Comment on: Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis-findings from a United Kingdom cohort.
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SUBMITTER: Al Arashi W
PROVIDER: S-EPMC6649944 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe impact of smoking on TNF inhibition (TNFi) therapy is unclear. We examined the effect of smoking on all-cause and cause-specific TNFi discontinuation in axial spondyloarthritis (axSpA).MethodsWe used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS). Patients fulfilling the ASAS criteria for axSpA, who started their first TNFi, were eligible for analysis. Inverse-probability weights were used to balance differences in baseline disease severity and other confounders. We used marginal structural Cox proportional hazard models to estimate hazard ratios (HR) for TNFi discontinuation according to smoking status. In analyses of cause-specific discontinuation, competing risk events were considered as censoring, using inverse-probability weights.ResultsA total of 758 participants were included in the analysis (66% male, mean age 45 years), providing 954 patient-years of follow-up. TNFi was discontinued in 174 (23%) patients, among whom 26% stopped due to infections, 20% due to other adverse events and 44% due to inefficacy or other reasons. Thirty-four percent were current smokers and 30% ex-smokers. Compared to never smokers, current smokers' risk of TNFi discontinuation was HR 0.79 (95%CI 0.53 to 1.20) and ex-smokers HR 0.68 (95%CI 0.45 to 1.04). Our data did not show evidence that current smoking influenced discontinuation due to infections (HR 0.79, 95%CI 0.40 to 1.54), other adverse events (HR 0.86, 95%CI 0.41 to 1.78) or inefficacy/other causes (HR 1.44, 95%CI 0.86 to 2.41).ConclusionBaseline smoking status did not impact TNFi discontinuation in this UK cohort of axSpA participants.
| S-EPMC6647300 | biostudies-literature
Project description:BackgroundThis study aimed to classify the distinct group of patients with axial spondyloarthritis (SpA) on tumour necrosis factor alpha inhibitors (TNFi) according to the baseline characteristics using a clustering algorithm.MethodsThe clinical characteristics and demographic data of patients with axial SpA included in the Korean College of Rheumatology Biologics and Targeted Therapy registry were investigated. The patterns of disease manifestations were examined using divisive hierarchical cluster analysis. After clustering, we compared the clinical characteristics of patients and the drug survival of TNFi between the classified groups.ResultsA total of 1042 patients were analysed. The cluster analysis classified patients into two groups: axial group predominantly showing isolated axial manifestations (n = 828) and extra-axial group more frequently showing extra-axial symptoms (n = 214). Almost all extra-axial symptoms (peripheral arthritis, enthesitis, uveitis, and psoriasis) were more frequently observed in the extra-axial group than in the axial group. Moreover, patients in the extra-axial group had shorter disease duration, later disease onset, and higher disease activity than those in the axial group. The disease activity was comparable between the two groups after 1 year of treatment with TNFi. Interestingly, the extra-axial group had a lower drug survival with TNFi than the axial group (p = 0.001).ConclusionsCluster analysis of patients with axial SpA using TNFi classified two distinct clinical phenotypes. These clusters had different TNFi drug survival, clinical characteristics, and disease activity.
| S-EPMC8591959 | biostudies-literature
Project description:The Assessment of Spondyloarthritis International Society (ASAS) health index (HI) is a novel tool for approaching disability, health, and functioning in spondyloarthritis (SpA). In the present study we compared ASAS HI between patients with ankylosing spondylitis (AS) and those with nonradiographic axial SpA (nr-axSpA). In addition, we identified predictors of ASAS HI. We designed this cross-sectional study using data from the Catholic Axial Spondyloarthritis COhort (CASCO), a prospective cohort from a single tertiary hospital. We compared baseline characteristics, including ASAS HI, between AS and nr-axSpA, and determined the frequency of each item constituting the ASAS HI. We used linear regression analysis to identify factors associated with ASAS HI. Total of 357 patients with axSpA-261 with AS and 96 with nr-axSpA-were included in analysis. AS patients were older and had higher ASAS HI than nr-axSpA. Among ASAS HI items, pain (item No. 1) and energy/drive (item No. 5) were the most common areas for which axSpA patients experienced discomfort. ASAS HI correlated with other SpA-related parameters such as BASDAI, ASDAS, and BASFI. Multivariable regression analysis of the axSpA group showed that high NSAID intake and mSASSS were positively associated with ASAS HI, whereas higher economic status and alcohol consumption were negatively associated with ASAS HI. Results were consistent in the AS group on subgroup analysis, whereas alcohol consumption was the only factor significantly associated with ASAS HI in the nr-axSpA group. In the present cohort study, patients with AS had poorer health status (higher ASAS HI) than those with nr-axSpA. Items proposed by AS patients (items No. 1 and 5) were the most frequently checked areas as axSpA patients feel discomfort, and this support that ASAS HI could practically assess actual discomfort of axSpA patient. ASAS HI was well correlated with known disease parameters, including activity, function, and quality of life; therefore, ASAS HI could be used in the future to represent the health status of SpA in a systematic way. Spinal structural damage (higher mSASSS), high NSAID intake, alcohol consumption, and economic status were predictors of ASAS HI in patients with axSpA, especially those with AS.
