Physical function, disease activity, and health-related quality-of-life outcomes after 3 years of adalimumab treatment in patients with ankylosing spondylitis.
ABSTRACT: We evaluated the three-year impact of adalimumab on patient-reported physical function and health-related quality-of-life (HRQOL) outcomes in patients with active ankylosing spondylitis (AS).The Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS) is an ongoing five-year study that included an initial 24-week, randomized, placebo-controlled, double-blind period, followed by open-label extension treatment with adalimumab. Clinical and HRQOL data collected for up to three years from ATLAS were used for these analyses. Patients were randomized to receive adalimumab 40 mg or placebo by subcutaneous injection every other week. Physical function was assessed by the Bath AS Functional Index (BASFI), as well as by the Short Form 36 (SF-36) Health Survey Physical Component Summary (PCS) and Physical Function subscale scores. HRQOL was assessed using the AS Quality of Life (ASQOL) questionnaire. Disease activity was assessed by the Bath AS Disease Activity Index (BASDAI).Of 315 patients enrolled in ATLAS, 288 (91%) participated in an open-label adalimumab treatment extension and 82% provided three-year outcome data. During the 24-week double-blind phase, adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the BASDAI (P < 0.001), BASFI (P < 0.001), ASQOL (P < 0.001), and both the SF-36 PCS (P < 0.001) and Physical Function subscale (P < 0.001) scores, but not the SF-36 Mental Component Summary score (P = 0.181) and Mental Health subscale scores (P = 0.551). Mean changes from baseline through three years of adalimumab treatment were statistically significant for the BASDAI (change score: -3.9, P < 0.001), BASFI (change score: -29.6, P < 0.001), SF-36 PCS (change score: 11.6, P < 0.001), and Physical Function (change score: 23.3, P < 0.001). Comparable results were observed for the other SF-36 scores and for the ASQOL (all P < 0.001).Adalimumab significantly improved disease activity, patient-reported physical function, and HRQOL. These benefits were maintained over three years of treatment in patients with AS.
Project description:Chronic pain and progressive loss of physical function with AS may adversely affect health-related quality of life (HRQoL). The objective of this study was to assess the 5-year data regarding spinal mobility, physical function and HRQoL in patients with AS who participated in the Adalimumab Trial Evaluating Long-term Efficacy and Safety for AS (ATLAS) study.Patients received blinded adalimumab 40 mg or placebo every other week for 24 weeks, then open-label adalimumab for up to 5 years. Spinal mobility was evaluated using linear BASMI (BASMIlin). BASDAI, total back pain, CRP, BASFI, Short Form-36 and AS quality of life (ASQoL) were also assessed. Correlations between BASMIlin and clinical, functional and ASQoL outcomes after 12 weeks and after 5years of adalimumab exposure were evaluated using Spearman's rank correlation. Associations were further analysed using multivariate regression.Three hundred and eleven patients received ?1 dose of adalimumab; 125 of the 208 patients originally randomized to adalimumab received treatment for 5 years. Improvements in BASMIlin were sustained through 5 years, with a mean change of -0.6 from baseline in the population who completed 5 years of treatment with adalimumab. Improvements in disease activity, physical function and ASQoL were also sustained through 5 years. BASMIlin was significantly correlated with all evaluated clinical outcomes (P < 0.001). The highest correlation was with BASFI at 12 weeks (r = 0.52) and at 5 years (r = 0.65). Multivariate regression analysis confirmed this association (P < 0.001).Treatment with adalimumab for up to 5 years demonstrated sustained benefits in spinal mobility, disease activity, physical function and HRQoL in patients with active AS. Spinal mobility was significantly associated with short- and long-term physical function in these patients.Clinicaltrials.gov; https://clinicaltrials.gov/NCT00085644.
