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We report an exploratory subgroup analysis of a Chinese phase 3 study to investigate the effect of baseline inflammation measured by magnetic resonance imaging (MRI) on ixekizumab efficacy in radiographic axial spondyloarthritis (r-axSpA).
Methods
Adults with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W) or placebo for 16 weeks. Endpoints analyzed by baseline Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine or sacroiliac joint (SIJ) inflammation score (< 2 or ≥ 2; elevated inflammation defined as score ≥ 2) were: Assessment of SpondyloArthritis International Society 40 (ASAS40); Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50); Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1; ASDAS clinically important improvement (CII; change from baseline ≥ 1.1); Patient Global Assessment of Disease Activity (PtGA); spinal pain; nocturnal spinal pain; stiffness/inflammation; function; fatigue; Short Form-36 Physical Component Score (SF-36 PCS); European Quality of Life 5 Dimensions 5 Levels visual analog scale (EQ-5D-5L VAS).
Results
Overall, 145 patients were included. At Week 16, ASAS40 response rates were numerically improved with IXEQ4W versus placebo in the SPARCC MRI spine score < 2 subgroup (40.9% vs. 14.3%; p = 0.088) and significantly improved in the ≥ 2 subgroup (37.3% vs. 5.9%; p < 0.001). ASAS40 response rates were significantly improved in the SPARCC MRI SIJ score < 2 (34.4% vs. 8.6%; p < 0.05) and ≥ 2 (41.5% vs. 8.1%; p < 0.001) subgroups. Similar results were obtained on BASDAI50, ASDAS < 2.1, and ASDAS CII. IXEQ4W significantly improved PtGA, inflammation, and fatigue across all subgroups. Spinal and nocturnal spinal pain were significantly improved in the SPARCC MRI spine score ≥ 2 subgroup and both SPARCC MRI SIJ score subgroups. Function and SF-36 PCS were significantly improved in the SPARCC MRI spine score ≥ 2 subgroup. There were no significant differences in EQ-5D-5L VAS.
Conclusion
These findings support IXEQ4W as an effective treatment for Chinese patients with r-axSpA, irrespective of baseline MRI inflammation.
Prior Publication: Partial results presented in this manuscript were accepted as a Poster Presentation (POS0801) at the European Congress of Rheumatology (EULAR) 2024 (12–15 June 2024) hosted in Vienna, Austria (https://doi.org/10.1136/annrheumdis-2024-eular.357).
Key Summary Points
Why carry out the study?
Ixekizumab, a high-affinity interleukin-17A inhibitor, has demonstrated efficacy irrespective of baseline inflammation status measured by C-reactive protein (CRP) or magnetic resonance imaging (MRI) in international populations with radiographic axial spondyloarthritis (r-axSpA)
A subgroup analysis of a Chinese phase 3 trial also showed that ixekizumab had efficacy irrespective of baseline inflammation status measured by CRP
This was a further subgroup analysis of the Chinese phase 3 trial to evaluate the efficacy of ixekizumab according to baseline inflammation status measured by MRI
What was learned from the study?
Findings from this exploratory subgroup analysis suggest that ixekizumab has rapid and sustained efficacy in the treatment of Chinese patients with r-axSpA, irrespective of normal or elevated baseline MRI scores
These results were consistent with previous observations and support the use of ixekizumab as an effective treatment option in Chinese patients with r-axSpA, even in the absence of baseline inflammation
Introduction
Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory condition that primarily impacts the spine and sacroiliac joints (SIJ) [1]. R-axSpA is often associated with reduced physical function and health-related quality of life (HRQoL) due to chronic back pain, spinal stiffness, and fatigue [2]. The current first-line pharmacological treatment for patients with r-axSpA is non-steroidal anti-inflammatory drugs (NSAIDs) [3‐5]. Second-line treatment options include biological and targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs and tsDMARDs, respectively), starting with tumor necrosis factor inhibitors (TNFis) or interleukin-17 (IL-17) inhibitors in current practice [3‐5].
