona con el PsAID12 / The activity of psoriatic arthritis with axial involvement correlates with the PsAID12

Objetivo: Determinar el impacto de la enfermedad en pacientes con artritis psoriásica (APs) en la práctica clínica diaria, y evaluar su relación con la actividad axial.Métodos: Se realizó un estudio transversal multicéntrico en pacientes consecutivos vistos desde enero 2021 hasta diciembre 2021 que cumplieron con los criterios CASPAR, con clínica dolor lumbar inflamatorio y prueba de imagen positiva, con o sin afectación periférica. También se recogieron datos demográficos, clínicos, analíticos, índice Health Assessment Questionnaire, PsAID12 e índices de actividad axial (BASDAI y ASDAS-PCR). Se dividió a los pacientes en 2 grupos según el alto o bajo impacto del cuestionario PsAID. Las variables continuas se mostraron como mediana (Q1-Q3) y las categóricas como porcentajes y frecuencias. Resultados: Se incluyeron 72 pacientes con afectación axial de los 269 evaluados con APs, 40 varones (55,6%), con una mediana de edad de 54,1 años y duración de la enfermedad de 7 años. El 28,3% de los pacientes eran obesos y el nivel sérico de PCR fue de 0,45mg/dl (0,08-1,10). El BASDAI fue de 4,2 (2,0-6,2) y el ASDAS-PCR de 2,4 (1,5-3,2), estando en baja actividad o remisión el 39,6%. La mediana de la puntuación total de PsAID fue de 3,9 (1,6-5,4), evaluado en 61 pacientes. Los pacientes que alcanzaron un PsAID12≤4 fueron el 63%, predominantemente varones, presentaron valores de PCR menores y se asoció a una menor puntuación de BASDAI y ASDAS-PCR. Conclusiones: Los pacientes con afectación axial reflejaban un bajo impacto de la enfermedad medido por PsAID12 y este se correlacionaba con baja actividad medido por BASDAI y el ASDAS-PCR.(AU)

Objective: To determine the impact of the disease in patients with PsA in daily clinical practice and to evaluate its relationship with its axial activity. Methods: A cross-sectional study was conducted in consecutive patients attended from January 2021 to December 2021 who met the CASPAR criteria, with clinical of inflammatory back pain and positive axial imaging, with or without peripheral involvement. Demographic, clinical, analytical data, HAQ index, PsAID12 and activity index (BASDAI and ASDAS-PCR) were also collected. Patients were divided into two groups, those with high impact and those with low impact according to PsAID results. Continuous variables are shown as median (Q1-Q3) and categorical variables as percentages and frequencies. Results: Of the 269 patients evaluated with PsA, 72 patients with axial involvement were included, 40 men (55.6%), with a median age of 54.1 years and disease duration of 7 years. 28.3% of the patients were obese and serum CRP level was 0.45mg/dl (0.08-1.10). BASDAI was 4.2 (2.0-6.2) and ASDAS-PCR was 2.4 (1.5-3.2), which translates into 39.6% of patients in low activity or remission. The median PsAID total score was 3.9 (1.6–5.4), evaluated in 61 patients. The patients who achieved a PsAID12≤4 were 63%, mostly men and with lower CRP levels than PsAID≥4 patients. In addition, low impact measured by the PsAID12 was associated with low results in BASDAI and ASDAS-PCR. Conclusions: Axial involvement reflected lower impact of the disease measured by PsAID12 and it is correlated with low activity measured by BASDAI and ASDAS-PCR.(AU)

Do Tofacitinib Generics Exhibit Conventional Synthetic Disease-Modifying Anti-rheumatic Drug and Non-steroidal Anti-inflammatory Drug-Sparing Ability in the Management of Axial Spondyloarthritis?

