Showing papers by "Maxime Dougados published in 2023"

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials

Abstract: Objectives Axial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are double-blind, phase 3 trials designed to evaluate efficacy and safety of bimekizumab, a novel dual interleukin (IL)-17A and IL-17F inhibitor, across the axSpA spectrum. Methods In parallel 52-week trials, patients with active disease were randomised 1:1 (nr-axSpA) or 2:1 (r-axSpA) to bimekizumab 160 mg every 4 weeks:placebo. From week 16, all patients received bimekizumab 160 mg every 4 weeks. Primary (Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40)) and secondary endpoints were assessed at week 16. Here, efficacy and treatment-emergent adverse events (TEAEs) are reported up to week 24. Results 254 patients with nr-axSpA and 332 with r-axSpA were randomised. At week 16, primary (ASAS40, nr-axSpA: 47.7% bimekizumab vs 21.4% placebo; r-axSpA: 44.8% vs 22.5%; p<0.001) and all ranked secondary endpoints were met in both trials. ASAS40 responses were similar across TNFi-naïve and TNFi-inadequate responder patients. Improvements were observed in Ankylosing Spondylitis Disease Activity Score (ASDAS) states and objective measures of inflammation, including high-sensitivity C-reactive protein (hs-CRP) and MRI of the sacroiliac joints and spine. Most frequent TEAEs with bimekizumab (>3%) included nasopharyngitis, upper respiratory tract infection, pharyngitis, diarrhoea, headache and oral candidiasis. More fungal infections (all localised) were observed with bimekizumab vs placebo; no major adverse cardiovascular events (MACE) or active tuberculosis were reported. Incidence of uveitis and adjudicated inflammatory bowel disease was low. Conclusions Dual inhibition of IL-17A and IL-17F with bimekizumab resulted in significant and rapid improvements in efficacy outcomes vs placebo and was well tolerated in patients with nr-axSpA and r-axSpA.

Factors associated with the retention of secukinumab in patients with axial spondyloarthritis in real-world practice: results from a retrospective study (FORSYA)

Abstract: Background Secukinumab efficacy and retention data are emerging in patients with axial spondyloarthritis (axSpA) in real-world settings. However, limited data are available on the predictive factors that affect the retention rate. The key objective was to determine whether objective signs of inflammation (OSI) were predictive of secukinumab retention at 1 year. Methods FORSYA is a French, multicentric, non-interventional, retrospective study in adult axSpA patients who received secukinumab treatment between its launch (11 August 2016) and 31 August 2018. The time to secukinumab discontinuation and retention were analysed using a Kaplan-Meier (KM) analysis. OSI was predefined by at least one of the criteria: C reactive protein ≥5 mg/L or erythrocyte sedimentation rate ≥28 mm/hour at secukinumab initiation or MRI inflammation at the sacroiliac or spine level. Results In total, 906 patients from 48 centres were included in the analysis, 42.2% of whom were men, with a mean age of 46.2±11.7 years and a mean disease duration of 9.3±9.1 years. The 1-year KM retention rate (95% CI) for secukinumab was 59% (55%–62%), whereas for patients with and without OSI, it was 58% (54%–62%) and 63% (53%–73%), respectively. In multivariate analysis, lack of prior exposure to tumour necrosis factor inhibitor (TNFi), absence of OSI and inflammatory bowel disease (IBD) were associated with a better retention of secukinumab at 1 year. Conclusion Following its approval in France, ~59% of axSpA patients retained secukinumab in daily practice, at 1 year. Prior exposure to TNFi, OSI and IBD were identified as risk factors for secukinumab discontinuation.

Stricter treat-to-target in RA does not result in less radiographic progression: a longitudinal analysis in RA BIODAM.

Abstract: OBJECTIVES To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active rheumatoid arthritis (RA) who start (new) DMARD-therapy. METHODS Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of 2 visits). The relation between T2T intensity and change in SvdH-score was modelled by generalised estimating equations. RESULTS In total, 511 patients were included (mean (SD) age: 56 (13) years; 76% female). Mean 2-year SvdH progression was 2.2 (4.1) units (median : 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval (parameter estimates (for yes vs no): +0.15 units (95%CI: -0.04-0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits) nor did it reduce progression in the subsequent 6-month interval. CONCLUSIONS In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude toward T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

Pos1544 long-term safety and efficacy of tofacitinib in patients with psoriatic arthritis by prior biologic disease-modifying antirheumatic drug exposure

Abstract: Patients (pts) with psoriatic arthritis (PsA) exposed to tumour necrosis factor inhibitors (TNFi) may have attenuated response or higher adverse event (AE) risk with subsequent treatment. Tofacitinib efficacy/safety in PsA pts was shown in 3 Phase (P)3 trials and 1 long-term extension (LTE) trial.Assess long-term safety/efficacy of tofacitinib in TNFi-inadequate responder (IR) and biologic disease-modifying antirheumatic drug (bDMARD)-naïve PsA pts.Pooled data from P3 trials (NCT01877668/NCT01882439/NCT03486457) of PsA pts receiving ≥1 tofacitinib dose and 1 LTE trial (NCT01976364) of PsA pts receiving tofacitinib 5 mg BID (dose switching allowed after 1 month) were stratified by TNFi-IR or bDMARD-naïve status at P3 trial baseline (BL). Safety assessed in P3/LTE trials. Efficacy assessed in LTE trial only to Month (M)36 (longitudinal models, data as observed): MDA and HAQ-DI (≥0.35 improvement) response rates and change from BL (Δ) in PASDAS. Data reported as all tofacitinib (pts receiving ≥1 tofacitinib dose) or constant tofacitinib 5 mg BID (pts assigned to tofacitinib 5 mg BID in P3/LTE trials or placebo→tofacitinib 5 mg BID in P3 trials and maintained this dose).408 TNFi-IR (incl. 29 TNFi-exposed with unknown IR status) and 562 bDMARD-naïve pts from P3/LTE trials were assessed. Differences in P3 trial BL characteristics in TNFi-IR vs bDMARD-naïve pts included longer disease duration (all tofacitinib, mean: 8.9 vs 5.6 years), higher HAQ-DI scores (mean: 1.2 vs 0.9) and a higher proportion (%) of pts aged ≥65 years (9.6 vs 7.7) and from North America (27.5 vs 8.0). Treatment-emergent AE (TEAE) incidence rates were higher in TNFi-IR vs bDMARD-naïve pts; serious AE (SAE), serious infection (SI) and herpes zoster (HZ; all tofacitinib) incidence rates were numerically higher in TNFi-IR vs bDMARD-naïve pts (confidence intervals [CIs] overlapped; Table 1). Deaths, malignancies excl. non-melanoma skin cancer (NMSC), NMSC, major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) events were observed (Table 1). Tofacitinib response/improvements were sustained to M36 in pts remaining in LTE trial, regardless of prior treatment. At all time points, TNFi-IR vs bDMARD-naïve pts had lower MDA response rates and slightly lower HAQ-DI response rates (Figure 1) and ΔPASDAS (all tofacitinib/constant tofacitinib 5 mg BID: M1 -2.3/-2.5 vs -2.9/-3.0; M6 -2.5/-2.8 vs -3.0/-3.1;M12 -2.7/-2.9 vs -3.0/-3.2; M24 -2.9/-3.1 vs -3.2/-3.4; M36 -3.0/-3.2 vs -3.1/-3.4).Table 1.Safety in P3/LTE trialsaAll tofacitinibConstant tofacitinib 5 mg BIDTNFi-IRbN=408 899 PYbDMARD-naïvecN=562 1255 PYTNFi-IR N=217 282 PYbDMARD-naïve N=325 422 PYn Incidence rate (95% CI)TEAE373181.8 (163.8, 201.2)457117.8 (107.3, 129.1)180219.6 (188.7, 254.2)240161.2 (141.5, 183.0)SAE678.2 (6.4, 10.5)716.0 (4.7, 7.6)259.5 (6.1, 14.0)235.6 (3.6, 8.4)Death10.1 (0.0, 0.6)10.1 (0.0, 0.4)10.4 (0.0, 2.0)10.2 (0.0, 1.3)SI131.5 (0.8, 2.5)110.9 (0.4, 1.6)51.8 (0.6, 4.1)51.2 (0.4, 2.8)HZ192.2 (1.3, 3.4)191.6 (0.9, 2.4)41.5 (0.4, 3.7)61.4 (0.5, 3.1)Malignancies excl. NMSCd30.3 (0.1, 1.0)121.0 (0.5, 1.7)20.7 (0.1, 2.5)51.2 (0.4, 2.8)NMSCd70.8 (0.3, 1.6)90.7 (0.3, 1.4)41.4 (0.4, 3.6)20.5 (0.1, 1.7)MACEd20.2 (0.0, 0.8)40.3 (0.1, 0.8)00.0 (0.0, 1.3)30.7 (0.2, 2.1)VTE00.0 (0.0, 0.4)20.2 (0.0, 0.6)00.0 (0.0, 1.3)00.0 (0.0, 0.9)aConcomitant csDMARD required at start of P3 trials; allowed but not required in LTE trialMedian exposure (range), days:b988 (1, 1544);c744 (1, 1715)dAdjudicatedn, number of pts with events; PY, pt-yearsFor pts remaining in LTE trial, tofacitinib efficacy was greater in bDMARD-naïve vs TNFi-IR pts; response was maintained over time in both groups. Incidence rates were higher for TEAEs and numerically higher for SAE, SI and HZ (all tofacitinib) in TNFi-IR vs bDMARD-naïve pts. Results consistent with other advanced PsA treatments. Limitations included small event numbers, as observed data and BL characteristic differences.This study was sponsored by Pfizer. Medical writing support, under the direction of the authors, was provided by Justine Juana, BHSc, CMC Connect, a division of IPG Health Medical Communications, and was funded by Pfizer, New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022; 175: 1298-1304).Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc and UCB, Maxime Dougados Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Helena Marzo-Ortega Consultant of: AbbVie, Biogen, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer Inc, Takeda and UCB, Grant/research support from: Janssen, Novartis and UCB, Mary Jane Cadatal Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cassandra Kinch Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Peter Nash Speakers bureau: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis and Pfizer Inc, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis and Pfizer Inc.

