scholarly journals Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Walter P. Maksymowych ◽  
Thomas Kumke ◽  
Simone E. Auteri ◽  
Bengt Hoepken ◽  
Lars Bauer ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Clinical Response ◽  
Clinical Outcomes ◽  
Certolizumab Pegol ◽  
Sensitivity Analyses ◽  
Inactive Disease ◽  
Hla B27 ◽  
Baseline Characteristics

Abstract Background Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP). Methods C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value <0.05 was required for forward selection into the model and p ≥0.1 for backward elimination. Missing data or values collected after switching to open-label treatment were accounted for using non-responder imputation. Sensitivity analyses accounted for patients with changes in non-biologic background medication. Results Of 317 enrolled patients, 159 and 158 were randomised to CZP and placebo, respectively. Younger age and male sex were identified as predictors of Week 12 response across all assessed efficacy outcomes in CZP-treated patients. Consistent predictors of Week 52 response, measured by ASDAS-MI, ASAS40 and BASDAI50, included human leukocyte antigen (HLA)-B27 positivity and sacroiliitis on MRI at baseline. MRI positivity was also predictive of achieving ASDAS-ID at Week 52. Sensitivity analyses were generally consistent with the primary analysis. In placebo-treated patients, no meaningful predictors of Week 52 response were identified. Conclusions In this 52-Week, placebo-controlled study in nr-axSpA patients with elevated CRP and/or active sacroiliitis on MRI at baseline, MRI sacroiliitis and HLA-B27 positivity, but not elevated CRP or responses at Week 12, were predictive of long-term clinical response to CZP. Findings may support rheumatologists to identify patients suitable for TNFi treatment. Trial registration ClinicalTrials.gov, NCT02552212. Registered on 15 September 2015

scholarly journals POS0896 PREDICTORS OF RESPONSE IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS RECEIVING CERTOLIZUMAB PEGOL IN THE C-AXSPAND STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 704.2-705
Author(s):  
W. P. Maksymowych ◽  
T. Kumke ◽  
S. Auteri ◽  
B. Hoepken ◽  
L. Bauer ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Predictive Factors ◽  
Axial Spondyloarthritis ◽  
Certolizumab Pegol ◽  
Controlled Study ◽  
Hla B27 ◽  
Predictors Of Response ◽  
Baseline Characteristics

Background:Identification of predictive clinical factors of long-term treatment response in non-radiographic axial spondyloarthritis (nr-axSpA) may contribute to improved management of patients with this chronic disease. Certolizumab pegol (CZP) is currently the only FDA-approved tumour necrosis factor inhibitor (TNFi) for treatment of nr-axSpA.1Objectives:To identify whether any demographic or baseline characteristics of nr-axSpA patients from the C-axSpAnd study2 are predictive of achieving a clinical response after 1 year of CZP treatment.Methods:C-axSpAnd (NCT02552212) was a phase 3, interventional multicentre study including a 52-week double-blind, placebo-controlled period. Full study design is reported elsewhere.2 Multivariate stepwise logistic regression analysis was used to identify predictors of response for the primary efficacy variable (Ankylosing Spondylitis Disease Activity Score – major improvement [ASDAS-MI] at Week 52) and the main secondary efficacy variable (Assessment of SpondyloArthritis international Society 40% [ASAS40] at Week 52) in patients randomised to CZP 200 mg every 2 weeks (Q2W). Predictive factors used in the model included demographic and baseline characteristics, and clinical outcomes at Week 12. A p value ≤0.05 was required for forward selection into the model and p=0.1 for backward elimination from the model. Non-responder imputation was used to account for missing data or values collected after switching to open-label treatment. A sensitivity analysis was conducted to account for patients who had changes in their non-biologic background medication during the 52-week placebo-controlled period.Results:A total of 159/317 patients were randomised to CZP 200 mg Q2W and 158/317 to placebo. Predictive factors identified for Week 52 ASDAS-MI in the CZP-treated patients included being positive for both presence of sacroiliitis on MRI (MRI+) and human leukocyte antigen (HLA)-B27 (HLA-B27+), having a higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline, and having a larger Week 12 improvement in ASDAS (Figure 1A). For ASAS40 response, MRI+/HLA-B27+ was also identified as a predictor of Week 52 response, along with a lower baseline Bath AS Metrology Index (BASMI) and larger Week 12 improvements in Patient Global Assessment of Disease Activity (PtGADA) and AS Quality of Life (ASQoL; Figure 1B). Sensitivity analysis identified the same predictors for ASDAS-MI and ASAS40, with the exception of change from baseline in PtGADA as a predictor of ASAS40. Sensitivity analysis also identified achievement of Week 12 ASAS40 as a predictor of Week 52 ASAS40. In placebo-treated patients, no meaningful predictors of response at Week 52 were identified.Conclusion:Presence of sacroiliitis on MRI and HLA-B27 positivity were identified as consistent predictors of Week 52 response (ASDAS-MI and ASAS40) in nr-axSpA patients treated with CZP. To our knowledge, this is the first report from an interventional 52-week placebo-controlled study in nr-axSpA to identify objective clinical features, particularly the presence of sacroiliac joint inflammation, as being predictive of response.References:[1]Ashrafi M. Curr Opin Rheumatol 2020;32:321–9.[2]Deodhar A. Arthritis Rheumatol 2019;71:1101–11.Acknowledgements:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, BMS, Boehringer, Eli Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Novartis, Pfizer, Thomas Kumke Shareholder of: UCB Pharma, Employee of: UCB Pharma, Simone Auteri Shareholder of: UCB Pharma, Employee of: UCB Pharma, Bengt Hoepken Shareholder of: UCB Pharma, Employee of: UCB Pharma, Lars Bauer Shareholder of: UCB Pharma, Employee of: UCB Pharma, Martin Rudwaleit Speakers bureau: AbbVie, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, UCB Pharma

