THE IMPACT OF PERSISTENT INFLAMMATORY CHANGES ON PREVALENCE OF FAT LESIONS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS TREATED WITH CERTOLIZUMAB PEGOL: 4-YEAR MRI RESULTS FROM RAPID-axSpA

Background:Axial spondyloarthritis (axSpA) is a chronic disease characterised by inflammation in the sacroiliac joints and spine, causing severe back pain and stiffness. Emerging evidence suggests chronic spinal inflammation may be associated with osteoproliferation leading to syndesmophyte formation and spinal ankylosis, with subsequent worsening of patient mobility and function.1Fatty lesions (FLs) on magnetic resonance imaging (MRI) T1 sequences are considered to be post-inflammatory precursors to these changes. Certolizumab pegol (CZP), an Fc-free, PEGylated tumour necrosis factor inhibitor (TNFi), has proven efficacy in treating the signs and symptoms of axSpA.2,3CZP has also been shown to decrease spinal and sacroiliac joint MRI inflammation, and limit radiographic progression of the spine over 4 years of treatment.4Objectives:To report the effect of early post-baseline (BL) inflammatory changes on fatty lesion prevalence over 4 years in a broad axSpA patient population treated with CZP.Methods:RAPID-axSpA (NCT01087762) was a phase 3 trial which was double-blind and placebo (PBO)-controlled to Week (Wk) 24, dose-blind to Wk 48 and open-label to Wk 204. CZP-randomised axSpA patients (Wk 0 CZP: 200 mg every 2 wks [Q2W] or 400 mg Q4W) continued their assigned dose throughout; PBO-randomised axSpA patients (Wk 0 PBO) received CZP from Wk 24, or if non-responders, from Wk 16 onwards. Blinded spinal MRI scans at Wks 0, 12, 48, 96 and 204 were assessed by 2 central readers to evaluate FL and inflammatory lesions in vertebral edges (VEs). Changes in FL prevalence are reported as odds ratios (OR; FL+/FL-) between time points or inflammation states, with nominal 95% confidence intervals (CI), for Wk 0 CZP. ORs were estimated from a logistic regression model for VE level data with random effects for patient and VE (within patient). The fixed model effects included time point, inflammatory status of VEs at BL and Wk 12, FL status at BL, and interactions if appropriate.Results:Of 325 axSpA patients, 89 and 47 initially randomised to CZP or PBO, respectively, had a BL and ≥1 post-BL MRI and therefore were eligible for these analyses. In these patients, a total of 3,127 of VEs were assessed at BL; inflammation was observed in 21.6% and FL in 29.3% of VEs, equating to mean counts of 5.0 and 6.7 per patient; 10.5% of VEs had both inflammation and FL at BL. At BL, FLs were relatively more often observed in inflamed VEs vs non-inflamed VEs: OR (95% CI) of 3.30 (1.94, 5.61). This difference increased over time, as the OR of FL at Wk 204 vs BL was 2.82 (1.70, 4.66) in VEs that were inflamed at BL compared with 1.08 (0.79, 1.48) in VEs that were not inflamed at BL (Figure 1A). Resolution of inflammation by Wk 12 appeared to lower the risk of FL prevalence over 4 years. When adjusted for BL VE status with respect to inflammation and FL, if inflammation prevailed at Wk 12, the OR of FL vs no FL was 1.80 (0.93, 3.49) at Wk 48, 2.54 (1.32, 4.91) at Wk 96 and 3.91 (1.87, 8.15) at Wk 204 (Figure 1B).Conclusion:This is the first report from a clinical interventional PBO-controlled study in a broad axSpA population showing that inflammation that prevailed after the start of TNFi treatment was associated with increased FL prevalence over 4 years. Reduction of inflammation by Wk 12 mitigated the risk of FL over the long-term, indicating the importance of early, effective and long-term treatment targeting inflammation. Similarly, a complete and persistent reduction of inflammation appears to be critical in these patients.References:[1]Maksymowych WP. Ann Rheum Dis 2013;72:23–8;2.Van der Heijde D. Rheumatology (Oxford) 2017;56:1498–509;3.Deodhar A. Arthritis Rheumatol 2019;71:1101–11;4.Van der Heijde D. Ann Rheum Dis 2018;77:699–705.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Sebastian Kruse: None declared, Simone Auteri Shareholder of: UCB Pharma, Employee of: UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Tommi Nurminen Employee of: UCB Pharma, Thomas Kumke Employee of: UCB Pharma, Bengt Hoepken Employee of: UCB Pharma, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma

Download Full-text

The impact of certolizumab pegol treatment on the incidence of anterior uveitis flares in patients with axial spondyloarthritis: 48-week interim results from C-VIEW

RMD Open ◽

10.1136/rmdopen-2019-001161 ◽

2020 ◽

Vol 6 (1) ◽

pp. e001161 ◽

Cited By ~ 2

Author(s):

Irene van der Horst-Bruinsma ◽

Rianne van Bentum ◽

Frank D Verbraak ◽

Thomas Rath ◽

James T Rosenbaum ◽

...