Impact of cardiovascular risk enrichment on incidence of major adverse cardiovascular events in the tofacitinib rheumatoid arthritis clinical programme

Abstract: rheumatoid

Enthesitis indices identify different patients with this characteristic in axial and peripheral spondyloarthritis and also in psoriatic arthritis: ASAS-PerSpA data

Abstract: Abstract Background In axial spondyloarthritis (axSpA), peripheral SpA (pSpA) and psoriatic arthritis (PsA), enthesitis is a hallmark clinical feature that can be assessed by the SPARCC index, LEI, MASES and MEI. These indices evaluate different locations, which may identify different numbers of patients with enthesitis among SpA subtypes. Thus, the aim of this study was to evaluate whether the proportion of patients with at least one enthesitis across these three most prevalent SpA subtypes differs according to the index used and to evaluate the level of agreement among indices in detecting patients with enthesitis. Methods A total of 4185 patients (2719 axSpA, 433 pSpA and 1033 PsA) from the international and cross-sectional ASAS-PerSpA study were included. The proportion of patients with enthesitis identified by the indices was evaluated across the three diseases. Pairwise agreement between indices was computed using Cohen’s kappa. Results The prevalence rates of patients with at least one enthesitis according to the MEI, MASES, SPARCC index and LEI were 17.2%, 13.5%, 10.7%, and 8.3%, respectively. In axSpA, the indices that identified the most patients with enthesitis were the MEI and MASES (98.7% and 82.4%, respectively); in pSpA and PsA, the indices that identified the most patients with enthesitis were the MEI and SPARCC index (MEI: 100% and SPARCC: 84.6%; MEI: 97.3% and SPARCC: 77%, respectively). In the total population, the MASES vs. MEI showed the strongest agreement (absolute agreement 96.3%; kappa: 0.86); similar results were obtained in axSpA patients (97.3%; 0.90). In pSpA and PsA patients, the SPARCC vs. MEI (97.2%; 0.90 and 95.4%; 0.83, respectively) showed the strongest agreement. Conclusions These results suggest that the prevalence of patients with enthesitis across SpA subtypes differs depending on the disease and the index used. The MEI and MASES appeared best for assessing enthesis in SpA and axSpA, while the MEI and SPARCC index appeared best for assessing enthesitis in pSpA and PsA.

Pos0341 performance analysis of a deep learning algorithm to detect positive sij mri according to the asas definition in axspa patients

Abstract: Magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) is an essential tool in the evaluation of patients with axial spondyloarthritis (axSpA). In-depth knowledge of characteristic MRI lesions and their definitions, as well as reliability of identification and scoring, varies amongst general radiologists and rheumatologists.[1]A deep learning algorithm was developed to detect the presence of inflammation in SIJ MRI (MRI+) scans with promising results.[2]The aim of this diagnostic performance study was to assess the ability of a deep learning algorithm to identify MRI+ scans in a study cohort of axSpA patients.731 baseline SIJ MRI scans were collected from two prospective randomised controlled trial cohorts in patients with non-radiographic (nr-) and radiographic (r-) axSpA (RAPID-axSpA [NCT01087762] and C-OPTIMISE [NCT02505542])[3,4]and were centrally evaluated by two expert readers (and adjudicator in case of disagreement) for the presence of inflammation by the 2009 Assessment in SpondyloArthritis international Society (ASAS) definition.[5]The MRI scans were processed by the previously trained deep learning algorithm,[2]blinded to clinical information and central expert readings.Performance evaluation included sensitivity, specificity, positive and negative predictive values (PPV and NPV), Cohen’s Kappa and the absolute agreement to assess the agreement between the deep learning algorithm and the human readers for the classification of MRI-SIJ scans. Bootstrapping was used to construct the 95% confidence interval (CI).Pooling the patients from RAPID-axSpA (n=152) and C-OPTIMISE (n=579) yielded a validation set of 731 patients (mean age: 34.2 years, SD: 8.6; 69.1% male) of which 44.6% were patients with nr-axSpA and 59.6% were MRI+ as per central readings.Comparing the trained algorithm with the human central readings for the classification of MRI+/MRI– on the pooled validation set yielded a sensitivity of 70% (95% CI: 66–73%), specificity of 81% (95% CI: 78–84%), PPV of 84% (95% CI: 82–87%), NPV of 64% (95% CI: 61–68%), Cohen’s kappa of 0.49 (95% CI: 0.43–0.55), and absolute agreement of 74% (95% CI: 72–77%;Table 1).A previously trained deep learning algorithm enabled acceptable detection of the presence of inflammation according to the 2009 ASAS MRI definition in axSpA patients from two clinical trials. This suggests that an MRI+ detection algorithm has the potential to support clinicians in identifying axSpA patients.[1]Bennett AN. J Rheumatol 2017;44(6):780–5;[2]Aouad T. Proc Int Conf Image Proc 2022;3351–5;[3]van der Heijde. Rheumatology. 2017;56(9):1498–1509;[4]Landewé RB. Ann Rheum Dis. 2020;79(7):920–28;[5]Rudwaleit M. Ann Rheum Dis 2009;68(6):777–83.Table 1.Performance results comparing the algorithm and the human readers for the classification of MRI-SIJ scans. The metric values are point estimate (95% CI).MetricAll (N=731)RAPID-axSpA (N=152)C-OPTIMISE (N=579)Central reading, MRI+; n(%)436 (59.6%)99 (65.1%)337 (58.2%)Sensitivity0.70(95% CI: 0.66–0.73)0.66(95% CI: 0.58–0.73)0.71(95% CI: 0.67–0.75)Specificity0.81(95% CI: 0.78–0.84)0.89(95% CI: 0.82–0.95)0.79(95% CI: 0.75–0.83)PPV0.84(95% CI: 0.82–0.87)0.92(95% CI: 0.87–0.96)0.83(95% CI: 0.79–0.86)NPV0.64(95% CI: 0.61–0.68)0.58(95% CI: 0.50–0.67)0.66(95% CI: 0.62–0.70)Cohen’s kappa0.49(95% CI: 0.43–0.55)0.48(95% CI: 0.36–0.61)0.49(95% CI: 0.42–0.56)Absolute agreement0.74(95% CI: 0.72–0.77)0.74(95% CI: 0.68–0.79)0.74(95% CI: 0.72–0.77)CI: confidence interval; MRI: magnetic resonance imaging; NPV: negative predictive value; PPV: positive predictive value; SIJ: sacroiliac joints.We thank the patients who participated. Funded by UCB Pharma. Editorial support provided by Costello Medical and funded by UCB Pharma.Joeri Nicolaes Shareholder of: UCB Pharma, Employee of: UCB Pharma, Evi Tselenti Employee of: Veramed statistical consultant for UCB Pharma, Theodore Aouad: None declared, Clementina López-Medina Speakers bureau: Eli Lilly, Novartis, UCB Pharma, MSD, Abbvie and Janssen, Consultant of: UCB Pharma, Eli-Lilly, and Novartis, Grant/research support from: Abbvie, UCB Pharma, Eli Lilly, and Novartis, Antoine Feydy Consultant of: Guerbet, Hugues Talbot: None declared, Bengt Hoepken Shareholder of: UCB Pharma, Employee of: UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Maxime Dougados Speakers bureau: UCB Pharma, Grant/research support from: UCB Pharma.

Pos0364 sex differential impact of co-morbidities on disease activity in spondyloarthritis: data from comospa study

