THU0400 CLINICAL COURSE OF EARLY AXIAL SPONDYLOARTHRITIS OVER TEN YEARS: LONG-TERM RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 437-437
Author(s):  
D. Poddubnyy ◽  
V. Rios Rodriguez ◽  
M. Torgutalp ◽  
M. Verba ◽  
J. Callhoff ◽  
...  

Background:Previous studies showed that patients with non-radiographic and radiographic axial spondyloarthritis (nr- and r-axSpA) have similar disease burden and similar response to anti-inflammatory therapy given similar level of inflammatory activity. Only little is known, however, about long-term disease course in patients with early axSpA.Objectives:To investigate the long-term (up to 10 years) clinical course of patients with early axSpA.Methods:In total, 525 patients with early axSpA (r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) were included. The final patient classification was based on central reading results in 458 patients with available pelvic X-rays, and on local rheumatologist judgement in 67 patients. A total of 251 patients were finally classified as r-axSpA and 274 as nr-axSpA. Clinical evaluation, which included disease activity (BASDAI, C-reactive protein – CRP, ASDAS) as well as therapy recording, was performed at baseline and every 6 months thereafter until year 2 and annually thereafter till year 10. Treatment was conducted at the discretion of the local rheumatologist.Results:Since the cohort has started prior to introduction of TNF inhibitors (TNFi), only 2% patients received TNFi at baseline that increased to 23% at year 10 (15% in nr-axSpA and 31% in r-axSpA) – Figure 1. The use of NSAIDs and csDMARDs decreased in both groups (Figure 1), while use of systemic steroids did not change substantially (9% at baseline, 8% at year 10). The proportion of patients with low disease activity according to BASDAI (<4) was higher in r-axSpA as compared to nr-axSpA at almost all time points, while the proportion of patients with low disease activity according to ASDAS (<2.1), as well as with ASDAS inactive disease (<1.3) was similar between nr-axSpA and r-axSpA (Figure 2). In the group of patients who completed year 10 (n=134 in total, 68 with nr-axSpA, 67 with r-axSpA) the same trends in therapy and disease activity were observed.Conclusion:Patients with nr-axSpA and r-axSpA showed a similar disease course in terms of disease activity on the group level. The drop-out rate in this observational cohort was overall high, but comparable between groups. The lower proportion of patients with nr-axSpA being treated with TNFi might reflect a later introduction of TNFi for this indication.Acknowledgments:GESPIC has been financially supported by the German Federal Ministry of Education and Research as well as by Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. From 2010 till 2019 GESPIC has been supported by Abbvie.Disclosure of Interests:Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Murat Torgutalp: None declared, Maryna Verba: None declared, Johanna Callhoff: None declared, Mikhail Protopopov Consultant of: Novartis, Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Judith Rademacher: None declared, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 54.1-54
Author(s):  
S. Kieskamp ◽  
D. Paap ◽  
M. Carbo ◽  
F. Wink ◽  
R. Bos ◽  
...  