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Ixekizumab is a high-affinity IL-17A inhibitor that demonstrated rapid and sustained improvements in the signs and symptoms of active r-axSpA in two international, phase 3 clinical trials (COAST-V and COAST-W) [6‐8]. In these studies, ixekizumab significantly improved disease activity, measured by Assessment of SpondyloArthritis International Society 40 (ASAS40) response rates, with a tolerable safety profile [6‐8], and improved patient-reported outcomes in patients with r-axSpA [9‐11]. Previous investigations have shown that baseline inflammation, as indicated by elevated C-reactive protein (CRP) levels or magnetic resonance imaging (MRI), is associated with better responses to TNFis in patients with axial spondyloarthritis [12, 13]. Consequently, physicians may be hesitant to prescribe bDMARDs or tsDMARDs in patients with r-axSpA who do not have baseline inflammation. However, patients with normal CRP levels generally have similar disease activity and disease burden compared with those with elevated CRP levels [14]. In a post hoc analysis of the COAST-V and COAST-W trials, ixekizumab improved disease activity in patients with r-axSpA even in the absence of baseline inflammation, as measured by Spondyloarthritis Research Consortium of Canada (SPARCC) MRI spine and sacroiliac joint (SIJ) scores and baseline CRP levels [15]. Of note, Chinese patients were not included in these analyses.
In China, axial spondyloarthritis has an estimated prevalence of 0.20–0.42% [16]. The efficacy and safety of ixekizumab in Chinese patients with r-axSpA was confirmed in a randomized, double-blind, placebo-controlled, phase 3 trial [17]. In subsequent subgroup analyses, ixekizumab was shown to improve disease activity, common disease symptoms, and overall HRQoL in Chinese patients with r-axSpA, irrespective of baseline inflammation as measured by CRP levels [14, 18]. Here, we present a further subgroup analysis of the Chinese phase 3 study to evaluate the efficacy of ixekizumab in Chinese patients with r-axSpA and normal or elevated baseline SPARCC MRI spine or SIJ inflammation scores.
Methods
Study Design and Patients
The methods and primary results from this randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ClinicalTrials.gov identifier: NCT04285229) have been reported previously [17]. Briefly, Chinese adults with active r-axSpA who were bDMARD-naïve or had previously experienced an inadequate response or intolerance to a TNFi were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or matched placebo subcutaneously for 16 weeks. At the end of the double-blind treatment period (Week 16), patients randomized to placebo were switched to IXEQ4W (starting dose 160 mg), and those randomized to IXEQ4W continued treatment until Week 52. The study was approved by local ethics committees (see Supplementary Table S1) and conducted in accordance with the Declaration of Helsinki and the Council of International Organizations of Medical Sciences International Ethical Guidelines. Written informed consent was collected from all patients.
Outcomes and Measurements
In this analysis, patients were categorized into subgroups defined by baseline SPARCC MRI spine or SIJ inflammation score (< 2 or ≥ 2), with normal/low inflammation defined as a score of < 2 and elevated inflammation defined as a score of ≥ 2 [15, 19, 20]. Disease activity through Week 52 was assessed in each subgroup using the following endpoints: ASAS40, defined as improvements of ≥ 40% and ≥ 2 units in three of four ASAS domains; 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50); Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1; and ASDAS clinically important improvement (CII), defined as a change from baseline of ≥ 1.1. Additional endpoints at Week 16 were ASAS response individual components including Patient Global Assessment of Disease Activity, spinal pain, inflammation, and function (Bath Ankylosing Spondylitis Functional Index score), patient-reported outcomes for nocturnal spinal pain and fatigue (BASDAI question 1), and HRQoL measured by Short Form-36 Physical Component Score (SF-36 PCS) and European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) visual analog scale (VAS) score.
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Statistical Analyses
All analyses were conducted in patients with baseline MRI data in the intention-to-treat (ITT) population, which included all patients who were randomized to treatment, regardless of whether they received the assigned study drug. Baseline values were taken as the last non-missing data recorded on or prior to the date patients first received study treatment (Week 0). The p values for treatment comparisons during the first 16 weeks were calculated using Fisher’s exact test. A mixed model for repeated measures (MMRM) was used to analyze continuous assessments (i.e., change from baseline), except for EQ-5D-5L VAS, which was assessed using an analysis of covariance (ANCOVA) model. The MMRM model was based on fixed factors, including treatment, baseline CRP status, prior TNFi use, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction (the variance-covariance matrix was unstructured). The ANCOVA model included treatment, baseline CRP status, prior TNFi use, and baseline value. In these analyses, p < 0.05 was considered statistically significant without multiple testing adjustment.
