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Infliximab treatment reduces depressive symptoms in patients with ankylosing spondylitis: an ancillary study to a randomized controlled trial (ASSERT).

ABSTRACT: BACKGROUND:Patients with ankylosing spondylitis (AS) are at increased risk of depression. This increased risk has been hypothesized to be solely secondary due to AS-related symptoms, or additionally due to a common inflammatory pathway. From a clinical perspective, it is important to know whether treatment with tumor necrosis factor alpha inhibitors reduces depressive symptoms, while from a pathophysiological point of view, it would be insightful to understand whether such an effect would be a direct result of reduced inflammation, the result of reduced AS-related symptoms, or both. The objective of this study was to evaluate the effect of infliximab on depressive symptoms in patients with AS in a randomized-controlled trial setting. METHODS:Data were retrieved from a subgroup of patients from the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT). Patients were randomly allocated to infliximab (n?=?16) or placebo (n?=?7) until week 24, after which all received infliximab until week 54. Associations between treatment group and depressive symptoms, measured with the Center for Epidemiological Studies Depression scale (CES-D, range 0-60 (best-worst)) at baseline and over time, were explored with generalized estimating equations (GEE). RESULTS:Mean CES-D score at baseline was 15.5 (SD 9.3) in the infliximab group and 17.3 (SD 5.7) in the placebo group. Twelve patients (52%) had a CES-D score > 16, suggestive for clinical depression. After 24?weeks, mean CES-D had decreased to 9.5 (SD 11.4) in the infliximab group, but was 18.0 (SD 6.9) in the placebo group. GEE revealed larger improvements in depressive symptoms (B?=?-?6.63, 95%CI -?13.35 to 0.09) and odds of possible depression (OR?=?0.02, 95%CI 0.00 to 0.72) in the infliximab group, compared to the placebo group. Both associations largely disappeared when adjusted for self-reported disease activity and/or physical function. Additional adjustment for C-reactive protein (CRP) did not change results. CONCLUSIONS:Depressive symptoms are common in patients with AS and active disease. Infliximab improves these depressive symptoms in AS when compared to placebo by improving disease symptoms. We did not find an indication for a direct link between CRP-mediated inflammation and depressive symptoms. TRIAL REGISTRATION:Trial registration (ASSERT): NCT00207701 . Registered on September 21, 2005 (retrospectively registered).

SUBMITTER: Webers C

PROVIDER: S-EPMC7523309 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Infliximab treatment reduces depressive symptoms in patients with ankylosing spondylitis: an ancillary study to a randomized controlled trial (ASSERT).

Webers Casper C Stolwijk Carmen C Schiepers Olga O Schoonbrood Thea T van Tubergen Astrid A Landewé Robert R van der Heijde Désirée D Boonen Annelies A

Arthritis research & therapy 20200929 1

<h4>Background</h4>Patients with ankylosing spondylitis (AS) are at increased risk of depression. This increased risk has been hypothesized to be solely secondary due to AS-related symptoms, or additionally due to a common inflammatory pathway. From a clinical perspective, it is important to know whether treatment with tumor necrosis factor alpha inhibitors reduces depressive symptoms, while from a pathophysiological point of view, it would be insightful to understand whether such an effect woul ...[more]

PMID: 32993799

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Project description:ObjectiveTo compare the relative efficacy of intravenous golimumab (GOL IV) and infliximab (IFX) for active ankylosing spondylitis (AS).MethodsPropensity score (PS) methods were used to compare the efficacy of GOL IV 2 mg/kg and IFX 5 mg/kg using individual patient data (IPD) from the active arms of the phase 3 GO-ALIVE and ASSERT studies. Outcomes included the proportion of patients with a ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score, and change from baseline in C-reactive protein (CRP) levels from weeks 4-52.ResultsBefore matching, 105 patients were treated with GOL IV and 201 patients were treated with IFX. After matching on all covariates, 118 patients were included in the ASAS20 analysis, 96 in the BASFI analysis, and 160 in the CRP analysis. After matching, GOL IV showed significantly greater improvement in ASAS20 response than IFX for weeks 28-44 (e.g., OR = 9.05 [95% CI 1.62-50.4] at week 44) and was comparable in change from baseline in BASFI scores and CRP levels to IFX at all time points. Results were robust for inclusion of different sets of covariates in scenario analyses.ConclusionsThis is the first analysis of its kind to leverage clinical trial data to compare two biologics using PS methods in the treatment of active AS. Overall, GOL IV was associated with greater improvement in ASAS20 response than IFX in patients with AS at 28, 36, and 44 weeks of follow-up. Key Points • Although intravenous golimumab (GOL IV) and infliximab (IFX) are the only two IV-based tumor necrosis factor (TNF) inhibitors with demonstrated phase 3 clinical efficacy in patients with ankylosing spondylitis (AS), no study has evaluated their comparative efficacy in a head-to-head trial. • Propensity score matching was used to derive indirect treatment comparisons of GOL IV and IFX for ≥ 20% in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change in Bath Ankylosing Spondylitis Functional Index (BASFI), and change in C-reactive protein (CRP) using individual patient data from the GO-ALIVE and ASSERT phase 3 trials. • Propensity score matched indirect comparisons showed improved relative efficacy of GOL IV compared to IFX; after matching for up to 16 baseline covariates, GOL IV was associated with significantly greater odds of ASAS20 response at weeks 28, 36, and 44 than IFX as well as equivalent changes from baseline in BASFI and CRP. • This novel application of propensity score matching using data from phase 3 trials, the first analysis of its kind in AS, allowed adjustment for important imbalances in prognostic factors between trials to generate estimates of comparative efficacy between GOL IV and IFX in the absence of a head-to-head trial between these treatments.