INTRODUCTION: Tofacitinib has emerged as a therapeutic option for axial spondyloarthritis (axSpA) following successful clinical trials. The evidence on the efficacy of tofacitinib generics in the management of axSpA is limited. In India, the usage of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is commonplace in the management of axSpA. Our primary aim was to identify the csDMARD and non-steroidal anti-inflammatory drug (NSAID)-sparing role of tofacitinib generics in an axSpA population. METHODS: This was a retrospective study in a real-world clinical setting. Data from nine rheumatology centers across India were analyzed for 168 patients with active axSpA who were initiated on generic tofacitinib 5 mg twice daily in conjunction with csDMARDs and NSAIDs, over a duration of six months. Our primary outcome was to evaluate the csDMARD and NSAID-sparing effect of tofacitinib generics, while the secondary outcome assessed safety profiles and efficacy at six months. RESULTS: The median Ankylosing Spondylitis Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR) score of the study population was 3.91 (3.26, 4.56). Alongside tofacitinib generics, 121 (72%) patients were co-administered csDMARDs (methotrexate/sulfasalazine/both), and 90 (53.6%) patients were co-administered NSAIDs. The csDMARD, NSAID, and combined csDMARD + NSAID-sparing effects of tofacitinib generics were seen in 85 (50.6%), 156 (92.9%), and 81 (48.2%) patients, respectively. Adverse events were mild and well-tolerated. At six months, 124 (57.9%) patients had attained clinically important improvement in ASDAS ESR score, and the median decrease in ASDAS ESR score was 2.02 (1.18, 2.96). CONCLUSION: This real-world study provides evidence supporting the csDMARD and NSAID-sparing ability of tofacitinib generics in the treatment of axSpA. Tofacitinib generics displayed a good safety profile and showed signals of efficacy as well.

Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: results from two phase 3 studies.

BACKGROUND: The objective of this post-hoc analysis was to assess the efficacy and safety of upadacitinib in psoriatic arthritis (PsA) patients with axial involvement. METHODS: Post-hoc analysis of SELECT-PsA 1 and SELECT-PsA 2 in patients randomized to upadacitinib 15 mg (UPA15), placebo (switched to UPA15 at week 24), or adalimumab 40 mg (ADA; SELECT-PsA 1 only). Axial involvement was determined by investigator judgement (yes or no; based on the totality of available clinical information, such as duration and characteristics of back pain, age of onset, and previous lab investigations and imaging, if available) alone, or investigator judgement and patient-reported outcome (PRO)-based criteria (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4 and BASDAI Q2 ≥ 4). Efficacy outcomes that describe axial disease activity, including BASDAI endpoints, such as change from baseline in the overall BASDAI score or proportion of patients achieving BASDAI50 (≥ 50% improvement from baseline), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints, such as mean change from baseline in overall ASDAS or proportion of patients achieving ASDAS inactive disease or low disease activity, were evaluated at weeks 12, 24, and 56, with nominal P-values shown. Treatment-emergent adverse events (TEAEs) are summarized through week 56. RESULTS: 30.9% of patients in SELECT-PsA 1 and 35.7% in SELECT-PsA 2 had axial involvement by investigator judgement alone; 22.6% (SELECT-PsA 1) and 28.6% (SELECT-PsA 2) had axial involvement by investigator judgement and PRO-based criteria. Greater proportions of patients achieved BASDAI50 with UPA15 versus placebo using either criterion, and versus ADA using investigator judgement alone, at week 24 in SELECT-PsA 1 (investigator alone: UPA15, 59.0%, placebo, 26.9%, P < 0.0001, ADA, 44.1%, P = 0.015; investigator and PRO-based: UPA15, 60.4%, placebo, 29.3%, P < 0.0001, ADA, 47.1%, P = 0.074), with comparable findings in SELECT-PsA 2. Similar results were observed with UPA15 for additional BASDAI and ASDAS endpoints at weeks 12 and 24, with improvements maintained at week 56. Rates of TEAEs were generally similar across sub-groups irrespective of axial involvement status. CONCLUSIONS: PsA patients with axial involvement determined by predefined criteria showed greater BASDAI and ASDAS responses with UPA15 versus placebo, and numerically similar/greater responses versus ADA. Safety results were generally comparable between patients with or without axial involvement. TRIAL REGISTRATION: ClinicalTrials.gov: SELECT-PsA 1, NCT03104400; SELECT-PsA 2, NCT0310437.

