AB0486 ONE-YEAR DIRECT COSTS OF BIOLOGICAL THERAPY IN ANKYLOSING SPONDYLITIS AND ITS PREDICTIVE FACTORS: DATA FROM THE MOROCCAN RBSMR REGISTRY

Background:NAObjectives:To estimate the annual direct costs of biological therapies in Spondyloarthropathies (SpA) and to establish possible factors associated with those costs.Methods:The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR). We included SpA patients with available 1-year data. Variables related to socioeconomic status, disease and biological therapy were collected. Differences in costs across groups were tested by Mann–Whitney and Kruskal–Wallis tests. Correlations analysis was performed in search of factors associated with high costs.Results:We included 89 SpA patients. The mean age was 40.6± 13.6 years, with male predominance 68.9 %. Patients received one of the following therapies: TNF-blockers (n =79), Biosimilar of TNF-blockers (n =8) and Il17-blockers (n =2). Median one-year biologic costs per patient were 9 569, 39 €. The total annual of biotherapies in AS patients was 851 675, 98 €.Figure 1Annual mean drug costs per treated patient (€: Euro)The costs are presented in Euro using an exchange rate of (1 Moroccan Dirham = 0.091Euro).TNF-blockers constituted 95 % of the total annual budget. Biosimilar of TNF-blockers and Il17-blockers represented 3 % and 2 % of this overall budget, respectively.Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation.No correlation was found between the annual direct costs of biotherapies and body mass index nor with BASFI or BASDAI.Conclusion:In Morocco, a developing country, the annual direct costs of biological therapies are high in AS patients. Our results may contribute to the development of strategies for better governance of these costs.Disclosure of Interests:None declared.

POS0939 WHEN DO THE ACTIVE SACROILIITIS MRI FINDINGS LOSS IN ANKYLOSING SPONDYLITIS? A RETROSPECTIVE, CROSS-SECTIONAL, OBSERVATIONAL STUDY

Background:Ankylosing Spondylitis (AS) is an inflammatory rheumatic disease that affects the spine and sacroiliac joints (SIJ). Non-steroidal anti-inflammatory drugs (NSAIDs), modifying antirheumatic drugs (DMARDs), and recently anti-TNF blockers, which are more costly than NSAIDs but used in resistant cases, are generally used in its treatment (1).Objectives:While SIJ-MRI is one of the imaging methods in the diagnosis of the disease, it is not yet used in its follow-up (2). We wanted to define when the activated SIJ-MRI findings, which showed early sacroiliitis, regressed according to the treatment option.Methods:Among the 8100 SIJ-MRIs taken in our hospital in the last 5 years, those that were reported normally were excluded from the study. Among the remaining 1150 patients with active or chronic SIJ findings, a total of 87 patients who were diagnosed with AS and had active SIJ findings in the first imaging and had a second SIJ-MRI examination for any reason were included in our retrospective, cross-sectional and observational study. According to the treatment option, how long the active SIJ-MRI findings disappeared was calculated in months using the Kaplan-Meier method.Results:Of the 87 patients examined in the study, 41 were women and 46 were men. The average age is 32.7. Active SIJ-MRI findings disappeared in a mean of 30.6 months for 11 of 24 patients who did not use any medication, in a mean of 33.9 months for 6 of 16 patients using NSAIDs, in a mean of 40.7 months for 14 of 34 patients using sulfasalazine, in a mean of 28.2 months for 3 of 6 patients using adalimumab, in a mean of 24.4 months for 3 of 5 patients using methotrexate, 11.9 month for 2 of 1 patient using certolizumab. There was no statistically significant difference between the groups.Conclusion:The signs of active sacroiliitis disappeared in less time in patients who did not receive any treatment than those using NSAIDs and sulfasalazine. Patients using anti-TNF blockers had earlier results than those using no medication. The reason for this may be the progressive course of patients who are switched to the next level of treatment and their late response to treatment, as well as the mechanism of the disease (2-3). This situation brings to the agenda the tendency of physicians to over-treat the disease. More randomized controlled studies are needed regarding new treatment options.References:[1]Braun J. ‘Axial spondyloarthritis including ankylosing spondylitis’ Rheumatology (Oxford). 2018 1;57(suppl_6):vi1-vi3.[2]Braun J, Baraliakos X, Golder W, Brandt J, Rudwaleit M, Listing J, Bollow M, Sieper J, van der Heijde D. Magnetic resonance imaging examinations of the spine in patients with ankylosing spondylitis, before and after successful therapy with infliximab. Arthritis & Rheumatism Vol. 48, No. 4, April 2003, pp 1126–1136.[3]Jee WH, McCauley TR, Lee SH, Kima SH, Ima SA, Had KY. Sacroiliitis in patients with ankylosing spondylitis: association of MR findings with disease activity. Magnetic resonance imaging 2004:22;245–250.Disclosure of Interests:None declared

Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo

ObjectivesAntitumour necrosis factor (TNF) therapy has revolutionised treatment of several chronic inflammatory diseases, including spondyloarthritis (SpA). However, TNF inhibitors (TNFi) are not effective in all patients and the biological basis for treatment failure remains unknown. We have analysed induced immune responses to define the mechanism of action of TNF blockers in SpA and to identify immunological correlates of responsiveness to TNFi.MethodsImmune responses to microbial and pathway-specific stimuli were analysed in peripheral blood samples from 80 patients with axial SpA before and after TNFi treatment, using highly standardised whole-blood stimulation assays. Cytokines and chemokines were measured in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, and gene expression was monitored using nCounter assays.ResultsAnti-TNF therapy induced profound changes in patients’ innate immune responses. TNFi action was selective, and had only minor effects on Th1/Th17 immunity. Modular transcriptional repertoire analysis identified prostaglandin E2 synthesis and signalling, leucocyte recirculation, macrophage polarisation, dectin and interleukin (IL)-1 signalling, as well as the nuclear factor kappa B (NF-kB) transcription factor family as key pathways targeted by TNF blockers in vivo. Analysis of induced immune responses before treatment initiation revealed that expression of molecules associated with leucocyte adhesion and invasion, chemotaxis and IL-1 signalling are correlated with therapeutic responses to anti-TNF.ConclusionsWe show that TNFi target multiple immune cell pathways that cooperate to resolve inflammation. We propose that immune response profiling provides new insight into the biology of TNF-blocker action in patients and can identify signalling pathways associated with therapeutic responses to biological therapies.

Interstitial Nephritis Presenting as Bilateral Renal Masses in a Pediatric Patient with Crohn’s Disease

We present the case of a teenage boy with Crohn’s disease treated with adalimumab who presented with discrete renal masses, found while undergoing evaluation for elevated creatinine and hypocalcemia. The MRI result, as well as the potential increased risk of malignancy in patients treated with TNF-blockers, both contributed to primary concerns of malignancy in this case. Pathology was consistent, however, with IN and not malignancy. The radiographic presentation of the IN in this case was very unusual, as IN can present as a striated nephrogram on imaging, but has not been described as discrete masses. We are not aware of any other cases of IN reported appearing this way on imaging.

AB0307 DOES FCGR2A, FCGR3A AND FCGR3B POLYMORPHISM CAN PREDICT ANTI-DRUG ANTIBODIES APPARITION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TNF-BLOCKERS?

Background:Fc gamma receptors (FcγRs) play a major role in the regulation of humoral immune responses. Single-nucleotide polymorphisms (SNPs) of FCGR2A and FCGR3A and FCGR3B can impact the expression level, IgG affinity and function of the CD32 and CD16 FcγRs in response to their engagement by the Fc fragment of IgG. It was described in patient treated for rheumatoid arthritis (RA), that such a polymorphism may influence patients response to TNF-blockers.Objectives:In this study, we aimed to investigate whether the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms can be involved in the genesis of anti-drug-antibody ADAb to anti-TNF therapy in RA patients under etanercept (ETA), adalimumab (ADL) and infliximab (INF).Methods:We included 47 patients treated for RA under TNF-blockers. To assess the association between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and immunogenicity of TNF-blockers, we used allele contrast, the recessive model, the dominant model, and the homozygote contrast. Quantitative measurements of the ADAbs was carried out by a commercial enzyme-linked immunosorbent assay (ELISA) kit (Promonitor)®after 6 months of treatment.Results:We involved 18 patients treated with ETA, 13 patients with ADL and 16 under INF. None of the patients under ETA has developed ADAb and respectively 1 and 7 patients developed immunogenicity with ADL and INF. We excluded patients under ETA from statistical study since they didn’t develop ADAb.A significant association was revealed between FCGR2A H131R polymorphism and immunogenicity of INF and ADL (table 1).Table 1.Association between FCGR2A polymorphism and immunogenicity to INF and ADLFCGR2A association with ADAb (n=29, crude analysis)GenotypeADAb=0ADAb=1OR (95% CI)P-valueH/H1 (4.8%)3 (37.5%)1.000.031H/R-R/R20 (95.2%)5 (62.5%)0.08 (0.01-0.98)There weren’t significant associations between ADAb’s development and FCGR3A F158V and FCGR3B NA1/NA2 polymorphism.Conclusion:FCGR2A R allele carriers show less susceptibility to develop ADAb to ADL and INF with follow-up times of 6 months. Our results provide an explanation for controversies in the relationships between FCGR2A H131R polymorphism and TNF-blockers response. Further studies with larger population of RA patients should be undertaken to confirm this hypothesis.References:NoneDisclosure of Interests:None declared

