The objective of this study was to assess treatment response to ixekizumab, an interleukin-17A antagonist, by shorter versus longer symptom duration (< 5 years vs. ≥ 5 years) in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) up to 52 weeks.
Methods
This post hoc analysis used data from three randomized, placebo-controlled trials including patients with r-axSpA from COAST-V [biologic disease-modifying anti-rheumatic drug (bDMARD)-naïve] and COAST-W (tumor necrosis factor inhibitor-experienced) and patients with nr-axSpA from COAST-X (bDMARD-naïve). Patients received ixekizumab (80 mg every 2 or 4 weeks) or placebo through Week 16 and ixekizumab to Week 52. Assessments included the Assessment in SpondyloArthritis international Society 40% improvement (ASAS40) and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity [LDA (< 2.1)] and Bath Ankylosing Spondylitis Disease Activity Index 50% improvement (BASDAI50) response rates through Week 52 and change from baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) at Week 16.
Results
Fewer patients treated with ixekizumab (pooled dosing) had shorter versus longer symptom duration [n = 33 vs. n = 306 (r-axSpA); n = 73 vs. n = 111 (nr-axSpA)]. Ixekizumab-treated patients with shorter versus longer symptom duration had numerically higher response rates at Week 16/Week 52 for ASAS40 [51.5/60.6 vs. 36.9/40.5 (r-axSpA); 42.5/54.8 vs. 36.0/41.4 (nr-axSpA)], ASDAS LDA [39.4/48.5 vs. 27.5/35.6 (r-axSpA); 32.9/49.3 vs. 27.9/36.9 (nr-axSpA)], and BASDAI50 [42.4/54.5 vs. 31.4/36.6 (r-axSpA); 38.4/49.3 vs. 27.9/34.2 (nr-axSpA)]. However, relative risk ratios at Week 16 did not significantly favor the shorter duration subgroup. Findings were comparable for SF-36 PCS at Week 16. The present findings should be interpreted in the context of small numbers of patients in some shorter duration subgroups.
Conclusion
Ixekizumab was shown to be efficacious in both patients with shorter or longer symptom duration and in r-axSpA or nr-axSpA.
Portions of this work were presented at the Annual Congress of the European Alliance of Associations for Rheumatology (EULAR), June 1–4, 2022, in Copenhagen, Denmark.
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Key Summary Points
Why carry out this study?
Symptom duration has been reported in previous studies to be a predictor of clinical response and less radiographic progression in the treatment of axial spondyloarthritis (axSpA).
We conducted post hoc analyses to evaluate the efficacy of ixekizumab in patients with shorter symptom duration (< 5 years) compared with patients with longer symptom duration (≥ 5 years) and both, radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA)
What was learned from the study?
Ixekizumab was shown to be effective in both patients with shorter (< 5 years) or longer symptom duration (≥ 5 years) with r-axSpA and nr-axSpA.
Overall, more studies with larger early axSpA and shorter symptom duration threshold populations are needed.
Introduction
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial skeleton (i.e., sacroiliac joints and spine). AxSpA can be divided into two classes, radiographic axSpA (r-axSpA) or non-radiographic axSpA (nr-axSpA), depending on the presence or absence of structural changes observed on conventional radiographs. However, patients often experience symptoms such as pain and stiffness for several years before radiographic damage is evident [1].
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Symptom duration has been reported in previous studies to be a predictor of clinical response and less radiographic progression in the treatment of axSpA [2‐6]. Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A [7]. Ixekizumab has demonstrated superior efficacy compared with placebo in the treatment of patients with axSpA covering the entire spectrum of the disease, in patients with r-axSpA in the COAST-V and COAST-W clinical trials [8], and in patients with nr-axSpA in the COAST-X clinical trial [9].
At the time of the design of this post hoc analysis, there was no consensus regarding the definition for early axSpA. The cut-off chosen for this analysis (< 5 years symptom duration) aligned with previously published standards; in a recent systematic review, among 61 studies that included the term “early axSpA,” the most common definition was symptom/disease duration < 5 years [10]. The objective of this pooled analysis of the COAST-V, COAST-W, and COAST-X trials was to assess treatment response to ixekizumab categorized by the duration since symptom onset (shorter, < 5 years versus longer, ≥ 5 years) in patients with r-axSpA or nr-axSpA.