Results
Patient Characteristics
The ITT population comprised 147 patients, of whom 145 (98.6%) had baseline MRI data by central reading and were included in this analysis. Of the patients with MRI data, 43 (29.7%) had a baseline SPARCC MRI spine score of < 2 (IXEQ4W, 22 [15.2%]; placebo, 21 [14.5%]), and 102 (70.3%) had a baseline SPARCC MRI spine score of ≥ 2 (both IXEQ4W and placebo, 51 [35.2%]). In addition, 67 (46.2%) patients had a baseline SPARCC MRI SIJ score of < 2 (IXEQ4W, 32 [22.1%]; placebo, 35 [24.1%]), and 78 (53.8%) had a baseline SPARCC MRI SIJ score of ≥ 2 (IXEQ4W, 41 [28.3%]; placebo, 37 [25.5%]). In general, baseline demographics and clinical characteristics were balanced between the IXEQ4W and placebo groups within each of the SPARCC MRI score subgroups (Table 1).
Table 1
Baseline demographic and clinical characteristics by baseline SPARCC MRI spine score and SPARCC MRI SIJ score (ITT population)
Baseline SPARCC MRI spine score < 2
Baseline SPARCC MRI spine score ≥ 2
Baseline SPARCC MRI SIJ score < 2
Baseline SPARCC MRI SIJ score ≥ 2
Placebo (n = 21)
IXEQ4W (n = 22)
Placebo (n = 51)
IXEQ4W (n = 51)
Placebo (n = 35)
IXEQ4W (n = 32)
Placebo (n = 37)
IXEQ4W (n = 41)
Age, years
34.2 ± 10.4
35.1 ± 11.7
34.3 ± 8.5
32.9 ± 7.4
34.7 ± 8.3
34.2 ± 7.4
33.9 ± 9.8
33.0 ± 10.0
Male
18 (85.7)
15 (68.2)
46 (90.2)
48 (94.1)
33 (94.3)
29 (90.6)
31 (83.8)
34 (82.9)
BMI, kg/m2
22.5 ± 4.3
22.8 ± 3.9
23.0 ± 3.6
24.1 ± 4.2
22.8 ± 2.9
23.6 ± 3.3
23.0 ± 4.5
23.7 ± 4.7
Disease duration since diagnosis, years
5.4 ± 4.6
5.2 ± 6.2
5.9 ± 5.6
6.7 ± 4.9
7.5 ± 5.8
6.6 ± 6.0
4.1 ± 4.3
5.9 ± 4.8
Prior TNFi use
2 (9.5)
3 (13.6)
7 (13.7)
5 (9.8)
4 (11.4)
3 (9.4)
5 (13.5)
5 (12.2)
ASDAS
3.3 ± 0.8
3.1 ± 0.7
3.6 ± 0.7
3.7 ± 0.8
3.4 ± 0.7
3.3 ± 0.9
3.6 ± 0.8
3.7 ± 0.7
BASDAI
5.8 ± 1.3
5.9 ± 1.2
5.9 ± 1.4
6.4 ± 1.4
5.6 ± 1.3
5.8 ± 1.4
6.2 ± 1.4
6.5 ± 1.3
ASAS response individual components
PtGA
5.8 ± 1.8
5.6 ± 1.7
5.9 ± 1.9
6.1 ± 2.0
5.7 ± 1.7
5.5 ± 2.1
5.9 ± 2.0
6.3 ± 1.6
Spinal pain
6.5 ± 1.3
6.3 ± 1.6
6.7 ± 1.5
7.1 ± 1.6
6.4 ± 1.5
6.4 ± 1.8
6.9 ± 1.4
7.2 ± 1.4
Inflammation
5.1 ± 1.4
5.4 ± 2.1
5.5 ± 1.9
6.2 ± 1.9
5.2 ± 1.7
5.3 ± 1.9
5.6 ± 1.9
6.4 ± 1.9
Function
4.5 ± 2.0
4.2 ± 2.4
4.9 ± 1.7
5.1 ± 2.0
4.8 ± 1.3
4.6 ± 1.9
4.7 ± 2.2
5.0 ± 2.3
Spinal pain at night
5.6 ± 2.0
6.4 ± 2.1
6.5 ± 1.8
6.5 ± 1.7
5.9 ± 1.5
5.8 ± 1.9
6.5 ± 2.1
7.0 ± 1.6
Fatigue
6.2 ± 1.6
6.2 ± 1.5
6.2 ± 1.5
6.5 ± 1.6
6.1 ± 1.6
6.1 ± 1.5
6.2 ± 1.5
6.6 ± 1.6
SF-36 PCS
38.2 ± 6.0
38.8 ± 7.4
38.2 ± 6.2
38.3 ± 6.6
38.3 ± 5.3
40.1 ± 6.3
38.1 ± 6.8
37.2 ± 7.0
EQ-5D-5L VAS score
67.1 ± 15.2
60.3 ± 21.1
57.9 ± 20.0
60.3 ± 18.6
63.9 ± 18.7
61.3 ± 16.8
57.5 ± 19.2
59.6 ± 21.2
Data are expressed as mean ± standard deviation or n (%)