scholarly journals THU0389 OBESITY IS A STRONG PREDICTOR OF WORSE CLINICAL OUTCOMES AND TREATMENT RESPONSES TO BIOLOGICS IN PATIENTS WITH ANKYLOSING SPONDYLITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 429.2-429
Author(s):  
L. Hu ◽  
X. Ji ◽  
F. Huang
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Normal Weight ◽  
Low Grade ◽  
Hla B27 ◽  
Treatment Responses ◽  
The Impact ◽  
Overweight Or Obesity

Background:Obesity population are rising rapidly and have become a major health issue. Studies have shown that obesity is a low-grade inflammatory status characterized by increase in proinflammatory cytokines.Objectives:To examine the impact of overweight or obesity on disease activity and treatment responses to biologics in patients with ankylosing spondylitis (AS) in a real-world setting.Methods:Body mass index (BMI) is available in 1013 patients from the Chinese Ankylosing Spondylitis Imaging Cohort (CASPIC). Differences in clinical outcomes (such as BASDAI, ASDAS, BASFI, and ASAS HI) and treatment responses to biologics (ΔBASDAI and ΔASDAS) over 3, 6, 9, and 12 months are assessed between BMI categories (normal weight BMI <24 kg/m2; overweight BMI=24-28 kg/m2; obesity BMI ≥28 kg/m2) using Kruskal-Wallis test. The association between BMI and clinical characteristics and treatment responses to biologics was determined, and multivariate median regression analyses were conducted to adjust for confounders (such as age, gender, smoke, and HLA-B27).Results:Among 1013 patients with AS, overweight accounts for 33%, while obesity for 12.4%. There were significant differences between patients who were obese or overweight and those with a normal weight regarding clinical outcomes (BASDAI: 2.90/2.56 vs 2.21; ASDAS-CRP: 2.20/1.99 vs 1.81; BASFI: 2.13/1.69 vs 1.38; ASAS HI: 6.87/5.29 vs 5.12 and BASMI: 2.35/1.76 vs 1.62; all P<0.05). After adjusting for age, gender, smoke, and HLA-B27, obesity remained associated with higher disease activity (BASDAI: β=0.55, P=0.005; ASDAS-CRP: β=0.40, P<0.001), poorer functional capacity (BASFI: β=0.58, P=0.001), worse health index (ASAS HI: β=1.92, P<0.001) and metrology index (BASMI: β=0.71, P=0.013). For TNFi users, BMI was found to be negatively correlated with changes in disease activity (ΔBASDAI and ΔASDAS) in the multivariate regression model (all P<0.05), and overweight and obese patients showed an unsatisfactory reduction in disease activity during 3-month, 6-month, 9-month, and 12-month follow-up period, compared to normal weight patients (all P<0.05).Conclusion:Overweight or obesity impacts greatly on clinical outcomes and treatment responses to biologics in patients with ankylosing spondylitis, which argues strongly for obesity management to become central to prevention and treatment strategies in patients with AS.References:[1]Maachi M, Pieroni L, Bruckert E, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 2004;28:993–7.Figure 1.Changes of disease activity for TNFi users during 3-, 6-, 9- and 12-month follow-up according to BMI categories. a: vs. normal weight, P<0.05 in 3 months; b: vs. normal weight, P<0.05 in 6 months; c: vs. normal weight, P<0.05 in 9 months; d: vs. normal weight, P<0.05 in 12 months.Acknowledgments:We appreciate the contribution of the present or former members of the CASPIC study group.Disclosure of Interests:None declared

