Testing if Micro-CT Is Capable of Quantitating the Extent of Proteoglycan-Aggrecan Induced Axial Spondyloarthritis in Mice

ObjectiveInjections of proteoglycan aggrecan (PGA) have been reported to induce axial spondyloarthritis (ax-SpA) in BALB/c mice. It is considered to be a model for radiographic ax-SpA. However, evaluation of the extent of axial disease by histopathological assessment of every intervertebral space is labor-intensive. The objective of our paper is to test the feasibility of Micro Computed Tomography (Micro-CT) in rapidly enumerating the number of intervertebral spaces affected in each mouse.MethodsArthritis was induced in BALB/c mice by intraperitoneal injections of PGA. Involvement of several spinal segments, and selected sacroiliac and hip joints were evaluated by histopathology. The involvement of all intervertebral spaces, sacroiliac and hip joints was evaluated by Micro-CT.ResultsBALB/c mice injected with PGA developed histopathology of SpA-like axial lesions, including spondylitis, sacroiliac joint arthritis and hip joint arthritis. Micro-CT allowed us to clearly enumerate the number of lesions in each mouse.ConclusionMicro-CT allows quantitative assessment of the extent of axial involvement in PGA-induced mouse spondylitis. This can be a useful tool in assessing therapeutic interventions.

Targeted Therapies in Axial Psoriatic Arthritis

Specific and high-quality evidence on the efficacy of the current targeted therapies for axial disease in psoriatic arthritis (axPsA) is still scarce. Indeed, almost all the cohorts investigated in clinical trials on PsA consisted of patients with peripheral arthritis, where a small number of them also had axial involvement. Only one randomized controlled trial was so far specifically designed to assess the efficacy of a biological disease-modifying antirheumatic drug (DMARD) in axPsA. For other biological and synthetic targeted DMARDs, the most specific evidence for treatment in axPsA is extrapolated from post-hoc analyses based on PsA patients with concomitant peripheral and axial manifestations. Furthermore, the current trials and post-hoc analysis on axPsA are affected by major limitations, including the lack of a widely accepted definition of axPsA and the lack of specific and validated outcome measures. Finally, poor data are available on the genetics of axPsA, although alleles differentially expressed in different patterns of axPsA might offer advantages in the prospective of personalized medicine in axPsA patients. Overall, this review suggests that there is an urgent need for more reliable evidence derived from studies specifically designed for axPsA and based on a validated definition of axPsA and on specific outcome measures.

Axial Psoriatic Disease: Clinical and Imaging Assessment of an Underdiagnosed Condition

The frequent involvement of the spine and sacroiliac joint has justified the classification of psoriatic arthritis (PsA) in the Spondyloarthritis group. Even if different classification criteria have been developed for PsA and Spondyloarthritis over the years, a well-defined distinction is still difficult. Although the majority of PsA patients present peripheral involvement, the axial involvement needs to be taken into account when considering disease management. Depending on the definition used, the prevalence of axial disease may vary from 25 to 70% in patients affected by PsA. To date, no consensus definition has been reached in the literature and the definition of axial involvement in PsA has varied from isolated sacroiliitis to criteria used in ankylosing spondylitis. This article reviews the unmet needs in the clinical and radiological assessment of axial PsA, reporting the various interpretations of axial involvement, which have changed over the years. Focusing on both imaging and clinical standpoints, we reported the prevalence of clinical and radiologic features, describing the characteristics of axial disease detectable by X-rays, magnetic resonance imaging, and PET-CT, and also describing the axial symptoms and outcome measures in patients affected by axial disease.