| S-EPMC6518358 | biostudies-literature
Project description:Objectives: To investigate the anatomical distribution, morphological abnormalities and response to adalimumab therapy of ultrasound(US)-detected peripheral enthesitis in patients with axial spondyloarthritis (SpA). Methods: In a randomized, placebo-controlled, double-blinded, investigator-initiated trial (NCT01029847), patients with axial SpA according to the Assessment of Spondyloarthritis International Society criteria were randomized to subcutaneous adalimumab 40 mg every other week or placebo from baseline to week 6. From week 6 to 24, all patients received adalimumab 40 mg every other week. Of 49 patients enrolled, 21 patients participated in our observational US sub-study. US assessment applying the OMERACT US definitions for enthesitis of 10 peripheral entheseal regions of the upper and lower extremities and clinical examination were performed at baseline, weeks 6 and 24. US was performed by one experienced investigator. Hypo-echogenicity, increased thickness and Doppler activity of the enthesis were considered signs of active inflammation, whereas insertional bone erosions, intratendinous calcifications, and enthesophytes were regarded as signs of structural lesions. Results: Enthesitis on US was mostly present in the lower limbs, especially in the Achilles tendon (81%), the quadriceps tendon (62%), and the greater femoral trochanter (52%). Structural lesions were predominant (38 vs. 12% of examined entheses with inflammatory changes), particularly in the entheses of the lower limbs, and exhibited no change during treatment. Conclusion: US-detected structural lesions were common while inflammatory lesions were relatively rare in patients initiating adalimumab due to axial SpA. Structural lesions did not appear to change during 24 weeks follow-up, suggesting that these lesions may not be helpful outcome measures in short-term clinical trials.
| S-EPMC7381133 | biostudies-literature
Project description:ObjectivesAdalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not consistent. We compared their effectiveness over 1 year in a prospective cohort.MethodsAnalyses were performed on subjects' first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified.ResultsThe study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response.ConclusionOver 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab.
| S-EPMC3475979 | biostudies-literature
Project description:BackgroundFew studies have investigated the impact of obesity on the response to tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). The aim of our study was to investigate the impact of different body mass index (BMI) categories on TNFi response in a large cohort of patients with axSpA.MethodsPatients with axSpA within the Swiss Clinical Quality Management (SCQM) program were included in the current study if they fulfilled the Assessment in Spondyloarthritis International Society (ASAS) criteria for axSpA, started a first TNFi after recruitment, and had available BMI data as well as a baseline and follow-up visit at 1 year (±6 months). Patients were categorized according to BMI: normal (BMI 18.5 to <25), overweight (BMI 25-30), and obese (BMI >30). We evaluated the proportion of patients achieving the 40% improvement in ASAS criteria (ASAS40), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued the TNFi were considered nonresponders. We controlled for age, sex, HLA-B27, axSpA type, BASDAI, BASMI, elevated C-reactive protein (CRP), current smoking, enthesitis, physical exercise, and co-medication with disease-modifying antirheumatic drugs, as well as with nonsteroidal anti-inflammatory drugs in multiple adjusted logistic regression analyses.ResultsA total of 624 axSpA patients starting a first TNFi were considered in the current study (332 patients of normal weight, 204 patients with overweight, and 88 obese patients). Obese individuals were older, had higher BASDAI levels, and had a more important impairment of physical function in comparison to patients of normal weight, while ASDAS and CRP levels were comparable between the three BMI groups. An ASAS40 response was reached by 44%, 34%, and 29% of patients of normal weight, overweight, and obesity, respectively (overall p = 0.02). Significantly lower odds ratios (ORs) for achieving ASAS40 response were found in adjusted analyses in obese patients versus patients with normal BMI (OR 0.27, 95% confidence interval (CI) 0.09-0.70). The respective adjusted ASAS40 OR in overweight versus normal weight patients was 0.62 (95% CI 0.24-1.14). Comparable results were found for the other outcomes assessed.ConclusionsObesity is associated with significantly lower response rates to TNFi in patients with axSpA.