Methods
Trial Design
COAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomized, controlled clinical trials that enrolled patients with r-axSpA. COAST-X (NCT02757352) was a phase 3, multicenter, randomized, controlled clinical trial that enrolled patients with nr-axSpA. Patients in COAST-V and COAST-X were biologic disease-modifying anti-rheumatic drug (bDMARD)-naïve, and patients in COAST-W were tumor necrosis factor inhibitor (TNFi)-experienced. Detailed trial designs have been previously reported for COAST-V [8, 11], COAST-W [8, 12], and COAST-X [9]. Data from these three pivotal trials were used to assess the efficacy and safety of ixekizumab in patients with axSpA through 52 weeks.
Ethical Approval
All trials were conducted in accordance with the ethical principles of the Declaration of Helsinki and were approved by the ethics review boards at each participating study site. The master ethics committee was Schulman Associates Institutional Review Board (IRB), Cincinnati, OH, USA (IRB reference numbers: COAST-V, 201506061; COAST-W, 201506079; COAST-X, 201601302). The full lists of study sites and investigators are reported in the primary manuscript supplements [9, 11, 12]. All patients provided written informed consent prior to participating in the trials.
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Trial Participants
Detailed patient eligibility criteria have been previously reported [8, 9, 11, 12]. Briefly, all three trials (COAST-V, COAST-W, and COAST-X) included adult patients (≥ 18 years old) with an established diagnosis of axSpA and fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for r-axSpA and nr-axSpA, respectively [13, 14]. All patients had active disease defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and total back pain score ≥ 4 on a numeric rating scale with inadequate response or intolerance to non-steroidal anti-inflammatory drug therapy. In COAST-V and COAST-W, patients were required to have fulfilment of ASAS criteria and evidence of radiographic sacroiliitis by modified New York (mNY) criteria and ≥ 1 spondyloarthritis (SpA) feature. In COAST-V, patients were required to be bDMARD-naïve. In COAST-W, patients were required to have prior treatment with 1 or 2 TNFi, discontinued because of inadequate response or intolerance. In COAST-X, patients were required to have fulfilment of ASAS criteria and evidence of inflammation of the sacroiliac joint on magnetic resonance imaging and ≥ 1 SpA feature or positivity of human leukocyte antigen B27 and 2 SpA features. In COAST-X, patients were required to be bDMARD-naïve, and patients meeting the radiologic criterion of the mNY criteria were excluded.
Randomization and Blinding
As previously described, in COAST-V, 341 participants with r-axSpA were randomized 1:1:1:1 to 80 mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE Q4W), placebo, or an active reference arm (40 mg adalimumab every 2 weeks) [8, 11]. In COAST-W, 316 patients with r-axSpA were randomized 1:1:1 to IXE Q2W, IXE Q4W, or placebo [8, 12]. In COAST-X, 303 patients with nr-axSpA were randomized 1:1:1 to IXE Q2W, IXE Q4W, or placebo [9]. The COAST-X trial was double-blind up to Week 52. The COAST-V and COAST-W trials were double-blind through Week 16 and included a dose double-blinded extension period up to Week 52.
Assessments
Endpoints examined in this post hoc study were ASAS ≥ 40% improvement (ASAS40), Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity [LDA (< 2.1)], and BASDAI ≥ 50% improvement (BASDAI50) response rates through Week 52, and change from baseline in the physical component of the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) at Week 16. These endpoints were assessed for patients with r-axSpA and nr-axSpA categorized by shorter (< 5 years) versus longer (≥ 5 years) symptom duration, with symptoms being indicative of the onset of axial disease. The relative risk ratio (RRR) and 95% confidence interval (CI) and the number needed to treat (NNT) were calculated at Week 16.
