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

2013 ◽  
Vol 73 (3) ◽  
pp. 587-594 ◽  
Author(s):  
Feng Huang ◽  
Jieruo Gu ◽  
Ping Zhu ◽  
Chunde Bao ◽  
Jianhua Xu ◽  
...  

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 and safety of adalimumab in Chinese patients with AS.MethodsChinese adults with active AS who had an inadequate response or were intolerant to ≥1 non-steroidal anti-inflammatory drugs were randomised to adalimumab 40 mg (N=229) or matching placebo (N=115) subcutaneously every other week (EOW) for 12 weeks, followed by a 12-week open-label adalimumab 40 mg EOW phase. The primary efficacy endpoint was the percentage of patients meeting the Assessment in Spondyloarthritis International Society (ASAS20) response criteria at week 12. The recently developed AS Disease Activity Score (ASDAS), as well as efficacy measures of spinal mobility, disease activity, physical function and quality of life were evaluated.ResultsAt week 12, adalimumab treatment resulted in a significantly greater percentage of ASAS20 responders than placebo (67.2% versus 30.4%, respectively; p<0.001). Differences in ASAS20 were observed as early as week 2 (42.8% vs 6.1%, respectively; p<0.001). The percentages of patients achieving ASAS40, ASAS 5/6 and ASDAS inactive disease were significantly greater with adalimumab than placebo at week 12 (all p<0.001). Tuberculosis was reported in one patient. No cases of malignancy, lymphoma, demyelinating disease or lupus-like syndrome were reported during the study.ConclusionsAdalimumab significantly reduced the signs and symptoms, improved physical function and quality of life of Chinese patients with active AS, and was generally safe and well tolerated in this population.

2017 ◽  
Vol 45 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Linda E. Dean ◽  
Gary J. Macfarlane ◽  
Gareth T. Jones

Objective.A chronic inflammatory condition manifesting in young adulthood, ankylosing spondylitis (AS) affects both physical and emotional quality of life (QOL). To inform future intervention strategies, this study aimed to (1) assess the QOL of patients with AS, and (2) identify potentially modifiable factors associated with reporting poor QOL.Methods.The Scotland Registry for Ankylosing Spondylitis collects clinical and patient-reported data on clinically diagnosed patients with AS across Scotland. QOL is measured using the ASQoL questionnaire [range: 0 (high) to 18 (poor)]. Potentially modifiable factors associated with reporting poor QOL (score 12–18) were examined using Poisson regression models, adjusted for a variety of demographic characteristics, plus various nonmodifiable factors. Results are given as risk ratios (RR) with 95% CI.Results.Data were available on 959 patients: 74% male, mean age 52 years (SD 13), median ASQoL 7.0 (interquartile range 2–12). Although many factors were univariately associated with poor QOL, 5 were identified as independent predictors: reporting moderate/severe fatigue (RR 1.60, 95% CI 1.13–2.28), poor physical function [Bath Ankylosing Spondylitis Functional Index (BASFI) ≥ 4: 3.46, 1.76–6.82], chronic widespread pain (CWP; 1.92, 1.33–2.75), high disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4: 1.52, 1.09–2.12], and poor spinal mobility [Bath Ankylosing Spondylitis Metrology Index (BASMI) ≥ 4: 1.52, 0.93–2.50]. For these factors, population-attributable risks ranged between 20% (disease activity) and 56% (physical function).Conclusion.We have identified 5 potentially modifiable factors independently associated with poor QOL. These findings provide evidence that in addition to traditional clinical targets (BASDAI, BASFI, and BASMI), focus on nonspecific symptoms (CWP and fatigue), perhaps with nonpharmacological therapies, may yield important improvements in QOL.


2019 ◽  
Vol 46 (10) ◽  
pp. 1277-1283 ◽  
Author(s):  
John D. Reveille ◽  
Atul Deodhar ◽  
Paul H. Caldron ◽  
Anna Dudek ◽  
Diane D. Harrison ◽  
...  