| S-EPMC5518107 | biostudies-literature
Project description:OBJECTIVES:To investigate the association between the extent of tapering tumor necrosis factor inhibitor (TNFi) and the likelihood of achieving inactive disease in patients with axial spondyloarthritis (axSpA) METHODS: We analyzed 1575 1-year follow-up interval data of 776 axSpA patients treated with TNFi for more than 1 year in a nationwide observational cohort. The decision on tapering TNFi was made by patients and their physicians. We quantified TNFi used during interval as a dose quotient (DQ). The intervals were classified into the heavy-tapering (DQ < 50), mild-tapering (DQ 50-99), and control groups (DQ = 100). Outcome variables included achieving Ankylosing Spondylitis Disease Activity Score-inactive disease (ASDAS-ID) and major clinical response of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) in the follow-up visit. The effects of TNFi tapering on the outcome were analyzed using the generalized estimating equation. RESULTS:At the baseline visit, 91.1% of the patients showed a high disease activity (ASDAS-CRP ≥ 2.1). DQ of each interval was significantly influenced by the ASDAS-CRP measure in the prior follow-up (P < 0.001). ASDAS-ID was observed in 42.3% of the intervals. A multivariable analysis showed that the likelihood of outcome achievement was comparable between the control and mild-tapering groups, but significantly decreased in the heavy-tapering group (vs. the control group, adjusted OR = 0.28, [95% CI, 0.08-0.94]). In contrast, the likelihood to achieve BASDAI50 response was not different among the groups. In the subgroup of patients who reached ASDAS-ID 1 year after TNFi treatment (n = 327), ASDAS-ID was observed in 66.1% of the subsequent intervals, and only the mild-tapering group showed a likelihood of target maintenance comparable with that of the control group (adjusted OR = 1.25 [0.41-3.80]). This likelihood decreased with an increase in ASDAS-CRP. CONCLUSION:Mild tapering of TNFi has efficacy comparable with that of the standard-dose treatment for ASDAS-ID achievement in patients with axSpA.
| S-EPMC6611048 | biostudies-literature
Project description:Axial spondyloarthritis (AxSpA) is an inflammatory spondyloarthritis (SpA) that has significant impact on a patient's life. Symptoms, including fatigue, sleep problems, depression, and sexual dysfunction, can profoundly impact health-related quality of life (HRQoL) and limit work, leisure, and daily activities. Available therapies effectively manage pain and inflammation in early-stage disease, but patients often continue to experience impaired HRQoL. Thus, there remains a need for new therapies with novel mechanisms that can stop disease progression, potentially reverse damage caused by AxSpA and improve HRQoL in patients with AxSpA. Newer biologic agents, such as those targeting the interleukin 17-interleukin 23 axis, have promising efficacy and may improve HRQoL for patients with AxSpA. The AxSpA has many negative effects on HRQoL. By targeting disease pathways responsible for the development of AxSpA, approved and emerging therapies potentially reduce disease activity and improve the functional status of patients with AxSpA. This narrative review reflects on the findings of studies evaluating HRQoL of individuals with AxSpA and the role of newer therapies.
