The Genetic Contribution to Drug Response in Spondyloarthritis: A Systematic Literature Review

Ortolan, Augusta; Cozzi, Giacomo; Lorenzin, Mariagrazia; Galozzi, Paola; Doria, Andrea; Ramonda, Roberta

doi:10.3389/fgene.2021.703911

Cited by 7 publications

(5 citation statements)

References 52 publications

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“… 41 Therefore, SEC can be considered as a drug of choice in patients with one or more previous TNFi failure. 42 – 44 Accordingly, a comparative real-life cohort study of two modes of biological action in axSpA, after prior withdrawal from at least one TNFi, showed that patients treated with SEC experienced outcomes comparable to those of patients treated with an alternative TNFi. 45 …”

Section: Discussionmentioning

confidence: 99%

“…41 Therefore, SEC can be considered as a drug of choice in patients with one or more previous TNFi failure. [42][43][44] Accordingly, a comparative real-life cohort study of two modes of biological action in axSpA, after prior withdrawal from at least one TNFi, showed that patients treated with SEC experienced outcomes comparable to those of patients treated with an alternative TNFi. 45 Furthermore, no differences in drug retention emerged between r-axSpA and nr-axSpA subjects, while some emerged regarding functional outcomes: r-axSpA patients presented worse clinical measures, physical functioning, and inflammatory activity.…”

Section: Discussionmentioning

confidence: 99%

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Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study

Ramonda

Lorenzin

Chimenti

et al. 2022

Therapeutic Advances in Musculoskeletal

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Objectives: To evaluate, in a multicentric Italian cohort of axial spondyloarthritis (axSpA) patients on Secukinumab (SEC) followed for 24 months: (1) the long-term effectiveness and safety of SEC; (2) the drug retention rate and low disease activity (LDA) measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4/Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and very low disease activity (VLDA) measured as BASDAI < 2/ASDAS < 1.3; (3) any differences in outcomes according to line of biological treatment (naïve/non-naïve), gender (male/female), subtype of axSpA [radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)]. Methods: Consecutive axSpA patients treated with SEC were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical-values were recorded at baseline (T0), 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug discontinuation and LDA at T6. Infections and adverse events were recorded. Results: A total 249 patients (47.8% male; median age 51) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA, and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0 = 3.5 (2.9–4.4) versus T24 = 1.9 (1.2–2.4); p = 0.02] and BASDAI [T0 = 6.5 (5.0–7.5) versus T24 = 2.8 (1.8–4.0); p = 0.03]. At T24, naïve patients showed better physical functioning and lower disease activity than non-naïve. After 24 months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAI < 4). Treatment was discontinued in 24.5% patients, mainly due to primary/secondary loss of effectiveness, and in 6.8% due to adverse events. Retention rate at T24 was 75% in the whole population, with some difference depending on gender ( p = 0.002). Conclusion: In a real-life clinical setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug retention rate. No differences were observed between r-axSpA and nr-axSpA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study

Ramonda

Lorenzin

Chimenti

et al. 2022

Therapeutic Advances in Musculoskeletal

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“…Cross-sectional studies were graded as follows: very good, 9–10; good, 7–8; satisfactory, 5–6; unsatisfactory, 0–4 31 . Cohort studies were graded as follows: very good, 8–9; good, 7; satisfactory, 5–6; unsatisfactory, 0–4 32 .…”

Section: Methodsmentioning

confidence: 99%

The relationship between tooth loss and hypertension: a systematic review and meta-analysis

Tada

Tano

Miura

2022

Sci Rep

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As tooth loss is the high end of periodontal problems and edentulous individuals are at higher risk of nutritional problems like obesity, understanding the association between tooth loss and hypertension is important for improving cardiovascular health. We searched for publications from the last two decades using three electronic databases (PubMed, Web of Science and Scopus) and conducted a systematic review and meta-analysis on the association between tooth loss and hypertension according to PRISMA-P guidelines. Quality assessments were performed using the Newcastle–Ottawa Scale and the GRADE approach. Twenty-four studies (20 cross-sectional, and 4 cohort) met the inclusion criteria for this review. Most cross-sectional studies showed that subjects with more tooth loss exhibited a greater proportion of hypertension and higher systolic blood pressure than those with less tooth loss. Meta-analyses revealed a statistically significant association between tooth loss and hypertension. The pooled odds ratios of hypertension for having tooth loss with no tooth loss and for edentulous with dentate were 2.22 (95% CI 2.00–2.45) and 4.94 (95% CI 4.04–6.05), respectively. In cohort studies, subjects with more tooth loss had a greater incidence of hypertension than those with less tooth loss during the follow-up period. The present systematic review and meta-analysis suggests that tooth loss is associated with an increased risk of hypertension and higher systolic blood pressure.

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“…The genetic contribution to drug response in SpA has been recently the subject of a systematic literature review by Ortolan et al. ( 30 ). Only 26 studies of 393 screened studies were analysed after selection process, 21 of them investigating TNF blockers efficacy.…”

Section: Treatmentmentioning

confidence: 99%

How to translate genetic findings into clinical applications in spondyloarthritis?

Frison,

Breban,

Costantino

2024

Front. Immunol.

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Spondyloarthritis (SpA) is characterized by a strong genetic predisposition evidenced by the identification of up to 50 susceptibility loci, in addition to HLA-B27, the major genetic factor associated with the disease. These loci have not only deepened our understanding of disease pathogenesis but also offer the potential to improve disease management. Diagnostic delay is a major issue in SpA. HLA-B27 testing is widely used as diagnostic biomarker in SpA but its predictive value is limited. Several attempts have been made to develop more sophisticated polygenic risk score (PRS). However, these scores currently offer very little improvement as compared to HLA-B27 and are still difficult to implement in clinical routine. Genetics might also help to predict disease outcome including treatment response. Several genetic variants have been reported to be associated with radiographic damage or with poor response to TNF blockers, unfortunately with lack of coherence across studies. Large-scale studies should be conducted to obtain more robust findings. Genetic and genomic evidence in complex diseases can be further used to support the identification of new drug targets and to repurpose existing drugs. Although not fully driven by genetics, development of IL-17 blockers has been facilitated by the discovery of the association between IL23R variants and SpA. Development of recent approaches combining GWAS findings with functional genomics will help to prioritize new drug targets in the future. Although very promising, translational genetics in SpA remains challenging and will require a multidisciplinary approach that integrates genetics, genomics, immunology, and clinical research.

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The Genetic Contribution to Drug Response in Spondyloarthritis: A Systematic Literature Review

Cited by 7 publications

References 52 publications

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study

The relationship between tooth loss and hypertension: a systematic review and meta-analysis

How to translate genetic findings into clinical applications in spondyloarthritis?

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