Abstract: Previous studies have examined the distinct phenotypes and the factors linked to disease activity and response to treatment in spondyloarthritis (SpA), some reporting several differences between men and women. However, there is still scarce literature on sex differences in SpA co-morbidities such as cardiovascular (CV) risk factors, osteoporosis, neoplasms or infections, or exploring sex differential impacts of these co-morbidities in the disease activity of SpA patients.To characterize differences in SpA associated co-morbidities between male and female patients and to evaluate the existence of a differential impact of these comorbidities on the disease activity between SpA gender.This is a post-hoc analysis of the COMOSPA study which included 3982 patients with SpA, 2588 male patients and 1394 female patients. Differences in co-morbidities regarding sex were assessed using logistic regression models. Co-morbidities were evaluated for their impact on disease activity indexes with linear models, which included sex and the comorbidity as explanatory variables, as well as their interaction. Age and treatment with bDMARDS were included as confounders. We retrieved odds ratios (OR) and group differences from these models to measure the magnitude of the effects and determined statistical significance at a level of p<0.05 using Wald tests.After statistical control for age and bDMARDS, our analysis found that men had a higher prevalence of several cardiovascular comorbidities such as hypertension (OR, 95%CI) (1.47, 1.23 - 1.77), dyslipidemia (1.29, 1.07 - 1.56), ischemic heart disease (2.77, 1.72 - 4.65) and renal deficiency (2.36, 1.46 - 4.01). Additionally, a greater proportion of men had a history of tuberculosis (1.59, 1.45 - 3.95), and a lower prevalence of fibromyalgia (0.47, 0.39 - 0.57). However, we did not find differences between men and women in terms of prevalence of neoplasms, osteoporosis, gastrointestinal disease, or severe infection (Table 1).Several co-morbidities were associated with disease activity equally in both sex, including CV conditions, severe infection, osteoporosis, chronic obstructive pulmonary disease, gastrointestinal disease and fibromyalgia. When comparing men and women patients, gastrointestinal ulcer and fibromyalgia associates with ASDAS and BASDAI and have a differential impact depending on sex. Specifically, fibromyalgia has a higher impact in men (ASDAS: 1.367 vs 1.612; BASDAI: 4.28 vs 4.70) (Figure 1).Our data show that co-morbidities occur similarly in men and female SpA patients, except for a higher frequency of CV co-morbidities in men and a higher prevalence of fibromyalgia in women. Moreover, fibromyalgia and gastro-intestinal ulcer evidenced a sex-specific association with disease activity among all the co-morbidities studied.Table 1.SpA patientsMale, n=2588Female, n=1394p-valueOR adjusted for age and ever bDMARDsp-valueAge,years42.9 (14.1)45.1 (13.4)<0.001Hypertension590/2570 (23%)292/1388 (21%)NS1.47 (1.23 - 1.77)<0.001Diabetes147/2570 (5.7%)72/1387 (5.2%)NS1.27 (0.94 - 1.72)NSDyslipidemia438/2556 (17.1%)218/1380 (15.8%)NS1.29 (1.07 - 1.56)0.009Renal deficiency74/2571 (2.9%)20/1387 (1.4%)0.0052.36 (1.46 - 4.01)<0.001Ischemic heart disease85/2569 (3.3%)21/1386 (1.5%)0.0012.77 (1.72 - 4.65)<0.001Stroke37/2570 (1.4%)13/1381 (0.9%)NS1.86 (1.00 - 3.66)NSHistory of tuberculosis79/2548 (3.1%)21/1382 (1.5%)0.0032.34 (1.45 - 3.95)<0.001Hospitalized for severe infection76/2556 (3%)39/1385 (2.8%)NS1.08 (0.73 - 1.61)NSAny neoplasm*60/2486 (2.4%)26/1342 (1.9%)NS1.51 (0.94 - 2.48)NSOsteoporosis341/2574 (13.2%)188/1388 (13.5%)NS1.06 (0.87 - 1.29)NSAny GI (diverticulitis or GI ulcer)291/2558 (11.4%)174/1376 (12.6%)NS0.93 (0.76 - 1.14)NSFM (extreme PRO definition)265/2569 (10.3%)271/1384 (19.6%)<0.0010.47 (0.39 - 0.57)<0.001SpA= spondyloarthritis; GI= gastro-intestinal; bDMARDs: biological disease-modifying antirheumatic drugs; FM= fibromyalgiaNIL.NIL.None Declared.

A deep learning model for the diagnosis of sacroiliitis according to Assessment of SpondyloArthritis International Society classification criteria with magnetic resonance imaging.

Abstract: The purpose of this study was to develop and evaluate a deep learning model to detect bone marrow edema (BME) in sacroiliac joints and predict the MRI Assessment of SpondyloArthritis International Society (ASAS) definition of active sacroiliitis in patients with chronic inflammatory back pain.MRI examinations of patients from the French prospective multicenter DESIR cohort (DEvenir des Spondyloarthropathies Indifférenciées Récentes) were used for training, validation and testing. Patients with inflammatory back pain lasting three months to three years were recruited. Test datasets were from MRI follow-ups at five years and ten years. The model was evaluated using an external test dataset from the ASAS cohort. A neuronal network classifier (mask-RCNN) was trained and evaluated for sacroiliac joints detection and BME classification. Diagnostic capabilities of the model to predict ASAS MRI active sacroiliitis (BME in at least two half-slices) were assessed using Matthews correlation coefficient (MCC), sensitivity, specificity, accuracy and AUC. The gold standard was experts' majority decision.A total of 256 patients with 362 MRI examinations from the DESIR cohort were included, with 27% meeting the ASAS definition for experts. A total of 178 MRI examinations were used for the training set, 25 for the validation set and 159 for the evaluation set. MCCs for DESIR baseline, 5-years, and 10-years follow-up were 0.90 (n = 53), 0.64 (n = 70), and 0.61 (n = 36), respectively. AUCs for predicting ASAS MRI were 0.98 (95% CI: 0.93-1), 0.90 (95% CI: 0.79-1), and 0.80 (95% CI: 0.62-1), respectively. The ASAS external validation cohort included 47 patients (mean age 36 ± 10 [SD] years; women, 51%) with 19% meeting the ASAS definition. MCC was 0.62, sensitivity 56% (95% CI: 42-70), specificity 100% (95% CI: 100-100) and AUC 0.76 (95% CI: 0.57-0.95).The deep learning model achieves performance close to those of experts for BME detection in sacroiliac joints and determination of active sacroiliitis according to the ASAS definition.

POS0650 FACING THE ISSUES OF CHANGE IN ENTRY VISIT DIAGNOSIS AND LOST OF FOLLOW-UP OVER TIME IN INCEPTION COHORTS: DATA FROM THE AXIAL SPONDYLARTHRITIS (AxSpA) DESIR COHORT

Abstract: Inception cohorts can be defined as long term follow-up of patients suffering at entry visit from a recent onset disease.Despite their huge advantage to better approach the truth in terms of long term prognosis of the disease, they are usually facing 2 issues: a) the possibility of a change in the entry visit (initial) diagnosis b) the missing data due to patients lost of follow-up.To evaluate both the frequency and the baseline predisposing factors of a) a change in the initial diagnosis b) the risk of loss of follow-up in the DESIR axSpA cohort.Study design:DESIR is an ongoing (10 year follow-up completed for all the patients) multicenter cohort of recent onset axSpA.Diagnosis: At entry visit and during the 10 year follow-up period, this diagnosis was based on the opinion of the treating rheumatologist with the requirement of a highly suspected diagnosis of axSpA at entry visit and after the first 2 years of follow-up the possibility to exclude the patients in case of a change in the initial axSpA diagnosis.Statistical analysis: Multiple imputation was used to address missing data and estimates the probabilities of a change in initial axSpA diagnosis for each patient lost of follow up. Predisposing factors of an unchanged initial axSpA diagnosis were then evaluated using a multivariate logistic regression model on imputed data sets. A multivariate cox survival analysis exploring factors associated to the overtime risk of loss of follow-up was also performed.Of the 708 enrolled patients, 45 were excluded from the cohort because of a documented change in the initial axSpA diagnosis (mechanical low back pain n = 30, fibromyalgia n = 13, chronic inflammatory rheumatic disease (n = 1 and no information n = 1).The classification criteria were fulfilled by 16/45 (36%) versus 413/663 (63%) and 21/45 (47%) versus 522/663 (81%) patients with a documented change versus no change in their entry visit diagnosis according to the ASAS ax-SpA and the AMOR criteria respectively.During the 10 year follow-up period, 300 patients were lost of follow-up. Based on imputation, among these 300 patients, 19 patients were systematically suspected to have a change in their initial axSpA diagnosis in all imputations while 173 patients were never “suspected” for this change; 42 patients were considered as suspected for a change in their initial axSpA diagnosis in at least 70% of imputations.Predisposing factors of an unchanged initial axSpA diagnosis were (odds ratio [95% CI]): radiographic SIJ structural damage: 17.0 [4.1; 71.0]; past or present psoriasis: 5.3 [2.0; 14.3]; CRP ≥ 6 mg/l: 2.7 [1.3; 5.3]; good response to NSAID: 2.5 [1.5; 4.2]; HLA B27 positivity: 2.0 [1.3; 3.3]; anterior chest wall pain: 2.0 [1.2; 3.3] and female gender: 1.9 [1.2; 3.0].Predisposing factors of the risk of loss of follow-up were: Age at back pain initiation< 45 years old: 1.8 [1.2; 2.9]; CRP < 6 mg/l: 1.5 [1.1; 1.9]; HLA B27 negativity: 1.4 [1.1; 1.8]; educational level < university: 1.4 [1.1; 1.8]; smoker: 1.3 [1.0; 1.6].These data suggest that a) a change in the entry visit diagnosis and the risk of follow-up have to be considered in inception cohorts b) statistical models including multiple imputations could facilitate the evaluation of long term prognosis of the disease.The authors would like to thank the investigators of the 25 centers and all the 708 enrolled patients. This study has been supported via unrestricted grants from Pfizer france and the French society of Rheumatology.None Declared.

Characterisation of gut microbiota composition in patients with axial spondyloarthritis and its modulation by TNF inhibitor treatment

Abstract: Objective To assess whether gut microbiota composition is associated with patient characteristics and may have predictive value on the response to TNF inhibitor (TNFi) treatment in axial spondyloarthritis (AxSpA). Methods The study involved 61 patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for AxSpA. All patients had active disease despite non-steroidal anti-inflammatory drugs intake and were eligible for treatment with a TNFi. At baseline, the mean Ankylosing Spondylitis Disease Activity Score was 2.9±1 and mean C reactive protein (CRP) level 9.7±11.4 mg/L. Bacterial 16S ribosomal RNA gene sequencing was performed on stool samples collected at baseline (month 0 (M0)) and 3 months after TNFi initiation (month 3 (M3)). Alpha and beta diversity metrics were calculated on the relative abundance of core operational taxonomic units (OTUs). Results The HLA-B27 status affected at least in part the global composition of faecal microbiota at M0 as well as the abundance/prevalence of several anaerobic bacteria in the families Oscillospiraceae, Lachnospiraceae and Bifidobacteriaceae. In contrast, smoking affected the global composition of faecal microbiota at both M0 and M3. The prevalence/abundance of seven bacterial OTUs at M0 was associated with response to TNFi treatment. One of the candidates, present only in non-responders, is the genus Sutterella, and the other six candidates are in the class Clostridia. Conclusions Several SpA patients’ characteristics modulate the composition of gut microbiota as did TNFi treatment. Moreover, the abundance/prevalence of seven OTUs at baseline may be used as a novel non-invasive index that predicts the response to TNFi with greater accuracy than HLA-B27 status, CRP level and measures of disease activity.