ASAS Assessment of SpondyloArthritis International Society, ASDAS Ankylosing Spondylitis Disease Activity Score, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BMI body mass index, EQ-5D-5L European Quality of Life 5 Dimensions 5 Levels, ITT intention-to-treat, IXEQ4W ixekizumab 80 mg every 4 weeks, MRI magnetic resonance imaging, PtGA Patient Global Assessment of Disease Activity, SF-36 PCS Short Form-36 Physical Component Score, SIJ sacroiliac joint, SPARCC Spondyloarthritis Research Consortium of Canada, TNFi tumor necrosis factor inhibitor, VAS visual analog scale
Disease Activity by Baseline SPARCC MRI Scores
Across all measures of disease activity, improvements with IXEQ4W versus placebo were observed at Week 16, and as early as Weeks 1 or 2, in all baseline SPARCC MRI subgroups. Irrespective of baseline SPARCC MRI scores, patients initially randomized to IXEQ4W showed sustained improvement in disease activity from Week 16 to Week 52, while those initially randomized to placebo showed improvement in disease activity from Week 16 after switching to IXEQ4W (Figs. 1, 2, 3, 4).
Fig. 1
ASAS40 response rates (NRI) over time by baseline SPARCC MRI spine score (A) and SPARCC MRI SIJ score (B) through Week 52 (ITT population). ***p < 0.001, **p < 0.01, *p < 0.05 versus placebo. The p values were calculated using Fisher’s exact test. ASAS40 Assessment of SpondyloArthritis International Society 40, ITT intention-to-treat, IXEQ4W ixekizumab 80 mg every 4 weeks, MRI magnetic resonance imaging, NRI non-responder imputation, SIJ sacroiliac joint, SPARCC Spondyloarthritis Research Consortium of Canada
BASDAI50 response rates (NRI) over time by baseline SPARCC MRI spine score (A) and SPARCC MRI SIJ score (B) through Week 52 (ITT population). ***p < 0.001, **p < 0.01, *p < 0.05 versus placebo. The p values were calculated using Fisher’s exact test. BASDAI50 Bath Ankylosing Spondylitis Disease Activity Index 50, ITT intention-to-treat, IXEQ4W ixekizumab 80 mg every 4 weeks, MRI magnetic resonance imaging, NRI non-responder imputation, SIJ sacroiliac joint, SPARCC Spondyloarthritis Research Consortium of Canada
ASDAS CII response rates (NRI) over time by baseline SPARCC MRI spine score (A) and SPARCC MRI SIJ score (B) through Week 52 (ITT population). ***p < 0.001, **p < 0.01, *p < 0.05 versus placebo. The p values were calculated using Fisher’s exact test. ASDAS Ankylosing Spondylitis Disease Activity Score, CII clinically important improvement, ITT intention-to-treat, IXEQ4W ixekizumab 80 mg every 4 weeks, MRI magnetic resonance imaging, NRI non-responder imputation, SIJ sacroiliac joint, SPARCC Spondyloarthritis Research Consortium of Canada
At Week 16, ASAS40 response rates were numerically improved with IXEQ4W versus placebo in the SPARCC MRI spine score < 2 subgroup (40.9% vs. 14.3%; p = 0.088) and significantly improved in the SPARCC MRI spine score ≥ 2 subgroup (37.3% vs 5.9%; p < 0.001) (Fig. 1A). ASAS40 response rates were significantly improved with IXEQ4W versus placebo in the SPARCC MRI SIJ score < 2 (34.4% vs. 8.6%; p < 0.05) and ≥ 2 (41.5% vs. 8.1%; p < 0.001) subgroups at Week 16 (Fig. 1B).
