Secukinumab in axial spondyloarthritis: a narrative review of clinical evidence.
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SUBMITTER: Braun J
PROVIDER: S-EPMC8404628 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSecukinumab is a biologic disease-modifying antirheumatic drug (bDMARD) that has demonstrated efficacy in the treatment of axial spondyloarthritis (axSpA, i.e., ankylosing spondylitis and non-radiographic axSpA) across various clinical trials. However, data of secukinumab in clinical practice is still limited. Here, we aimed to provide real-world data on secukinumab use, effectiveness, and persistence in axSpA.Patients and methodsRetrospective, multicenter study of patients with a diagnosis of axSpA treated with secukinumab at 12 centers up to June 2021 in the Valencian Community (Spain). Information was gathered on BASDAI measurement, pain, patient and physician global assessment (ptGA, phGA) using a 100-mm visual analog scale (VAS), persistence and other secondary variables by treatment line (first, second, and ≥ third) for up to 24 months.Results221 patients were included (69% men; mean age [standard deviation, SD]: 46.7 [12.1] years old). Secukinumab was used as a first-line bDMARD in 38% of patients, as a second-line in 34% and as a ≥ hird-line in 28%. The percentage of patients achieving low disease activity (BASDAI<4) increased from 9% at baseline to 48% at month 6 and was maintained (49%) up to month 24. The greatest improvement in BASDAI was observed in naïve patients (month 6: -2.6; month 24: -3.7), followed by second-line (month 6: -1.9; month 24: -3.1) and ≥ third-line (month 6: -1.3; month 24: -2.3) patients. Reductions in mean pain VAS (-23.3; -31.9), ptGA (-25.1; -31.9) and phGA (-25.1; -31) were also observed at 6 and 24 months. Secukinumab showed an overall 12-months persistence rate of 70% (95% confidence interval [CI]: 63-77%) and a 24-months persistence rate of 58% (95% CI, 51-66%). Patients receiving first-line secukinumab had the highest 24-months persistence rate (p = 0.05).ConclusionSecukinumab improved disease activity in axSpA patients, especially in naive, and second-line patients, which was accompanied by high persistence rates up to 24 months.
| S-EPMC10213893 | biostudies-literature
Project description:Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disorder that causes chronic pain, primarily in the spine and sacroiliac joints. It is characterized by the presence of type 1 major histocompatibility complex HLA-B27 genetic marker, arthritis in peripheral joints, enthesitis and/or dactylitis and extra-articular manifestations. Current guidelines recommend biological therapy when first-line therapy is not sufficiently effective. The finding that the interleukin (IL)-17 axis is vital for the pathogenesis of axSpA propelled the development of secukinumab, a fully human monoclonal antibody directed against IL-17A. The present review provides evidence on the efficacy and safety of secukinumab in the treatment of radiographic and non-radiographic axSpA from nine randomized controlled phase III trials, as well as evidence from real-world observational analyses. The primary endpoint in six clinical trials was the proportion of patients meeting the Assessment of SpondyloArthritis international Society criteria for either 20% or 40% improvement (ASAS20, ASAS40) at week 16. Significantly more patients achieved the primary endpoint with secukinumab compared with placebo in all the studies except MEASURE 4. Both clinical trials and real-world studies showed significant improvements in the secondary endpoints of disease activity, quality of life, and pain and fatigue relative to placebo. The benefits of secukinumab were generally sustained during longer-term (up to 5 years) treatment. Overall, secukinumab was well tolerated with a low frequency of adverse events and treatment persistence was high in the real-world setting. Although indirect comparisons suggest that secukinumab and adalimumab have comparable efficacy and safety, they are being directly compared in the ongoing SURPASS study. During the current coronavirus disease 2019 (COVID-19) pandemic, it is advisable to continue biological therapy in patients who do not have severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, but interrupt treatment during an infection, reinitiating once the patient has recovered from the infection. In conclusion, secukinumab is a largely safe and effective treatment for radiographic and non-radiographic axSpA.