Objective.Evaluate safety and efficacy of intravenous (IV) golimumab (GOL) in patients with active ankylosing spondylitis (AS) through 1 year.Methods.A total of 208 patients were randomized to IV infusions of GOL 2 mg/kg (n = 105) at weeks 0, 4, and every 8 weeks thereafter or placebo (n = 103) at weeks 0, 4, and 12, then crossover to GOL at weeks 16, 20, and every 8 weeks thereafter through Week 52. Efficacy was assessed using the Assessment of Spondyloarthritis international Society (ASAS) criteria, the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Bath Ankylosing Spondylitis Functional Index (BASFI). Health-related quality of life was assessed using the AS Quality of Life (ASQoL) index. Efficacy and safety were monitored through Week 52 and Week 60, respectively.Results.The primary endpoint (ASAS20) and all controlled endpoints at Week 16 were achieved. At Week 52, 69.5% and 65.0% of patients in the GOL group and placebo crossover group, respectively, achieved an ASAS20; 56.2% and 51.5% achieved an ASAS40; 56.2% and 55.3% achieved a BASDAI50; 24.8% and 24.3% achieved ASAS partial remission; and 25.7% and 26.2% met ASDAS inactive disease criteria (all last observation carried forward). Mean changes from baseline to Week 52 in BASFI and ASQoL scores were similar between the GOL group and the placebo crossover group (BASFI: −2.7 and −2.6; ASQoL: −5.5 and −5.4). Through Week 60, 55.4% of all GOL-treated patients had ≥ 1 adverse events (AE); 3.4% had ≥ 1 serious AE.Conclusion.Efficacy was maintained through 1 year with IV GOL 2 mg/kg among patients with active AS. AE were consistent with the known safety profile of GOL.


2017 ◽  
Vol 42 (06) ◽  
pp. 544-550
Author(s):  
C. Hillebrecht ◽  
B. Wolff ◽  
H. Kleine ◽  
C. Baerwald ◽  
J. Kuipers

Abstract Summary Background Rheumatology practice has seen an increasing development and use of scores to assess disease activity, loss of physical function, quality of life and radiographic damage. Study results, in particular for rheumatoid arthritis, demonstrate that target-oriented treatment concepts using scores lead to improved treatment results (Treat-to-Target). Objective To review how frequently scores are used in daily rheumatological practice to assess disease activity, loss of physical function and treatment response in patients with ankylosing spondylitis and how much treatment decisions are influenced by the use of these scores. Methods A Germany-wide prospective multicentre study 74 sites (61 rheumatologists in private practice and 13 hospital-based rheumatologists) documented the use of scores for assessing disease activity, treatment response, quality of life and imaging results in patients with ankylosing spondylitis (AS) (18–83 years) over 3 consecutive visits. A total of 1 476 fully evaluable visits of 492 patients [326 (66.26%) men and 166 (33.74%) women] were recorded. Results The most commonly used scores were BASDAI (n=1.134, 84% of all visits) and BASFI (n=500, 37.5%). At least one score was calculated in 1.335 visits (90.45%); a combination of several scores was calculated in 748 visits (50.68%). Only in 141 visits (9.55%) no scores were calculated at all. Scores were used independently of patients’ age, duration of treatment, medication, and treatment changes and region of the participating rheumatologist. Scores recording treatment response (ASAS response) or quality of life were recorded in a few cases only. The average influence of a score on a treatment decision was 5.67 on a scale from 0 to 10.


2014 ◽  
Vol 41 (6) ◽  
pp. 1095-1103 ◽  
Author(s):  
Désirée van der Heijde ◽  
Atul Deodhar ◽  
Jürgen Braun ◽  
Michael Mack ◽  
Benjamin Hsu ◽  
...  

Objective.To evaluate the effects of golimumab therapy on achieving inactive disease or major improvement, as assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS), and improvements in health-related quality of life (HRQOL) and productivity through 2 years in patients with AS.Methods.In the phase III GO-RAISE trial, 356 patients were randomized to placebo with crossover to golimumab 50 mg at Week 24 (n = 78), golimumab 50 mg (n = 138), or golimumab 100 mg (n = 140) at baseline and every 4 weeks. The proportions of patients with ASDAS major improvement (improvement ≥ 2.0) or inactive disease (score < 1.3) were determined. HRQOL was assessed using the 36-item Medical Outcomes Study Short Form-36 physical/mental component summary (SF-36 PCS/MCS) scores (normal score ≥ 50). The effect of disease on productivity was assessed by visual analog scale (0–10). Regression analyses on the association of disease activity and HRQOL were performed. The final assessment was at Week 104.Results.Significantly greater proportions of golimumab-treated patients achieved ASDAS major improvement or inactive disease at weeks 14 and 24 versus placebo. Through Week 104, patients who achieved ASDAS inactive disease or major improvement had significantly greater improvements in SF-36 PCS and MCS scores and productivity than did patients not meeting these targets. Among all patients, achieving ASDAS inactive disease at weeks 52 and 104 was associated with normalized SF-36 PCS/MCS scores and significant improvements in work productivity.Conclusion.Greater proportions of golimumab-treated patients achieved ASDAS major improvement or inactive disease and improved HRQOL versus placebo. Achieving an inactive disease state by ASDAS criteria (< 1.3) was associated with normalized HRQOL through 2 years.