Pos0253 factors associated with treatment pathways in early axial spondyloarthritis: a multistate analysis of the 10-year follow-up of the desir cohort

Abstract: Current recommendations for the management of patients with axial spondyloarthritis (axSpA) emphasize the need of individualized strategy in the therapeutic decision [1,2]. Thus, many factors seem to impact this strategy.The objectives of the study were to describe the therapeutic strategies observed in axSpA, and to assess the factors associated with treatment changes over time.This study included patients with axSpA from the French prospective cohort DESIR, with a follow-up of 10 years. A multi-state model was built, including 4 treatment states with an increasing gradation (“none”, “non-steroidal anti-inflammatory drugs (NSAID)”, “conventional synthetic DMARD (csDMARD)”, “TNF inhibitors (TNFi)”), and 6 possible transitions from one state to another. Estimation of the restricted mean sojourn times spent in each state from the state occupation probabilities was performed. Then, Cox regression models were used to study the potential impact of factors on transitions.686 of the 708 patients which had more than one visit were analyzed. At cohort entry, 199 (29.0%) were untreated, 427 (62.2%) received NSAID, and 60 (8.7%) received csDMARD. Over the 10 years of follow-up, patients mostly received NSAID (46.4% of the time) followed by TNFi (24.4% of the time). In multivariable analysis (figure 1), presence of sacroiliitis on radiography, internal bowel disease and articular index were associated with transition to NSAID. Duration in the previous state was often a significant protective factor associated with transition to csDMARD or TNFi. Finally, the several disease activity outcomes were associated with most transitions.This was the first study using a multistate model to easily represent the different states, transitions and their associated factors. There appeared to be subcategories of axSpA patients with different management (including some without any treatment), and a significant proportion of patients treated with csDMARD.Figure 1.Multistate model representation. Each arrow corresponds to a possible transition (n=6). Number at baseline denotes the number of patients who started from the state at baseline. The number of events and factors significantly associated with each transition in the multivariable analysis are written near to the corresponding arrow.NSAID refers to non-steroids anti-inflammatory drugs, csDMARD stands for conventional synthetic Disease Modifying Anti-Rheumatic Drug, and TNFi for tumor necrosis factor inhibitors.[1]van der Heijde D, Ramiro S, Landewé R, Baraliakos X, Van den Bosch F, Sepriano A, et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017;76:978–91.https://doi.org/10.1136/annrheumdis-2016-210770.[2]Wendling D, Hecquet S, Fogel O, Letarouilly J-G, Verhoeven F, Pham T, et al. 2022 French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis. Joint Bone Spine 2022;89:105344.https://doi.org/10.1016/j.jbspin.2022.105344.NIL.Elodie Portier: None declared, Sylvie Chevret: None declared, Adeline Ruyssen-Witrand: None declared, Anouk Walter Petrich: None declared, Maxime Dougados: None declared, Anna Moltó Consultant of: Abbvie, BMS, Biogen, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Grant/research support from: Pfizer, UCB.

Pos1123 impact of the time of initiation and line of biologic therapy on the retention rate of secukinumab (secu) in axial spondyloarthritis (axspa). data from the french multicenter retrospective forsya study

Abstract: The characteristics of patients receiving a new therapy might differ overtime since its launch (date of its availability in a specific region/country); the differences in these characteristics might impact the efficiency of this treatment.To compare the one year retention rate of SECU in axSpA and its predisposing factors with regard to its time of initiation (e.g. right after its launch or later).Study design: Retrospective multicenter French study of axSpA patients a) having initiated and received at least one dose of SECU b) with at least a one year follow-up.Study periods: Two cohorts were evaluated with regard to the time of initiation of SECU:Cohort (C1): between August 11th, 2016 (time of the launch of SECU in France) and Aug 3st2018;Cohort 2 (C2): between sept 1st2018 and Nov 13, 2020 (remotely from the launch).Statistical analysis: The one year retention rate of SECU was estimated using the Kaplan Meier technic and Cox models and was used to compare the retention rate performed in C1 and C2. Preselected factors of SECU retention at 1 year (≥1 Objective Sign of Inflammation [CRP> N, MRI-inflammation at the sacroiliac or spine level], age, sex, BMI, smoking, HLA B27, non-radiographic vs radiographic axSpA, past or present uveitis/ Inflammatory Bowel Disease (IBD)/ psoriasis/ arthritis or synovitis, diagnostic delay, disease duration, SEC line of biologic therapy, SECU maintenance dose, concomitant csDMARD/ oral corticosteroids/ proton pomp inhibitor at SECU initiation, history of depression/ fibromyalgia) were analyzed by univariate and multivariate cox model regression. Only variables with <20% missing data were included in the model after multiple imputation and stepwise selection (significance level for entering variables = 20%; for removing variables = 10%).In total, 906 pts in C1 and 758 pts in C2 from 50 centers were included in the analysis. Pts characteristics (male: 42.8%, mean age: 46.5 ± 11.9 years, mean disease duration: 9.2± 9.4 years) were similar between the 2 cohorts. The 1 year retention rate was better in C2 vs C1 (64% [61-68%] vs 59% [55-62%], Hazard Ratio (HR)=0.84 [0.72-0.98], p = 0.03). Between C1 and C2, the proportion of patients receiving SECU as the 1stor 2ndline of biologic therapy increased from 23% to 40%. In the multivariate analysis, line of biologic therapy was the single predictive factor of the 1 year retention rate of SECU in both cohorts with a better retention rate for the 1stline of biologic therapy (Table 1).Table 1.Impact of SECU line on SECU retention rate at 1 year with regard of its time of initiationSECU line (* reference)Survival probability estimate at 1 year (95% CI)#HRadjusted[95% CI]$p vs refp type IIICohort 1†1stL (n=68; 8%)*70% [59%-81%]0.0842ndL (n=132, 15%)62% [54%-70%]1.53 [0.91; 2.57]0.107≥ 3rdL (n=676, 77%)57% [53%-61%]1.67 [1.06; 2.62]0.028Cohort 2†1stL (n=93, 13%)*78% [69%-86%]0.0072ndL (n=192, 27%)63% [56%-70%]1.92 [1.18; 3.13]0.009≥ 3rdL (n=437, 60%)62% [57%-66%]2.11 [1.32; 3.35]0.002†See Methods for explanation# without imputation for missing data$ Adjustment on: C1 (OSI, IBD, History of depression or anti-depressive concomitant treatment); C2 (OSI, History of depression or anti-depressive concomitant treatment, disease duration, corticosteroids)Interpretation HR > 1: the hazard of discontinuation at 1 year is X times higher vs referenceL = Line of biologic therapyThese data showing a better retention rate at 1 year remotely from the launch of SECU, probably explained by its use at an earlier stage of the disease, suggest a change in the behavior of prescribing physicians probably reflecting a better confidence in this treatment. These data also underline the interest of iterative evaluations of treatments used in daily practice.Authors thank the participating investigators, centers and patients. NOVARTIS Pharma France financially supported this study.Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Audrey Lardy-Cléaud: None declared, Emilie Desfleurs Employee of: Novartis employee, Pascal Claudepierre Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, Pfizer, Roche-Chugai, Bristol-Myers Squibb, MSD, UCB, Novartis, Janssen, Lilly, Celgene, 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, Biogen, MSD, Pfizer, Adeline Ruyssen-Witrand Speakers bureau: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Mylan, Novartis, Pfizer, Roche Chugai, Sanofi, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Mylan, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Mylan, Pfizer Inc, Alain Saraux Speakers bureau: Abbvie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, GSK, Lilly, Merck Sharp, Nordic, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Lilly, Novartis, Pfizer, Grant/research support from: Roche-Chugai, Lilly, Fresenius, 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, Daniel Wendling Speakers bureau: AbbVie, BMS, MSD, Pfizer, Roche Chugai, Amgen, Nordic Pharma, UCB, Novartis, Lilly, Sandoz, Grunenthal, Janssen, Galapagos, Consultant of: Novartis, 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,

Op0056 sensitivity to change of structural lesions in early axial spondyloarthritis after 10 years of follow up. data from desir cohort