Background:Up to 40% of ankylosing spondylitis patients report persistently high pain scores of >4 (scale of 0-10) even after responding to long-term TNF-alpha blocking therapy.[1] In other rheumatic diseases, nociplastic pain (due to altered functioning of the nervous system leading to peripheral and central sensitization) is common.[2] In axial spondyloarthritis (axSpA), patient illness and pain perceptions were shown to influence disease outcome.[3] Therefore, we hypothesized that central sensitization and patients’ illness perceptions are associated with persistently high disease activity in axSpA.Objectives:To investigate to what extent central sensitization, pain catastrophizing and patients’ perceptions play a role in axSpA and to explore associations with disease activity.Methods:Between April and September 2019, consecutive outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort,[4] an ongoing large prospective cohort, were included in this study. Besides the standardized assessments, patients filled out three additional questionnaires: Central Sensitization Inventory (CSI), Pain Catastrophizing Scale (PCS) and Revised Illness Perception Questionnaire (IPQ-R). Univariable and multivariable linear regression analyses were used to investigate the association of CSI, PCS and each of the eight subscales of the IPQ-R, and disease activity assessments ASDAS-CRP, BASDAI, and CRP. We corrected for the following potential confounders: gender, symptom duration, BMI, educational level, smoking status and HLA-B27 status.Results:Of 171 included patients, 58% were male, 79% were HLA-B27 positive, median symptom duration was 21 (IQR 10-32), mean ASDAS-CRP 2.1 ± 1.0, mean BASDAI 3.9 ± 2.2 and median CRP 2.9 (IQR 1.2-6.3). Mean CSI score was 37.8 ± 14.1 (scale of 0-100), and 44% of patients scored ≥40 on the CSI.[5] Median PCS score was 15 (IQR 7-22) (scale of 0-52), median IPQ-R illness identity subscore 3 (IQR 2-4) (scale of 0-14) and mean IPQ-R treatment control subscore 18.1 ± 3.4 (scale of 5-25). In univariable regression analysis, CSI and PCS scores and IPQ-R subscores all showed significant associations with ASDAS-CRP, and all except the IPQ-R subscale personal control showed significant associations with BASDAI. Only IPQ-R treatment control was significantly associated with CRP. Central sensitization, two IPQ-R subscales (perceived treatment control and the number of symptoms patients attributed to their axSpA: illness identity) and BMI were independently associated with disease activity assessments BASDAI (R2=0.46) and ASDAS-CRP (R2=0.36) (Figure 1).Conclusion:In this axSpA population with long-term disease, 44% scored above the CSI cutoff point of 40, indicating a high probability of central sensitization. CSI score, illness identity and treatment control were independently associated with disease activity assessments.References:[1]Arends Set al.Clin Exp Rheumatol 2017;35(1):61-8.[2]Meeus Met al.Semin Arthritis Rheum 2012;41(4):556-67.[3]Van Lunteren Met al. Arthritis Care Res (Hoboken) 2018;70(12):1829-39.[4]Arends Set al.Arthritis Res Ther 2011;13(3):R94.[5]Neblett Ret al.J Pain 2013;14(5):438-45.Disclosure of Interests:Stan Kieskamp: None declared, Davy Paap: None declared, Marlies Carbo: None declared, Freke Wink Consultant of: Abbvie, Janssen, Reinhard Bos: None declared, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant of: Consultant for Bristol-Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Speaker for Bristol-Myers Squibb and Novartis., Suzanne Arends Grant/research support from: Grant/research support from Pfizer, Anneke Spoorenberg: None declared


2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Daniel F. McWilliams ◽  
Shimin Rahman ◽  
Richard J. E. James ◽  
Eamonn Ferguson ◽  
Patrick D. W. Kiely ◽  
...  

Abstract Background RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities. Methods People from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups. Results DAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode. Conclusion Flares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1727.2-1728
Author(s):  
L. Vargas Cruz ◽  
J. Boechat Farani ◽  
J. Rabello Costa ◽  
F. Menegat ◽  
J. V. Andrade Águas ◽  
...  