2020 ◽  
Vol 16 (4) ◽  
pp. 311-318 ◽  
Author(s):  
Gehan Elolemy ◽  
Ahmed Aboughanima ◽  
Sahar Ganeb ◽  
Haytham Elziat

Background: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease leading to functional limitations and subsequently impaired quality of life (QoL). Despite the fact that QoL was recognized as a significant perception, it was excluded from the core domains (defined by the Assessment of Spondyloarthritis International Society), because of ambiguity of measurement choice. Aim: To assess QoL in patients with AS using a generic; Short Form-36 (SF-36) and a diseasespecific; Ankylosing Spondylitis quality of life (ASQoL) instruments and to explore its relationship to the clinical characteristics, disease activity, functional status, and radiographic severity. Methods: A total of 47 AS patients who fulfilled modified New York criteria were included. Disease activity, functional status, spinal mobility, and radiographic severity were assessed by Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI) and Bath AS Radiology Index (BASRI) respectively. SF-36 and ASQoL instruments evaluated Qol. Results: Physical health was more affected especially in patients with peripheral arthritis by SF-36 (p=0.008) and ASQoL (p=0.022) scores. Both SF-36 total and ASQoL scores correlated significantly with BASDAI (r = -0.329, p = 0.024 and r = 0.420, p = 0.003), BASFI (r = -0.399, p = 0.005 and r = 0.513, p=0.001) and BASMI (r = -0.382, p = 0.008 and r = 0.482, p= 0.001) respectively. Conclusion: QoL was impaired in AS patients with highest impact on physical health especially in association with peripheral arthritis. SF-36 and ASQol have a comparable achievement in the evaluation of QoL in AS patients and both physical function and spinal mobility were identified as predictors of poor QoL.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1272.2-1272
Author(s):  
W. Zhou ◽  
J. Guo ◽  
R. Zhao ◽  
C. Dong ◽  
Z. Gu

Background:Ankylosing spondylitis (AS) is a systemic chronic inflammatory disease, which most likely occurs in young men. It mainly affects sacroiliac joints, axial skeleton, thoracic cage and seriously decreasing quality of life in AS patients[1,2]. In recent years, fatigue of AS patients has been paid more and more attention[3]. Fatigue is a complex feeling, diseased individuals describe fatigue as a sense of tiredness at rest, exhaustion with activity, lack of energy which affects daily work, inertia or lack of endurance, or as loss of vitality. It has been confirmed that fatigue is not only a symptom but may also be quantified by fatigue scores and can be modified by various measures depending on the underlying cause[4]. However, there has been no study about fatigue in AS patients in China.Objectives:This study aimed to evaluate the predictors of fatigue and the effects of fatigue on HR-QoL among patients with AS.Methods:A total of 150 AS patients were involved in the study. A series of questionnaires included: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), the 10 cm Visual Analog Scale (VAS), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Pittsburgh Sleep Quality Index (PSQI), the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Short Form 36 Health Survey (SF-36) and the Fatigue Severity Scale(FSS). Independent samples t-test, Mann–Whitney U-test, Chi-square analysis, Pearson /Spearman correlation and binary logistic regression were used to analyze the data.Results:The results demonstrated that 48.7% individuals with AS suffered from fatigue. Compared with AS patients without fatigue, AS patients with fatigue showed higher WHR(P<0.05), increased BASDAI (P<0.01) and poorer BASFI (P<0.05). Meanwhile, AS patients with fatigue tended to have more severe pain(P<0.05), higher degree of anxiety(P=0.001), more serious functional disability(P=0.001) and worse sleep quality(P=0.001). Binary logistic regression indicated that WHR (OR=1.78,P<0.05), BASDAI (OR=1.34,P=0.01), sleep disturbance (OR=2.35,P<0.05) were independent predictors of fatigue in AS patients. Additionally, the occurrence of fatigue significantly reduced the quality of life in AS patients both physically and psychologically.Conclusion:These findings suggested that medical personnel should pay more attention to AS patients with fatigue and take effective measures to relieve fatigue.References:[1]Law L, Beckman Rehnman J, Deminger A, Klingberg E, Jacobsson LTH, Forsblad-d’Elia H (2018) Factors related to health-related quality of life in ankylosing spondylitis, overall and stratified by sex. Arthritis research & therapy 20 (1):284. doi:10.1186/s13075-018-1784-8[2]Hanson A, Brown MA (2017) Genetics and the Causes of Ankylosing Spondylitis. Rheumatic diseases clinics of North America 43 (3):401-414. doi:10.1016/j.rdc.2017.04.006[3]Ulus Y, Akyol Y, Bilgici A, Kuru O (2019) Association of work instability with fatigue and emotional status in patients with ankylosing spondylitis: comparison with healthy controls. Clinical rheumatology 38 (4):1017-1024. doi:10.1007/s10067-018-4366-x[4]Finsterer J, Mahjoub SZ (2014) Fatigue in healthy and diseased individuals. The American journal of hospice & palliative care 31 (5):562-575. doi:10.1177/1049909113494748Acknowledgments:Thanks to all the authors for their efforts and thanks to all members of the Department of Rheumatology of Affiliated Hospital of Nantong University for their helpfulness in the acquisition of data.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1709-1710
Author(s):  
A. M. Orbai ◽  
J. Gratacos-Masmitja ◽  
E. Dokoupilova ◽  
B. Combe ◽  
A. Constantin ◽  
...  