Project description:To evaluate the effect of secukinumab (interleukin-17A inhibitor) on patient-reported outcomes in patients with active ankylosing spondylitis (AS).In this phase III study, 371 patients were randomized (1:1:1) to receive intravenous (IV) secukinumab 10 mg/kg at baseline and weeks 2 and 4 followed by subcutaneous (SC) secukinumab 150 mg every 4 weeks (IV?150 mg group), or SC secukinumab 75 mg every 4 weeks (IV?75 mg group), or placebo. Patient-reported outcomes included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI criteria for 50% improvement (BASDAI 50), Short Form 36 (SF-36) physical component summary (PCS) score and mental component summary (MCS) score, Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, Bath Ankylosing Spondylitis Functional Index (BASFI), EuroQol 5-domain (EQ-5D) questionnaire, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Work Productivity and Activity Impairment-General Health questionnaire (WPAI-GH).At week 16, secukinumab IV?150 mg or IV?75 mg was associated with statistically and clinically significant improvements from baseline versus placebo in the BASDAI (-2.3 for both regimens versus -0.6; P?<?0.0001 and P?<?0.001, respectively), SF-36 PCS (5.6 for both regimens versus 1.0; P?<?0.0001 and P?< 0.001, respectively), and ASQoL (-3.6 for both regimens versus -1.0; P?<?0.0001 and P?<?0.001, respectively). Clinically significant improvements in the SF-36 MCS, BASFI, EQ-5D, and BASDAI 50 were observed with both secukinumab groups versus placebo at week 16; improvements were also observed in the FACIT-F and WPAI-GH. All improvements were sustained through week 52.Our findings indicate that secukinumab provides significant and sustained improvements in patient-reported disease activity and health-related quality of life, and reduces functional impairment, fatigue, and impact of disease on work productivity in patients with active AS.
Project description:Axial spondyloarthritis (ax-SpA) is a chronic inflammatory disease of the spine causing pain, stiffness, loss in physical function, and fatigue. Therefore, the physical and psychological burden of having this chronic disease can reduce the quality of life. We aimed to explore the relationship between demographic- and disease-related variables and health-related quality of life (HRQoL) in patients with ax-SpA.Demographic- and disease-related, HRQoL-related and treatment data were collected. Disease measures included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the BAS Functional Index (BASFI), the BAS Global (BAS-G) score, the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), the Health Assessment Questionnaire (HAQ) and co-morbidity. HRQoL was assessed using the SF-36 and the utility measures SF-6D and 15D. Variables associated with HRQoL were identified in unadjusted and adjusted analyses.We examined 380 patients with ax-SpA (67% men) with a mean age of 46 years. Among them, 86% reported exercising >1 h per week. Mean values were as follows: BASDAI, 3.17; MASES, 3.19; BASFI, 2.71; BAS-G. 3.88; and HAQ, 0.56. The percentage of current users of NSAIDs was 44%, and of DMARDs 23%. In multivariate analyses, exercising 1-3 h per week (B = 2.73, p = 0.022) and exercising >3 h per week (B = 2.71, p = 0.020), lower HAQ scores (B = -4.61, p = 0.001), lower BASFI scores (B = -1.05, p = 0.010) and lower BAS-G scores (B = -0.91, p = 0.001) were independently associated with higher SF-36-PCS scores, whereas modest alcohol consumption (B = 4.63, p = 0.018) and a lower BAS-G score (B = -1.73, p < 0.001) were independently associated with higher SF-36-MCS scores. Exercising 1-3 h per week (B = 0.032, p = 0.004) and exercising >3 h per week (B = 0.036, p = 0.001), lower HAQ scores (B = -0.051, p < 0.001), lower BAS-G scores (B = -0.010, p < 0.001) and co-morbidity (B = -0.014, p = 0.004) were independently associated with higher 15D scores. Finally, exercising 1-3 h per week (B = 0.045, p = 0.001) and exercising > 3 h per week (B = 0.053, p < 0.001), lower HAQ scores (B = -0.054, p = 0.001) and lower BAS-G scores (B = -0.020, p < 0.001) were associated with higher SF-6D scores.In patients with ax-SpA, a low level of physical activity, impaired physical function and impaired general well-being were independently and consistently associated with a decreased HRQoL across all applied measures.
