Tumor Necrosis Factor Inhibitors Reduce Spinal Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: A Longitudinal Analysis From the Alberta Prospective Cohort

Sepriano, Alexandre; Smolen, Josef S; Wichuk, Stephanie; Chiowchanwisawakit, Praveena; Paschke, Joel; Heijde, Desirée van der; Landewé, Robert; Maksymowych, Walter P.

doi:10.1002/art.41667

Cited by 32 publications

(29 citation statements)

References 39 publications

(60 reference statements)

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“…These ndings are in line with previous publications, where despite an acceptable concordance between patient groups de ned by BASDAI ≥ 4 and ASDAS ≥ 2.1 (25,26), ASDAS is the preferred tool for assessing disease activity (10). As reported by previous authors, a longitudinal relationship between ASDAS and subsequent syndesmophyte formation was found, while such a relationship between BASDAI and syndesmophytes was far weaker (3,27). Furthermore, ASDAS shows a better correlation than BASDAI when measurements of disease activity assessed by patients and physicians are compared (28).…”

Section: Discussionsupporting

confidence: 91%

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

Llop

Moreno

Navarro-Compán

et al. 2021

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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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Section: Discussionsupporting

confidence: 91%

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

Llop

Moreno

Navarro-Compán

et al. 2021

Preprint

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“…With current approved therapeutics for SpA failing to fully prevent disease progression despite providing symptomatic relief and some modulation of progression of structural damage with TNFi ( Haroon et al, 2013 ; Koo et al, 2020 ; Sepriano et al, 2021 ), there is a clear unmet medical need for novel DMARDs. TYK2 is implicated in multiple chronic inflammatory diseases, including SpA, through genetic associations and a central role in IL-23 activation of innate, innate-like and adaptive immune cells.…”

Section: Discussionmentioning

confidence: 99%

From Science to Success? Targeting Tyrosine Kinase 2 in Spondyloarthritis and Related Chronic Inflammatory Diseases

et al. 2021

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Spondyloarthritis (SpA) is a family of inflammatory arthritic diseases, which includes the prototypes of psoriatic arthritis and ankylosing spondylitis. SpA is commonly associated with systemic inflammatory diseases, such as psoriasis and inflammatory bowel disease. Immunological studies, murine models and the genetics of SpA all indicate a pathogenic role for the IL-23/IL-17 axis. Therapeutics targeting the IL-23/IL-17 pathway are successful at providing symptomatic relief, but may not provide complete protection against progression of arthritis. Thus there is still tremendous interest in the discovery of novel therapeutic targets for SpA. Tyrosine kinase 2 (TYK2) is a member of the Janus kinases, which mediate intracellular signaling of cytokines via signal transducer and activator of transcription (STAT) activation. TYK2 plays a crucial role in mediating IL-23 receptor signaling and STAT3 activation. A plethora of natural mutations in and around TYK2 have provided a wealth of data to associate this kinase with autoimmune/autoinflammatory diseases in humans. Induced and natural mutations in murine Tyk2 largely support human data; however, key inter-species differences exist, which means extrapolation of data from murine models to humans needs to be done with caution. Despite these reservations, novel selective TYK2 inhibitors are now proving successful in advanced clinical trials of inflammatory diseases. In this review, we will discuss TYK2 from basic biology to therapeutic targeting, with an emphasis on studies in SpA. Seminal studies uncovering the basic science of TYK2 have provided sound foundations for targeting it in SpA and related inflammatory diseases. TYK2 inhibitors may well be the next blockbuster therapeutic for SpA.

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“…In the third study, however, the direct effect of bDMARDs remained statistically significant after adjusting for ASDAS. 46 Almost all studies reporting the time-varying structural effect of TNFi have handled time-varying confounding. Even though residual confounding is still a possibility, it can be argued that its likelihood is lower as compared with other types of studies discussed above.…”

Section: Comparative Studies With Variable Exposure To Treatmentmentioning

confidence: 99%

“…In the third study, however, the direct effect of bDMARDs remained statistically significant after adjusting for ASDAS. 46 …”

Section: Causal Treatment Effects In Observational Researchmentioning

confidence: 99%

Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference

et al. 2021

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Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Available therapeutic options include biological disease-modifying antirheumatic drugs (bDMARDs), which have been proven effective in suppressing inflammation in several randomised controlled trials (RCT), the gold standard for evaluating causal treatment effects. RCTs are, however, unfeasible for testing structural effects in axSpA mainly due to the low sensitivity to change of the mSASSS. The available literature therefore mainly includes observational research, which poses serious challenges to the determination of causality. Here, we review the studies testing the effect of bDMARDs on spinal radiographic progression, making use of the principles of causal inference. By exploring the assumptions of causality under counterfactual reasoning (exchangeability, positivity and consistency), we distinguish between studies that likely have reported confounded treatment effects and studies that, on the basis of their design, have more likely reported causal treatment effects. We conclude that bDMARDs might, indirectly, interfere with spinal radiographic progression in axSpA by their effect on inflammation. Innovations in imaging are expected, so that placebo-controlled trials can in the future become a reality. In the meantime, causal inference analysis using observational data may contribute to a better understanding of whether disease modification is possible in axSpA.

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Tumor Necrosis Factor Inhibitors Reduce Spinal Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: A Longitudinal Analysis From the Alberta Prospective Cohort

Cited by 32 publications

References 39 publications

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

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

From Science to Success? Targeting Tyrosine Kinase 2 in Spondyloarthritis and Related Chronic Inflammatory Diseases

Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference

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