Background:Patients with psoriatic arthritis (PsA) experience substantial functional impairment, which impacts on health-related quality of life.1Evidence from randomized clinical trials (RCTs) suggests better patient-reported functional outcomes when lower disease activity is achieved.2,3,4Objectives:To evaluate the impact of achieving DAPSA remission (REM) or low disease activity (LDA) on long term function measured by HAQ-DI. To verify predictors of achieving a minimum clinically important difference (MCID) in HAQ-DI (≤ -0.35).Methods:This is a longitudinal analysis of a real-life retrospective cohort. Inclusion criteria were adult patients fulfilling CASPAR criteria for PsA with at least 4 years of follow-up in the PsA Clinic. Demographic and clinical data were extracted from electronic medical records. Comparison of HAQ-DI variation between patients with DAPSA REM/LDA and those with moderate/high disease activity was performed using generalized estimating equation (GEE), adjusted by Bonferroni test. Correlation between HAQ-DI and DAPSA was analyzed by Spearman correlation method. A multivariate hierarchical regression model was applied in order to evaluate predictors of achieving a MCID in HAQ-DI scores.Results:Seventy-three patients were included in the analysis, of which 58.9% were female, with a median (25/75th) of 8 (3-15) years since PsA diagnosis and a mean follow up time of 6.2±1.2 years. In total, 37% of patients (N=27) presented a MCID in HAQ-DI during the follow-up. Function measured by HAQ-DI was determined by PsA disease activity measured by DAPSA (interaction test: p <0.0001) (Figure 1). A moderate and statistically significant correlation between ΔDAPSA and ΔHAQ-DI was observed (rs= 0.60; p<0.001) (Figure 2), demonstrating that a decrease in PsA disease activity was associated to improvement in function. Only patients in DAPSA REM demonstrated a constant declining in HAQ-DI scores during the 6 years of follow-up (Figure 1). White ethnicity and older age at baseline were predictors for not achieving MCID in HAQ-DI (RR 0.33 95% CI 0.16-0.67, p=0.002 and RR 0.96 95% CI 0.93-0.98, p<0.0001, respectively), while higher scores of HAQ-DI at baseline were predictors of achieving a MCID (RR 1.71 95%CI 1.12-2.60, p=0.013).Figure 1.Variation in HAQ-DI according to PsA disease activity measured by DAPSAFigure 2.Correlation between changes in PsA disease activity (ΔDAPSA) and changes in functional indices (ΔHAQ-DI) over three years of follow-upConclusion:In PsA, patients who maintained DAPSA REM/LDA over time had better long term functional outcomes. Higher HAQ-DI scores at baseline, non-white ethnicity and younger age were predictors for achieving a clinical significant improvement in HAQ-DI.References:[1]Mease P et al. Semin Arthritis Rheum. 2018 Dec;48(3):436-448.[2]Coates, LC et al. The Lancet. 2015 Dec; 386, 19-26.[3]Aletaha D et al. Ann Rheum Dis. 2017;76(2):418-421.[4]Kavanaugh A et al. Annals rheum Dis 2014; 73: 1689-94.Median HAQ-DIFollow-up in yearsDisclosure of Interests:Larissa Vargas Cruz: None declared, Júlia Boechat Farani: None declared, Júlia Rabello Costa: None declared, Franciele Menegat: None declared, João Victor Andrade Águas: None declared, Bruna Ruschel: None declared, Andrese Aline Gasparin: None declared, Claiton Brenol: None declared, Charles Kohem Grant/research support from: This work was sponsored by the regional society of rheumatology (Sociedade de Reumatologia do Rio Grande do Sul)., Penelope Palominos Grant/research support from: This work was sponsored by the regional society of rheumatology (Sociedade de Reumatologia do Rio Grande do Sul).


2021 ◽  
Author(s):  
Maria Llop ◽  
Mireia Moreno ◽  
Victoria Navarro-Compán ◽  
Xavier Juanola ◽  
Eugenio de Miguel ◽  
...  

Abstract Background: To evaluate the influence of the disease activity on radiographic progression in axial spondyloarthritis (axSpA) patients treated with TNF inhibitors (TNFi).Methods: The study included 101 axSpA patients from the Spanish Register of Biological Therapy in Spondyloarthritides (REGISPONSERBIO), which had clinical data and radiographic assessment available. Patients were classified into 2 groups based on the duration of TNFi treatment at baseline: i) long-term treatment (≥4 years) and ii) no long-term treatment (< 4 years). Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. Disease activity differences between patients’ groups at each time point were assessed using a linear mixed-effect model.Results: Radiographic progression was defined as an increase in ≥2 mSASSS units. At inclusion, approximately half of the patients (45.5%) were receiving long-term treatment with TNFi (≥4 years). In this group of subjects, a significant difference in averaged Ankylosing Spondylitis disease Activity Score (ASDAS) across follow-up was found between progressors and non-progressors (2.33 vs 1.76, p=0.027, respectively). In patients not under long-term TNFi treatment (54.5%) though, no significant ASDAS differences were observed between progressors and non-progressors until the third year of follow-up. Furthermore, no significant differences were found in progression status, when disease activity was measured by Bath Ankylosing spondylitis Disease Activity Index (BASDAI) and C reactive protein (CRP).Conclusions: Patients on long-term TNFi treatment with a mean sustained low disease activity measures by ASDAS presented lower radiographic progression than those with active disease.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 80.1-81
Author(s):  
C. Lukas ◽  
A. Tournadre ◽  
M. C. Picot ◽  
E. Nogué ◽  
E. Dernis ◽  
...  