Statistical Analysis
Intent-to-treat patients who were eligible per protocol were included in this post hoc analysis. Data were summarized by symptom duration (< 5 and ≥ 5 years) and by treatment: placebo to Week 16 and combined IXE Q4W and IXE Q2W (total ixekizumab) to Week 52. For ASAS40, ASDAS LDA, and BASDAI50, response rates were calculated using non-responder imputation, and relative risk of response (ixekizumab vs. placebo), RRR (< 5 vs. ≥ 5 years symptom duration), and NNT at Week 16 are presented. For SF-36 PCS, least squares mean and standard error are presented. Treatment comparisons at Week 16 within each subgroup were conducted using the Cochran–Mantel–Haenszel test or the Fisher exact test for categorical endpoints, and analysis of covariance for continuous endpoints. Inferential testing was not performed if a subgroup was < 10% of the total population. Missing data were handled using non-responder imputation for categorical endpoints and modified baseline observation carried forward for continuous endpoints. Analyses were performed using Statistical Analysis System version 9.4 (SAS Institute, Cary, NC, USA).
Results
A total of 341 patients were randomized in COAST-V [11], 316 patients in COAST-W [12], and 303 patients in COAST-X [9]. Demographic and baseline disease characteristics are presented in Table 1 for patients with r-axSpA and nr-axSpA treated with ixekizumab (combined IXE Q4W and IXE Q2W, n = 523), categorized by shorter versus longer symptom duration (< 5 years vs. ≥ 5 years; for placebo data see Supplemental Table S1). Overall, in this post hoc analysis, more patients had longer versus shorter symptom duration [r-axSpA, n = 306 (90.3%) vs. n = 33 (9.7%); nr-axSpA, n = 111 (60.3%) vs. n = 73 (39.7%), respectively; Table 1]. Mean symptom duration for total ixekizumab was approximately 2–3 years in patients with shorter duration for both r-axSpA (3.1 years) and nr-axSpA (2.4 years) compared with mean symptom duration of approximately 17–18 years in patients with longer duration (r-axSpA: 18.5 years; nr-axSpA: 17.3 years; Table 1).
Table 1
Demographics and baseline disease characteristics for patients with r-axSpA or nr-axSpA treated with ixekizumab (combined IXE Q4W and IXE Q2W) by symptom duration subgroup
r-axSpA
nr-axSpA
< 5 years symptom duration (n = 33)
≥ 5 years symptom duration (n = 306)
< 5 years symptom duration (n = 73)
≥ 5 years symptom duration (n = 111)
Age, years
33.1 (8.2)
45.1 (12.1)
31.9 (10.1)
46.4 (11.9)
Male, n (%)
26 (78.8)
245 (80.1)
40 (54.8)
53 (47.7)
Duration of symptoms since axSpA onset, years
3.1 (1.2)
18.5 (10.1)
2.4 (1.4)
17.3 (9.8)
csDMARD use, n (%)
14 (42.4)
93 (30.4)
25 (34.2)
53 (47.7)
Prior use of TNFi, n (%)
11 (33.3)
176 (57.5)
–
–
ASDAS score
3.9 (0.8)
4.0 (0.8)
3.8 (0.8)
3.9 (0.8)
BASDAI score
7.2 (1.6)
7.3 (1.4)
7.0 (1.3)
7.3 (1.3)
SF-36 PCS score
34.0 (7.7)
32.9 (7.6)
32.8 (7.9)
32.6 (7.0)
SF-36 MCS score
46.8 (14.2)
47.1 (11.6)
48.1 (12.5)
47.0 (12.4)
CRP, mg/L
12.3 (15.1)
17.0 (25.2)
12.1 (17.5)
12.0 (18.2)
CRP >5.00 mg/L, n (%)
21 (63.6)
202 (66.0)
42 (57.5)
60 (54.1)
Data are mean (standard deviation) unless otherwise specified
For ixekizumab-treated patients with r-axSpA, ASAS40 response rates at Week 16 were 51.5% for patients with shorter versus 36.9% for those with longer symptom duration (Week 52, 60.6% vs. 40.5%, respectively; Fig. 1a). For ixekizumab-treated patients with nr-axSpA, ASAS40 response rates at Week 16 were 42.5% for shorter versus 36.0% for longer symptom duration (Week 52, 54.8% vs. 41.4%, respectively; Fig. 1b). For ASAS40 in r-axSpA patients, the RRR (95% CI) at Week 16 for shorter versus longer symptom duration was 1.32 (0.42, 4.17), while for nr-axSpA patients, the RRR for shorter versus longer symptom duration was 1.36 (0.54, 3.39) (Fig. 1e). Results were comparable for ASDAS LDA (Fig. 1c, d, and e) and BASDAI50 (Supplemental Figure S1), with numerically greater response for the shorter duration subgroup after Week 16, but RRRs at Week 16 did not significantly favor the shorter versus the longer duration subgroups. Trends for IXE Q4W were similar to those seen for the combined IXE Q2W and IXE Q4W population (Supplemental Figures S2 and S3).