Outcomes in Juvenile-Onset Spondyloarthritis

Some studies have suggested children with juvenile onset spondyloarthritis (JoSpA) have a relatively poor outcome compared to other juvenile idiopathic arthritis (JIA) categories, in regards to functional status and failure to attain remission. Thus, in the interest of earlier recognition and risk stratification, awareness of the unique characteristics of this group is critical. Herein, we review the clinical burden of disease, prognostic indicators and outcomes in JoSpA. Of note, although children exhibit less axial disease at onset compared to adults with spondyloarthritis (SpA), 34–62% have magnetic resonance imaging (MRI) evidence for active inflammation in the absence of reported back pain. Furthermore, some studies have reported that more than half of children with “enthesitis related arthritis” (ERA) develop axial disease within 5 years of diagnosis. Axial disease, and more specifically sacroiliitis, portends continued active disease. The advent of TNF inhibitors has promised to be a “game changer,” given their relatively high efficacy for enthesitis and axial disease. However, the real world experience in various cohorts since the introduction of more widespread TNF inhibitor usage, in which greater than a third still have persistently active disease, suggests there is still work to be done in developing new therapies and improving the outlook for JoSpA.

POS0239 ROOT JOINT INVOLVEMENT IN SPONDYLOARTHRITIS: A POST-HOC ANALYSIS FROM THE INTERNATIONAL ASAS-PERSPA STUDY

Background:In patients with spondyloarthritis (SpA), root joint diseases (RJD), i.e. hip or shoulder involvement, may be associated with a distinct disease phenotype compared to those with other affected joints. The ASAS-PerSpA study (PERipheral involvement in SPondyloArthritis) [1], offers a unique opportunity to study the phenotypes of patients with RJD in a global cohort.Objectives:Primary objective was to compare the clinical characteristics of SpA patients with and without RJD. Secondary objectives were to compare the prevalence of RJD across the different SpA subtypes and the different regions of the world, compare the severity of axial disease as well as the disease burden in SpA patients with and without RJD.Methods:This is a post-hoc analysis of the ASAS-PerSpA study, which included 4,465 patients with any subtype of SpA (axial SpA (axSpA), peripheral SpA (pSpA), psoriatic arthritis (PsA), inflammatory bowel disease associated SpA (IBD-SpA), reactive arthritis (ReA) and Juvenile SpA (Juv-SpA)) according to the rheumatologist’s diagnosis. RJD was defined as a positive answer by the investigator to the following question: “Do you consider that the patient has ever suffered from RJD (e.g. hip, shoulder) related to SpA?” In case of a positive answer, a potential specific treatment (e.g. Total Articular Replacement) was investigated. The patient’s characteristics were compared between those with and without RJD involvement, using Chi-2 or Fisher exact test for the categorical variables and t-test for the continuous variables. Two separate multivariable stepwise binary logistic regression analyses were conducted to identify factors associated with the dependent variables “hip involvement” and “shoulder involvement”.Results:RJD occurred in 1,503 patients (33.7%), with more prevalent hip (24.2%) than shoulder (13.2%) involvement. The prevalence of RJD as a group was the highest in Juv-SpA (52.7%), followed by pSpA (44.3%) and axSpA (33.9%). The highest prevalence of RJD was found in Asia and the lowest in Europe and North America. Among patients with hip involvement, 6.0% had a history of hip replacement (highest in the Middle East and North Africa and Latin America); among patients with shoulder involvement, 0.8% had a history of shoulder replacement. Hip had a distinct pattern of associations compared to shoulder involvement (Figure 1). Hip involvement was significantly associated with the SpA main diagnosis (highest in pSpA, lowest in PsA), younger age at first SpA symptom, lower prevalence of family history of psoriasis, positive HLA-B27, occiput-to-wall distance>0, and treatment with cs-DMARDs and b-DMARDs. Shoulder involvement was associated with the SpA main diagnosis (highest in Juv-SpA and pSpA, lowest in axSpA), older age at first SpA symptom, higher prevalence of enthesitis, dactylitis, tender joints count, IBD, occiput-to-wall distance>0, EQ5D score and treatment with cs-DMARDs.Conclusion:Hip involvement was more prevalent than shoulder involvement in patients with SpA, and had a distinct phenotype resembling axial disease whereas shoulder involvement was mostly associated with features of peripheral disease. Hip and shoulder involvement should be analyzed separately in future studies rather than under the RJD entity.References:[1]Lopez-medina, C. et al. Prevalence and Distribution of Peripheral Musculoskeletal Manifestations in Axial Spondyloarthritis, Peripheral Spondyloarthritis and Psoriatic Arthritis: Results of the International, Cross-sectional ASAS-PerSpA Study. RMD Open; 2021;7:e001450.Disclosure of Interests:None declared

