BackgroundThe ultimate goal of treatment in axial spondyloarthritis (axSpA) is sustained remission. Data on predictors of sustained remission are scarce in axSpA.ObjectivesTo determine predictors of sustained remission in people with axSpA after treatment with their first biological disease-modifying anti-rheumatic drug (bDMARD).MethodsHacettepe University Rheumatology Biologic Registry (HUR-BIO) is a prospective, single center registry of rheumatic disease patients treated with bDMARDs. Patients with axSpA were selected and sustained remission defined as attainment of Assessment of SpondyloArthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis (AS) Disease Activity Score C-reactive protein Inactive Disease (ASDAS-ID) for two or more consecutive visits spanning ≥6 months during follow-up. Patients achieving and not achieving sustained remission were compared using the independent t-test. Multivariable logistic regression analysis was performed to determine independent factors predictive of sustained remission. Variables with a p-value<0.1 were re-tested in multivariable models. Forward selection was performed until the best-fit model was obtained, taking possible confounders into account. Two separate multivariable models were built, one with and one without the covariate “achievement of remission at 3-6 months”, to assess consistency of findings and to account for missing information regarding remission status between 3 and 6 months.ResultsData on 990 patients with sustained remission data were available. Of these, 299 (30%) were in sustained remission, while 691 (70%) were not. Patients in sustained remission were younger, had earlier disease onset, were more frequently male, had lower BMI and were more frequently HLA-B27 positive, compared to patients not in sustained remission. Furthermore, at the start of bDMARD treatment, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and patient global assessment (PGA, 0-10 scale) were lower, while acute phase reactants (ESR and CRP) were higher, in the sustained remission group. In multivariable analysis, male gender (OR 2.2, 95% CI 1.21-3.95), concomitant conventional synthetic DMARD (csDMARD) use (OR 3.63, 95% CI 1.29-10.19), PGA (OR 0.96, 95% CI 0.95-0.98), and early achievement (between 3-6 months) of remission (OR 13.1, 95% CI 7.13-24.02) were independently associated with sustained remission (Table 1, model 1). In the model without the variable early achievement of remission (Table 1, model 2), similar and a few additional associations were described: age at diagnosis (OR 0.97, 95% CI 0.96-0.99), male gender (OR 2.31, 95% CI 1.60-3.35), concomitant csDMARD use (OR 1.88 95% CI 1.23-2.86), PGA (OR 0.98, 95% CI 0.97-0.99), BASDAI (OR 0.87, 95% CI 0.78-0.96), and baseline symptom duration (OR 0.97, 95% CI 0.94-0.99).Table 1.Multivariable analysis (best-fit model) of predictors of sustained remissionModel 1Model 2CovariatesMultivariable Analysis (n= 541)Multivariable Analysis (n=739)OR (95% CI)p-valueOR (95% CI)p-valueAge at diagnosisNSNS0.97 (0.96-0.99)0.006Male sex2.84 (1.71-4.70)<0.0012.31 (1.60-3.35)<0.001Concomitant csDMARD use (at baseline or follow-up)2.94 (1.57-5.51)0.0011.88 (1.23-2.86)0.003Baseline PGA0.97 (0.96-0.98)<0.0010.98 (0.97-0.99)0.002Baseline BASDAINSNS0.87 (0.78-0.96)0.009Baseline symptom durationNSNS0.97 (0.94-0.99)0.021Achievement of remission at 3-6 months after baseline11.70 (7.11-19.23)<0.001NANANA: not applicable; NS: not selected (not contributing to the model). Baseline refers to start of bDMARD treatment.ConclusionThis study demonstrates that patients in sustained remission after starting bDMARD treatment have distinctive characteristics compared to patients not in sustained remission. These data can be used to aid clinical and personalized management of axSpA, and to facilitate better communicate between health care professionals and patients regarding the course and prognosis of their condition.Disclosure of InterestsBayram Farisogullari: None declared, Gözde Kübra Yardimci: None declared, Emre Bilgin: None declared, Ertugrul Cagri Bolek: None declared, Emine Duran: None declared, Gizem Ayan: None declared, Zehra Özsoy: None declared, Gullu Sandal Uzun: None declared, Mustafa Ekici: None declared, Erdinc Unaldi: None declared, Levent Kiliç: None declared, Ali Akdoğan: None declared, Omer Karadag: None declared, Şule Apraş Bilgen: None declared, Sedat Kiraz: None declared, Ali İhsan Ertenli: None declared, Umut Kalyoncu: None declared, Pedro M Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB
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
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