Fig. 1
Response rates, number needed to treat, and relative risk of response by shorter versus longer symptom duration (defined as < 5 vs. ≥ 5 years) for patients with r-axSpA and nr-axSpA treated with ixekizumab (combined IXE Q4W and IXE Q2W) or PBO. a ASAS40 for r-axSpA through Week 52. b ASAS40 for nr-axSpA through Week 52. c ASDAS LDA response rates for r-axSpA through Week 52. d ASDAS LDA response rates for nr-axSpA through Week 52. e Number needed to treat to achieve ASAS40 or ASDAS LDA at Week 16. *p < 0.05; **p < 0.01; ***p < 0.001 vs. PBO at Week 16 using Cochran–Mantel–Haenszel test stratified by study (patients with r-axSpA) or the Fisher exact test (patients with nr-axSpA). ASAS40 Assessment of SpondyloArthritis international Society 40% improvement, ASDAS Axial Spondyloarthritis Disease Activity Score, IXE ixekizumab, LDA low disease activity (ASDAS < 2.1), NA not applicable as inferential testing was not performed if a subgroup was < 10% of the total population, nr-axSpA non-radiographic axial spondyloarthritis, NRI non-responder imputation, NS not significant, PBO placebo, r-axSpA radiographic axial spondyloarthritis
With regard to NNT estimates, these favored the shorter over the longer symptom duration subgroup for ASAS40 (r-axSpA 2.9 and 4.7, respectively; nr-axSpA 4.1 and 6.5, respectively). Similar results were seen for ASDAS LDA (4.0 and 8.1, respectively; all Fig. 1e), and BASDAI50 in patients with nr-axSpA (3.3 and 9.4, respectively; Supplemental Figure S1c). For ASDAS LDA in patients with r-axSpA, NNT favored the longer symptom duration subgroup over shorter duration subgroup (4.7 and 8.6, respectively; Fig. 1e), while for BASDAI50 in patients with r-axSpA, the NNT for shorter and longer symptom duration subgroups were similar (5.0 and 5.3, respectively; Supplemental Figure S1c).
In addition, SF-36 PCS at Week 16 was compared between ixekizumab and placebo by symptom duration subgroup. For patients with longer symptom duration, improvements were significantly greater with ixekizumab versus placebo (r-axSpA 6.8 ixekizumab, 2.9 placebo, p < 0.001; nr-axSpA 7.1 ixekizumab, 4.4 placebo, p = 0.037; Fig. 2). For patients with shorter symptom duration, differences versus placebo did not achieve statistical significance (NS) or could not be evaluated (NA) because of the low number of patients [r-axSpA 7.9 ixekizumab, 2.7 placebo, NA; nr-axSpA 9.0 ixekizumab, 6.0 placebo, NS (p = 0.067)] (Fig. 2; IXE Q4W only, Supplemental Figure S4).