Background:Anti-TNF treatments (TNFi) have shown high efficacy in axial spondyloarthritis (ax-SpA) with inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs). However their effect remains predominantly symptomatic, and their long-term tolerance as well as significant societal cost justify investigation about a potential reduction in drug dosage, or –most feasible and comfortable for the patient– increase in intervals between doses.Objectives:To assess if a progressive and monitored reduction of administered TNFi by increase of intervals between injections results in a comparable proportion of patients remaining after 12 months (m) in low disease activity state despite a decreased cumulative treatment dose received.Methods:Non-inferiority randomized controlled trial, having included adult patients with ax-SpA fulfilling ASAS criteria, already treated by anti-TNF, and in stable low disease activity for at least 6 m (current and at least 6 m old BASDAI<4/10), who were randomized into 2 groups: either keeping on their usual treatment with stable doses (“unchanged” group), or progressive spacing of injections of their treatment (“spacing” group). Follow-up was done every 3 m during 12 m, with regular monitoring of disease activity and, in patients from the group “spacing”, modification of the rhythm of injections according to disease activity and predefined standardized protocol (either increase or decrease (step-back) of intervals between injections). The primary endpoint was the difference of proportions of patients having a low disease activity state (BASDAI<4/10) after 12 m of follow-up between the 2 groups. It was estimated on the ITT population after multiple imputation. The 90% confidence interval associated was calculated using the Farrington-Manning method and the lower bound was compared to the non-inferiority margin of -20%. With an expected proportion of 85% patients remaining in low disease activity in the unchanged group, and α and β risks at respectively 5% and 90%, the required number of patients was calculated at 358, and thus 398 had to be included with a 10% expected proportion of patients with unavailable data.Results:398 patients were randomized in 23 French rheumatology units (197 and 201 in the spacing and unchanged groups respectively), and 389 included in analyses (9 did not receive the allocated treatment). Mean (SD) age was 44.3 (12.4) years, 71.2% were males. Mean (SD) BASDAI at inclusion was 1.45 (1.02). TNFi used were etanercept (35.7%), adalimumab (33.9%), infliximab (20.6%), golimumab (9.3%) and certolizumab (0.5%). For the 373 patients with complete follow-up (93.7%), 162/184 (88.0%) had a low disease activity in the “spacing” group vs. 173/189 (91.5%) in the “unchanged” group at 12 m. After multiple imputation for the 16 patients with missing data, the difference of proportion between the two groups was estimated to -4.18% [CI90% -10.0; 1.7], thus confirming the non-inferiority of the “spacing” procedure. In the “spacing” group at 12 m, 134/162 (82.7%) patients in low disease activity were still receiving a lowered TNFi dose.Conclusion:In ax-SpA patients with BASDAI<4 for at least 6 months under TNFi, it is possible to increase intervals between injections while maintaining a low disease activity by adjusting treatment with quarterly monitoring of SpA activity.Disclosure of Interests:Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Anne Tournadre Speakers bureau: Abbvie, Fresenius, Janssen, MSD, Pfizer, Roche Chugai, Sanofi, Paid instructor for: Fresenius, Consultant of: Abbvie, Fresenius, Lilly, Novartis, Sanofi, Grant/research support from: Fresenius, Novartis, Pfizer, UCB, Marie Christine Picot: None declared, Erika Nogué: None declared, Emmanuelle Dernis Speakers bureau: Roche chugai, UCB, BMS, Novartis, Lilly, Mylan, Pfizer, Celgène, Consultant of: UCB, MSD, BMS, Lilly, Novartis, Philippe Goupille Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Jacques Morel Speakers bureau: Abbvie, Biogen, BMS, Fresenius Kabi, Lilly, Mylan, Novartis, Pfizer, Sanofi, Consultant of: Abbvie, BMS, Boerhinger Ingelheim, Galpaagos, GSK, Lilly, Novartis, Sanofi


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 194.2-194
Author(s):  
A. Ruyssen-Witrand ◽  
V. Rousseau ◽  
A. Sommet ◽  
P. Goupille ◽  
Y. Degboe ◽  
...  

