BackgroundAchievement of remission is a desirable outcome in axSpA, and the identification of remission predictors may further aid in the clinical and personalised management of the disease.ObjectivesTo systematically review and summarize the predictors of remission in patients with axSpA.MethodsA comprehensive search was performed in MEDLINE, EMBASE, Cochrane CENTRAL, and 2020-2021 abstracts of ACR and the EULAR annual meetings. To identify the relevant studies, medical subject headings and keywords related to “axial spondyloarthritis”, “remission,” and “prognostic study” were used. Studies were included if: patients were diagnosed with axSpA by a physician; age ≥18 years; the study assessed the potential predictive or prognostic factors related to remission, according to any definition; and the statistical analysis included multivariable analysis. The methodological quality of the included studies was assessed using the Quality of Prognosis Studies in Systematic Reviews tool.ResultsThe systematic literature review (SLR) comprised 22 articles from 4245 citations identified in our search (Figure 1). Two studies investigated “sustained remission” (at least in 3 consecutive follow-up visits), while the others assessed “point remission” (at single points in time). The most commonly used remission criteria were Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (14 studies) and Assessment of SpondyloArthritis international Society partial remission (ASAS-PR; 11 studies) criteria. However, other non-validated definitions, most of them including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) cut-offs, were also used. In 19 studies, subjects were treated with biological disease-modifying antirheumatic drugs (bDMARDs) with or without concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or non-steroidal anti-inflammatory drugs (NSAIDs), while in one study patients were treated with a Janus kinase inhibitor, upadacitinib. Study duration ranged from 12 weeks to 8 years. Younger age, HLA-B27 positivity, male gender, lower baseline BASDAI, lower baseline Bath Ankylosing Spondylitis Functional Index (BASFI) and treatment with tumour necrosis factor inhibitor (TNFi), were the most consistent predictors of remission. Additionally, lower baseline ASDAS-CRP, lower body mass index (BMI), shorter disease duration, TNFi naivety, and concomitant use of csDMARDs were found to be predictors of remission in two studies each. Other predictors were only found to be associated with remission in single studies, namely: higher education level, more intense morning stiffness, lower baseline total back pain score, history of peripheral arthritis, no smoking, higher pain catastrophizing, lower modified Rheumatic Disease Comorbidity Index, fulfilment of ASAS clinical arm criteria, fulfilment of European Spondyloarthropathy Study Group criteria, lower erythrocyte sedimentation rate, higher Spondyloarthritis Research Consortium of Canada magnetic resonance imaging (MRI) sacroiliac joint (SIJ) and spinal inflammation score, positive MRI of the SIJ, lower Bath Ankylosing Spondylitis Metrology Index, lower Health Assessment Questionnaire for the Spondyloarthropaties, lower global pain, lower back pain score and lower enthesitis index. Of note, contradictory data were found regarding CRP and NSAIDs usage.Figure 1.Flow chart of study selectionConclusionThirty-four predictors of remission in axSpA were identified. However, many of these predictors were only identified in one or two studies. Considering the differences in study design, particularly characteristics of the population, duration of remission and remission criteria, further well-designed studies are needed to allow generalisation of the identified predictors to the general axSpA population.AcknowledgementsWe would like to thank Kate Brunskill, librarian of University College of London, for the support and review of the search strategy.Disclosure of InterestsAna Sofia Pinto: None declared, Bayram Farisogullari: None declared, Pedro Machado Speakers bureau: Received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Consultant of: Received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript
BackgroundAlthough it may be difficult to detect changes in spinal mobility on the short term, spinal mobility is considered an important measure to assess the efficacy of drugs used to treat axial spondyloarthritis (axSpA). However, few studies evaluated the long-term impact of biologic treatment on spinal mobility.ObjectivesTo describe the long-term effect of TNF inhibitors (TNFi) on spinal mobility in patients with axSpA, and to determine whether the use of TNFi treatment influences spinal mobility, and if this due to a direct or indirect effect (mediated by disease activity).MethodsWe performed a retrospective observational study, using data collected from patients with a clinical diagnosis of axSpA treated with TNFi at a tertiary care centre where disease activity and metrology assessments are routinely done. Adult patients with at least two Bath Ankylosing Spondylitis Metrology Index (BASMI) measurements were included. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score C-reactive protein (ASDAS). The longitudinal association between TNFi and improvement in BASDAI/ASDAS was tested using a linear mixed effects model with BASMI as dependent variable. To test whether TNFi had a direct effect on BASMI, not mediated by disease activity, we tested that TNFi treatment was not conditionally independent of BASMI given BASDAI/ASDAS (Figure 1). We tested whether the nodes TNFi and BASMI were disconnected if we removed BASDAI and ASDAS. To test this conditional independence, we first built a linear mixed effects model for BASMI given BASDAI or ASDAS when the patient was under TNFi and used this model to predict a 95% confidence interval (CI) for BASMI given the data for BASDAI/ASDAS when the patient was without TNFi. We checked whether the true value of BASMI lay within this 95% CI and performed a hypothesis test for binomial distribution where H0: p=0.95. To test for the indirect effect of TNFi on BASMI reduction, mediated through the disease activity, we regressed BASMI on BASDAI/ASDAS, TNFi (if there was a direct effect), demographics, presence of radiographic (r-) axSpA and HLA-B27 positivity, using a linear mixed effects model adjusted for within-patient