POS0930 SECUKINUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS AND AXIAL MANIFESTATIONS: PREDICTORS OF RESPONSE FROM THE DOUBLE-BLIND, RANDOMISED, PHASE 3B MAXIMISE TRIAL

Background:Psoriatic arthritis (PsA) is a heterogeneous disease with variability of response to different therapeutic modalities.1 Identifying potential demographic and disease characteristics as predictors of treatment response may define personalised treatment optimisation strategies.2–3Objectives:This post-hoc exploratory analysis of the MAXIMISE trial4 investigated the differential treatment effect of demographics and baseline characteristics as predictive factors in biologic naïve patients with active PsA and symptoms of active spinal disease.Methods:The full analysis set (FAS) comprised of all patients from the randomised set assigned to study treatment, fulfilling the predefined clinical criteria for active axial disease and for whom Assessment of SpondyloArthritis International Society (ASAS) 20 data were available at Week 12. The research hypothesis was that the odds ratio associated with the effect of treatment on ASAS20 responder status at Week 12 would be different depending on 12 pre-specified predictor variables. A logistic regression model was initially fitted to the FAS that included 12 pre-specified covariates. A second logistic regression model was then fitted to the FAS that allowed for all 12 pre-specified variables to interact with treatment.5 The log-likelihood of the two fitted models were compared using a likelihood ratio test at a pre-specified significance level of 20% (i.e. P-value ≤0.20) to test whether any of the predefined variables interacted with treatment. If the above test was statistically significant at the 20% level of statistical significance the variables of the second model were formally examined to determine whether the overall effect of treatment is not applicable. Three forest plots were produced, one for each treatment group. Hypothesis tests were employed to determine the strength of evidence for each individual variable.Results:The likelihood ratio test provided evidence against the assumption that the overall effect of treatment is applicable to all patients (P-value = 0.08). Notably, the odds of being an ASAS20 responder if nail dystrophy is present at baseline were 3 times greater in the secukinumab 150 mg group and 5 times greater in the 300 mg group compared with placebo (interaction P-value = 0.029). Although males fare worse than females in the placebo group, in the secukinumab 150 mg and 300 mg treatment groups the odds of being a responder were similar to females (interaction P-value = 0.039). Current smokers were less likely to be ASAS20 responders compared to never smokers regardless of treatment group (interaction P-value = 0.589) (Figure 1). Age, CRP level, Berlin MRI spine/SIJ score, time since first axial signs, number of swollen joints, new bone formation and BMI did not show a differential treatment effect on ASAS20 responses.Conclusion:Of the 12 baseline variables of a unique population of 473 PsA patients with active axial disease diagnosed by clinical criteria, our analyses showed evidence of a differential treatment effect most notably for nail dystrophy suggesting that the presence of nail dystrophy may predict a better response to secukinumab in PsA patients with axial manifestations.References:[1]Coates LC, Helliwell PS. Clin Med (Lond). 2017;17(1):65–70.[2]Watson DS, et al. BMJ. 2019;364:l886.[3]Hügle M, et al. Rheumatol Adv Pract. 2020;4(1):rkaa005.[4]Baraliakos X, et al. Ann Rheum Dis. Published Online First: 17 Dec 2020. doi:10.1136/annrheumdis-2020-218808.[5]Peto R, et al. Br J Cancer. 1977;35(1):1–39.Figure 1.Forest plots of the adjusted odds ratio by treatment using interaction modelDisclosure of Interests:Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, and UCB., Consultant of: AbbVie, BMS, Celgene, Chugai, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, and Novartis., Effie Pournara Shareholder of: Novartis, Employee of: Novartis, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB., Grant/research support from: Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, and Galapagos., Helena Marzo-Ortega Consultant of: Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, Takeda and UCB., Grant/research support from: Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, Takeda and UCB., Philip J Mease Speakers bureau: AbbVie, Amgen, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Galapagos, Celgene, Genentech, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: AbbVie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, SUN, and UCB., Roisin White Shareholder of: Novartis, Employee of: Novartis, Eamonn O’Brien Shareholder of: Novartis, Employee of: Novartis, Barbara Schulz Employee of: Novartis, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis.

POS1043 NETAKIMAB REDUCES PSORIATIC ARTHRITIS ACTIVITY IN PATIENTS WITH OR WITHOUT AXIAL DISEASE: SUBANALYSIS OF THE PATERA STUDY

Background:PATERA is an ongoing phase 3 international double-blind, placebo-controlled clinical study of netakimab (NTK) in psoriatic arthritis (PsA) (NCT03598751). Netakimab (NTK) is an anti-interleukin-17A monoclonal antibody approved for psoriasis, ankylosing spondylitis, PsA in Russia and Belarus.Objectives:A subanalysis was performed to define the impact of NTK on PsA activity depending on the presence of axial disease: a subset of patients with inflammatory back pain (IBP) according to self-reported ASAS IBP criteria, 2009 (IBP(+) was compared to those without IBP (IBP(-)).Methods:194 eligible adult patients with PsA fulfilling the CASPAR criteria, with inadequate response to csDMARD or one TNFi, were randomly assigned to receive NTK 120mg or placebo at weeks 0,1,2,4,6,8,10,14,18,22. Patients with missing values for categorical variables were considered as non-responders in the analysis. For quantitative variables, missing values were replaced using the multiple imputation method.Results:97 PsA patients (N=54 IBP(+), N=43 IBP(-)) received NTK. Both subpopulations were comparable in gender, age and PsA activity at baseline. The treatment led to a pronounced decline in PsA activity in both subpopulations, significant differences between arms were observed only in DAPSA remission and very low disease activity (VLDA) at week 24 (Figure 1A). Changes from baseline in DAS28-CRP were consistent between IBP(+) and IBP(-) patients with a rapid decline during the first month with further improvement up to week 24 (Figure 1B). A similar trend was observed PsA-specific composite responder index (PSARC) (data not shown). A comparable percentage of IBP(+) and IBP(-) patients achieved PSARC at each timepoint of evaluation with 87% and 86% of responders respectively at week 24.Conclusion:NTK significantly improved PsA activity regardless of the presence of IBP.Figure 1.PsA activity after 24-week treatment with NTK. (A) Percentage of patients with DAPSA remission (0-4), very low disease activity (VLDA), minimal disease activity (MDA) at week 24; (B) change from baseline in DAS28-CRPAcknowledgements:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Tatiana Korotaeva Speakers bureau: Abbvie, Biocad, Eli Lilly, Johnson & Johnson, Janssen, Novartis, Pfizer, UCB, Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, V Mazurov: None declared, Aleksey Samtsov: None declared, Vladislav Khayrutdinov: None declared, Andrey Bakulev: None declared, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Anna Eremeeva Employee of: Biocad.

AB0540 COMPARISON OF EQ-5D HEALTH STATUS IN PSORIATIC ARTHRITIS PATIENTS WITH OR WITHOUT AXIAL DISEASE: RESULTS OF SUBANALYSIS OF THE PATERA STUDY