THU0042 DIFFERENTIAL EFFECT OF ABATACEPT VS TNF BLOCKERS, ON THE FREQUENCY OF CIRCULATING FOLLICULAR HELPER (TFH) AND PERIPERAL HELPER (TPH) T CELLS IN RHEUMATOID ARTHRITIS

Background:CXCR5+PD-1hifollicular helper (Tfh) and CXCR5-PD-1hiperipheral helper (Tph) T cells play an important role in the pathogenesis of Rheumatoid Arthritis (RA) by providing help to autoantibody secreting B cells. Whereas Tfh cells typically dwell in the germinal centers of lymphoid organs, Tph cells accumulate at inflamed tissues. An increased frequency of Tph cells and of circulating counterparts of Tfh cells have been described in the peripheral blood of patients with seropositive RA.Objectives:To examine the effect of treatment escalation using biological agents (TNF blockers or abatacept), on the frequency of circulating Tfh (cTfh) and Tph (cTph) cells in RA.Methods:Peripheral blood was drawn from seropositive RA patients with an incomplete response to csDMARDS (n=29) who initiated biological therapy with TNF blockers (TNFb) (n= 17) or abatacept (n= 12), prescribed based on routine clinical practice. cTfh and cTph cell frequencies were determined by flow cytometry of freshly isolated PBMCs at the basal visit and 6 months after starting treatment escalation. For each patient, an age and gender-matched healthy control (HC) was also studied at both time points (n=29).Results:As compared with HC, active RA patients receiving csDMARDs demonstrated a baseline increased frequency of both cTfh and cTph cells. A significant improvement of disease activity as determined by the DAS28 score (ΔDAS28>2.0) was apparent in all of the patients 6 months after initiating biologicals. At that time point, a significant reduction of the previously elevated cTph cell frequency was observed in both treatment groups. However, cTfh cells remained elevated in patients receiving TNFb notwithstanding a good therapeutic response, whereas subjects receiving abatacept experienced a significant abatement of their cTfh cell frequency. Experimental variation of the cTfh and cTph cell numbers in HC was minimal.Conclusion:Abatacept but not TNFb, are able to bring down cTfh cell numbers in RA. This indicates that costimulation blockade can help attain an immunological remission, whereas TNF neutralization may allow a persistent pathogenic germinal center overactivity. At the same time, treatment with both abatacept and TNF blockers results in a downmodulation of the previouly elevated cTph cell numbers, in parallel with the remitting local joint inflammation.References:[1]Simpson N et al, Arthritis Rheum 2010; Craft J, Nat Rev Rheumatol 2012; Arroyo-Villa I et al., Arthritis Res Ther 2014; Rao DA et al., Nature 2017.Disclosure of Interests:Paula Fortea-Gordo Grant/research support from: BMS, Diana Peiteado: None declared, Alejandro Villalba: None declared, Maria-Jose Santos-Bornez Grant/research support from: BMS, Laura Nuño: None declared, Irene Monjo: None declared, Alejandro Balsa Grant/research support from: BMS, Roche, Consultant of: AbbVie, Gilead, Lilly, Pfizer, UCB, Sanofi, Sandoz, Speakers bureau: AbbVie, Lilly, Sanofi, Novartis, Pfizer, UCB, Roche, Nordic, Sandoz, Maria-Eugenia Miranda-Carus Grant/research support from: BMS, Roche