Abstract: The change over time of the structural damage of axial spondyloarthritis (axSpA) is important to consider since it may reflect the severity of the disease. In axSpA this structural damage can be evaluated either at the sacroiliac joints (SIJ) or spine level, and also either on conventional radiographs or Magnetic Resonance Imaging (MRI).To evaluate the sensitivity to change of different structural imaging outcomes over 10 years of follow-up in patients with early axSpA.Patients with early onset (≤3 years) axSpA (according to the treating rheumatologist) from the DESIR cohort were included. Radiographs and MRI of the SIJ and spine were obtained at baseline, 1, 2, 5 and 10 years in 4 separate reading waves. Images were scored by 3 trained central readers (wave 1 only 2 readers with one adjudicator) unaware of chronology. The yearly rate of change (ROC) of each outcome was analyzed using generalized estimation equations (GEEs) including all patients with ≥1 score from ≥1 reader from ≥1 wave and using time (years) as explanatory variable. All outcomes (see the list on Table 1) were standardized (difference between the individual’s value and the population mean divided by the population SD). In addition, the relative standardized ROC (i.e., the standardized yearly ROC of an outcome divided by the corresponding rate of a reference imaging outcome) was calculated, with a value >1 reflecting larger sensitivity, and <1 lower sensitivity compared to the reference. Finally, the relative standardized ROC per anatomic site was calculated.Among all locations and modalities, the change in ≥3 fatty lesions was the outcome with the highest sensitivity to change (standardized ROC 0.073 per year). Considering as reference the modified New York criteria (mNY), the two most sensitive to change outcomes in SIJ (taking into account both MRI and radiographs) were ≥3 fatty lesions and the absolute number of fatty lesions on MRI (relative standardized ROC per year 4.867 and 4.130, respectively). Similarly, the most sensitive to change lesion in the spine (both MRI and radiographs) was the mSASSS score (relative standardized ROC per year 1.778) considering ≥1 syndesmophyte as the reference.MRI structural outcomes in the SIJ, in particular fatty lesions, are more sensitive to change than radiographic outcomes. On the other hand, mSASSS remains the most sensitive method, even if compared to MRI of the spine.Table 1.Sensitivity of change of the structural lesions.Standardized ROC per yearRelative standardized ROCRelative standardized ROC per anatomic sitePelvic radiographsmNY dichotomous0.0151 (reference)1 (reference)mNY 1-grade change0.0171.1331.133mNY 1-grade change and value >=20.0110.7330.733mNY continuous grade (range 0-8)0.0161.0671.067MRI of the SIJ≥5 fatty lesions and/or erosions0.053*3.5333.533≥3 erosions0.0100.6670.667≥3 fatty lesions0.073*4.8674.867No. of erosions (range 0-40)0.0120.8000.800No. of fatty lesions (range 0-40)0.062*4.1304.130Total structural lesions without sclerosis (range 0-104)0.0312.0672.067Spine radiographs≥ 1 syndesmophyte0.0271.8001 (reference)mSASSS score (range 0-72)0.0483.2001.778MRI of the spine≥5 fatty lesions-0.036*2.4001.333Total structural lesions (range 0-322)0.0372.4601.370No. of fatty lesions (range 0-92)0.0352.3301.296No. of corner erosions (range 0-92)0.0181.2000.667*Quadratic distributionNIL.NIL.Clementina López-Medina Speakers bureau: AbbVie, Eli Lilly, Novartis, Janssen, UCB Pharma, Consultant of: Eli Lilly, Novartis, UCB Pharma, Anna Moltó Consultant of: AbbVie, Biogen, BMS, Cyxone, Eisai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Alexandre Sepriano Speakers bureau: Abbvie, UCB and Lilly, Sofia Ramiro Consultant of: AbbVie, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sanofi, UCB, Maxime Dougados Consultant of: UCB.

Pos0675 low rate of switching from nr-axspa to r-axspa after 10 years of follow up in early axial spondyloarthritis. data from desir cohort

Abstract: Previous evidence suggests that radiographic progression occurs slowly in the sacroiliac joints (SIJ) of patients with axial spondyloarthritis and that bone marrow edema (BME) on MRI-SIJ can, at least in part, explain such progression. However, information about the long-term course of radiographic structural damage at the SIJ level in patients with early axSpA is still scarce.To evaluate the proportion of patients switching from non-radiographic axSpA (nr-axSpA) to radiographic axSpA (r-axSpA) after 10 years of follow-up and whether BME on MRI-SIJ at baseline is associated with the r-axSpA status over time.Patients with ≤3 years axSpA onset (according to the treating rheumatologist) from the DESIR cohort were included. The radiographic status of the patients (r-axSpA versus nr-axSpA) was based on the fulfillment of the mNY criteria (i.e. at least a bilateral grade 2 or a unilateral grade 3 on pelvic radiographs according to 2 out of 3 central readers). BME on MRI-SIJ was defined as positive ASAS definition according to 2 out 3 central readers at baseline. Information on mNY criteria was obtained in four reading waves: wave 1 (baseline (BL), wave 2 (BL and 2Y), wave 3 (BL, 2 and 5Y) and wave 4 (BL, 5 and 10Y). Images were scored by 3 trained central readers (wave 1: 2 readers + adjudicator), all of them unaware of the chronology of the images and the results of the other modality. A “progressor” was defined as a patient switching from nr-axSpA to r-axSpA. A “regressor” was defined as a patient switching from r-axSpA to nr-axSpA. The % of mNY net progressors (i.e. number of “progressors” minus number of “regressors” divided by the total number of patients) was assessed in “completers” (i.e., with pelvic radiographs available at BL and 10y in wave 4). A sensitivity analysis was conducted using a multilevel GEE model (‘integrated analysis’) that included all waves from all patients with at least one available mNY score from at least one reader available (“intention-to-follow” population). From this model, we estimated the absolute change per year in the percentage of mNY-positive cases with and without adjusting for the use of anti-TNF drugs. Finally, the effect of BME on MRI-SIJ at baseline on mNY positivity over 10 years, adjusting for potential confounders (Figure 1) were evaluated in a multivariable GEE model in the “intention-to-follow” population.Completers included 299 patients (mean age 34.5Y and 48.2% males), while the intention-to-follow population included 704 participants (mean age 33.7Y and 46.2% males). In the completers, the net % of progressors (switch from nr-axSpA to r-axSpA) was 5.7%.In the intention-to-follow population, there was a 0.91% (95%CI 0.60-1.20) increase per year in the probability of being mNY-positive (i.e. a progression of 9.1% after 10Y). After adjusting for anti-TNF use, this percentage decreased to 0.48% (95%CI 0.15-0.82) per year. The HLA-B27 status modified the association between BME on MRI-SIJ at baseline and mNY-positivity over 10 years (interaction p-value: <0.001). BME on MRI-SIJ was associated with being mNY positive over time in both HLA-B27 positive (OR 6.25 (95%CI 5.36-7.30)) and HLA-B27 negative patients (OR 3.03 (95%CI 2.42-3.80)), but the association was stronger in the former (Figure 1). In addition, male sex, symptom duration >1.5Y, ASDAS >2.1 (in HLA-B27 negatives) and smoking (in HLA-B27 positives) were also associated with being mNY-positive over 10 years.Patients with early axSpA have a low likelihood of changing from nr-axSpA to r-axSpA over 10 years, especially when considering the use of anti-TNF. Local inflammation on MRI-SIJ is strongly associated damage accrual in the SIJ over time, in particular in patients who are HLA-B27 positive.Figure 1.Baseline characteristics associated with radiographic sacroiliitis after 10 years of follow-up in axSpA patients with early onset (multivariable integrated analysis using four DESIR reading waves and stratified on HLA-B27).NIL.NIL.Anna Moltó Consultant of: AbbVie, Biogen, BMS, Cyxone, Eisai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Clementina López-Medina Speakers bureau: AbbVie, Eli Lilly, Novartis, Janssen, UCB Pharma, Consultant of: Eli Lilly, Novartis, UCB Pharma, Manouk de Hooge Consultant of: UCB, Miranda van Lunteren: None declared, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Novartis, Alexandre Sepriano Speakers bureau: Abbvie, UCB and Lilly, Consultant of: Abbvie, UCB and Lilly, Sofia Ramiro Consultant of: AbbVie, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sanofi, UCB, Maxime Dougados Consultant of: UCB.

Real-world evidence of the use of the infliximab biosimilar SB2: data from the PERFUSE study

Abstract: Abstract Objective PERFUSE is a non-interventional study of 1233 adult patients (rheumatology, n = 496; IBD, n = 737) receiving routine infliximab (IFX) biosimilar SB2 therapy. The aim of this report was to investigate the 12-month persistence, effectiveness and safety outcomes of routine SB2 treatment in patients with chronic inflammatory rheumatic disease. Methods Patients with a diagnosis of RA, PsA or axial spondyloarthritis (axSpA) were assigned to one of three study cohorts according to whether SB2 treatment initiated after September 2017 had been the first IFX treatment (IFX naïve) or followed transition from reference IFX (IFX ref) or another IFX biosimilar (IFX bs). Outcomes to month 12 (±2) included persistence (primary outcome), SB2 dose, disease status, immunogenicity and safety. Results At month 12, persistence on SB2 in IFX-naïve, IFX ref and IFX bs cohorts, respectively, [mean percentage (95% CI)] by indication was as follows: 59% (36.1, 76.2), 75% (57.5, 86.1) and 85% (69.6, 93.0) for RA (n = 98); 64% (34.3, 83.3), 87% (65.6, 95.7) and 83% (60.0, 93.1) for PsA (n = 62); and 56% (44.4, 66.5), 80% (70.8, 86.1) and 80% (72.5, 85.6) for axSpA (n = 336). Disease activity was comparable at baseline and month 12 within the IFX ref and bs subgroups of all cohorts by indication. No immunogenicity concerns or new safety signals were detected. Conclusion SB2 was safe and effective in IFX-naïve patients and in patients transitioned from prior IFX ref or bs. Trial registration clinicaltrials.gov, NCT03662919

Pos0659 comparison of metrological properties of the s-scaiss versus the sparcc scoring system for the detection/quantification of inflammation at mri-sij in spondylarthritis: data from the desir cohort