Background:It is recommended to target remission when treating a patient with a chronic inflammatory rheumatism. To date, drug-free (DF) remission has been poorly investigated in axial Spondyloarthritis (axSpA).Objectives:1/To estimate the frequency of patients in DF remission after 5 years of follow-up in a cohort of early axSpA and 2/to assess the factors associated with 5-year DF Remission.Methods:Patients: All patients included in DESIR (DEvenir des Spondyloarthrites Indifférenciées Récentes) cohort were selected for this analysis.Definition of 5-year DF Remission: 1/all patients in ASAS partial remission and/or ASDAS<1.3 at 5 year visit and 2/ taking no disease modifying anti-rheumatic drugs (DMARDs, including synthetic and biologics) only at 5-year visit (patients could have received DMARD before the 5-year visit) and 3/ with a NSAIDs score ≤ 25 at the 5-year visit.Covariates analysed: age, gender, smoking status, body mass index, disease classification criteria (ASAS, Amor, ESSG, New York), presentation at onset (peripheral or extra-articular features), disease activity at onset (BASDAI, ASDAS-CRP, CRP, MASES, TJC or SJC), functional impairment at baseline (BASFI, HAQ-AS, BASMI), comorbidities, baseline imaging data (radiographic sacroiliitis, mSASSS, MRI sacroiliitis, spine MRI Berlin score), NSAID intake within 6 months before baseline visit and 5-year treatment intake (including DMARDs, corticoids and NSAIDs).Statistical analysis: The associations between each of these clinical factors and the 5-year DF remission were tested by logistic regression. A multivariate model was built, stepwise procedure, to identify the independent variables associated with 5-year DF remission.Results:Of the 708 patients included in DESIR cohort, 419 were seen at the 5-year visit and 72 (17.0%) were in DF remission (50% of males, aged of 33.08 years (SD:8.0), disease duration: 1.26 years (SD: 0.72), HLA-B27 in 71%, 26.4% had a MRI sacroiliitis). Patients in 5-year DF remission had lower symptom duration (1.3 year versus 1.6 year, p=0.01) had lower disease activity (BASDAI at baseline: 30.1 versus 46.1, p<0.0001, ASDAS-CRP: 1.96 versus 2.75, p<0.0001, CRP: 3.9 versus 8.6, p=0.01) had less peripheral involvement (at least 1 enthesitis at baseline: n=33 (45.8%) versus n=226 (65.1%), p=0.002; at least 1 painful joint at baseline: n=24 (33.3%) versus n=196 (56.5%), p=0.0006) less functional impairment (HAQ-AS: 0.32 versus 0.69, p< 0.0001, BASFI: 14.3 versus 32.1, p<0.0001, BASMI: 1.98 versus 2.51, p<0.0001), and had lower NSAIDs intake at baseline (NSAIDs score: 28.2 versus 48.1, p=0.0001). Interestingly, there was no difference in sacroiliac bone marrow oedema on MRI while Berlin scores on spine MRI were lower in patients in 5-year DF remission (Berlin score mean: 0.41 versus 1.24, p=0.03). During the 5 years of follow-up, patients in 5-year DF remission received less often analgesics (n=46 (63.9%) versus n=297 (85.3%), p<0.0001) and anti-TNF (n=1 (1.4%) versus n=182 (52.5%), p<0.0001), but there was no difference in NSAID or csDMARD intake between groups until the 4-year visit. After multivariate analysis, the variables that remained associated with 5-year DF remission were lower symptom duration (OR[95%CI]=0.58[0.36-0.88], p=0.01), lower baseline ASDAS-CRP (OR[95%CI]=0.50[0.32-0.76], p=0.002) or NSAIDs score (OR[95%CI]=0.54[0.34-0.81], p=0.004) and not initiating an anti-TNF during the 5 years of follow-up (OR[95%CI]=0.029[0.00-0.14], p=0.0005).Conclusion:DF remission is rare, 5 years after onset of axSpA. Patients with longer symptom duration, higher baseline ASDAS-CRP and NSAIDs scores were less often in DF remission, while imaging and biological data did not predict DF remission.Disclosure of Interests:Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Vanessa Rousseau: None declared, Agnès Sommet: None declared, Philippe Goupille Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Yannick Degboe: None declared, Arnaud Constantin: None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 432-433
Author(s):  
W. P. Maksymowych ◽  
H. Marzo-Ortega ◽  
M. Ǿstergaard ◽  
L. S. Gensler ◽  
J. Ermann ◽  
...  