Similar results were obtained on other measures of disease activity. At Week 16, the BASDAI50 response rate with IXEQ4W versus placebo was numerically improved in the SPARCC MRI spine score < 2 subgroup (45.5% vs. 19.0%; p = 0.104) and significantly improved in the SPARCC MRI spine score ≥ 2 (35.3% vs. 5.9%; p < 0.001), SPARCC MRI SIJ score < 2 (37.5% vs. 8.6%; p < 0.01) and ≥ 2 (39.0% vs. 10.8%; p < 0.01) subgroups (Fig. 2A, B). The ASDAS < 2.1 response rate at Week 16 was numerically improved with IXEQ4W versus placebo in the SPARCC MRI spine score < 2 subgroup (45.5% vs. 23.8%; p = 0.203) and significantly improved in the baseline SPARCC MRI spine score ≥ 2 (52.9% vs. 3.9%; p < 0.001), SPARCC MRI SIJ score < 2 (56.3% vs. 5.7%; p < 0.001), and SPARCC MRI SIJ score ≥ 2 (46.3% vs. 13.5%; p < 0.01) subgroups (Fig. 3A, B). At Week 16, the ASDAS CII response rate was numerically greater with IXEQ4W versus placebo in the SPARCC MRI spine score < 2 subgroup (45.5% vs. 23.8%; p = 0.203) and significantly greater in the SPARCC MRI spine score ≥ 2 (66.7% vs. 5.9%; p < 0.001) and SPARCC MRI SIJ score < 2 (53.1% vs. 5.7%; p < 0.001) and ≥ 2 (65.9% vs. 16.2%; p < 0.001) subgroups (Fig. 4A, B).
ASAS Response Individual Components, Nocturnal Spinal Pain, Fatigue, and HRQoL by Baseline SPARCC MRI Scores
The changes from baseline at Week 16 in ASAS response individual components, nocturnal spinal pain, fatigue, and HRQoL for the SPARCC MRI subgroups are presented in Fig. 5. IXEQ4W versus placebo significantly improved Patient Global Assessment of Disease Activity, inflammation, and fatigue across all SPARCC MRI spine and SIJ score subgroups. Spinal pain and nocturnal spinal pain showed a numerical improvement in the SPARCC MRI spine score < 2 subgroup and were significantly improved in the SPARCC MRI spine score ≥ 2 subgroup and SPARCC MRI SIJ score < 2 and ≥ 2 subgroups. Improvements in function and SF-36 PCS were significant in the SPARCC MRI spine and SIJ score ≥ 2 subgroups, but only numerical in the score < 2 subgroups. Numerical improvements in EQ-5D-5L VAS score were observed across all SPARCC MRI spine and SIJ score subgroups.