| S-EPMC5617559 | biostudies-other
Project description:IntroductionRadiography is an unreliable and insensitive tool for the assessment of structural lesions in the sacroiliac joints (SIJ). Magnetic resonance imaging (MRI) detects a wider spectrum of structural lesions but has undergone minimal validation in prospective studies. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Sacroiliac Joint (SIJ) Structural Score (SSS) assesses a spectrum of structural lesions (erosion, fat metaplasia, backfill, ankylosis) and its potential to discriminate between therapies requires evaluation.MethodsThe SSS score assesses five consecutive coronal slices through the cartilaginous portion of the joint on T1-weighted sequences starting from the transitional slice between cartilaginous and ligamentous portions of the joint. Lesions are scored dichotomously (present/absent) in SIJ quadrants (fat metaplasia, erosion) or halves (backfill, ankylosis). Two readers independently scored 147 pairs (baseline, 2 years) of scans from a prospective cohort of patients with SpA who received either standard (n?=?69) or tumor necrosis factor alpha (TNF?) inhibitor (n?=?78) therapy. Smallest detectable change (SDC) was calculated using analysis of variance (ANOVA), discrimination was assessed using Guyatt's effect size, and treatment group differences were assessed using t-tests and the Mann-Whitney test. We identified baseline demographic and structural damage variables associated with change in SSS score by univariate analysis and analyzed the effect of treatment by multivariate stepwise regression adjusted for severity of baseline structural damage and demographic variables.ResultsA significant increase in mean SSS score for fat metaplasia (P?=?0.017) and decrease in mean SSS score for erosion (P?=?0.017) was noted in anti-TNF? treated patients compared to those on standard therapy. Effect size for this change in SSS fat metaplasia and erosion score was moderate (0.5 and 0.6, respectively). Treatment and baseline SSS score for erosion were independently associated with change in SSS erosion score (??=?1.75, P?=?0.003 and ??=?0.40, P?<?0.0001, respectively). Change in ASDAS (??=?-0.46, P?=?0.006), SPARCC MRI SIJ inflammation (??=?-0.077, P?=?0.019), and baseline SSS score for fat metaplasia (??=?0.085, P?=?0.034) were independently associated with new fat metaplasia.ConclusionThe SPARCC SSS method for assessment of structural lesions has discriminative capacity in demonstrating significantly greater reduction in erosion and new fat metaplasia in patients receiving anti-TNF? therapy.
| S-EPMC4060567 | biostudies-literature
Project description:AIMS:To estimate predictors of time to smoking relapse and test if prediction varied by quit duration. DESIGN:Longitudinal cohort data from the International Tobacco Control Four-Country survey with annual follow up collected between 2002 and 2015. SETTING:Canada, United States, United Kingdom and Australia. PARTICIPANTS:A total of 9171 eligible adult smokers who had made at least one quit attempt during the study period. MEASUREMENTS:Time to relapse was the main outcome. Predictor variables included pre-quit baseline measures of nicotine dependence, smoking and quitting-related motivations, quitting capacity and social influence, and also two post-quit measures, use of stop-smoking medications and quit duration (1-7 days, 8-14 days, 15-31 days, 1-3 months, 3-6 months, 6-12 months, 1-2 years and 2+ years), along with socio-demographics. FINDINGS:All factors were predictive of relapse within the first 6 months of quitting but only wanting to quit, quit intentions and number of friends who smoke were still predictive of relapse in the 6-12-month period of quitting [hazard ratios (HR) = 1.20, P < 0.05; 1.13, P < 0.05; and 1.21, P < 0.001, respectively]. Number of friends smoking was the only remaining predictor of relapse in the 1-2 years quit period (HR = 1.19, P = 0.001) with none predictive beyond the 2-year quit period. Use of stop-smoking medications during quit attempts was related negatively to relapse during the first 2 weeks of quitting (HR = 0.71-0.84), but related positively to relapse in the 1-6-month quit period (HR = 1.29-1.54). Predictive effects of all factors showed significant interaction with quit duration except for perceiving smoking as an important part of life, prematurely stubbing out a cigarette and wanting to quit. CONCLUSIONS:Among adult smokers in the United States, Canada, United Kingdom and Australia, factors associated with smoking relapse differ between the early and later stages of a quit attempt, suggesting that the determinants of relapse change as a function of abstinence duration.
| S-EPMC5993599 | biostudies-literature