Abstract: Different tools to quantify inflammatory changes in sacroiliac (SI) MRI have been developed. The Spondyloarthritis Research Consortium of Canada (SPARCC) appears to be the most sensitive to change, as it has demonstrated a good discriminating capacity. In a previous work of our group, we described the development of a fast, easy and reliable method to quantify the bone marrow edema (BME) in MRI-SIJ, through a semi-automatic process with a computer tool called SCAISS. SCAISS uses both semi-axial and semi-coronal slices from the MRI-SIJ. Since many centres only perform semi-coronal slices, we developed a simplified tool (s-SCAISS) that only requires the assessment of semi-coronal slices.To compare inter-rater reliability, discriminative validity and sensitivity to change using the s-SCAISS system, and compared to the SPARCC system, in patients presenting with inflammatory low back pain suggestive of axial spondyloarthritis from the DEvenir des Spondylarthopathies Indifférenciées Récentes (DESIR) cohort.MRI-SIJ image of 206 patients collected at baseline of the DESIR cohort and after a first one year follow-up were analyzed (46.6% male, mean age 33.6 ± 8.8 years). Inter-reader reliability (3 readers for s-SCAISS and 2 central core readers for SPARCC) was assessed using intraclass correlation coefficients (ICC). Discriminative validity testing was performed by calculating the Area Under the Curve (AUC), sensitivity, specificity and likelihood ratios for different cut-off points for the classification of presence/absence of BME in SI, using positive/negative MRI as the gold standard according to DESIR core readers. Sensitivity to change was evaluated in subjects with improvement in illness activity testing differences between paired measures. Three different criteria were considered to define activity improvement: a change in ASDAS score at 12 months of 1.1 (Clinical Important Improvement -CII-) and 2 points (Major Improvement -MI-) and a reduction ≥ 50% of the initial BASDAI score (BASDAI50).Inter-rater reliability:Both s-SCAISS and SPARCC showed good inter-reader reliability: In baseline MRI: ICC 0.95 and 0.82, respectively; At 1 year MRI: ICC 0.80 and 0.79, respectively.Discriminative validity: Of the 206 patients included in our study, 70 (34%) fulfilled the ASAS criteria for presence of Inflammation on MRI, The AUC for EMO detection was excellent for both systems (0.88 and 0.98 for SCAISS and SPARCC, respectively). The optimal cut-off point for s-SCAISS was 60 u (Sens 83%, Esp 80%) and for SPARCC 1.25 u (Sens 93% and Esp 94%). Using the s-SCAISS cut-off point of 60 u, and the one 1.25 for SPARCC, 165 patients (81.3%) and 189 patients (93.1%), respectively were classified in accordance with the ASAS definition of the presence or absence of inflammation at MRI evaluated by the human central readers.Sensitivity to change: Of the 206 patients included, at 1 year after baseline assessment, 48 (23.3%), 17(8.3%) and 54 (26.2%) patients had a CII, MI and BASDAI50, respectively. In these patients with improved disease activity, the mean (SD) s-SCAISS score at baseline was 404.1 (SD 1055.1), 185.7 (262.7) and 375.3 (SD1008.8), respectively. While at 12 months it decreased to 72.6 (SD134.8), 46.1 (SD72.1) and 76 (SD151.7). The means of paired differences were 331.4 (SD 1019.6), 139.7 (SD 240.8) and 298.3 (SD 976.9), respectively, all of them with p<0.05. As expected, the AUC for the detection of CII, MI and BASDAI50 for both systems were poor (s-SCAISS 0.61, 0.63 and 0.58 and for SPARCC 0.7, 0.66, 0.60, respectively).The MRI-SIJ EMO quantification system with s-SCAISS is as reliable and sensitive to change as SPARCC. The apparent advantage of SPARCC over s-SCAISS is artefactualised by the fact that the definition of the presence or absence of ASAS criteria for sacroiliitis is determined by the same readers who assess SPARCC.We thank all DESIR-cohort patients and all individuals involved with creating and maintaining the cohort. The DESIR cohort was sponsored by the Département de la Recherche Clinique et du Développement, Assistance Publique Hôpitaux de Paris. We are also grateful to the heads of the participating regional centres.None Declared.

Pos1120 impact of baseline crp level on secukinumab (sec) retention in axial spondyloarthritis (axspa): results of the french retrospective study forsya

Abstract: While data on real-life SEC retention rate in patients (pts) with axSpA is accumulating, there are few data on predictive factors for this retention. Presence of objective sign of inflammation (OSI), especially increased baseline CRP level, is known to be predictive of efficacy of anti-TNFs and their retention in axSpA.To assess whether OSI, especially increased baseline CRP level, were predictive of SEC retention at 1 year in axSpA.French retrospective study collecting between October 2019 and September 2020 data from axSpA pts a) having initiated and received at least one dose of SEC between August 11th2016 and August 31st2018, b) with at least a one-year follow-up period. Retention rate of SEC at 1 year was estimated by the Kaplan Meier (KM) method. OSI were defined by at least one of the following: CRP ≥5 mg/l or ESR ≥28 mm/h if CRP not available (CRP+) within the 3 months before initiation of SEC and MRI inflammation at the sacroiliac or spine level (MRI+) at any time.The a priori selected potential predictive factors of the SECU 1 year retention(CRP+, MRI+, age, sex, BMI, smoking, HLA B27, non-radiographic vs radiographic axSpA, past or present uveitis/Inflammatory Bowel Disease/psoriasis/arthritis or synovitis, diagnostic delay, disease duration, SEC line of biologic therapy, SEC maintenance dose, concomitant csDMARD/oral corticosteroids/proton pomp inhibitor at SEC initiation, history of depression/fibromyalgia) were analyzed by cox model regression. Only variables with <20% missing data were included in the model after imputation and stepwise selection (significance level for entering variables =20%; significance level for removing variables =10%), except for CRP and MRI which were forced into the model whatever their significance level or rate of missing data.In total, 906 pts from 47 centers (male: 42.2%, mean age: 46.2 ± 11.7 years, mean disease duration: 9.3 ± 9.1 years) were included in the analysis. The mean baseline CRP (± SD) was 11.1 ± 17.5 mg/L. At initiation of SEC, 86.3% of pts had ≥ 1 OSI (41.3% CRP+, and 69.4% MRI+) and respectively 8.0%, 14.9% and 77.1% were in 1st, 2ndand ≥ 3rdline (L) of biologic/targeted synthetic DMARD. The 1-year retention rate for SEC was 59% [95%CI: 55%-62%]. This retention at one year was 62.4% vs 59.1% and 57.4% vs 66% in patients with CRP+ vs CRP- and MRI+ vs MRI- respectively. In univariate cox regression, CRP+ was not predictive of SEC discontinuation at 1 year (HR = 0.90 [0.71-1.16]; p=0.422 nor was MRI+ (HR=1.29 [0.99; 1.68]; p=0.063). In multivariate cox analysis, after adjustment, these results were confirmed for CRP+ but MRI+ was identified as predictive of a worst SEC retention at 1 year (Table 1). In multivariate analysis lack of prior exposure to anti-TNF inhibitors, absence of IBD and absence of history of depression were also associated with a better SEC retention at 1 year (at 10%).Table 1.Retention of secukinumab at 1 year according to components of at least one sign of inflammation with univariate and multivariate (after multiple imputation + stepwise selection) cox regressionsPredictive factor (*reference)Modality (N)Retention of SEC at 1 year (%)#Univariate cox regressionMultivariate cox regression**pHR [95% CI]pHR [95% CI]CRP ≥ 5 mg/l or ESR ≥ 28 mm/h (if CRP not available)Yes (N=282)62.4%0.4220.90 [0.71-1.16]0.3280.90 [0.73-1.11]No (N=398)*59.1%MRI signs of inflammation at sacroiliac joint or spineYes (N=487)57.4%0.0631.29 [0.99-1.68]<.0011.49 [1.18-1.89]No (N=214)*66.0%# without imputation for missing data**Adjustment on IBD, secukinumab treatment line, history of depression or anti-depressive concomitant treatmentInterpretation HR > 1: the hazard of discontinuation at 1 year is X times higher vs referenceThe overall retention of SEC at 1 year in daily practice in France was 59% for axSpA patients, independently of CRP level at SEC initiation.Authors thank the participating investigators, centers and patients. NOVARTIS Pharma France financially supported this study.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, Biogen, MSD, Pfizer, Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, and Sandoz, Audrey Lardy-Cléaud: None declared, Emilie Desfleurs Employee of: Novartis employee, Pascal Claudepierre Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, Pfizer, Roche-Chugai, Bristol-Myers Squibb, MSD, UCB, Novartis, Janssen, Lilly, Celgene, Adeline Ruyssen-Witrand Speakers bureau: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Fresenius-Kabi, Galapagos, Janssen, Lilly, MSD, Mylan, Nordic-Pharma, Novartis, Pfizer, Roche Chugai, Sanofi, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Mylan, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Mylan, Pfizer Inc, Alain Saraux Speakers bureau: Abbvie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, GSK, Lilly, Merck Sharp, Nordic, Novartis, Pfizer, Roche-Chugai, UCB, Consultant of: Abbvie, Lilly, Novartis, Pfizer, Grant/research support from: Roche-Chugai, Lilly, Fresenius, 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, 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, Daniel Wendling Speakers bureau: AbbVie, BMS, MSD, Pfizer, Roche Chugai, Amgen, Nordic Pharma, UCB, Novartis, Lilly, Sandoz, Grunenthal, Janssen, Galapagos, Consultant of: Novartis.

Pos1370 metabolic syndrome is associated with more pain in hand osteoarthritis: results from the digicod cohort