Fig. 5
Changes from baseline in ASAS components, PROs, and HRQoL by baseline SPARCC MRI spine (A, B) and SIJ (C, D) scores (< 2 or ≥ 2) at Week 16 (ITT population). aFor EQ-5D-5L VAS, the number of patients was 21 in the placebo group for baseline SPARCC MRI spine score < 2, 51 in each of the placebo and IXEQ4W groups for baseline SPARCC MRI spine score ≥ 2, 32 in the IXEQ4W group for baseline SPARCC MRI SIJ score < 2, and 37 in the placebo group for SPARCC MRI SIJ score ≥ 2. ***p < 0.001, **p < 0.01, *p < 0.05 versus placebo. An MMRM model was used to analyze all endpoints except for EQ-5D-5L, which was assessed using an ANCOVA model. The MMRM model included treatment, baseline CRP status, prior TNFi use, baseline value, visit, baseline value-by-visit, and treatment-by-visit interaction as fixed factors (the variance-covariance matrix was unstructured). The ANCOVA model included treatment, baseline CRP status, prior TNFi use, and baseline value. Baseline values were defined as the last non-missing assessments recorded on or prior to the date of first study drug injection at Week 0. ANCOVA analysis of covariance, ASAS Assessment of SpondyloArthritis International Society, CRP C-reactive protein, EQ-5D-5L European Quality of Life 5 Dimensions 5 Levels, HRQoL health-related quality of life, ITT intention-to-treat, IXEQ4W ixekizumab 80 mg every 4 weeks, LSM least squares mean, MMRM mixed model for repeated measures, MRI magnetic resonance imaging, PROs patient reported outcomes, PtGA Patient Global Assessment of Disease Activity, SE standard error, SF-36 PCS Short Form-36 Physical Component Score, SIJ sacroiliac joint, SPARCC Spondyloarthritis Research Consortium of Canada, TNFi tumor necrosis factor inhibitor, VAS visual analog scale
Findings from this subgroup analysis of a Chinese phase 3 study suggest that IXEQ4W has rapid and sustained efficacy in the treatment of Chinese patients with r-axSpA, irrespective of normal or elevated inflammation status at baseline as measured by MRI. This is consistent with results from previous subgroup analyses of the same study, which showed that IXEQ4W improved disease activity, common disease symptoms, and HRQoL in Chinese patients with r-axSpA, irrespective of baseline inflammation as measured by CRP levels [14, 18]. The present findings are also in accordance with those from a previous analysis of the COAST-V and COAST-W trials conducted in international populations with r-axSpA, in which IXEQ4W was shown to improve ASAS40 response rates, irrespective of baseline CRP levels or SPARCC MRI inflammation scores [15]. Safety data for the overall population are available in the original publication of the study and were consistent with the known safety profile of ixekizumab [17].
Although sample sizes within subgroups were small, significant improvements in disease activity at Week 16 were observed with IXEQ4W versus placebo in patients with normal or elevated baseline SPARCC MRI SIJ scores. These improvements also reached statistical significance in the subgroup with elevated baseline SPARCC MRI spine scores. Similar results were seen for several of the r-axSpA symptom endpoints. In the combined analysis of the international COAST-V and COAST-W trials, improvements in ASAS40 response rates with ixekizumab (IXEQ4W or ixekizumab 80 mg every 2 weeks [IXEQ2W]) versus placebo were statistically significant irrespective of normal or elevated SPARCC MRI spine scores [15].
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Our findings are also consistent with studies of other IL-17 inhibitors in r-axSpA [21, 22]. An analysis showed that, compared with placebo, netakimab improved ASAS-recommended activity, spinal mobility, and function at Week 16 regardless of baseline SPARCC MRI SIJ scores or CRP levels [21]. Similarly, secukinumab improved ASAS40 response rates compared with placebo in patients with normal or elevated MRI SIJ status [22]. In both studies, higher response rates were noted for subgroups with higher levels of inflammation [21, 22]. The efficacy of IL-17 inhibitors in improving patient symptoms in the absence of measurable baseline inflammation may reflect the ability of these agents to influence pain signaling pathways as well as inflammatory responses [23, 24].
Limitations of the present findings include the post hoc exploratory nature of the analyses, small sample sizes, and lack of multiple testing adjustment, meaning that the statistical significance was nominal. These factors may limit the generalizability of the findings and therefore the results should be interpreted with caution. Nonetheless, the results were consistent with those reported previously [14, 15, 18]. Although a dichotomous cutoff of 2 is widely used for SPARCC MRI inflammation [15, 19, 20], there are limitations with this classification. Notably, the SPARCC MRI scoring system does not comprehensively capture every aspect of inflammation [15]; consequently, the patients with SPARCC MRI spine scores < 2 in this analysis may have had inflammation at locations that were not investigated, leading to underestimation of treatment needs. Studies have also shown false-positive results using a SPARCC MRI score ≥ 2 in healthy individuals, athletes, and postpartum women, which can be attributed to bone marrow edema lesions caused by mechanical stress on the joints [25‐28]. A SPARCC MRI score can be high because of the presence of one intense lesion or several small lesions across different sites; therefore, dichotomizing this continuous inflammatory measure into two categories (negative vs. positive) loses information on disease severity and the distribution of inflammation [20]. Moreover, there is evidence that ixekizumab may reduce pain by non-inflammatory mechanisms in addition to the reduction of measurable inflammation [24]. These factors may have confounded the present results. In addition, due to the small sample sizes, it was not possible to conduct more refined analyses, for example, of outcomes in patients with both SPARCC MRI spine and SIJ scores < 2 or ≥ 2. Such analyses are planned in a larger pooled population of patients with r-axSpA.