Sustained low functional impairment in axial spondyloarthritis (axSpA): which are the primary outcomes that should be targeted to achieve this?

OBJECTIVES: To (i) determine whether sustained disease activity states, as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), impact function, and (ii) evaluate characteristics predicting sustained low functional impairment in a prospective axial spondyloarthritis (axSpA) cohort. METHODS: Biologic Treatment Registry Across Canada (BioTRAC) was a multi-center, prospective registry that collected real-world data on axSpA patients receiving infliximab or golimumab between 2006 and 2017. Generalized estimating equations (GEE) were used to test baseline characteristics, treatment, and duration (at 6 and 12 months vs. only at 6 or 12 months vs. neither) of low BASDAI (< 3), ASDAS-inactive disease (ID)(< 1.3), and ASDAS-low disease activity (LDA) in predicting sustained low Bath Ankylosing Spondylitis Functional Index (BASFI)(< 3) between 12 and 18 months. The adjusted impact of achieving low disease state at 6 and/or 12 months on BASFI at 18 months was analyzed by generalized linear models. RESULTS: Eight hundred ten patients were enrolled. 33.7%, 13.4%, and 24.7% achieved sustained low BASDAI, ASDAS-ID, and ASDAS-LDA, respectively. In univariable GEE of baseline variables, age and baseline BASDAI, BASFI, and ASDAS significantly predicted sustained low BASFI. In multivariable GEE, sustained low BASDAI (p < 0.001), low BASDAI only at 6 or 12 months (p = 0.001), and baseline BASFI (p < 0.001) were the only predictors of sustained low BASFI. Sustained ASDAS-ID (p = 0.040) and ASDAS-LDA (p < 0.001) were also predictors when forced into the model. Similar results were obtained when evaluating the BASFI score at 18 months. CONCLUSION: Sustained BASDAI < 3 may be a valid and feasible target for a treat-to-target strategy in axSpA having function as treatment goal.

Effectiveness and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a 52-week real-life study in an Italian cohort.

BACKGROUND: Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. METHODS: We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. RESULTS: Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. CONCLUSION: In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study.

INTRODUCTION AND OBJECTIVES: Understanding the disease activity is fundamental to improve patient prognosis and patients' quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. METHODS: Observational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). RESULTS: 313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). CONCLUSIONS: Almost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.

Disease control in patients with ankylosing spondylitis in real clinical practice in Spain: Results of the MIDAS study / Control de la enfermedad en pacientes con espondilitis anquilosante en la práctica clínica habitual en España: Resultados del estudio MiDAS

Introduction and objectives: Understanding the disease activity is fundamental to improve patient prognosis and patients’ quality of life. MiDAS study described disease activity in ankylosing spondylitis (AS) Spanish patients and the proportion of them with controlled disease. Methods: Observational, cross-sectional, multicenter study carried out under conditions of routine clinical practice. Adult (≥18 years) patients with ≥6 months since AS diagnosis treated ≥3 months prior to inclusion. The primary endpoint was the percentage of patients with low disease activity assessed through BASDAI (primary endpoint) and ASDAS-CRP (secondary endpoint). Results: 313 AS patients included: 75.7% male; 78.5% HLA-B*27 positive; mean (SD) baseline age of 50.4 (12.0) years; mean (SD) disease duration of 15.5 (11.6) years; 73.5% were treated with biological disease-modifying antirheumatic drugs (DMARDs), 22.4% with non-biological DMARDs and 53.7% with non-steroidal anti-inflammatory drugs, alone or in combination. Monotherapy with biologics and non-biologics was used by 29.7% and 26.8% of patients, respectively. According to BASDAI, 38.0% were in remission (BASDAI≤2) and 64.5% showed adequate disease control (BASDAI<4). According to ASDAS-CRP, 29.4% achieved remission (ASDAS-CRP<1.3) and 28.1% low disease activity (1.3≤ASDAS-CRP<2.1). Conclusions: Almost two thirds of the AS patients recruited had low disease activity, with about one third of them being in remission (BASDAI≤2, ASDAS-CRP<1.3). These results highlight the existing room for improvement in treating AS patients in clinical practice.(AU)

Introducción y objetivos: Comprender la actividad de la enfermedad es fundamental para mejorar el pronóstico y la calidad de vida de los pacientes. El estudio MiDAS describió la actividad de la enfermedad en pacientes españoles con espondilitis anquilosante (EA) y la proporción de ellos con enfermedad controlada. Métodos: Estudio observacional, transversal, multicéntrico, realizado en condiciones de práctica clínica habitual. Pacientes adultos (≥18años) con ≥6meses desde el diagnóstico de EA tratados ≥3meses antes de la inclusión. La variable principal fue el porcentaje de pacientes en baja actividad, evaluado mediante BASDAI (variable principal) y ASDAS-CRP (variable secundaria). Resultados: Hubo 313 pacientes con EA incluidos: 75,7% varones; 78,5% HLA-B*27 positivos; edad media (DE) basal de 50,4 (12,0) años; duración media (DE) de la enfermedad de 15,5 (11,6) años; el 73,5% fueron tratados con fármacos antirreumáticos modificadores de la enfermedad (FAME) biológicos, el 22,4% con FAME no biológicos y el 53,7% con antiinflamatorios no esteroideos, solos o en combinación. La monoterapia con biológicos y no biológicos fue utilizada por el 29,7 y el 26,8% de los pacientes, respectivamente. Según BASDAI, el 38,0% estaban en remisión (BASDAI≤2) y el 64,5% mostraron un adecuado control de la enfermedad (BASDAI<4). Según ASDAS-CRP, el 29,4% alcanzaron remisión (ASDAS-CRP<1,3) y el 28,1% baja actividad de la enfermedad (1,3≤ASDAS-CRP<2,1). Conclusiones: Casi dos tercios de los pacientes con EA incluidos presentaban baja actividad de la enfermedad, con aproximadamente un tercio de ellos en remisión (BASDAI≤2, ASDAS-CRP<1,3). Estos resultados destacan el margen de mejora existente para tratar pacientes con EA en la práctica clínica.(AU)

External validation of the alternative Ankylosing Spondylitis Disease Activity Score in three randomized clinical trials of ixekizumab.

OBJECTIVES: The alternative ASDAS (altASDAS) is an index that can be used when patient global assessment is unavailable. Our aim was to test the truth and discrimination aspects according to OMERACT filter 2.0 of the altASDAS in an external cohort. METHODS: Cohorts from the COAST trials of ixekizumab (COAST-V, -W, -X; 16-week primary endpoint) enrolling radiographic/non-radiographic axial SpA patients were pooled. The ASDAS [original formula with patient global assessment (PGA)] and altASDAS were calculated. Truth was assessed by agreement with the continuous ASDAS [intraclass correlation coefficients (ICCs)] and ASDAS disease activity (DA) states (weighted κ), Bland-Altman plots [mean difference (MD) and 95% limits of agreement (LoA)] and Pearson's correlations between altASDAS/ASDAS and other constructs. Discrimination was tested by the ability of altASDAS to distinguish high/low DA according to nocturnal pain >6/10 as an external anchor and agreement (κ) with ASDAS in major improvement (MI) and clinically important improvement (CII). RESULTS: A total of 958 patients were included. For truth, agreement with ASDAS was very good (ICC = 0.99, κ = 0.91), MD with ASDAS was 0.03 (95% LoA -0.31-0.24) and correlation coefficients of altASDAS with related constructs were within a prespecified 0.3-wide band around those between ASDAS and the same construct. For discrimination, the altASDAS discriminated between DA states and agreed with ASDAS response (κ MI = 0.91, CII = 0.93). CONCLUSIONS: The altASDAS was truthful and discriminative in an external cohort and as such has been fully validated to be used in cases when PGA is unavailable.

Fibromyalgia in Spondyloarthritis: Prevalence and Effect on Disease Activity and Treatment.

BACKGROUND: Fibromyalgia may be associated to Spondyloarthritis with which it shares some common symptoms such as sleep disorders, fatigue and diffuse pain, leading to diagnostic and treatment dilemmas. OBJECTIVES: We aimed to determine the prevalence of fibromyalgia in axial spondyloarthritis and to determine how fibromyalgia might influence the assessments of disease activity and how it might impact treatment. METHODS: An observational cross-sectional study was conducted. The study included 100 patients with axial spondyloarthritis according to the Assessment of SpondyloArthritis international Society criteria. Fibromyalgia was diagnosed based on the 2010 American College of Rheumatology criteria. Demographics, disease characteristics, activity parameters and treatment were compared between patients with and without fibromyalgia. Patients were recruited from the hospitalization unit and the outpatient clinic of rheumatology. RESULTS: The mean age of patients was 44.65 ± 13.13 years, with a sex ratio equal to 2. The prevalence of fibromyalgia was 20%. Fibromyalgia associated factors were advanced age and a late age at the onset of axial spondyloarthritis. Disease activity parameters such as global pain VAS, BASDAI, ASDAS-ESR, ASDAS-CRP, BASFI and BAS-G as well as MASES and BASMI were significantly higher in the presence of FM. Doses of paracetamol were significantly higher among FM+ patients. Also, treatment duration of the current anti-TNF alpha agent was significantly shorter among FM+ patients. CONCLUSION: Our study showed that fibromyalgia was associated with axial spondyloarthritis in 20% of patients. Its presence was associated with higher disease activity parameters and negative impact on the treatment.

Effectiveness and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a 52-week real-life study in an Italian cohort

Abstract Background Secukinumab has shown high efficacy in randomized controlled trials in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Here, we investigated its real-life effectiveness and tolerability in a cohort of AS and PsA patients. Methods We retrospectively analyzed medical records of outpatients with AS or PsA treated with secukinumab between December 2017 and December 2019. ASDAS-CRP and DAS28-CRP scores were used to measure axial and peripheral disease activity in AS and PsA, respectively. Data were collected at baseline and after 8, 24, and 52 weeks of treatment. Results Eighty-five adult patients with active disease (29 with AS and 56 with PsA; 23 males and 62 females) were treated. Overall, mean disease duration was 6.7 years and biologic-naïve patients were 85%. Significant reductions in ASDAS-CRP and DAS28-CRP were observed at all time-points. Body weight (in AS) and disease activity status at baseline (particularly in PsA) significantly affected disease activity changes. ASDAS-defined inactive disease and DAS28-defined remission were achieved in comparable proportions between AS and PsA patients, at both 24 weeks (45% and 46%) and 52 weeks (65.5% and 68%, respectively); male sex was found an independent predictor of positive response (OR 5.16, P = 0.027). After 52 weeks, achievement of at least low disease activity and drug retention were observed in 75% of patients. Secukinumab was well-tolerated and only mild injection-site reactions were recorded in 4 patients. Conclusion In a real-world setting, secukinumab confirmed great effectiveness and safety in both AS and PsA patients. The influence of gender on treatment response deserves further attention.

[Activity of ankylosing spondylitis in women within one year after childbirth].

AIM: To assess the dynamics of activity of ankylosing spondylitis (AS) during the year after childbirth, to identify predictors of high activity. MATERIALS AND METHODS: 75 pregnant with confirmed AS (modified New York criteria, 1984) were included for prospective observation. Of these, 44 women were followed up for 1 year after delivery. The average age of the patients was 32.55.8 years, the duration of the disease was 149.096.3 months. Lactation was established in 40 women and the duration was 10 [4; 12] months. RESULTS: The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) at 1, 6 and 12 months after giving birth was 2.4 [1.4; 4.2], 2.6 [1.4; 4.4] and 2.7 [1.5; 4.1], respectively (p0.05). ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score C-reactive protein) was 2.0 [1.2; 2.7], 1.9 [1.4; 2.5] and 1.7 [1.3; 2.3], respectively (p0.05). There were no differences between the values of BASDAI, ASDAS-CRP between women with and without lactation. Predictors of high AS activity (BASDAI4) 1 month after delivery were: BASDAI4 in the 1st (odds ratio OR 8.1; 95% confidence interval CI 1,837,0) and 2nd trimesters of pregnancy (OR 5.1, 95% CI 1.220.6); NRS back pain 4 in the 2nd trimester (OR 4.3, 95% CI 1.117.2); cancellation of biological disease-modifying antirheumatic drugs therapy in the 1st trimester of pregnancy (OR 21.0, 95% CI 1.0440.9). Predictors of high AS activity in 6 months after delivery were: BASDAI4 in the 1st (OR 6.5, 95% CI 1.528.7), in the 2nd (OR 6.7, 95% CI 1.627.8) and in the 3rd trimesters of pregnancy (OR 8.7, 95% CI 1.938.6); high activity in 1 month after delivery (OR 4.0, 95% CI 1.015.9). CONCLUSION: AS activity remains stable for 1 year after delivery. High AS activity during pregnancy was a risk factor for high activity within 6 months after delivery.

The BASDAI Cut-Off for Disease Activity Corresponding to the ASDAS Scores in a Taiwanese Cohort of Ankylosing Spondylitis.

Objectives: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort. Methods: From November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5). Results: In our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively. Conclusion: We propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.

Residual Disease in Patients with Axial Spondyloarthritis: A Post-Hoc Analysis of the QUASAR Study.

In this study, we evaluated the presence of residual disease in patients with axial spondyloarthritis (axSpA) in remission/low disease activity (LDA) status. This cross-sectional post-hoc analysis of the QUASAR study involving 23 rheumatology centres across Italy included adults with axSpA classified according to the Assessment of SpondyloArthritis International Society criteria. Patients with inactive disease (score < 1.3) or at least LDA status (score < 2.1) at baseline visit according to Ankylosing Spondylitis Disease Activity Score were investigated to evaluate how residual disease activity impacts patients' quality of life. They were assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) and EuroQoL 5-Dimension 5-Level (EQ-5D-5L) questionnaires. This study included 480 patients with axSpA (mean age, 47.5 ± 12.9 years, 64% male). In total, 123 patients (25.6%) had inactive disease and 262 (54.6%) had at least LDA. Using the ASQoL, ranges of 10−25% and 20−40% of patients with inactive disease and with LDA status, respectively, experienced tiredness/fatigue. Despite being classified with inactive disease, 48.8% of patients reported light pain/discomfort according to the EQ-5D-5L, with 4.1% reporting moderate pain/discomfort, whereas 55.7% of patients with LDA reported light pain/discomfort and 13% had moderate pain/discomfort. Using the ASQoL questionnaire, in patients with at least LDA, a higher proportion of women compared with males and a higher proportion of patients > 48 years of age (vs. patients ≤ 48 years) experienced tiredness. In this post-hoc analysis, ≥25% of axSpA patients in remission/LDA status were still burdened by residual disease, mainly characterised by pain and fatigue.

The roles of Single Nucleotide Polymorphism (SNP) Endoplasmic Reticulum Aminopeptidase 1 (ERAP 1) gene in axial spondyloarthritis Indonesian adults.

Background: Axial Spondyloarthritis (AxSpA) is chronic inflammatory arthritis involving the axial joint whose pathogenesis is related to the SNP ERAP1 gene, HLA B27, and cytokine proinflammatory (IL-17A and IL-23). Objective: Analyzed the role of SNP gene ERAP1 on disease activity and proinflammatory cytokines. Methods: This study comprised of two phases including a cross-sectional study and an in-vitro experiment in post-test with a control-group design. Participants underwent a PCR investigation searching for HLA-B27. Disease activities were measured by Ankylosing Spondylitis Disease Activity Score-Erythrocyte Sedimentation Rate (ASDAS-ESR) and modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS). Subjects with HLA-B27 positive underwent PCR ERAP1 gene rs27434, genome-sequencing, and analysis. ELISA sandwich method was used to measure ERAP-1, IL-17, and IL-23 levels with lipopolysaccharide and IFN-γ induction. Analysis using independent t-test, Mann Whitney, and Pearson correlation test with p < 0.05. Results: The average ASDAS-ESR was 3.33 ± 0.89 and the average mSASSS was 26.53 ± 9.90. In HLA B27 positive group, SNP ERAP1 gene rs 27434 in which alleles A changed to G and A/G with genotypes AA to AG/GG was observed. SNPs of the ERAP1 gene had a correlation on mSASSS (r = 0.553; p < 0.05) and no correlation on ASDAS-ESR (r = 0.232; p = 0.235). There were significant differences observed in the SNP ERAP1 gene on ERAP1 and IL-17A levels in subjects with lipopolysaccharide and IFN-γ induction (p = 0.05) but no significant difference in IL-23 levels (p > 0.05). Conclusion: The SNP ERAP1 gene affects mSASSS value, ERAP1 levels, and IL-17A levels whereas ASDAS-ESR value and IL-23 level were not associated.

Validation of the ASDAS with a quick quantitative CRP assay (ASDAS-Q) in patients with axial SpA: a prospective multicentre cross-sectional study.

Objectives: The objective of the study was to validate the Ankylosing Spondylitis Disease Activity Score (ASDAS) based on a quick quantitative C-reactive protein (qCRP) assay (ASDAS-Q) in a multicentre, prospective, cross-sectional study in patients with axial spondyloarthritis (axial SpA). Methods: Disease activity assessment was performed in prospectively recruited patients with axial SpA. Routine laboratory CRP was determined in the central laboratory of each study centre, while quick qCRP and erythrocyte sedimentation rate (ESR) were measured locally. Consequently, ASDAS-CRP, ASDAS-Q using the qCRP and ASDAS-ESR were calculated. The absolute agreement on the disease activity category ascertainment was analysed with cross-tabulations and weighted Cohen's kappa. Bland-Altman plots and intraclass correlation coefficients (ICCs) were used to analyse the criterion validity. Results: Overall, 251 axial SpA patients were included in the analysis. The mean qCRP value (6.34 ± 11.13 mg/l) was higher than that of routine laboratory CRP (5.26 ± 9.35 mg/l). The ICC for routine laboratory CRP versus qCRP was 0.985 [95% confidence interval (CI): 0.972-0.991]. Comparing ASDAS-Q with ASDAS-CRP, 242 of 251 (96.4%) patients were assigned to the same disease activity categories with a weighted Cohen's kappa of 0.966 (95% CI: 0.943-0.988) and ICC of 0.997 (95% CI: 0.994-0.999). Conclusions: ASDAS-Q showed an almost perfect agreement with ASDAS-CRP in the assignment to specific disease activity categories. Consequently, ASDAS-Q using the qCRP value can be applied as an accurate and quickly available alternative to ASDAS-CRP, thus facilitating the implementation of the treat-to-target concept in clinical trials and clinical routine.