correlation.Figure 1.Indirect effect of TNFi on BASMI (represented by the full line), through the influence of TNFi on disease activity, adjusted by other confounders and direct effect of TNFi on BASMI (dashed line), independently of disease activity.ResultsData from 188 patients and 1326 visits were analysed. Mean age was 45.6 (SD 11.6) years, mean disease duration was 15.8 (SD 9.64) years, 152 (80.9%) were male, 120 (73.6%) had r-axSpA, and 83 (74.8%) were HLA-B27 positive. Mean follow-up time was 8.0 (SD 4.4) years, ranging from 0.8 to 18.2 years. Treatment with TNFi was significantly associated with long-term improvement in BASMI (B=-0.423, 95% CI=[-0.553,-0.292], p<0.001). An indirect effect of TNFi on BASMI improvement was observed, mediated by reduction in disease activity, measured by BASDAI (B=0.146, 95% CI=[0.092, 0.200], p<0.001) or ASDAS (B=0.405, 95% CI=[0.260, 0.549], p<0.001). Using conditional independence tests, a direct effect of TNFi on BASMI improvement was also observed, independently of disease activity, when BASDAI was used (p<0.001) as a covariate, but not when ASDAS was used (p=0.3104). The direct effect of TNFi (B=-0.300, 95% CI=[-0.576,-0.025], p<0.001) on BASMI was estimated in the BASDAI-adjusted mixed effects model.ConclusionTNFi are effective at improving BASMI in patients with axSpA, in a real-life setting. This effect is mainly explained by the reduction in disease activity. However, a direct effect of TNFi on BASMI could also be demonstrated, when disease activity was measured by BASDAI, suggesting that ASDAS captures additional factors that can influence spinal mobility. These potential factors deserve further investigation, but they could for example include biomechanical properties of tendons and myofascial tissue.Disclosure of InterestsAna Sofia Pinto: None declared, Bohao Yao: None declared, Claire Harris: None declared, Rhys Hayward: None declared, Andrew Keat: None declared, Pedro Machado Speakers bureau: Received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to thismanuscript, Consultant of: Received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to thismanuscript
BackgroundBiological drugs have revolutionized the treatment of rheumatic diseases, and the recent expiry of the patents for many biological agents has led to the marketing of highly similar, low-cost versions known as biosimilars. However, questions regarding its efficacy compared to bio-originator drugs, in a real-life setting, have been raised. National Institute for Health and Care Excellence (NICE) guidelines state that the response to biologic disease-modifying anti-rheumatic drugs (bDMARDs) should be assessed 12 weeks after the beginning of the drug. Treatment should only be continued if there is clear evidence of response, defined as a reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score to 50% of the pre-treatment value or by 2 or more units and a reduction in the 10-cm spinal pain visual analogue scale (VAS) by 2 cm or more.ObjectivesTo compare the response to adalimumab (ADA) originator and biosimilar in bDMARD-naïve patients with axial spondyloarthritis (axSpA) and in patients who switched from originator to biosimilar drug, accordingly to NICE guidelines; to compare the effectiveness and safety of the originator and biosimilar drugs in patients with axSpA, measured by persistence rates (PR) over three years.MethodsA retrospective observational single-centre UK study was performed in bDMARD-naïve patients with a clinical diagnosis of axSpA who initiated treatment with ADA (original or biosimilar) and in patients who switched from originator to biosimilar drug. Descriptive statistics were used. Disease activity at baseline and follow-up data at 3 and 6 months of treatment was compared using the chi-square test. The Kaplan-Meier method was used to calculate persistence rates in biologic treatment over time. Reasons for discontinuing therapy were summarized using descriptive statistics and stratified by treatment.ResultsA total of 153 patients were included: 83 patients started on original ADA, 31 started on biosimilar ADA and 40 switched from original to biosimilar drug. The population’s baseline characteristics are similar in the three groups. However, some differences were found, namely disease duration was longer in the group that did switch and the disease activity is similar in patients who started original and biosimilar ADA and was lower in the group of patients who switched from original to the biosimilar. The 3-year PR was not significantly different between originator and biosimilar ADA in bDMARD naïve patients and in the group of patients that switched from original drug to biosimilar drug (p=0.080), as shown in Figure 1. In the original ADA group, 3-years PR was 67.5% with a median time-on-drug (TOD) of 29.5 months; for biosimilar drug, 3-years PR was 64.5%, with a median TOD of 24.2 months. In patients who switched from original to biosimilar drug, 3-years PR was 77.5% with a median TOD of 30.3 months. Response to treatment according to NICE guidelines was similar between original and biosimilar drugs (p>0.05). Overall, 47 (30.7%) patients stopped adalimumab (27 patients on original drug and 20 on biosimilar drug). Discontinuations due to adverse events and inefficacy were the most frequent, and there were no significant differences between original and biosimilar drugs. Other reasons for discontinuation were less frequent, such as patient choice, loss of follow-up and death, and again without differences between original and biosimilar drugs.Figure 1.Drug survival in the three adalimumab groups (original adalimumab – blue line, biosimilar adalimumab – red line, and switch from original to biosimilar adalimumab – green line)ConclusionAdalimumab original and biosimilar used as a first-line biological treatment showed similar effectiveness and safety in our long-term cohort of patients with axSpA. Switch from original to biosimilar drug showed to have a good persistence on drug after three years of follow-up (77.5%).Disclosure of InterestsAna Sofia Pinto: None declared, Kalveer Flora: None declared, Dilpreet Matharu: None declared, Anthony Isaacs: None declared, Pedro Machado Speakers bureau: Received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Consultant of: Received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.