Keyword(s):

Incidence Rate ◽

Anterior Uveitis ◽

Poisson Regression ◽

Axial Spondyloarthritis ◽

Certolizumab Pegol ◽

Tnf Inhibitor ◽

Open Label ◽

Before And After ◽

History Of ◽

The Impact

BackgroundAcute anterior uveitis (AAU) is the most common extra-articular manifestation in patients with axial spondyloarthritis (axSpA). C-VIEW investigates the impact of the Fc-free TNF inhibitor certolizumab pegol (CZP) on AAU flares in patients with active axSpA at high risk of recurrent AAU.MethodsC-VIEW (NCT03020992) is a 96-week ongoing, multicentre, open-label, phase 4 study. Included patients had an axSpA diagnosis, a history of recurrent AAU (≥2 AAU flares, ≥1 flare in the year prior to study entry), HLA-B27 positivity, active disease, and failure of ≥2 non-steroidal anti-inflammatory drugs. Patients received CZP 400 mg at Weeks 0/2/4, then 200 mg every 2 weeks up to 96 weeks. This 48-week pre-planned interim analysis compares AAU flare incidence in the 48 weeks before and after initiation of CZP treatment, using Poisson regression to account for possible within-patient correlations.ResultsIn total, 89 patients were included (male: 63%; radiographic/non-radiographic axSpA: 85%/15%; mean axSpA disease duration: 8.6 years). During 48 weeks’ CZP treatment, 13 (15%) patients experienced 15 AAU flares, representing an 87% reduction in AAU incidence rate (146.6 per 100 patient-years (PY) in the 48 weeks pre-baseline to 18.7 per 100 PY during CZP treatment). Poisson regression analysis showed that the incidence rate of AAU per patient reduced from 1.5 to 0.2 (p<0.001). No new safety signals were identified.ConclusionsThere was a significant reduction in the AAU flare rate during 48 weeks of CZP treatment, indicating that CZP is a suitable treatment option for patients with active axSpA and a history of recurrent AAU.

Download Full-text

P181 Long-term improvement in axial spondyloarthritis clinical outcomes following 2-weeks of intensive education and rehabilitation: results from the Bath residential rehabilitation programme

Rheumatology ◽

10.1093/rheumatology/keab247.176 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Rosie Barnett ◽

Anita McGrogan ◽

Matthew Young ◽

Charlotte Cavill ◽

Mandy Freeth ◽

...

Keyword(s):

Quality Of Life ◽

Physical Activity ◽

Disease Activity ◽

Axial Spondyloarthritis ◽

Rehabilitation Programme ◽

Spinal Mobility ◽

The Impact

Abstract Background/Aims Axial spondyloarthritis (axSpA) is a chronic rheumatic condition, characterised by inflammatory back pain - often associated with impaired function and mobility, sleep disturbance, fatigue, and reduced quality of life. Despite the vast advances in pharmacological treatments for axSpA over the last few decades, physical activity and rehabilitation remain vital for effective disease management. At the Royal National Hospital for Rheumatic Diseases in Bath (RNHRD), the 2-week inpatient axSpA rehabilitation programme has been integral to axSpA care since the 1970’s. Prior research has demonstrated significant short-term improvements in spinal mobility (BASMI), function (BASFI) and disease activity (BASDAI) following course attendance. However, the long-term outcomes are yet to be evaluated in this unique cohort. Methods Since the early 1990’s, clinical measures of spinal mobility, function and disease activity have been routinely collected at the RNHRD at all clinical appointments through administration of the BASMI, BASFI and BASDAI, respectively. Dates of attending the axSpA course and standard clinical and treatment follow-up data were also collected. Multiple linear regression models were used to investigate the impact of course attendance on final reported BASMI, BASDAI and BASFI scores (final score=most recent). Length of follow-up was defined as time between first and last recorded BASMI. Results Of the 203 patients within the Bath SPARC200 cohort, 77.8% (158/203) had attended at least one rehabilitation course throughout follow-up. 70.0% (140/203) of patients were male. The mean duration of follow-up was 13.5 years (range 0-35 years); 28.1% (57/203) of individuals with 20+ years of follow-up. Course attendance (yes versus no) significantly reduced final BASMI score by 0.84 (p = 0.001, 95%CI -1.31 to -0.37) and final BASDAI score by 0.74 (p = 0.018, 95%CI -1.34 to -0.13). Although course attendance reduced final BASFI by 0.45 (95%CI -1.17 to 0.28), this relationship did not reach significance (p = 0.225). Whilst minimally clinically important difference (MCID) is, to our knowledge, yet to be defined for BASMI, MCIDs were achieved long-term for both BASDAI and BASFI - defined by van der Heijde and colleagues in 2016 as 0.7 and 0.4 for BASDAI and BASFI, respectively. Conclusion These results provide novel evidence to support the integral role of education, physical activity and rehabilitation in the management of axSpA. Future work should investigate additional outcomes of critical importance to patients and clinicians, such as fatigue, quality of life and work productivity. Furthermore, a greater understanding of the factors that confound these outcomes may provide insights into those patients who may most benefit from attending a 2-week rehabilitation course. In addition to facilitating identification of those patients who may require additional clinical support. Disclosure R. Barnett: None. A. McGrogan: None. M. Young: None. C. Cavill: None. M. Freeth: None. R. Sengupta: Honoraria; Biogen, Celgene, AbbVie, Novartis, MSD. Grants/research support; Novartis, UCB.