Background:Ixekizumab (IXE), a high-affinity anti-interleukin-17A monoclonal antibody, is effective in patients (pts) with active non-radiographic axial spondyloarthritis (nr-axSpA), who had elevated C-reactive protein (CRP) and/or active sacroiliitis on magnetic resonance imaging (MRI).1Objectives:To determine if disease activity and patient-reported outcomes at Week 16 were similar between groups after stratifying pts by CRP/sacroiliac joint (SIJ) MRI status at baseline.Methods:COAST-X (NCT02757352) included pts with active nr-axSpA and objective signs of inflammation, i.e. presence of sacroiliitis on MRI (Assessment of Spondyloarthritis International Society [ASAS]/ Outcome Measures in Rheumatology criteria) or elevation of serum CRP (>5.0 mg/L). Pts were randomized 1:1:1 to receive subcutaneous 80 mg IXE every 4 weeks (Q4W) or Q2W, or placebo (PBO). Depending on the baseline values of CRP and MRI SIJ (Spondyloarthritis Research Consortium of Canada [SPARCC] score), pts in the intent-to-treat population (N=239) were divided into 3 subgroups (CRP >5 and MRI ≥2; CRP ≤5 and MRI ≥2; CRP >5 and MRI <2). Logistic regression analysis with treatment, subgroup, and treatment-by-subgroup interaction was used to detect treatment group differences in ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) <2.1 (low disease activity), and Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50) responses at Week 16. Analysis of covariance model with baseline value, treatment, subgroup, and treatment-by-subgroup interaction was used to detect the treatment group difference in change from baseline in Short Form-36 physical component score (SF-36 PCS).Results:The proportion of pts achieving ASAS40 (primary endpoint), ASDAS <2.1, and BASDAI50 (secondary endpoints) was higher in IXE treatment groups compared to PBO at Week 16 (Figure 1). The response rates in IXE-treated subjects were higher in all subgroups (CRP >5 and MRI ≥2; CRP ≤5 and MRI ≥2; CRP >5 and MRI <2) without consistent differences in efficacy between the subgroups. Similarly, pts in the IXE groups showed improvement in SF-36 PCS scores (secondary endpoint) versus pts on PBO at Week 16 (Figure 2).Conclusion:Pts with active nr-axSpA and objective signs of inflammation at baseline who were treated with IXE showed an overall improvement in the signs and symptoms of the disease. The efficacy was not different between pts with both elevated CRP and active sacroiliitis on MRI and pts with either elevated CRP or active sacroiliitis on MRI.References:[1]Deodhar A, et al.Lancet.2020.Disclosure of Interests:Walter P Maksymowych Grant/research support from: Received research and/or educational grants from Abbvie, Novartis, Pfizer, UCB, Consultant of: WPM is Chief Medical Officer of CARE Arthritis Limited, has received consultant/participated in advisory boards for Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Received speaker fees from Abbvie, Janssen, Novartis, Pfizer, UCB., Helena Marzo-Ortega Grant/research support from: Janssen, Novartis, Consultant of: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Lianne S. Gensler Grant/research support from: Pfizer, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, GSK, Novartis, UCB, Joerg Ermann Grant/research support from: Boehringer-Ingelheim, Pfizer, Consultant of: Abbvie, Eli Lilly, Janssen, Novartis,Pfizer, Takeda, UCB, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Rebecca Bolce Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Soyi Liu Leage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Gabriel Doridot Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Vladimir Geneus Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ann Leung: None declared, David Adams Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 6-6
Author(s):  
A. Ortolan ◽  
S. Ramiro ◽  
F. A. Van Gaalen ◽  
T. K. Kvien ◽  
R. B. M. Landewé ◽  
...  