Conclusion
Findings from this exploratory subgroup analysis suggest that IXEQ4W is associated with rapid and sustained efficacy in the treatment of Chinese patients with r-axSpA across both normal and elevated baseline inflammation status as measured by MRI. As the statistical power of this subgroup analysis was limited, the results should be interpreted with caution. In line with previous investigations, our findings support use of ixekizumab as an effective treatment option for Chinese patients with r-axSpA, irrespective of baseline inflammation levels.
Acknowledgements
The authors thank all study participants.
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Medical Writing/Editorial Assistance
Medical writing was provided by Dr. Zipei Xiao from Eli Lilly and Company, who was assisted by Sharon Gladwin from Rude Health Consulting, Ltd., with funding from Eli Lilly and Company. This manuscript complied with international guidelines for Good Publication Practice (GPP3).
Declarations
Conflict of Interest
Yan Yan and Hongying Li are employees of Eli Lilly and Company. Xiaoxia Zhu, Jiankang Hu, Dongzhou Liu, Jingyang Li, Huaxiang Wu, Lingyun Sun, Lie Dai, Chunyu Tan, Zhijun Li, Zhengyu Xiao, Yongfu Wang, Lingli Dong, and Hejian Zou have no conflicts of interest to declare.
Ethical Approval
The study was approved by local ethics committees (see Supplementary Table S1) and conducted in accordance with the Declaration of Helsinki and the Council of International Organizations of Medical Sciences International Ethical Guidelines. Written informed consent was collected from all patients.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Efficacy of Ixekizumab in Chinese Patients with Radiographic-Axial Spondyloarthritis by Baseline Inflammation Status on Magnetic Resonance Imaging
Verfasst von
Xiaoxia Zhu
Jiankang Hu
Dongzhou Liu
Jingyang Li
Huaxiang Wu
Lingyun Sun
Lie Dai
Chunyu Tan
Zhijun Li
Zhengyu Xiao
Yongfu Wang
Lingli Dong
Yan Yan
Hongying Li
Hejian Zou
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Wenn ein Speiserest die Atemwege blockiert, zählt jede Minute. Um gravierende neurologische Schäden zu vermeiden, sollten vor allem ältere Menschen in die Notaufnahme gebracht werden – selbst wenn der Übeltäter bereits entfernt wurde. Das verdeutlicht eine Studie aus Japan.
Deutschland ist ein Koloskopieland. Doch ist das eine gute Idee? Oder würde der Stuhltest ausreichen, um Darmkrebs im frühen Stadium zu erkennen? Prof. Markus M. Lerch und Prof. Ulrike Denzer diskutieren die Vor- und Nachteile der Screening-Verfahren. Außerdem gibt die Endoskopie-Expertin Prof. Denzer Tipps, wie suspekte Darmpolypen effektiv erkannt und abgetragen werden können.
Je höher der BMI, umso höher ist das Risiko, bei einer Infektion zu sterben. Das gilt nicht nur für Covid-19, sondern für Infektionen allgemein. Bei einer Grad-III-Adipositas ist die Mortalität während einer Infektion sogar verdreifacht. Darauf deuten Daten aus Finnland und Großbritannien.
Periphere Fazialisparesen sollten nicht vorschnell als idiopathisch klassifiziert werden. Vor allem bei atypischen Manifestationen gilt es, auf dem Quivive zu sein. Der Fall einer 73-Jährigen zeigt, warum.