Project description:BACKGROUND:Ankylosing spondylitis (AS) begins early in life and often leads to reduced physical function, but less is known about the impacts it has on health-related quality of life (HRQoL). The aims of this study were to assess HRQoL using the Short Form-36 (SF-36) in a cohort of patients with AS compared with controls and to examine associations between SF-36 scores and spinal radiographic changes, physical function, disease activity and demographic data overall and stratified by sex. METHODS:A cohort of patients with AS from Western Sweden were assessed using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with spinal radiographs, clinical examination and questionnaires, including the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Patient Global (BASG) and SF-36. Each patient's SF-36 results were compared with those of five age-matched and sex-matched persons (n = 1055) from the SF-36 Swedish normative population database. Associations between SF-36 physical component summary (PCS) and mental component summary (MCS) scores and disease-related and demographic factors were investigated using univariate and multivariable ogistic regression analyses with PCS and MCS below/above their respective median values as dependent variables. RESULTS:A total of 210 patients, age (median, IQR) 49.0 (21.2) years, symptom duration 24.0 (21.0) years, men 57.6% and HLAB27 87.1% were included. Patients with AS scored significantly lower (p < 0.001) compared to controls in all SF-36 domains and component summaries; PCS 42.4 (14.5) in AS versus 52.4 (11.8) in controls and MCS 47.9 (20.0) in AS versus 54.1 (10.1) in controls. Both men and women scored significantly lower in PCS compared with MCS. Multivariable logistic regression analyses revealed that living without a partner (OR 2.38, 95% CI 1.00-5.67), long symptom duration (year in decade OR 1.66, 95% CI 1.16-2.37), higher BASFI (OR 1.98, 95% CI 1.46-2.70) and ASDAS ≥ 2.1 (OR 3.32, 95% CI 1.45-7.62) were associated with worse PCS, while living without a partner (OR 3.04, 95% CI 1.34-6.91), fatigue (visual analogue scale for global fatigue greater than the median (OR 6.36, 95% CI 3.06-13.19) and ASDAS ≥ 2.1 (OR 2.97, 95% CI 1.41-6.25) with worse MCS. Some differences between sexes were observed in the results. CONCLUSIONS:The patients with AS had significantly lower HRQoL compared with controls. PCS was more affected compared to MCS in both sexes. Both disease-related and demographic factors were associated with HRQoL, partly overlapping for PCS and MCS. Factors associated with HRQoL showed some differences between sexes. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may potentially be improved. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00858819 . Registered on 9 March 2009. Last updated on 28 May 2015.
Project description:Objectives:Tofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ?1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668]). Methods:Patients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ?minimum clinically important differences (MCID); and scores ?normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments. Results:At month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p?0.05); SF-36v2 social functioning with 5 mg twice daily (p?0.05). Percentages reporting improvements ?MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p?0.05) and were similar with adalimumab. Conclusion:csDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3.
Project description:BACKGROUND:Increased levels of cytokines, including interleukin-6 (IL-6), reflect inflammation and have been shown to be predictive of therapeutic responses, fatigue, pain, and depression in patients with rheumatoid arthritis (RA), but limited data exist on associations between IL-6 levels and health-related quality of life (HRQoL). This post hoc analysis of MONARCH phase III randomized controlled trial data evaluated the potential of baseline IL-6 levels to differentially predict HRQoL improvements with sarilumab, a fully human monoclonal antibody directed against both soluble and membrane-bound IL-6 receptor ? (anti-IL-6R?) versus adalimumab, a tumor necrosis factor ? inhibitor, both approved for treatment of active RA. METHODS:Baseline serum IL-6 levels in 300/369 randomized patients were categorized into low (1.6-7.1?pg/mL), medium (7.2-39.5?pg/mL), and high (39.6-692.3?pg/mL) tertiles. HRQoL was measured at baseline and week (W)24 and W52 by Short Form 36 (SF-36) physical/mental component summary (PCS/MCS) and domain scores, Functional Assessment of Chronic Illness Therapy -fatigue, and duration of morning stiffness visual analog scale (AM-stiffness VAS). Linear regression of changes from baseline in HRQoL (IL-6 tertile, treatment, region as a stratification factor, and IL-6 tertile-by-treatment interaction as fixed effects) assessed predictivity of baseline IL-6 levels, with low tertile as reference. Pairwise comparisons of improvements between treatment groups were performed by tertile; least squares mean differences and 95% CIs were calculated. Similar analyses evaluated W24 patient-level response on minimum clinically important differences (MCID). RESULTS:At baseline, patients with high versus medium or low IL-6 levels (n?=?100, respectively) reported worse (nominal p?<?0.05) SF-36 MCS and role-physical, bodily pain, social functioning, role-emotional domain, and AM-stiffness VAS scores. There was a greater treatment effect with sarilumab versus adalimumab in high tertile versus low tertile groups in SF-36 PCS, physical functioning domain, and AM-stiffness VAS (nominal interaction p?<?0.05). PCS improvements ?MCID were higher in high (odds ratio [OR] 6.31 [2.37, 16.81]) versus low (OR 0.97 [0.43, 2.16]) tertiles with sarilumab versus adalimumab (nominal interaction p?<?0.05). Adverse events between IL-6 tertiles were similar. CONCLUSIONS:Patients with high baseline IL-6 levels reported better improvements in PCS, physical functioning domain, and AM-stiffness scores with sarilumab versus adalimumab and safety consistent with IL-6R blockade. TRIAL REGISTRATION:NCT02332590 . Registered on 5 January 2015.