| S-EPMC8627156 | biostudies-literature
Project description: Not available
| S-EPMC9945485 | biostudies-literature
Project description:Abstract Objectives The aim was to evaluate retention rates for secukinumab in patients with active PsA or radiographic axial spondyloarthritis (r-axSpA) treated in routine UK clinical practice. Methods SERENA (CAIN457A3403) is an ongoing, non-interventional, international study of patients with moderate-to-severe chronic plaque psoriasis, active PsA or active r-axSpA, who had received secukinumab for ≥16 weeks before enrolment. The primary objective of this interim analysis was to assess treatment retention rates in patients with PsA or r-axSpA who were enrolled and followed for ≥2 years at centres in the UK. The safety analysis set includes all patients who received at least one dose of secukinumab. The target population set includes all patients who fulfilled the patient selection criteria. Results The safety set comprised 189 patients (PsA, n = 81; r-axSpA, n = 108), and the target population set comprised 183 patients (PsA, n = 78; r-axSpA, n = 105). In the safety set, 107 patients (45 of 81 with PsA and 62 of 108 with r-axSpA) had previously received a biologic agent. Retention rates were similar between patients with PsA and r-axSpA after 1 year (PsA 91.0%, 95% CI: 84.0, 98.0; r-axSpA 89.2%, 95% CI: 82.7, 95.7) and 2 years (PsA 77.6%, 95% CI: 67.6, 87.7; r-axSpA 76.2%, 95% CI: 67.4, 85.0) of observation. Overall, 17.5% of patients (33 of 189) experienced at least one treatment-related adverse event, and 12.7% of patients (24 of 189) discontinued secukinumab because of adverse events. Conclusion This analysis of real-world data from the UK demonstrates high retention rates for secukinumab over 2 years in patients with PsA or r-axSpA, with a favourable safety profile.
| S-EPMC10472087 | biostudies-literature
Project description:ObjectivesTo 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)].MethodsConsecutive 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.ResultsA 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).ConclusionIn 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.
| S-EPMC9058366 | biostudies-literature
Project description:ObjectivesTo explore differences in axial spondyloarthritis (axSpA) clinical phenotype around the world in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS).MethodIMAS was a cross-sectional online survey (2017-2022) of 5557 unselected axSpA patients from 27 countries. We analysed across five geographic regions the age at symptom onset, diagnostic delay, gender, HLA-B27, family history, extra-musculoskeletal manifestations, presence of comorbidities, disease activity (BASDAI), level of spinal stiffness and treatments.ResultsOf 5557 IMAS participants, 3493 were from Europe, 770 from North America, 600 from Asia, 548 from Latin America and 146 from South Africa. Age at symptom onset ranged between 25 and 30 years and was higher in Latin America. Diagnostic delay was longest in South Africa and lowest in Asia. The lowest HLA-B27 positivity was observed in Latin America and the highest in Asia. Extra-musculoskeletal manifestations were the lowest in Europe. Mean disease activity (BASDAI) was 5.4, with highest values in South Africa and lowest in Asia. Most of the patients had used NSAIDs for their condition and less than half had ever taken conventional synthetic DMARDS; both were more frequent in Latin America and South Africa. Almost half of the patients had ever taken biologic DMARDs, more frequent use being in the Americas.ConclusionThere is great heterogeneity of axSpA clinical phenotype presentation around the world. AxSpA manifests differently in different regions, so further understanding of these differences of phenotypes is needed to achieve early diagnosis and initiation of optimal disease treatment in axSpA in the different regions.
| S-EPMC11371368 | biostudies-literature
Project description:Identification of axial spondyloarthritis (axSpA) remains challenging, frequently resulting in a diagnostic delay for patients. Current benchmarks of delay are usually reported as mean data, which are typically skewed and therefore may be overestimating delay. Our aim was to determine the extent of median delay patients' experience in receiving a diagnosis of axSpA and examine whether specific factors are associated with the presence of such delay. We conducted a systematic review across five literature databases (from inception to November 2021), with studies reporting the average time period of diagnostic delay in patients with axSpA being included. Any additional information examining associations between specific factors and delay were also extracted. A narrative synthesis was used to report the median range of diagnostic delay experienced by patients with axSpA and summarise which factors have a role in the delay. From an initial 11,995 articles, 69 reported an average time period of diagnostic delay, with 25 of these providing a median delay from symptom onset to diagnosis. Across these studies, delay ranged from 0.67 to 8 years, with over three-quarters reporting a median of between 2 years and 6 years. A third of all studies reported median delay data ranging from just 2 to 2.3 years. Of seven variables reported with sufficient frequency to evaluate, only 'gender' and 'family history of axSpA' had sufficient concordant data to draw any conclusion on their role, neither influenced the extent of the delay. Despite improvements in recent decades, patients with axSpA frequently experience years of diagnostic delay and this remains an extensive worldwide problem. This is further compounded by a mixed picture of the disease, patient and healthcare-related factors influencing delay. Key points • Despite improvements in recent decades, patients with axSpA frequently experience years of diagnostic delay. • Median diagnostic delay typically ranges from 2 to 6 years globally. • Neither 'gender' nor 'family history of axSpA' influenced the extent of diagnostic delay experienced. • Diagnostic delay based on mean, rather than median, data influences the interpretation of the delay time period and consistently reports a longer delay period.