Download Full-text

THU0378 DO COMORBIDITIES DECREASE THE FIRST TNF-INHIBITOR RETENTION AND TREATMENT RESPONSE IN AXIAL SPONDYLOARTHRITIS PATIENTS? DATA FROM TURKBIO

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2925 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 422-423

Author(s):

Y. Erez ◽

A. Karakas ◽

S. B. Kocaer ◽

T. Yüce İnel ◽

S. Gulle ◽

...

Keyword(s):

Disease Activity ◽

Treatment Response ◽

Axial Spondyloarthritis ◽

Cerebrovascular Event ◽

Tnf Inhibitor ◽

Drug Survival ◽

Drug Retention ◽

Significant Difference ◽

Baseline Characteristics ◽

The Impact

Background:The frequency of comorbidities has increased in spondyloarthritis patients compared to the general population. The effect of comorbidities on tumour necrosis factor alpha inhibitor (TNFi) drug retention and treatment response has not been well evaluated.Objectives:The purpose of this study to assess the impact of comorbidities on the first TNFi drug survival and treatment response in patients with axial spondyloarthritis (axSpA) registered in theTURKBIOdatabase.Methods:In this study, the frequency of comorbidities, disease activity scores at baseline and month 6 and drug retention were recorded in AxSpA patients iniating first TNFi treatment between 2011 and 2019. Kaplan Meier plot and log rank tests were used for drug survival analysis. Cox regression analysis with HR was performed to evaluate the correlation between comorbidities and drug survival.Results:There were 2428 patients with AxSpA (39.3% female) who used their first TNFi during the study period. Among them, a total of 770 (31%) had at least one comorbid disease. Hypertension was the most common comorbidity (9.7%), followed by the affective disorders (8%) and chronic lung disease (5.8%). The baseline characteristics of patients are shown in Table 1.The presence of any comorbidity did not impact the first TNFi retention (Figure 1). When comorbidities were analysed seperately, we found that only history of cerebrovascular event was negatively associated with drug retention rate (HR: 6.9, p:0.008). There was no statistically significant difference in Bath AS Disease Activity Index 50% (BASDAI50) response between patients with and without comorbidity at 6 months. Less axSpA patients with comorbidity achieved a ASDAS score ≤ 2.1 compared to patients without comorbidity at 6 months.Table 1.Baseline Characteristics of PatientsRadiographic Spondyloarthritis, n (%)2318 (95.5)Female, n(%)954 (39.3)Age, year42.2±11.8Age at diagnosis, years32.5± 11.3Age at initial TNFi, years39.4 ± 11.1Symptom duration, years9.7± 7.5Time to initial TNFi, years7±6.8HLA-B27- positivity, n (%)1144 (47.1)Smokers, n (%)1068 (44)Baseline BASDAI35.5±22.2Baseline ASDAS-CRP2.8±1.1Baseline CRP (mg/L)15.7±24.4VAS global patient46.6±28.7-Quantitative variables are presented as mean ± SD, and qualitative variables are presented as frequency and percentage-ASDAS-CRP, Ankylosing Spondylitis Disease Activity Score using C-reactive protein VAS, visual analogue scaleConclusion:The results of this study demonstrated that the presence of previous cerebrovascular event decreased the first TNFi survival in patients with axSpA. It also suggested that comorbidities might decrease TNFi treatment response.Disclosure of Interests:None declared

Download Full-text

Parietaria Allergy: An Intriguing Challenge for the Allergist

Medicina ◽

10.3390/medicina54060106 ◽

2018 ◽

Vol 54 (6) ◽

pp. 106

Author(s):