Project description:Previously, many studies have evaluated quality of life (QoL) in patients with ankylosing spondylitis (AS), however, none of them specifically investigated the correlation between pain-related disability measured by Oswestry Disability Index (ODI) and QoL in AS patients. In addition, the correlation between global kyphosis (GK) in lateral plain radiographs and QoL in AS patients remains unclear up to now. Therefore, this study aimed to evaluate QoL and correlation with clinical and radiographic variables in AS patients, especially to figure out the relationship about the pain-specific disability measured by ODI, GK and QoL.From January 2008 to November 2015, two hundred and forty-five consecutive patients with an average age of 36.2 ± 10.9 years (range, 17-66 years) satisfying the Modified New York Criteria for AS from a single institution were enrolled. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and Bath Ankylosing Spondylitis Global score (BAS-G) were applied to assess the disease activity, functional status, spinal mobility and overall feeling of AS patients, respectively. ODI was recorded to evaluate low back pain-related disability. QoL was evaluated by the Short Form-36 (SF-36). According to global kyphosis (GK) measured on standing lateral full-spine radiographs, the patients were divided into two groups: mild kyphotic group (GK < 70°,n = 176) and severe kyphotic group (GK ≥ 70°,n = 69).The scores of BASDAI, BASFI, BASMI and ODI had significant negative correlations with all SF-36 subscale scores (P < 0.01). BASFI and BASMI scores of severe kyphotic group were much higher than those of mild kyphotic group, respectively (P = 0.005 and P = 0.001, respectively) and the score of physical function (PF) subscale in severe kyphotic group was significantly higher than that in mild kyphotic group (P = 0.046) as well. Notably, the scores of ODI, BASFI and BASMI were the major predictors of PF subscale score of SF-36.Poor QoL is significantly correlated with high disease activity, poor functional status and decreased spinal mobility in AS. GK is significantly associated with functional status, spinal mobility and QoL in AS patients. ODI, BASFI and BASMI are the major predictors of PF subscale of SF-36.
Project description:To evaluate the impact of adalimumab on health-related quality of life (HRQOL) for patients with moderate to severe plaque psoriasis.Psoriasis is a chronic, inflammatory, immune-mediated disease that has a significant impact on patients' HRQOL. Adalimumab is a fully human monoclonal antibody that blocks tumor necrosis factor, a pro-inflammatory cytokine, and is effective and well-tolerated for patients with moderate to severe psoriasis.Data were obtained for a secondary analysis of patients in a randomized, controlled Phase III trial evaluating the effect of adalimumab in patients with psoriasis (N = 1,205). Patients with moderate to severe psoriasis were randomized in a 2:1 ratio to adalimumab 80 mg (two 40 mg injections administered subcutaneously at baseline followed by one 40 mg injection every other week from Week 1 to Week 15) or placebo. Short Form-36 (SF-36) Health Survey scores of psoriasis patients were used to assess HRQOL and were compared with United States (US) population norms at baseline and Week 16.Baseline Physical Component Summary (PCS) scores for the placebo and adalimumab groups were similar to the general US population. Baseline mean Mental Component Summary (MCS) scores were significantly lower for the adalimumab and placebo groups compared with the general population (47.4, 47.7, and 50.8 points, respectively; p < 0.0001). PCS scores at Week 16 for patients receiving adalimumab had improved and were significantly greater than scores for the general US population (52.7 vs 48.9; p < 0.001). Compared with the general US population, MCS scores at Week 16 were similar for patients receiving adalimumab (51.2 vs 50.8; p = 1.000) and lower for patients receiving placebo (50.8 vs 48.7; p < 0.0001).Psoriasis has a broad impact on patient functioning and well-being. Improvement in skin lesions and joint symptoms associated with adalimumab treatment was accompanied by improvements in HRQOL to levels that were similar to or greater than those of the general US population.Clinicaltrials.gov NCT00237887.