Fig. 2
SF-36 Physical Component Summary at Week 16 by shorter versus longer symptom duration (defined as < 5 vs. ≥ 5 years) for patients with r-axSpA and nr-axSpA treated with ixekizumab (combined IXE Q4W and IXE Q2W) or PBO. *p < 0.05; ***p < 0.001 vs. PBO using an ANCOVA model including baseline SF-36 score, study (patients with r-axSpA), treatment, subgroup, and treatment-by-subgroup interaction. ANCOVA analysis of covariance, IXE ixekizumab, LSM least square mean, mBOCF modified baseline observation carried forward, NA not applicable as inferential testing was not performed if a subgroup was < 10% of the total population; nr-axSpA non-radiographic axial spondyloarthritis, NS not significant, PBO placebo, PCS Physical Component Summary, r-axSpA radiographic axial spondyloarthritis, SE standard error, SF-36 36-Item Short Form Health Survey, Q2W every 2 weeks, Q4W every 4 weeks
In this post hoc analysis, ixekizumab was efficacious in both patients with less than or greater than 5 years symptom duration in patient populations with r-axSpA and with nr-axSpA. Following the placebo-controlled period, the shorter symptom duration subgroup had numerically greater response versus the longer duration subgroup at Weeks 20–52 across the measures assessed in both r-axSpA and nr-axSpA. However, in statistical comparisons based on RRR (thus taking placebo response into account) at Week 16, significantly better responses were not consistently observed for the shorter versus the longer symptom duration subgroup. This lack of significant differences based on RRR should not be overinterpreted, as the number of patients with shorter symptom duration, particularly in the placebo subgroup in the r-axSpA studies, was quite limited. Finally, trends observed for the IXE Q4W dose subgroup alone were similar to those observed for the combined ixekizumab dose subgroup. These results were similar to a previous study on early (< 2 years symptom duration) versus established (≥ 2 years symptom duration) axSpA, which showed comparable ASAS40 and BASDAI50 responses between groups [15]. However, only a limited number of patients with early disease were recruited (20%), limiting the comparison [15]. Overall, more studies with larger early axSpA population are needed to show whether early treatment leads to more pronounced benefits on disease outcomes at certain cut-off points (i.e., 1, 2 or 5 years) among patients with early axSpA versus established disease [15, 16].
Overall, NNT to achieve ASAS40 response at Week 16 with ixekizumab was lower for patients with shorter symptom duration versus those with longer symptom duration. This was also observed for NNT to achieve ASDAS LDA response at Week 16 for patients with nr-axSpA; however, for patients with r-axSpA to achieve ASDAS LDA at Week 16, NNT was greater for shorter versus patients with longer symptom duration. This appears unexpected, yet is readily explained by the high response rate in the small placebo subgroup with shorter symptom duration (n = 18). Notably, differences for patients receiving placebo between the symptom duration subgroups for ASDAS40 for both r-axSpA and nr-axSpA and for ASDAS LDA for nr-axSpA were relatively limited or showed greater improvement in the longer symptom duration subgroup; whereas for ASDAS LDA for r-axSpA there was a substantial difference between placebo response in the two symptom duration subgroups favoring the shorter symptom duration subgroup (Fig. 1), which may have impacted both the NNT and RRR findings. For BASDAI50, NNT for r-axSpA patients was essentially equivalent between the symptom duration subgroups, while for nr-axSpA, the pattern of numerically higher NNT for the longer duration subgroup was observed.
Several limitations should be considered for this post hoc study. Importantly, there were substantially fewer patients with shorter than longer symptom duration, in particular in r-axSpA where the ratio was almost 1:10, and the smaller population size for the shorter duration subgroup should be considered when interpreting these results. For example, at Week 16, in patients with r-axSpA and shorter symptom duration there were only 18 patients in the placebo subgroup, which could increase the potential variability of mean response compared with larger groups. This finding should be considered as it may have contributed to the unexpected RRR and NNT findings for ASDAS LDA in r-axSpA patients at Week 16. Another limitation was that patients with r-axSpA were pooled from two clinical studies, where patients were bDMARD-naïve (COAST-V) or had failure to TNFi (COAST-W), which could have contributed to heterogeneity of response. Finally, in this analysis, we have used a cut-off for shorter axSpA symptom duration of 5 years, which was the most commonly used cut-off at the time the analyses were designed and performed [10]; however, the ASAS-SPEAR (SPondyloarthritis EARly definition) project recently published a recommendation for a cut-off of ≤ 2 years for early disease [16]. Unfortunately, the limitations noted herein regarding the already small number of patients with shorter symptom duration derived using a 5-year cut-off do not support the utility of reanalyzing our current dataset using a more restrictive ≤ 2-year cut-off.