Background:Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite index measuring disease activity in axial spondyloarthritis (axSpA). It includes questions from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Patient Global Assessment (PGA), and inflammation biomarkers. However, ASDAS calculation is not always possible because PGA is sometimes not collected.Objectives:To develop an alternative ASDAS to be used in research settings when PGA is unavailable.Methods:Longitudinal data from 4 axSpA cohorts and 2 RCTs were combined. Observations were randomly split in a development (N=1026) and a validation cohort (N=1059). Substitutes of PGA by BASDAI total score, single or combined individual BASDAI questions, and a constant value, were considered. In the development cohort, conversion factors for each substitute were defined by Generalized Estimating Equations. Validation was performed in the validation cohort according to the OMERACT filter, taking into consideration: 1) Truth (agreement with original-ASDAS in the continuous score, by intraclass correlation coefficient -ICC- and in disease activity states, by weighted kappa) 2) Discrimination (standardized mean difference –SMD- of ASDAS scores between high/low disease activity states defined by external anchors e.g Patient Acceptable Symptom State –PASS-; agreement -kappa- in the % of patients reaching ASDAS improvement criteria according to alternative vs. original formulae) 3) Feasibility.Results:Taking all psychometric properties into account and comparing the different formulae (Table), alternative-ASDAS using BASDAI total as PGA replacement proved to be: 1) truthful (agreement with original-ASDAS: ICC=0.98, kappa=0.90); 2) discriminative: it could discriminate between high/low disease activity states (e.g. scores between PASS no/yes: SMD=1.37 versus original-ASDAS SMD=1.43) and was sensitive to change (agreement with original-ASDAS in major improvement/clinically important improvement criteria: kappa=0.93/0.88; 3) feasible (BASDAI total often available; conversion coefficient≈1).Table.Psychometric properties of alternative ASDAS formulaeConclusion:Alternative-ASDAS using BASDAI total score as PGA replacement is the most truthful, discriminative and feasible instrument. This index enables ASDAS calculation in existing cohorts without PGA.Disclosure of Interests:Augusta Ortolan: None declared, Sofia Ramiro: None declared, Floris A. van Gaalen: None declared, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Pedro M Machado Consultant of: PMM: Abbvie, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Speakers bureau: PMM: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Adeline Ruyssen-Witrand Grant/research support from: Abbvie, Pfizer, Consultant of: Abbvie, BMS, Lilly, Mylan, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Astrid van Tubergen Consultant of: Novartis, Caroline Bastiaenen: None declared, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1552.3-1552
Author(s):  
A. Mekinian ◽  
D. Saadoun ◽  
J. C. N. F. [email protected] ◽  
I. Q. M. F. [email protected] ◽  
P. Jégo ◽  
...  

Objectives:To assess long term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK).Methods:In this multicenter, prospective, open-labelled trial, we aim to evaluate the benefit of adding tocilizumab to steroids in treatment-naïve patients with TAK, on discontinuation of steroids after 6 months of tocilizumab treatment, and to assess relapse-free survival following tocilizumab discontinuation.Results:Thirteen patients with TAK were included, with a median age of 32 years [19-45] and 12 (92%) females. Six (54%) patients met the primary end-point. Among 11 (85%) patients which achieved remission at 6 months, 6 (54%) have reached primary endpoint.. Among the 5 remaining patients which continued steroids, 3 had a prednisone-equivalent dosage < 5mg/day. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3-4] at baseline, versus 1 [0-2] after 6 months; p <0.001), ITAS-2010 score (5 [2-7] versus 3 [0-8]; p = 0.002), and ITAS-A score (7 [4-10] versus 4 [1-15]; p = 0.0001)]. All patients discontinued tocilizumab after 7 infusions, and no other immunosuppressive drugs was introduced, except for 1 patient which received methotrexate. After 9 and 12 months, respectively 7 (54%) and 6 (50%) patients achieved remission with less than 7.5 mg/day of prednisone, and 9 (69%) and 9 (75%) with doses <10 mg/day. During the 12 months follow-up after tocilizumab discontinuation, a relapse occurred among 5 patients (45%) out of 11 in which achieved remission after 6 months of tocilizumab.No severe AEs were considered related to study treatment and none required tocilizumab interruption or dose reduction. No deaths have occurred during the study period.Conclusion:Tocilizumab seems an effective steroid sparing therapy in TAK but its effect appears to be suspensive.Disclosure of Interests:Arsene Mekinian: None declared, david Saadoun: None declared, [email protected] [email protected]: None declared, [email protected] [email protected]: None declared, Patrick Jégo: None declared, [email protected] [email protected]: None declared, wxv wxv: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Mathieu Vautier: None declared, [email protected]>; [email protected]>;: None declared, Patrice cacoub: None declared, olivier fain: None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 327.1-328
Author(s):  
A. Kavanaugh ◽  
M. H. Buch ◽  
B. Combe ◽  
L. Bessette ◽  
I. H. Song ◽  
...  