Abstract: While association between metabolic syndrome (MetS) (combining central obesity, diabetes, dyslipidemia and/or hypertension) and the risk of osteoarthritis (OA) disease risk remains controversial at the structural level, MetS could be involved in OA-related pain. To analyze such an association, investigating hand OA is more relevant than knee OA to avoid the strong influence of weight on bearing joints.To determine whether the presence of MetS is associated or not with a higher pain level in hand OA.This cross-sectional study involved patients included in the hospital-based hand OA DIGICOD cohort, for whom all baseline variables of interest were available (NCT01831570). The characteristics were described and compared according to the presence or absence of MetS (Adult Treatment Panel III criteria). We searched for an association between MetS and several outcomes measuring different aspects of OA-related pain (hand pain intensity using visual analog scale (VAS) on activity, VAS pain at rest, hand pain in various situations using the self-reported Australian Canadian Osteoarthritis Hand Index (AUSCAN) pain subscore, Arthritis Impact Measurement Scale (AIMS2) pain subscore assessing the OA pain nonspecifically related to hands, number of painful hand joints on pressure) using 2 logistic regression models:model 1: adjustment for age, sex, and the radiological Kellgren-Lawrence (KL) total sum score.model 2: model 1 + hospital anxiety and depression (HAD) scale.All pain outcomes were binarized by their median values defining thus high and low pain levels. Results are presented as odds ratios (OR) with 95% confidence intervals (CIs). The reference group was “no MetS” (MetS-).A total of 359 patients (85% women, 66.3±7.4 years) were analyzed out of 425 included, including 128 (36%) patients with MetS (MetS+). The 2 groups (MetS+ and MetS-) did not differ in their demographic characteristics except for BMI (27.1±4.5 and 24.0±3.8 kg/m2, p<0.0001), age (67.9±7.1 and 65.5±7.5, p=0.003), KL sum score (48.9±17.7 and 44.5±17.5, p=0.03), and HAD (13.7±6.7 and 12.1±5.7, p=0.02) (Table 1).MetS was associated with a higher VAS pain at activity (median: 44/100) in model 1 (OR=1.63, 95%CI (1.04; 2.56), p=0.03) but this association was attenuated with further adjustment on HAD scale (OR=1.48, 95%CI (0.94; 2.35), p=0.09) (Table 1). MetS was also associated with a higher AUSCAN pain (median: 20/100) in non-adjusted analysis but this did not persist in adjusted model 2. No association was found with VAS pain at rest or the number of painful joints on pressure. MetS was associated with a higher AIMS2 pain subscore (median: 33/100) in both models (OR=1.70, 95%CI (1.06;2.74), p=0.03).Table 1.Association between metabolic syndrome and pain in hand osteoarthritis according to various measurement tools*Unadjusted modelAdjusted for age, sex, KL total sum scoreAdjusted for age, sex, KL total sum score and HADAUSCAN Pain subscore ≥ 201.59 (1.03; 2.46)°1.51 (0.97; 2.37)1.40 (0.89; 2.21)AIMS 2 pain score ≥ 331.89 (1.21; 2.95)°1.90 (1.20; 3.01)°1.70 (1.06; 2.74)°VAS at rest ≥ 151.39 (0.90; 2.15)1.39 (0.89; 2.17)1.30 (0.82; 2.04)VAS at activity ≥ 441.64 (1.06; 2.54)°1.63 (1.04; 2.56)°1.48 (0.94; 2.35)Number of painful joints ≥31.38 (0.88; 2.17)1.38 (0.87; 2.20)1.32 (0.83; 2.12)° Statistically significant*Data are OR (95% CI) given for Mets+ versus Mets-.MetS was associated with more hand pain in hand OA, partly mediated by anxiety-depression. MetS also increased the risk of OA pain nonspecifically related to hands suggesting a higher susceptibility to joint pain in general in patients with MetS.NIL.NIL.None Declared.

Pos0687 long term (10 year) clinical outcome of recent onset axial spondyloarthritis (axspa): data from the desir cohort

Abstract: The information related to the long term outcome of a disease is of huge interest for the clinicians in daily practice to facilitate the information of the patients recently diagnosed as axSpA.The data from inception cohorts are better approaching the truth of this long term prognosis in comparison to the conventional retrospective cohorts mainly conducted in patients with advanced and severe disease managed in tertiary referral centers.To evaluate the 10 year clinical outcome (and its predisposing factors) of patients suffering from recent onset axSpA in the DESIR cohort.Study design: DESIR is an ongoing (10 year follow-up completed for all the patients) multicenter cohort of recent onset axSpA.Diagnosis: At entry visit and during the 10 year follow-up period, the diagnosis was based on the opinion of the treating physician with a requirement of a diagnosis of axSpA at entry and the possibility to exclude the patients after the first 2 years follow-up period in case of a change in this diagnosis.Management during the 10 year period: the investigators were in charge of the data collection required by the protocol but the management (treatment regimens) was only based on the decision of the treating rheumatologist.Statistical analysis: Data presented here are the ones issued a)from the analyses on the completers (observed data) and b) after multiple imputations considering the missing data due to the patients lost of follow-up (imputed data).Of the 708 enrolled patients, 45 were excluded from the cohort because of a change in the entry visit diagnosis, 3 patients died (suicide n = 1, colorectal cancer n = 1, sudden death n=1), 300 were lost of follow-up and 360 patients completed the 10 year period.A -Based on the analyses of the 10 year completers (n=360)No patient necessitated a spinal vertebrotomy, one single patient had a bilateral total hip replacement.A pension from the national health care system was provided to 16% patients because an invalidity related to the axSpA disease.A csDMARD (methotrexate and/or sulfasalazine) has been prescribed in 32% and a biotherapy in 55%.The prevalence of the main extra-musculoskeletal features increased from 18 to 30%, 10 to 18% and 5 to 10% from baseline to year 10 for psoriasis, acute anterior uveitis and inflammatory bowel disease respectively.The prevalence of the main comorbidities increased from 3 to 8%, 0 to 3%, 5 to 15%, 0 to 4%, 1 to 3% and 0 to 2%, from baseline to year 10 respectively for severe GI events, MACE, hypertension, diabetes, tuberculosis and other severe infections respectively.B-Based on the analyses of the 10 year completers (n=360) (observed data) and the 663 patients with unchanged initial axSpA diagnosis (imputed data)An acceptable status at year 10 was observed in 77%,70 [63; 77]%,;49% 43 [37; 49]%; 55% 48 [41; 56]% considering an acceptable PASS, BASDAI < 30, ASDAS < 2.1 for the observed (%) and imputed (% and [95%CI]) data respectively.The impact of the disease on the daily life of the patients was evaluated by different parameters: ASAS HI ≤ 5 (41 [35; 47]%, SF36 physical score (42 [40; 44]) and SF36 mental score (43 [40; 46]).The multivariate analysis of the baseline predisposing factors of an acceptable status at year 10 defined as an ASDAS score<2.1 picked-up the following variables: short (<1.5year)delay between the first symptoms and the baseline visit: OR= 1.46[0.93;2.29],socio-professional level (white collar): OR=1.87[1.20;2.90] and baseline BASDAI score<40, OR=1.91[1.23;2.94]These data are suggesting a favorable 10 year outcome in terms of stringent measures such as the requirement to surgery contrasting with a relatively less favorable outcome with regard to patient reported outcomes. These data should improve and facilitate the information provided to the patients at the time of their diagnosis.The authors would like to thank all the investigators of the 25 participating centers as well as all the 708 enrolled patients.This study has been financially supported via unrestricted grants from PFIZER and the French Society of Rheumatology.None Declared.

Pos0671 validation of two response and one status measures of the asas health index versus external anchors in patients with axial spondyloarthritis

Abstract: Improvement in functioning and health as assessed by the ASAS Health Index (HI) is an important outcome of interventions in patients with axial spondyloarthritis (axSpA). The ability of various ASAS HI thresholds to discriminate between treatment arms of an active comparator trial have been demonstrated recently by our group with absolute improvement in the ASAS HI in general being superior to relative changes [1, 2].To assess whether ASAS HI response measures (absolute improvement of ≥3.0 and relative improvement of ≥30%) and reaching a status of good global functioning (ASAS HI ≤5.0) adequately discriminate between the changes and states in relevant external outcomes.In this post-hoc analysis from the tight-controlled, treat-to-target (T2T) trial TICOSPA (2), data of active axSpA patients randomized to either the T2T arm (visits every 4 weeks, prespecified strategy of treatment intensification until achieving low disease activity) or usual care (UC; visits every 12 weeks, treatment at the rheumatologist’s discretion) were used. The performance of ASAS HI response- and status scores against change (ASAS-40/ BASDAI-50 response, change in patient global/ BASDAI, and ASDAS improvement) and external status scores (ASAS partial remission, ASDAS status) was assessed, respectively. Analysis were performed by comparing the mean values and proportion of responses of continuous and dichotomous response outcomes, by t-tests. Missing data on outcomes was handled by non-responder imputation (NRI).ASAS HI was available in 160 patients, both at baseline and at week 48. At w48, an ASAS HI improvement of ≥30%, improvement of ≥3 points and ASAS HI ≤5.0 was achieved by 56 (35%), 51 (31.9%) and 54 (33.7%) patients, respectively. Patients with a meaningful improvement in global functioning had a larger reduction in patient global and disease activity as well a greater chance to reach remission compared to patients with no significant improvement in global functioning (Table 1). Health outcomes were not different between the two response measures of ASAS HI. Patients who achieved ASAS partial remission, ASDAS inactive disease or ASDAS low activity at week 48 were more likely to have an ASAS HI ≤ 5.0 compared with patients who did not achieve such states (Figure 1).We demonstrated discriminant capacity of both, the relative and the absolute response measures of the ASAS HI. Both thresholds proved to have external validity and were able to discriminate between active treatment arms.[1]EULAR 2022,[2]Molto A et al. Ann Rheum Dis 2021Figure 1.Proportion of patients reaching status of good global functioning at week 48Table 1.Comparison of clinical outcomes and ASAS HI response at follow upASAS HI response = > 30% improvement (NRI)ASAS HI response = > 3 points improvement (NRI)Yes(n=56)No(n=104)pYES(n=51)No(n=109)pASAS40 response at w4848.2%21.2%<0.00151.0%(21.1%<0.001BASDAI 50 at w4871.4%28.8%<0.00168.6%32.1%<0.001ASDAS Major improvement (0 to 48w)23.2%6.7%0.00523.5%7.3%0.008ASDAS Clinically Important Improvement (0 to 48w)62.5%24.0%<0.00160.8%26.6%<0.001Change in Patient Global (0 to 48w)Mean (SD)-3.54 (2.77)-1.81 (2.61)<0.001-3.73 (2.85)-1.80 (2.53)<0.001Median [Min. Max]-4.00 [-10.0. 6.00]-1.00 [-8.00. 3.00]-4.00 [-10.0. 6.00]-1.00 [-8.00. 3.00]Missing0 (0%)18 (17.3%)0 (0%)18 (16.5%)Change in BASDAI (0 to 48w)Mean (SD)-2.79 (2.09)-1.42 (2.04)<0.001-2.95 (2.17)-1.40 (1.96)<0.001Median [Min. Max]-2.60 [-8.90. 1.40]-1.25 [-8.60. 3.00]-3.00 [-8.90. 1.40]-1.20 [-8.60. 3.00]Missing0 (0%)18 (17.3%)0 (0%)18 (16.5%)NIL.None Declared.