Project description:Patients with ankylosing spondylitis (AS) experience impaired physical function and reduced quality of life, which puts this group at high risk for depression. Identifying factors associated with depressive symptoms could improve outcomes for this at-risk group. However, few studies have examined the relationship between demographic and clinical variables and depressive symptoms in patients with AS. This cross-sectional correlation study recruited patients with AS by convenience sampling from the division of immunology and rheumatology of a medical center in Northern Taiwan. Participants (N = 120) included 91 males and 29 females, age ? 20 years. Data were collected from chart reviews, and structural questionnaires, which included demographic information regarding employment status, history of falls, impact of AS on work; clinical information relative to AS was obtained from structural questionnaires: the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional index (BASFI), Numerical Rating Scale (NRS), Body Image Scale (BIS), and Beck Depression Inventory-II (BDI-II). Multiple regression analysis identified predictors of depression. The mean BDI-II score was 9.50 ± 8.30; 25% had scores indicating mild to severe depressive symptoms. Mean score on the BIS was 68.17 ± 16.14; 14.2% had fallen within the previous year; and 57.5% reported AS affected their work. Variables associated with depressive symptoms were work affected by AS (? = 0.14, p = .049), occurrence of a fall within the previous year (? = 0.14, p = .032), higher scores on the BASDAI (? = 0.21, p = .032), and lower body image (? = -0.38, p < .001). Clinical professionals should regularly assess patients with AS for depressive symptoms. Health care planning should provide instruction in fall prevention and control of disease activity, and strategies to improve body image, which could improve patients' self-management capabilities and body image as well as mitigate depressive symptoms.

Project description:BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory autoimmune disease. Kunxian capsule, a Chinese patent medicine which has been used in the treatment of immunologic diseases for many years in China, has anti-inflammatory and immunoregulatory effects. This study investigates the efficacy and safety of Kunxian capsules in the treatment of AS.MethodThis was a randomized, double-blind, parallel control clinical trial involving 80 patients with AS who fulfilled the modified New York criteria (1984) and had active disease defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥40 mm under background stable nonsteroidal anti-inflammatory drugs (NSAIDs) for more than 4 weeks. Patients were randomly divided into two groups, the Kunxian group and the placebo group, and Kunxian (0.6 g, three times per day) and the placebo were provided for 12 weeks. The primary endpoint was the Assessment of SpondyloArthritis international Society (ASAS) 20 response rate at week 12. The secondary endpoints were ASAS 40, BASDAI 50, the Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and Ankylosing Spondylitis Disease Activity Score on the basis of C-reactive protein level (ASDAS-CRP) at weeks 2, 6, and 12.ResultsThe primary endpoint of ASAS 20 at week 12 was achieved in 13 of 35 patients (37.1 %) among the Kunxian group, compared with 4 of 33 (12.1 %) in the placebo group (p < 0.05). Significant improvement (BASDAI 50) was also observed between the Kunxian group and the placebo group at week 6 (14 (40 %) and 5 (15.5 %), respectively, p < 0.05). At weeks 2, 6, and 12, the ASDAS-CRP level of the Kunxian group was significantly lower than that of the placebo group, especially at week 6 (p < 0.01). Kunxian obviously reduced CRP levels compared to placebo at weeks 2, 6, and 12 (p < 0.05). Compared with the placebo, Kunxian was associated with greater improvements in signs and symptoms of patients with AS from the baseline to week 12, and significant intergroup differences of additional composite indices of disease activity (i.e., erythrocyte sedimentation rate, patient global assessment of disease activity, total back pain, level of morning stiffness, tender joints, and BASFI scores) were also observed.ConclusionKunxian capsule significantly decreased the disease activity of patients with AS.Trial registrationNCT00953979 . Registered on 5 August 2009.

Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

Infliximab treatment reduces depressive symptoms in patients with ankylosing spondylitis: an ancillary study to a randomized controlled trial (ASSERT).

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Infliximab treatment reduces depressive symptoms in patients with ankylosing spondylitis: an ancillary study to a randomized controlled trial (ASSERT).

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