MRI Detection of Active Sacroiliitis in First Degree Relatives of Ankylosing Spondylitis Patients with Clinical and Laboratory Correlations

2021 ◽  
Author(s):  
Haron Obaid ◽  
Stephan Milosavljevic ◽  
Udoka Okpalauwaekwe ◽  
Brenna Bath ◽  
Catherine Trask ◽  
...  
Keyword(s):  
Back Pain ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Hla B27 ◽  
Physical Test ◽  
First Degree Relatives ◽  
Pain Provocation ◽  
History Of ◽  
Active Sacroiliitis

Abstract Background. Detection of ankylosing spondylitis (AS) in the preclinical stage could help prevent long term morbidity in this patients’ population. The aim of this study was to examine the prevalence of active sacroiliitis in first-degree relatives of AS patients using MRI with clinical and laboratory correlations as these patients may benefit from MRI screening and early treatment.Methods. Seventeen first-degree relatives of AS patients were recruited prospectively. AS screening questionnaires (Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index & Visual Analogue Scale), blood tests (C-Reactive Protein, HLA-B27), and an MRI of the SIJs were taken. Two musculoskeletal radiologists interpreted the MRI scans, and two physiotherapists applied four symptom provocation tests (Gaenslen's test, posterior pelvic pain provocation test, Patrick's Faber (PF) test and palpation of the long dorsal SIJ ligament test), and two functional movement tests (active straight leg raise and Stork test). Results. Seven (41%) of the 17 participants demonstrated MRI evidence of active sacroiliitis. Of the 7 participants with active sacroiliitis, two (29%) had no history of recent low back pain (LBP), two (29%) had negative HLA-B27, and one (14%) participant had neither back pain nor positive HLA-B27. The Cohen's Kappa score for the interobserver agreement between the radiologists was 1.00 (p-value <0.0001). Despite fair to strong between therapist agreement for the physical test outcomes (Kappa 0.26 to 1.00), the physical test results per se did not have any predictive association with a positive MRI.Conclusions. MRI detected active sacroiliitis in 41% of first-degree relatives of AS patients. The lack of a history of prior LBP or positive HLA-B27 in active sacroiliitis participants might suggest that MRI screening for this high-risk population is warranted; however, further larger studies are needed to help elucidate its cost-effectiveness and long-term benefits.

scholarly journals Early response to adalimumab predicts long-term remission through 5 years of treatment in patients with ankylosing spondylitis

2011 ◽  
Vol 71 (5) ◽  
pp. 700-706 ◽  
Author(s):  
Joachim Sieper ◽  
Désirée van der Heijde ◽  
Maxime Dougados ◽  
L Steve Brown ◽  
Frederic Lavie ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Early Response ◽  
Inactive Disease ◽  
Sustained Remission ◽  
Efficacy And Safety ◽  
Open Label

ObjectivesTo describe the efficacy and safety through 5 years of adalimumab treatment in patients with ankylosing spondylitis (AS), and to identify predictors of remission.MethodsPatients with active AS were followed up to 5 years during a 24-week randomised, controlled period, followed by an open-label extension. Disease activity and clinical improvement were evaluated by Assessment in Spondyloarthritis International Society (ASAS) responses, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Kaplan–Meier was used to identify patients with sustained ASAS partial remission (PR) or ASDAS inactive disease (ID) for three or more consecutive visits spanning ≥6 months. Logistic regression was used to identify factors associated with remission. Explanatory variables included baseline demographic and disease characteristics and week 12 responses.ResultsOf the 311 patients who received at least one dose of adalimumab, 202 (65%) completed the 5-year study. Among 125 patients who received 5 years of adalimumab, 70%, 77%, 51% and 61% achieved ASAS40, BASDAI 50, ASAS PR and ASDAS ID, respectively. Of 311 adalimumab-treated patients, 45% and 55% achieved sustained ASAS PR and ASDAS ID at any time during study participation. The strongest predictor of remission at years 1 and 5 and of sustained remission was achieving remission at 12 weeks of treatment; baseline characteristics showed weaker associations. Adverse events were comparable with previous reports on adalimumab safety.ConclusionsIn patients with active AS, the efficacy and safety of adalimumab were maintained through 5 years with about half of the patients experiencing sustained remission at any time during the study. Early achievement of remission was the best predictor of long-term and sustained remission.