Pos0303 impact of pregnancy on sacroiliac imaging in women with axial spondyloarthritis: results of the analysis of the desir cohort

Abstract: Axial spondyloarthritis (axSpA) is typically characterized by imaging (radiographs or MRI) abnormalities of the sacroiliac joints (SIJ). Also, inflammatory lesions of the SIJ have been observed in healthy women post-partum [1,2]. However, the impact of pregnancy on imaging abnormalities in women with axSpA is unknown.The objective of this study was to evaluate impact of pregnancy on SIJ imaging in patients with early axSpA.Data of all women with early axSpA from the DESIR prospective cohort were included, with a follow-up of 5 years. Description of demographic disease characteristics, obstetric history, and SIJ imaging abnormalities (i.e. sacroiliitis on radiographs and on MRI, based on local and central reading) was performed in all women. SIJ abnormalities were compared depending on the history of past pregnancy (t-test and chi-square as appropriate). Furthermore, in nulligravidae females at baseline who presented an incident pregnancy during follow-up, SIJ abnormalities were compared before/after pregnancy, using paired-test.381 patients were included in the analysis. 142 (37%) were nulligravidae at baseline, and were younger (28 vs 39 years old) and had higher educational level (74 vs 52% university level).Sacroiliitis on MRI and X-ray were more frequent in nulligravidae women (16.9% vs 9.9%, p = 0.05 and 33.8% vs 19.4%, p < 0.01, respectively).Among them, 38 (10% of all patients) presented an incident pregnancy during follow-up and had an available imaging before and after pregnancy: overall no significant changes were observed with regard to both radiographic and MRI imaging abnormalities of the SIJ, except for an increase on the New York score of the left SIJ, and surprisingly, a trend towards a reduction on the proportion of MRI sacroiliitis and SPARCC score after pregnancy (table 1).Table 1.Imaging characteristics in women with axSpA who had first pregnancy during follow up, with description before/after delivery and paired-test with Mc Nemar of Student test (for binary and continuous variables, respectively).Imaging criteria(mean (sd) or number (%))Before pregnancy (N = 38)After delivery (N = 38)Paired test (Mc Nemar or Student)Radiographic criteriaX-ray sacroiliitis8 (21.1%)9 (23.7 %)p = 0.37New York score on right sacroiliac joint0.66 (1.06)0.67 (0.86)p = 1New York score on left sacroiliac joint0.67 (1.07)0.95 (0.95)p = 0.037Any erosion in the sacroiliac joints9 (23.7%)9 (23.7%)p = 0.48Any joint widening in the sacroiliac joints03 (7.9%)NAAny sclerosis in the sacroiliac joints6 (15.8%)9 (23.7%)p = 0.13Any partial or total ankylosis in the sacroiliac joints1 (2.6%)2 (5.3%)p = 0.48MRI criteriaSacroiliitis on MRI18 (47.3%)2 (5.2%)p = 0.074SPARCC score3.94 (7.63)0.39 (0.74)p = 0.15≥ 3 fatty lesions on MRI4 (10.5%)1 (2.6%)p = 1≥ 3 erosions on MRI1 (2.6%)0NA≥ 5 fatty lesions and/or erosions on MRI1 (2.6%)1 (2.6%)p = 1Number of any lesions on sacroiliac joint(0 to 144)1.81 (3.36)1.8 (2.92)p = 0.1Number of enthesitis(0 to 12)0 (0)0 (0)NANumber of erosions(0 to 40)0.84 (2.36)0.42 (0.7)p = 1Number of fatty lesions(0 to 40)0.97 (2.01)1 (2.02)p = 0.15Number of sclerosis(0 to 40)0 (0)0.26 (0.86)p = 0.29Number of partial or total ankylosis(0 to 24)0 (0)0 (0)NAIn an early SpA cohort, the occurrence of a first pregnancy did not seem to increase the number of imaging abnormalities of the SIJ.[1]Seven S, Østergaard M, Morsel-Carlsen L, Sørensen IJ, Bonde B, Thamsborg G, et al. Magnetic Resonance Imaging of Lesions in the Sacroiliac Joints for Differentiation of Patients With Axial Spondyloarthritis From Control Subjects With or Without Pelvic or Buttock Pain: A Prospective, Cross-Sectional Study of 204 Participants. Arthritis Rheumatol 2019;71:2034–46.https://doi.org/10.1002/art.41037.[2]Agten CA, Zubler V, Zanetti M, Binkert CA, Kolokythas O, Prentl E, et al. Postpartum Bone Marrow Edema at the Sacroiliac Joints May Mimic Sacroiliitis of Axial Spondyloarthritis on MRI. AJR Am J Roentgenol 2018;211:1306–12.https://doi.org/10.2214/AJR.17.19404.NIL.None declared.

Pos0244 protocol violation in a treat-to-target strategy in axial spondyloarthritis: data from the open-label, pragmatic, cluster-randomised ticospa trial

Abstract: Despite the ASAS-HI (primary outcome) did not reach statistical significance in the TICOSPA trial, other clinically relevant secondary outcomes were numerically higher in the treat-to-target (T2T) strategy in comparison to Usual Care (UC), including the ASAS-HI. Three hypotheses have been considered to explain this observation: a lack of power, the risk of protocol violations in the T2T arm and the potential optimal care in the UC arm.a) To evaluate the proportion of patients (pts) with protocol violations in the T2T group during the 48 weeks (48W) of follow up as well as the impact and predictive factors of such violation; b) to compare the proportion of pts treated according to the ASAS/EULAR 2016 management recommendations for axSpA over the follow-up period in both arms.Study design:pragmatic, prospective, cluster-randomized controlled, 48W trial (NCT03043846) with 18 participating centers.Inclusion criteria: Pts with a diagnosis of axSpA and fulfilling ASAS criteria, non-optimally treated with NSAIDs, bDMARD-naïve and ASDAS >2.1.Study treatment regimens:SpA expert centers were selected to participate in the study: then, they were randomly allocated (1:1) to the treatment arm: a) T2T: the management strategy was pre-specified based on strict application of 2016 ASAS/EULAR axSpA recommendations (Q4W), with a target of ASDAS <2.1; b) UC: treatment decisions at the rheumatologist’s discretion (Q12W).Statistical analysis:a) Protocol violations:in the T2T arm were evaluated at every visit by the question “Was the recommendation for treatment from last visit followed by physician and patient?”. Factors associated with at least one protocol violation over the study were evaluated using multivariate logistic regression. Outcomes at 48W were compared between T2T violators (T2T-V) vs. T2T non-violators (T2T-NV) vs. UC using ANOVA test; b)optimal care in UC:proportion of pts treated according to the 2016 ASAS/EULAR recommendations over the follow-up period in both arms were compared.160 pts initiated the trial (T2T:80 and UC:80).a) Protocol violations:In the T2T arm, 41/80 (51.2%) pts violated the protocol during at least one visit. A total of 27.7% violations were represented by a lack of switching to a second NSAID and 41.2% by a lack of initiation of a first bDMARD. Baseline predictive factors independently associated with the protocol violation were the country (France vs. others; OR 3.8 (95%CI 1.1-15.0)), female sex (OR 4.4 (1.5-15.1)), diagnosis delay ≤7 years (OR 3.4 (1.1-11.9)), HLA-B27 negative (OR 6.4 (1.6-32.2)) and CRP≥6mg/L (OR 4.2 (1.3-15.9)). After 48W of follow-up, T2T-NV vs. T2T-V showed similar ratios of ASAS-HI improvement. ASDAS-LDA, ASDAS-ID and ASDAS-CII outcomes were more prevalent in T2T-NV vs. T2T-V, although these differences did not reach statistical significance (Table 1). b)Optimal care in UC: the proportion of pts managed according to the 2016 ASAS/EULAR recommendations was very high in both arms, i.e. always above 75% also in the UC arm, although no statistical differences were found (p=0.490) (Figure 1).The prevalence of pts violating the protocol in the T2T arm was high, although it did not explain the non-significance of the primary outcome in the TICOSPA trial (ASAS-HI improvement). In contrast, the proportion of pts managed according to the ASAS/EULAR recommendations in the UC arm was very high, suggesting that the UC group was optimally treated.Table 1.Impact of protocol violation across groupsGroupsp-valueT2T-NV N = 39T2T-V N = 41UC N = 80ANOVAT2T-NV vs. T2T-VT2T-NV vs. UCT2T-V vs. UCASAS40 W4814 (35.9%)16 (39.0%)19 (24.1%)0.1770.7730.1770.087ASDAS-LDA W4824 (61.5%)19 (46.3%)32 (40.5%)0.0870.1730.0270.504ASDAS-ID W4811 (28.2%)8 (19.5%)10 (12.7%)0.1170.3610.0380.319ASDAS-CII W4822 (56.4%)16 (39.0%)26 (32.9%)0.0490.1200.0150.506ASDAS-MI W486 (15.4%)8 (19.5%)9 (11.4%)0.4790.6270.5650.226ASAS-HI improvement W4814 (35.9%)16 (39.0%)21 (26.6%)0.3220.7730.2970.162NIL.NIL.Clementina López-Medina Speakers bureau: AbbVie, Eli Lilly, Novartis, Janssen, UCB Pharma, Consultant of: Eli Lilly, Novartis, UCB Pharma, Filip van den Bosch Consultant of: AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. Director of Imaging Rheumatology bv., Maxime Dougados Consultant of: UCB, Anna Moltó Consultant of: AbbVie, Biogen, BMS, Cyxone, Eisai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma.