Primary inefficacy of TNF inhibitors in patients with axial spondyloarthritis: a long-term follow-up of 25 patients

Background:Clinical efficacy of TNF inhibitors (TNFi) in axial spondyloarthritis (axSpA) has been widely probed in randomized control trials. In clinical practice, some studies suggested that long-term (more than 4 years) treatment with TNFi could slow down radiographic progression in axSpA; however, whether this treatment inhibits structural damage remains unclear.Objectives:To evaluate radiographic progression in axSpA patients receiving long-term TNFi (over 4 years) in comparison with patients starting TNFi.Methods:A total of 204 patients with axSpA were included in the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO). Out of these, 80 patients (31 starting TNFi and 49 under long-term TNFi) were included in this study based on the availability of spinal radiographs (cervical and lumbar lateral views), at two time points. Radiographs in patients starting TNFi were available: i) at baseline (before TNFi) and ii) after 3 to 5 years of TNFi therapy (mean follow-up 3.7±0.8), while in long-term TNFi patients, these were available: i) at one follow-up visit at least 4 years later since TNFi was started and ii) after 3 to 5 years of this visit (mean follow-up 3.5±1.1). Two trained readers, not blinded for chronological order, independently scored lateral cervical and lumbar spine images according to the mSASSS system (0-72). Following definitions for progression were used: change of the absolute scores, change of ≥2 units, development of new syndesmophytes, and development of new syndesmophytes or growth of the existing syndesmophytes.Results:Reliability of both readers was excellent with intraclass correlation coefficients (ICCs) of 0.98 (0.98-0.99) at inclusion and 0.98 (0.97-0.99) at follow-up. Most patients (82.5%) were classified as radiographic axSpA. Mean BASDAI at first visit (i) was of 5.0±2.4 for starting TNFi patients and of 3.2±1.9 for long-term TNFi patients. The table depicted the results for radiographic scores and progression. Mean mSASSS score at first visit (i) was 15.8±21.5 and 15.1±18.4 units for starting TNFi and long-term TNFi patients, respectively. The change score between both visits was 2.3±4.2 and 2.3±4.1, respectively. Similarly, no differences were found for change of ≥2 points (32.3% in starting TNFi and 35% in long-term TNFi patients). However, development of new syndesmophytes or growth of the existing syndesmophytes were found to be more frequently (but not significant) in starting TNFi patients compare to long-term TNFi patients.Conclusion:In patients with axSpA treated with TNFi in clinical practice radiographic progression is observed, independently of the time under this therapy. Nevertheless, the development and growth of syndesmophytes seem to be lower in long-term treated patients.Table.Starting TNFi patientsLong-term TNFi patients*p-valuePresence of syndesmophytes at first visit, % (n)45.2% (14)53.1% (26)NSPresence of syndesmophytes at follow up, %51.6% (16)55.1% (27)NSMean change score, mean ± SD2.32 ± 4.192.26 ± 4.09NSChange of ≥ 2 units in the score % (n)32.3% (10)34.7% (17)NSDevelopment of new syndesmophytes, % (n)29% (9)18.4% (9)0.3Progression or development of new syndesmopyhtes % (n)29% (9)22.4% (11)0.5* Patients with more than 4 years under TNFi treatmentDisclosure of Interests:María LLop Vilaltella Speakers bureau: Janssen and Pfizer, Mireia Moreno: None declared, 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, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Font Ugalde Pilar: None declared, Teresa Clavaguera Speakers bureau: novartis, BMS, Faes, Luis F. Linares Ferrando: None declared, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Xavier Juanola-Roura: None declared

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Sustained Low Disease Activity Measured By ASDAS Slow Radiographic Spinal Progression in Axial Spondyloarthritis Patients Treated With TNF-inhibitors. Data from REGISPONSERBIO

10.21203/rs.3.rs-705421/v1 ◽

2021 ◽

Author(s):

Maria Llop ◽

Mireia Moreno ◽

Victoria Navarro-Compán ◽

Xavier Juanola ◽

Eugenio de Miguel ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Radiographic Progression ◽

Axial Spondyloarthritis ◽

Term Treatment ◽

Tnf Inhibitors ◽

Low Disease Activity ◽

Long Term Treatment

Abstract Background: To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).Methods: The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: i) long-term treatment (≥4 years) and ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model.Results: Radiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP).Conclusions: Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.

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Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

Behavioral and Brain Sciences ◽

10.1017/s0140525x1800105x ◽

2019 ◽

Vol 42 ◽

Cited By ~ 2

Author(s):

John P. A. Ioannidis

Keyword(s):

Mental Health ◽

Mental Disease ◽

Brain Disorders ◽

Social Stressors ◽

Labor Education ◽

Mental Diseases ◽

Long Term Follow Up ◽

Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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