Project description:<h4>Objectives</h4>Associations between BMI and health-related quality of life (HRQoL) in SLE have been implied, but data are scarce. We determined the impact of overweight and obesity on HRQoL in a large SLE population.<h4>Methods</h4>We pooled cross-sectional baseline data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N?=?1684). HRQoL was evaluated using the 36-item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and the European Quality of Life 5-dimension questionnaire (EQ-5D). Comparisons between BMI groups were conducted using the Mann-Whitney U test and adjustments using linear regression. Clinical relevance was determined by minimal clinically important differences (MCIDs).<h4>Results</h4>In total, 43.2% of the patients had BMI above normal and 17.4% were obese. Overweight and obese patients reported worse SF-36 physical component summary (PCS), physical functioning, role physical, bodily pain and FACIT-Fatigue scores than normal weight patients. Divergences were greater than corresponding MCIDs and more prominent with increasing BMI. Despite no clinically important difference in SF-36 mental component summary scores across BMI categories, patients experienced progressively diminished vitality and social functioning with increasing BMI. In linear regression analysis, BMI above normal and obesity were associated with worse PCS (standardized coefficient ??=?-0.10, P?<?0.001 and ??=?-0.17, P?<?0.001, respectively), FACIT-Fatigue (??=?-0.11, P?<?0.001 and ??=?-0.16, P?<?0.001) and EQ-5D (??=?-0.08, P?=?0.001 and ??=?-0.12, P?<?0.001) scores, independently of demographic and disease-related factors. The impact of BMI on the PCS and FACIT-Fatigue was more pronounced than that of SLE activity.<h4>Conclusion</h4>Patients with SLE and BMI above normal experienced clinically important HRQoL diminutions in physical aspects, fatigue and social functioning. A survey of potential causality underlying this association is warranted.
Project description:To evaluate the effect of golimumab on physical function, health-related quality of life (HRQOL), and productivity in psoriatic arthritis (PsA).GO-REVEAL was a multicenter, randomized, placebo-controlled study. Adult patients with active PsA (n = 405) received golimumab (50 or 100 mg) or placebo every 4 weeks, with early escape at week 16 (placebo → 50 mg, 50 → 100 mg) or placebo crossover to golimumab 50 mg at week 24. Patient-reported outcomes included physical function (Health Assessment Questionnaire [HAQ] disability index [DI] score), HRQOL (36-item Short Form health survey [SF-36] mental component summary [MCS] and physical component summary [PCS] scores), and productivity (home/school/work). Clinical response was assessed using the 28-joint Disease Activity Score using the C-reactive protein level (DAS28-CRP) and the Psoriasis Area and Severity Index (PASI) score for arthritis and skin symptoms, respectively.At week 24, golimumab-treated patients had significant mean improvements in HAQ DI (0.36), SF-36 (PCS 7.83, MCS 3.84), and productivity (2.24) scores compared with placebo (-0.01, 0.67, -0.60, and 0.08, respectively; P < 0.001 for all). Also, greater proportions of golimumab- than placebo-treated patients had clinically meaningful improvements in HAQ DI (≥0.30) and SF-36 PCS and MCS (≥5) scores at week 24 (P < 0.05). Also at week 24, improvements in DAS28-CRP scores were significantly but moderately correlated with improvements in HAQ DI, SF-36 PCS, and productivity scores. Correlations between these patient-reported outcomes and improvements in PASI, enthesitis, and dactylitis scores were very weak. Improvements in HAQ DI, SF-36, and productivity scores were similar among all groups by week 52 and week 104 when including placebo → golimumab crossover patients.Golimumab-treated patients had significant improvements in physical function, HRQOL, and productivity through week 24; these improvements correlated with clinical improvement in signs and symptoms of peripheral arthritis and were sustained through 2 years.