Ankylosing Spondylitis Disease Activity Score Inactive Disease Research Articles

Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study

BackgroundUpadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.MethodsPatients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.ResultsOf 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.ConclusionsUpadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.Trial registrationNCT02049138.

Early Improvements in Disease Activity Indices Predict Long-Term Clinical Remission Suggested by the Treat-to-Target Strategy in Patients with Ankylosing Spondylitis Receiving TNF-α Inhibitor Treatment.

This study evaluated the possibility of clinical remission suggested by the treat-to-target strategy and identified predictors of clinical remission in 139 patients with ankylosing spondylitis (AS) receiving tumor necrosis factor-α inhibitors (TNFi). Clinical remission criteria selected were AS Disease Activity Score Inactive Disease (ASDAS-ID) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 2 with normal C-reactive protein (CRP) levels (BASDAI-CRP). The longitudinal relationship between clinical parameters and clinical remission was assessed using generalized estimating equations (GEEs). Responders to ASDAS-ID and BASDAI-CRP increased from 32.4% to 68.9% and from 39.9% to 75.2% at months 3 and 33, respectively. Responders to ASDAS-ID and BASDAI-CRP almost overlapped. In the univariable GEE model, age and 3-month improvement in BASDAI, ASDAS-CRP, physician and patient global assessments, and spinal pain predicted clinical remission achievement, while the presence of syndesmophytes predicted ASDAS-CRP achievement, and normalized CRP at 3 months was associated with BASDAI-CRP achievement. Multivariable GEE analysis revealed age (odds ratio (OR): 0.67; 95% confidence interval (CI), 0.49–0.93) and 3-month BASDAI improvement (OR: 1.70; CI, 1.19–2.41) as independent predictors of ASDAS-ID achievement and age (OR: 0.69; CI, 0.54–0.89), 3-month BASDAI improvement (OR: 2.00; CI, 1.45–2.76), and normalized CRP at 3 months (OR: 3.72; CI, 1.39–9.95) as independent predictors of BASDAI-CRP achievement.

Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies

IntroductionClinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score ≤ 2.MethodsThe analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored.ResultsAt week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P < 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI ≤ 2, 74.3%). Remission was also associated with improved PROs over 156 weeks.ConclusionsSecukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS.Trial registrationClinicalTrials.gov: NCT01358175, NCT01863732, and NCT01649375Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-020-00269-6.

FRI0273 EFFECTIVENESS AND RETENTION RATE OF SECUKINUMAB FOR PSORIATIC ARTHRITIS AND AXIAL SPONDYLOARTHRITIS: REAL-LIFE DATA FROM THE ITALIAN LORHEN REGISTRY

Background:Observational data on the use of secukinumab for the treatment of spondyloarthritides are still lacking. Large population-based registries that allow long-term follow-up have been increasingly used to investigate the performance of biologic drugs in a real life setting.Objectives:The aim of this study is to evaluate the effectiveness and the retention rate of secukinumab in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients in a real-life setting over a 3-year follow-up period.Methods:Data of all PsA and axSpA patients (diagnosed according to CASPAR and ASAS criteria, respectively) treated with secukinumab were prospectively collected in the Italian multicentric LORHEN registry. Effectiveness was measured as the mean change from baseline of Disease Activity in PSoriatic Arthritis score (DAPSA) in PsA and Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. Rates of DAPSA remission and ASDAS inactive disease were also computed. The 3-year retention rate was calculated by the Kaplan-Meier method and compared between PsA and axSpA by a log-rank test. A descriptive analysis of reasons for discontinuation was performed.Results:The study population included 195 PsA (55.4% females, mean age 50.7 [±11.8] years, mean disease duration 10 [±7.8] years, mean baseline DAPSA 23.12 [±12.3]) and 94 axSpA (61.7% males, mean age 49.1 [±12.7] years, mean disease duration 10.4 [±9.4] years, mean baseline ASDAS 3.41 [±1.1]) patients who received secukinumab as first (26.5 and 33%, respectively) or subsequent biologic agent. Compared with baseline, the 3-, 6- and 12-month mean values of both DAPSA (12.6 [±9], 11.2 [±10.5] and 9.3 [±7.5], respectively) and ASDAS (2.23 [±0.9], 2.15 [±0.9], and 1.84 [±0.9], respectively) were significantly decreased (p&lt;0.001 for all the timepoints). The 3-, 6-, and 12-month rates of remission/inactive disease were 15.5, 25.4, and 30.5% in PsA and 18, 23.7, and 28.6% in axSpA group, respectively. One- and 3-year retention rate (figure 1) were respectively 79.4% and 66.6% in PsA and 72.3% and 70.1% in axSpA patients, with no significant difference between the two groups (p=0.517). The most frequent reason for withdrawal was inefficacy in both PsA (n=41) and axSpA (n=20), whereas only 8 PsA and 6 axSpA patients discontinued secukinumab because of adverse events.Conclusion:Our data confirmed in a real-life setting the 1-year clinical efficacy and the 3-year survival of secukinumab in both PsA and axSpA. The safety profile of secukinumab was very favorable for both the indications. No significant differences were observed in the performance of secukinumab between ax-SpA and PsA.