| S-EPMC9187558 | biostudies-literature
Project description:Cardiovascular manifestations are common in patients suffering axial spondyloarthritis and can result in substantial morbidity and disease burden. To give an overview of this important aspect of axial spondyloarthritis, we conducted a systematic literature search of all articles published between January 2000 and 25 May 2023 on cardiovascular manifestations. Using PubMed and SCOPUS, 123 out of 6792 articles were identified and included in this review. Non-radiographic axial spondyloarthritis seems to be underrepresented in studies; thus, more evidence for ankylosing spondylitis exists. All in all, we found some traditional risk factors that led to higher cardiovascular disease burden or major cardiovascular events. These specific risk factors seem to be more aggressive in patients with spondyloarthropathies and have a strong connection to high or long-standing disease activity. Since disease activity is a major driver of morbidity, diagnostic, therapeutic, and lifestyle interventions are crucial for better outcomes. Key Points • Several studies on axial spondyloarthritis and associated cardiovascular diseases have been conducted in the last few years addressing risk stratification of these patients including artificial intelligence. • Recent data suggest distinct manifestations of cardiovascular disease entities among men and women which the treating physician needs to be aware of. • Rheumatologists need to screen axial spondyloarthritis patients for emerging cardiovascular disease and should aim at reducing traditional risk factors like hyperlipidemia, hypertension, and smoking as well as disease activity.
| S-EPMC10497445 | biostudies-literature
Project description:BackgroundRadiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here.MethodsIn the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or placebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0-8) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; range, 0-72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0-24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0-69).ResultsOverall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, - 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNY-negative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syndesmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], - 1.23 [2.81] vs - 0.37 [1.90] with placebo) was sustained through week 104 (- 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104).ConclusionStructural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years.Trial registrationClinicalTrials.gov, NCT02696031.
| S-EPMC10186767 | biostudies-literature
Project description:INTRODUCTION:Few studies have evaluated the impact of delayed diagnosis of axial spondyloarthritis (axSpA) on the overall burden of disease. The objective of this review was to evaluate the available literature on the clinical, economic, and humanistic burden of delayed diagnosis in patients with axSpA. METHODS:This systematic literature review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the MEDLINE and Embase databases for English-language publications of original research articles (up to July 12, 2018) and conference abstracts (January 1, 2014, to July 12, 2018) reporting studies of adult patients with delayed diagnosis of axSpA associated with clinical, economic, or humanistic burden. Retrieved publications were screened for eligibility by two independent reviewers; discrepancies were resolved by a third independent reviewer. Data were extracted by one reviewer and validated by a second independent reviewer. RESULTS:A total of 1391 publications were retrieved, of which 21 met the inclusion criteria and were included in the analysis. Of these, 15 reported data on clinical burden, nine on economic burden, and six on humanistic burden, with eight studies reporting a combination of clinical, economic, and/or humanistic burden. Patients with a delayed diagnosis of axSpA generally had higher disease activity, worse physical function, and more structural damage than those who received an earlier diagnosis. Patients with a delayed diagnosis also had a greater likelihood of work disability and higher direct and indirect healthcare costs than those who received an earlier diagnosis. Delayed diagnosis was associated with a greater likelihood for depression, negative psychological impacts, and worse quality of life. CONCLUSIONS:Delayed axSpA diagnosis was associated with more functional impairment, higher healthcare costs, and worse quality of life, highlighting the importance of early recognition of axSpA to reduce extensive burden on patients and society. Plain language summary available for this article.
| S-EPMC7021861 | biostudies-literature