Conclusion
Based on this post hoc analysis, ixekizumab was efficacious in both symptom duration subgroups in patients with r-axSpA and nr-axSpA. Patients with shorter symptom duration had numerically better response at Week 16 and Week 52; however, differences in response versus placebo were not statistically significant between the symptom duration subgroups at Week 16. Further analyses of other studies with greater sample size and using shorter symptom duration cut-offs would be helpful to further explore these findings. Safety signals might be anticipated in older patients with longer symptom duration, and this would be interesting to investigate in future studies.
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Acknowledgements
The authors would like to thank the investigators of COAST-V, COAST-W, and COAST-X for their contributions and the patients who participated in these studies.
Medical Writing, Editorial, and Other Assistance
Medical writing assistance was provided by Melody Pupols, PhD, and Thomas Melby, MS, of Syneos Health, and funded by Eli Lilly and Company. Statistical analysis assistance was provided by So Young Park, PhD, an employee of Eli Lilly and Company.
Declarations
Conflict of Interest
Victoria Navarro-Compán has served as a speaker, consultant, and/or instructor for AbbVie, Alfasigma, Eli Lilly and Company, Fresenius Kabi, Galapagos, Janssen, Novartis, Pfizer, and UCB Pharma, and has received grant and/or research support from ASAS and Novartis. John D. Reveille has served as a consultant for Eli Lilly and Company and has received grant and/or research support from Eli Lilly and Company. Proton Rahman has served as a speaker and instructor for Abbott, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB Pharma, and has received grant and/or research support from Janssen and Novartis. José A. Maldonado-Cocco has served as a speaker and consultant for and has received grant and/or research support from AbbVie, Bristol Myers Squibb, Gilead Sciences, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB Pharma, and Wyeth. Marina Magrey has served as a speaker and/or consultant for AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB Pharma. Rebecca Bolce is a former and Tommaso Panni, and Andris Kronbergs are current employees and shareholders of Eli Lilly and Company. Martin Rudwaleit has served as a speaker, consultant, and/or instructor for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB Pharma.
Ethical Approval
The trials described herein were conducted in accordance with the ethical principles of the Declaration of Helsinki and were approved by the ethics review boards at each participating study site. The master ethics committee was Schulman Associates IRB, Cincinnati, OH, USA (IRB reference numbers: COAST-V, 201506061; COAST-W, 201506079; COAST-X, 201601302). All patients provided written informed consent prior to participating in the trials.
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Ixekizumab Improves Signs, Symptoms, and Quality of Life in Patients with Axial Spondyloarthritis Irrespective of Symptom Duration
Verfasst von
Victoria Navarro-Compán
John D. Reveille
Proton Rahman
José A. Maldonado-Cocco
Marina Magrey
Rebecca Bolce
Tommaso Panni
Andris Kronbergs
Martin Rudwaleit
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Ein nachlassender Geruchssinn könnte ein Hinweis auf ein erhöhtes Risiko für die koronare Herzkrankheit (KHK) sein. In einer Analyse von über 5.000 älteren Erwachsenen war die Assoziation in den ersten Jahren nach Testung am stärksten und nahm mit der Zeit ab.
Eine umfangreichere molekulardiagnostische Aufarbeitung kann bei metastasiertem Brustkrebs mehr therapierelevante Angriffsstellen aufdecken als das Standardvorgehen, was sich in Behandlungsvorteile übersetzt. Dafür sprechen zumindest die ersten Ergebnisse der deutschen CATCH-Studie.
Dank verbesserter Therapieoptionen können Frauen mit zystischer Fibrose (CF) heute häufiger Kinder bekommen. Eine retrospektive Analyse aus England zeigt, dass dabei nur selten Komplikationen auftreten.
In zwei Phase-3-Studien zeigte eine Therapie mit dem Antisense-Oligonukleotid Olezarsen einen starken Triglyzerid-senkenden Effekt bei Betroffenen mit schwerer Hypertriglyzeridämie. Auch das Risiko für akute Pankreatitiden reduzierte sich.