scholarly journals Sustained clinical response and safety of etanercept in patients with early axial spondyloarthritis: 10-year results of the ESTHER trial

2021 ◽  
Vol 13 ◽  
pp. 1759720X2098770
Author(s):  
Fabian Proft ◽  
Anja Weiß ◽  
Murat Torgutalp ◽  
Mikhail Protopopov ◽  
Valeria Rios Rodriguez ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Clinical Response ◽  
Activity Index ◽  
Entire Group ◽  
Life Questionnaire ◽  
Etanercept Treatment ◽  
Entire Treatment Period

Aims: Long-term data on TNFi treatment in patients with axSpA is scarce. The objective of this analysis was to assess long-term clinical efficacy of etanercept in early axSpA [including both non-radiographic and radiographic axSpA forms], who participated in the long-term (until year 10) extension of the ESTHER-trial. Methods: In the previously reported ESTHER-trial, patients with early active axSpA were randomized to treatment with etanercept ( n = 40) or sulfasalazine ( n = 36) during the first year. Patients in remission discontinued their therapy and were followed up until the end of year 2; in case of remission-loss, etanercept was (re)-introduced and continued until the end of year 10. If remission was not achieved at year 1, patients continued receiving (or were switched to) etanercept for up to 10 years. Results: A total of 19 patients (12 with r-axSpA and 7 with nr-axSpA at baseline) out of the initial 76 patients (= 25%) completed year 10 of the study. In the entire group, a sustained clinical response was seen over 10 years of follow up in the as-observed analysis. Completers were significantly more often male and showed lower values of patient and physician global assessments of disease activity, Ankylosing Spondylitis Disease Activity Score (ASDAS), and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) scores at baseline as compared with non-completers. When analyzing clinical data of the completers, mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) values were constantly below 2 and mean ASDAS below 2.1 during follow up with no statistically significant differences between the r-axSpA and nr-axSpA subgroups. A total of 39 serious adverse events were documented over the 10 years, while six of them were seen as possibly associated with the etanercept treatment, which led in five patients to treatment discontinuation. Conclusion: A sustained clinical response was observed over the 10 years of the study with comparable response and drop-out rates between r-axSpA and nr-axSpA. Etanercept was well tolerated across the entire treatment period and showed a good safety profile with no new safety signals.

Consistently Good Clinical Response in Patients with Early Axial Spondyloarthritis After 3 Years of Continuous Treatment with Etanercept: Longterm Data of the ESTHER Trial

2014 ◽  
Vol 41 (10) ◽  
pp. 2034-2040 ◽  
Author(s):  
In-Ho Song ◽  
Kay-Geert Hermann ◽  
Hildrun Haibel ◽  
Christian E. Althoff ◽  
Denis Poddubnyy ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Clinical Response ◽  
Axial Spondyloarthritis ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Continuous Treatment ◽  
Inactive Disease ◽  
Entire Group ◽  
Study Population

Objective.In patients with early active axial spondyloarthritis (axSpA) with a disease duration of < 5 years, the longterm efficacy of 3 years of continuous etanercept (ETN) treatment was assessed.Methods.In a previously reported ESTHER trial, patients with axSpA were randomized to treatment with ETN (n = 40) versus sulfasalazine (SSZ; n = 36) in the first year. We analyzed the clinical, laboratory, and magnetic resonance imaging (MRI) response in the pooled dataset of patients (study population; n = 61), including patients with ankylosing spondylitis (AS, n = 31) and nonradiographic axSpA (nr-axSpA, n = 30) who were continuously treated with ETN for 3 consecutive years. Data were analyzed using the last observation carried forward and completer analysis.Results.In the entire group of patients in the study population (n = 61), the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.7 (± 1.3) at baseline to 2.6 (± 2.4) at Year 3. The Ankylosing Spondylitis Disease Activity Score (ASDAS) decreased from 3.4 (± 0.8) to 1.5 (± 1.0). Also, mean values for MRI spine and sacroiliac joint scores showed a significant decrease. Response rates in the nr-axSpA group were similar and at least as good compared to the AS group for all outcome measures. When comparing remission stages, we found that ASDAS inactive disease correlated better with C-reactive protein and MRI remission than with Assessment of SpondyloArthritis international Society partial remission.Conclusion.There was a consistent and sustained clinical response in patients with early axSpA treated with ETN over 3 years. ClinicalTrials.gov registration number NCT00844142.

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