Background:Netakimab (NTK) is an anti-interleukin-17A monoclonal antibody approved for psoriasis, ankylosing spondylitis, psoriatic arthritis (PsA) in Russia and Belarus. PATERA is an ongoing phase 3 international double-blind, placebo-controlled clinical study of NTK in PsA (NCT03598751).Objectives:A subanalysis was performed to assess the effect of NTK on domains of the 5-level EuroQol 5 Dimensions questionnaire (EQ-5D-5L) in patients with inflammatory back pain (IBP) (IBP(+)) and without (IBP(-)) at baseline according to self-reported ASAS IBP criteria, 2009.Methods:194 adult patients with PsA (CASPAR criteria, 2006) with inadequate response to csDMARD or one TNFi, were randomly assigned to receive NTK 120mg or placebo at weeks 0,1,2,4,6,8,10,14,18,22. The proportion of patients reported >1 problem in each domain was evaluated. Patients with missing values were considered as non-responders in the analysis.Results:97 PsA patients (N=54 IBP(+), N=43 IBP(-)) received NTK. The subpopulations didn’t differ significantly in gender, age, and PsA activity at baseline. Comparable percentage of patients reported any problems for each domain at baseline (p≥0.05) (data not shown). IBP(-) subpopulation had a greater improvement for all domains except of anxiety/depression. The absolute declines for IBP(+) vs IBP(-) patients were as followed: 24.1% vs 41.9% (mobility), 18.5 vs 41.9% (self-care), 24.0% vs 51.1% (usual activities), 24.1% vs 37.2% (pain/discomfort), 33.3% vs 9.3% (anxiety/depression). However, the only significant difference between IBP(+) and IBP(-) was observed in usual activity (Figure 1).Conclusion:NTK resulted in the growing improvement of each EQ-5D-5L domain through 24 weeks irrespectively of the presence of IBP. IBP(-) subjects showed trend to greater benefit compared to IBP(+).Figure 1Percentage of patients reported any problems in (A) pain/discomfort, (B) in usual activity at each visitAcknowledgements:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, Tatiana Korotaeva Speakers bureau: Abbvie, Biocad, Eli Lilly, Johnson & Johnson, Janssen, Novartis, Pfizer, UCB, V Mazurov: None declared., Aleksey Samtsov: None declared., Vladislav Khayrutdinov: None declared., Andrey Bakulev: None declared., Alena Kundzer: None declared., Nikolaj Soroka: None declared., Anna Eremeeva Employee of: Biocad.

AB0534 THE IMPACT OF AXIAL INVOLVEMENT ON ACR RESPONSE IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS OF SUBANALYSIS OF THE PATERA STUDY

Background:Inflammatory back pain (IBP) is a common symptom of axial disease in patients with psoriatic arthritis (PsA). The reported prevalence of axial disease in patients with PsA is quite variable and must be taken into account while choosing treatment strategy. Netakimab (NTK) is an anti-interleukin-17A monoclonal antibody approved for psoriasis, ankylosing spondylitis, PsA in Russia and Belarus.Objectives:A subanalysis was aimed to investigate the ACR (American College of Rheumatology) 20/50/70 response rate in PsA patients with/without the axial disease, defined by the presence of IBP according to self-reported ASAS IBP criteria, 2009 at baseline.Methods:PATERA is an ongoing phase 3 international double-blind, placebo-controlled clinical study (NCT03598751). 194 adult patients with PsA (CASPAR criteria, 2006) with inadequate response to csDMARD or one TNFi, were randomly assigned to receive NTK 120mg or placebo at weeks 0,1,2,4,6,8,10,14,18,22. The ACR response was calculated in NTK-treated patients with IBP (IBP(+)) and NTK-treated patients without IBP (IBP(-)) according to self-reported ASAS IBP criteria, 2009. Patients with missing values for categorical variables were considered as non-responders in the analysis.Results:97 PsA patients (N=54 IBP(+), N=43 IBP(-)) received NTK. Both subpopulations were comparable in gender, age, and PsA activity at baseline. There were no significant differences in ACR20 achievement between the groups (Figure 1). The percentage of patients with ACR50 was significantly (p<0.05) higher in the IBP(-) subpopulation at weeks 4-20 (data not shown), but not at week 24 with 63% IBP(+) and 79% IBP(-) responders (p≥0.05). Similarly, IBP(+) patients had a lower frequency of ACR70 response (Figure 1).Conclusion:NTK is effective in PsA treatment irrespectively of the presence of axial disease. Both IBP(-) and IBP(+) subpopulations achieved ACR20/50/70 as well, however, the benefit in IBP(-) patients was more pronounced.Figure 1ACR response ratesAcknowledgements:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Tatiana Korotaeva Speakers bureau: Abbvie, Biocad, Eli Lilly, Johnson & Johnson, Janssen, Novartis, Pfizer, UCB, Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, V Mazurov: None declared., Aleksey Samtsov: None declared., Vladislav Khayrutdinov: None declared., Andrey Bakulev: None declared., Alena Kundzer: None declared., Nikolaj Soroka: None declared., Anna Eremeeva Employee of: Biocad.