Eligibility criteria for biologic disease-modifying antirheumatic drugs in axial spondyloarthritis: going beyond BASDAI

ObjectivesTo compare definitions of high disease activity of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in selecting patients for treatment with biologic...

The Sex Influence on Response to Tumor Necrosis Factor-α Inhibitors and Remission in Axial Spondyloarthritis.

The aim of this study was to evaluate the influence of sex on response to treatment and disease remission in patients with axial spondyloarthritis (axSpA). In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria for axSpA, and treated with adalimumab, etanercept, golimumab, or infliximab, were studied. We compared clinical characteristics, patient-reported outcomes, disease activity, function, and response to treatment in male and female patients with this disease. Three hundred forty patients with axSpA (270 with ankylosing spondylitis, 19 with psoriatic arthritis with axial involvement, and 51 with nonradiographic axSpA) were studied. Male subjects had a significantly higher prevalence of grade IV sacroiliitis, higher levels of serum C-reactive protein, lower Maastricht Ankylosing Spondylitis Enthesitis Score, and fatigue when compared with females. Further, Kaplan-Meier survival curves showed that the rate of partial remission, ASAS40 response, and Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement, but not ASDAS inactive disease, were significantly lower in female patients. Our data suggest that female sex was associated with a lower rate of response to treatment and of disease remission in patients with axSpA treated with antitumor necrosis factor-α drugs.

The Sex Influence on Response to Tumor Necrosis Factor-α Inhibitors and Remission in Axial Spondyloarthritis.

The aim of this study was to evaluate the influence of sex on response to treatment and disease remission in patients with axial spondyloarthritis (axSpA). In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria for axSpA, and treated with adalimumab, etanercept, golimumab, or infliximab, were studied. We compared clinical characteristics, patient-reported outcomes, disease activity, function, and response to treatment in male and female patients with this disease. Three hundred forty patients with axSpA (270 with ankylosing spondylitis, 19 with psoriatic arthritis with axial involvement, and 51 with nonradiographic axSpA) were studied. Male subjects had a significantly higher prevalence of grade IV sacroiliitis, higher levels of serum C-reactive protein, lower Maastricht Ankylosing Spondylitis Enthesitis Score, and fatigue when compared with females. Further, Kaplan-Meier survival curves showed that the rate of partial remission, ASAS40 response, and Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement, but not ASDAS inactive disease, were significantly lower in female patients. Our data suggest that female sex was associated with a lower rate of response to treatment and of disease remission in patients with axSpA treated with antitumor necrosis factor-α drugs.

Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS)

ObjectiveTo evaluate efficacy and safety of ustekinumab in patients with ankylosing spondylitis (AS).MethodsIn this prospective, open-label, single-arm, proof-of-concept clinical trial (ClinicalTrials.gov identifier NCT01330901), ustekinumab in a dose of 90 mg...

THU0367 Fast Relapse Upon Discontinuation of Tumor Necrosis Factor Blocking Therapy in Patients with Peripheral Spondyloarthritis

BackgroundTumour necrosis factor (TNF) blockade is highly effective for the treatment of spondyloarthritis (SpA). Unfortunately, in axial SpA, anti-TNF therapy discontinuation leads to fast disease relapse in almost all patients....

Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial

Background and objectivesEfficacy of adalimumab for ankylosing spondylitis (AS) has been established for Western populations but not in the Chinese population. This study is the first to evaluate the efficacy...

Efficacy and safety of adalimumab for the treatment of peripheral arthritis in spondyloarthritis patients without ankylosing spondylitis or psoriatic arthritis

ObjectivesTo evaluate the efficacy and safety of adalimumab in patients with peripheral spondyloarthritis (SpA) not fulfilling the criteria for ankylosing spondylitis (AS) or psoriatic arthritis (PsA).Methods40 patients with active peripheral...

Early response to adalimumab predicts long-term remission through 5 years of treatment in patients with ankylosing spondylitis

ObjectivesTo describe the efficacy and safety through 5 years of adalimumab treatment in patients with ankylosing spondylitis (AS), and to identify predictors of remission.MethodsPatients with active AS were followed up...