Background:Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets IL-17A, has shown improvements compared to placebo (PBO) not only in disease activity but also in various patient-reported outcomes (PROs) assessing physical function, quality of life (QoL), and work productivity in PsA patients treated for 24 weeks and sustained up to 52 weeks.1, 2Objectives:To report the effects of treatment with IXE on these PROs after up to 3 years of treatment.Methods:In SPIRIT-P2 (NCT02349295), a Phase 3 trial, 363 adult patients with active PsA and prior inadequate response or intolerance to 1 or 2 TNF inhibitors (TNFis) were randomized 1:1:1 to IXE 80 mg every 4 weeks (IXEQ4W; N=122) or every 2 weeks (IXEQ2W; N=123), or PBO (N=118) in the double-blind treatment period (Weeks 0-24). Both IXE regimens had a starting dose of 160 mg. Results are reported from a subset of the intent-to-treat population who were randomized to IXE at baseline (Week 0). The following PROs were assessed during Weeks 0-156: HAQ-DI (minimally clinically important difference [MCID] an improvement ≥0.35), medical outcomes survey Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS), European Quality of Life 5 Dimensions Visual Analog Scale (EQ-5D VAS), and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP; absenteeism, presenteeism, work productivity, and activity impairment). Missing values were imputed by observed analysis and modified baseline observation carried forward (mBOCF) for continuous data or by modified non-responder imputation (mNRI) for categorical data.Results:Mean baseline scores for SF-36 (PCS and MCS), EQ-5D VAS, and WPAI-SHP (Figure 1) and HAQ-DI (mean [SD]: IXEQ4W=1.2 [0.6]; IXEQ2W=1.2 [0.6]), indicated impaired physical function and QoL. The percentage of patients of who completed 156 weeks of the study in IXEQ4W and IXEQ2W arms were 57.4% (n=70) and 44.7% (n=55), respectively. Patients receiving IXE treatment up to 3 years reported sustained improvements in SF-36 (PCS and MCS), EQ-5D VAS, and WPAI-SHP (presenteeism, work productivity, and activity impairment) (Figure 1). Observed HAQ-DI mean change from baseline in IXEQ4W: -0.46 (0.62) and IXEQ2W: -0.48 (0.55). The percentage of IXE treated patients achieving MCID for HAQ-DI (improvement ≥0.35) was sustained at 3 years (Figure 2).Figure 1.Summary of Patient-Reported Outcomes presented as change from baseline at Week 156 (Observed and mBOCF): Intent-to-Treat Population (Patients Randomized to IXE at Baseline)Figure 2.Patients achieving HAQ-DI MCID Response up to Week 156 (Observed) and at Week 156 (mNRI) among patients with HAQ-DI≥0.35 at baseline: Intent-to-Treat Population (Patients Randomized to IXE at Baseline)Conclusion:Improvements in PROs, measuring physical and mental function, quality of life, and work productivity are maintained up to 3 years with IXE treatment in patients with active PsA who have had an inadequate response or intolerance to 1 or 2 TNFis.References:[1]Nash P, et al. Lancet. 2017;389(10086):2317-2327.[2]Genovese MC, et al. Rheumatology (Oxford). 2018;57(11):2001-2011.Disclosure of Interests:Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service., Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Eva Dokoupilova Grant/research support from: Eli Lilly and Abbvie, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Arnaud Constantin Grant/research support from: Study was sponsored by Sanofi Genzyme, Consultant of: Consulting fees from Abbvie, BMS, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, Amanda M. Gellett Shareholder of: Eli Lilly and company, Employee of: Eli Lilly and company, Aubrey Trevelin Sprabery Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Julie Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Vladimir Geneus Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB


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