Background:The primary treatment goal for patients (pts) with rheumatoid arthritis (RA) is a state of sustained clinical remission (REM) or low disease activity (LDA).1,2Objectives:To assess the long-term sustainability of responses to upadacitinib (UPA), a JAK inhibitor, with or without background csDMARD(s) in pts with RA.Methods:Data are from two phase 3 randomized, controlled trials of UPA in RA pts with roughly similar baseline disease characteristics: SELECT-NEXT enrolled pts with an inadequate response (IR) to csDMARD(s) on background stable csDMARD(s) receiving UPA 15 mg or 30 mg once daily or placebo for 12 weeks (wks); SELECT-MONOTHERAPY enrolled methotrexate (MTX)-IR pts receiving UPA 15 mg or 30 mg monotherapy or blinded MTX for 14 wks. After 12/14 wks, pts could enter a blinded long-term extension and receive UPA 15 mg or 30 mg for up to 5 years. This post hoc analysis evaluated clinical REM (CDAI ≤2.8; SDAI ≤3.3), LDA (CDAI≤10; SDAI≤11), and DAS28(CRP) <2.6/≤3.2 at first occurrence before Wk 84; additionally, these measures were evaluated at 3, 6, and 12 months after the first occurrence for the total number of pts randomized to UPA 15 mg. Sustainability of response was evaluated by Kaplan-Meier only for those pts who achieved REM/LDA and was defined as time to the earliest date of losing response at two consecutive visits or discontinuation of study drug. The predictive ability of time to clinical REM/LDA was assessed using Harrell’s concordance (c)-index (for reference, an index ~ 0.5, indicates no ability to predict; an index of 1 or -1 would be a perfect prediction). The last follow up dates were 22 March, 2018 (SELECT-NEXT) and 25 May, 2019 (SELECT-MONOTHERAPY), when all pts had reached the Wk 84 visit.Results:Through Wk 84, the percent of treated pts achieving CDAI REM/LDA was 43%/79% for those receiving UPA 15 mg with background csDMARD(s) (SELECT-NEXT) and 37%/76% for those receiving UPA 15 mg without background csDMARD(s) (SELECT-MONOTHERAPY). 35%/25% of pts randomized to UPA 15 mg with background csDMARD(s) and 27%/23% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI REM through 6/12 months after the first occurrence. 64%/56% of pts randomized to UPA 15 mg with background csDMARD(s) and 61%/56% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI LDA through 6/12 months after the first occurrence (Figure 1). Time to initial clinical REM/LDA did not appear to be associated with sustained disease control. The c-indices (95%CI) for CDAI REM in the UPA 15 mg with background csDMARD(s) and UPA 15 mg without background csDMARD(s) groups were 0.541 (0.47, 0.62) and 0.568 (0.49, 0.65) and that of LDA were 0.521 (0.46, 0.58) and 0.498 (0.43, 0.56), respectively. Through last follow-up visit, 55% of pts receiving UPA 15 mg with background csDMARD(s) and 62% of pts receiving UPA 15 mg without background csDMARD(s) remained in CDAI REM while 72% and 70% of pts remained in CDAI LDA, respectively (Figure 2). Similar results were observed across other disease activity measures (SDAI REM/LDA and DAS28(CRP) <2.6/≤3.2).Conclusion:More than a quarter and more than a half of pts with RA and prior IR to csDMARD(s) receiving UPA with or without background csDMARD therapy achieved sustained clinical REM and LDA, respectively, across disease activity measures. Sustainability of responses appeared comparable among pts receiving UPA with or without background csDMARDs through up to 84 wks.References:[1]EULAR: Smolen JS, et al. Ann Rheum Dis 2017;76:960–977.[2]ACR: Singh et al. Arthritis & Rheumatology Vol. 68, No. 1, January 2016, pp 1–26.Disclosure of Interests: :Arthur Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/research support, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB


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