Giorgio Ciprandi ◽

Paola Puccinelli ◽

Cristoforo Incorvaia ◽

Simonetta Masieri

Keyword(s):

Clinical Practice ◽

Symptom Severity ◽

Pollen Season ◽

Clinical Characteristics ◽

Allergen Immunotherapy ◽

Correct Diagnosis ◽

Mediterranean Area ◽

Pollen Exposure ◽

Inflammatory Changes ◽

The Impact

Parietaria pollen is the most important cause of pollen allergies in the Mediterranean area, as Parietaria is widespread in this region. Many issues are associated with Parietaria allergy, including the duration of the pollen season (many doctors in fact believe that it lasts throughout the year), pollen load (which seems to be increasing over time), the impact of age (on IgE production and symptom severity), inflammatory changes (after pollen exposure), and the choice of allergen immunotherapy (AIT). In addition, molecular diagnostics allows for the defining of a correct diagnosis, differentiating between mere sensitization and true allergy. This review considers these topics and will hopefully help the allergist in clinical practice. Parietaria allergy is an intriguing challenge for the allergist in clinical practice, but it may be adequately managed by knowing the peculiarities of respective territories and the clinical characteristics of each patient.

Download Full-text

Effect of certolizumab pegol over 96 weeks of treatment on inflammation of the spine and sacroiliac joints, as measured by MRI, and the association between clinical and MRI outcomes in patients with axial spondyloarthritis

RMD Open ◽

10.1136/rmdopen-2017-000430 ◽

2017 ◽

Vol 3 (1) ◽

pp. e000430 ◽

Cited By ~ 11

Author(s):

Jürgen Braun ◽

Xenofon Baraliakos ◽

Kay-Geert Hermann ◽

Robert Landewé ◽

Pedro M Machado ◽

...

Keyword(s):

Axial Spondyloarthritis ◽

Certolizumab Pegol ◽

Sacroiliac Joints

Download Full-text

The impact of axial spondyloarthritis on quality of life (QoL): a comparison with the impact of moderate to end-stage chronic kidney disease on QoL

Quality of Life Research ◽

10.1007/s11136-018-1900-x ◽

2018 ◽

Vol 27 (9) ◽

pp. 2321-2327 ◽

Cited By ~ 5

Author(s):

Yu Heng Kwan ◽

Warren Fong ◽

Priscilla How ◽

Hwee-Lin Wee ◽

Ying Ying Leung ◽

...

Keyword(s):

Quality Of Life ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Axial Spondyloarthritis ◽

End Stage ◽

The Impact

Download Full-text

Axial Spondyloarthritis and New Bone Formation

Osteologie/Osteology ◽

10.1055/a-1618-4717 ◽

2021 ◽

Vol 30 (04) ◽

pp. 311-318

Author(s):

Uta Syrbe

Keyword(s):

Bone Formation ◽

Structural Damage ◽

Axial Spondyloarthritis ◽

Clinical Symptoms ◽

Research Work ◽

New Bone Formation ◽

Sacroiliac Joints ◽

Spine Mobility ◽

Vertebral Bodies ◽

Inflammatory Changes

AbstractAxial spondyloarthritis is an inflammatory disease of the axial skeleton. Its pathogenesis is only partly understood. At the beginning, there are inflammatory changes in the sacroiliac joints which are followed by inflammation in vertebral bodies and in facet joints. Low back pain occurring in the morning hours is the dominant clinical symptom. In the early phase, inflammatory changes are detectably by MRI. Inflammation promotes a process of joint remodelling in the sacroiliac joints which leads to erosions, sclerosis and bony bridging, i. e. ankylosis, which are detectable by X-ray. In the spine, vertical osteophytes developing at sites of previous inflammation connect vertebral bodies as syndesmophytes. Additional ossification of longitudinal ligaments contributes to the so-called bamboo spine. Ossification of the spine promotes fixation of a severe kyphosis of the thoracic spine which strongly impairs spine mobility and quality of life. High disease activity seems a prominent risk factor for development of structural damage. However, although NSAIDs improve clinical symptoms, they do not reduce new bone formation. In contrast, TNFα and IL-17 inhibitors seem to retard new bone formation apart from their clinical efficacy. Research work of the last years identified immunological pathways of inflammation. However, the trigger and cellular components of the immune reaction in the bone marrow are still poorly defined. Osteoclasts are involved in the destruction of the subchondral bone, while osteoblasts facilitate new bone formation and cartilage ossification. This review gives an overview about diagnostics and therapy of axSpA and about risk factors for the development of structural damage. Concepts about the immune pathogenesis and joint remodeling in AS are given under recognition of genetic and histopathological studies.

Download Full-text