Abstract: Vaccines are highly effective in preventing COVID-19 associated hospitalization and deaths. Strong and persistent immune responses are critical to provide protection for patients with immunomodulatory therapies. Objectives To assess humoral and cellular immune responses following 2 doses of an anti-SARS-CoV-2 mRNA based vaccine in rheumatoid arthritis (RA). Immune responses in patients treated with csDMARDs, bDMARDs (with the exception of rituximab) and JAK inhibitors were compared to healthy controls (HC) over 24 weeks. In addition, disease activity by CDAI and vaccine-induced side effects were prospectively monitored. Methods The RECOVER trial ( R heumatoid C ovid-19 V accin e Immune R esponse) is a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 HC. Clinical assessment and blood sampling was performed at baseline, 3 weeks after the 1 st and 2 weeks after the 2 nd vaccine dose and at week 12 and 24 after the 1 st . Antibody response to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The seroprofiling assay ABCORA, which has been suggested as a surrogate for neutralization, 1 was used to determine IgG, IgA and IgM responses to RBD, S1, S2 and N. The neutralizing activity NT50 at week 12 was assessed against Wuhan-Hu-1 pseudoviruses (HIV-based). IFN-y ELISpots were applied to detect spike-reactive T cell responses after in vitro stimulation with a spike peptide mix. Results Baseline characteristics of participants are detailed in Table 1. Vaccination was well tolerated with no differences between RA patients and HC. At baseline, the majority of RA patients were in remission/LDA (57/77, 74%), this proportion decreased to 51% (39/77) after the second vaccine dose (p = 0.005). Treatment adjustments were required in 11/77 patients. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein). In contrast to HC, anti-S titers were lower at all timepoints with significantly reduced titers observed in patients on abatacept and JAK inhibitors (Figure 1). Potent neutralizing activity (NT50 ≥ 250)) was detected in all HC at week 12, in contrast to 62% RA patients. NT50 correlated to the results based on the ABCORA assay. Peak anti-S titers (2 weeks after 2 nd vaccine) were predictive of NT50 ≥ 250 at week 12 (p 〈 0.0001). In contrast to marked differences in the humoral immune responses, spike-protein specific IFN-α secreting T cells were largely unaltered by different DMARD regimen. Table 1. Baseline characteristics RA patients (n = 77) HC (n = 21) p-value Age (yrs), mean (± SD) 64 (13) 44 (14) 〈 0.0001 Female, n (%) 46 (60) 15 (71) NS Vaccination type mRNA-1273, n (%) 12 (16) 0 (0) 0.06 BNT162b2, n (%) 65 (84) 21 (100) Disease activity (CDAI ) Remission (≤ 2.8), n (%) 17/77 (22) Low (2.9 - 10), n (%) 40/77 (52) Moderate (10.1 - 22.0), n (%) 15/77 (20) High (22.1 - 76.0), n (%) 5/77 (7) DMARD therapy Mono csDMARDs, n (%) 22/77 (29) bDMARDs, n (%) 35/77 (46) Mono bDMARDs, n (%) 14/35 (40) JAKi, n (%) 20/77 (26) Mono JAKi, n (%) 8/20 (40) Prednisone, n (%) 25/77 (33) Mean daily dose (mg ± SD) 5.6 ± 3.6 Conclusion RA patients, in comparison with HC, revealed a slower kinetic and lower magnitude of humoral immune responses depending on the treatment regimen while T cell responses were largely maintained. Peak anti-S responses two weeks after the second vaccine were able to predict the development of potent neutralizing activity and should therefore be considered to individually tailor vaccination strategies. References [1]Abela I et al. Nature Commun 2021. doi.org/10.1038/s41467-021-27040-x Disclosure of Interests Kristin Schmiedeberg: None declared, Irene A. Abela: None declared, Natalia Barbara Pikor: None declared, Nicolas Vuilleumier: None declared, Magdalena Schwarzmueller: None declared, Selina Epp: None declared, Sabrina Pagano: None declared, Sarah Grabherr: None declared, Angelica Brooke Patterson: None declared, Madalina Nussberger: None declared, Alexandra Trkola: None declared, Burkhard Ludewig: None declared, Johannes von Kempis: None declared, Andrea Rubbert-Roth Speakers bureau: Abbvie, Pfizer, Sanofi, UCB, BMS, Lilly, Gilead, Roche, Consultant of: Abbvie, Gilead, Lilly, BMS, Sanofi

Abstract: Patients on immunomodulatory treatments mount an attenuated immune response following mRNA COVID-19 vaccination, yet long-term studies of vaccine-induced anti-SARS-CoV-2 antibody (Ab) kinetics are missing. Objectives In this prospective observational study, we mapped the humoral antibody response to mRNA COVID-19 vaccines up to 24 weeks post full vaccination in patients with inflammatory rheumatic diseases (IRDs). We aimed to assess differences due to treatment, age, past SARS-CoV-2 infection, and vaccine (BNT162b2 vs. mRNA-1273). Methods Adult patients from the SCQM cohort who assented to an mRNA COVID-19 vaccine were recruited between 3/21 – 9/21. Participants answered questionnaires via an app and received kits for the self-collection of capillary blood samples at baseline, 4, 12, and 24 weeks post full vaccination. Samples were tested for IgG Ab against the S1 domain of the SARS-CoV-2 spike protein (anti-S1-IgG) using the EUROIMMUN ELISA. To examine differences in Ab titres arising from the defined parameters, while accounting for inter-assay variability, mixed effects continuous outcome logistic regression models were applied at each timepoint. Results Samples were obtained from 570 patients: 67% female, mean age 53 y (SD 12 y) with 37% RA, 36% axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARDs & no glucocorticoids; 15%), csDMARDs (10%), TNFi (48%), IL-1/6/17/23i (14%), JAKi (6%), rituximab (RTX; 4%), or abatacept (ABA; 2%) in mono/combination therapy at the first vaccination. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. For any Ab threshold, the odds of having a higher Ab titre at 4, 12, and 24 weeks post full vaccination were 3.3 – 4 times higher with mRNA-1273 compared to BNT162b2 (Table 1, Figure 1). TNFi, JAKi, RTX, and ABA as monotherapy resulted in significantly lower Ab levels compared to no medication at almost all timepoints. In combination therapy, TNFi, IL-1/6/17/23i, RTX, and csDMARDs led to consistently lower Ab titres at all timepoints compared to respective monotherapy. Table 1. The OR of being above a given Ab threshold, regardless of the threshold. Ref. levels: mean age, no medication, no past SARS-CoV-2 inf., BNT162b2. Included in model but not shown: diagnosis, infrequently used medication (all non-signif.) Weeks post full vacc. 4 12 24 OR (95% CI); p Age 0.96 (0.94 – 0.97) **** 0.98 (0.96 – 0.996) * 0.98 (0.97 – 1.00) mRNA-1273 (vs BNT162b2) 3.28 (2.34 – 4.61) **** 3.96 (2.83 – 5.54) **** 3.94 (2.93 – 5.50) **** Past COVID inf. (vs none) 7.56 (4.32 – 13.2) **** 8.14 (4.78 – 13.86) **** 11.65 (6.62 – 20.50) **** csDMARD † 1.27 (0.67 – 2.41) 1.78 (0.94 – 3.35) 1.70 (0.86 – 3.36) TNFi † 0.46 (0.28 – 0.71) **** 0.30 (0.19 – 0.48) **** 0.13 (0.081 – 0.22) **** IL-1/6/17/23i † 0.97 (0.54 – 1.75) 1.04 (0.57 – 1.89) 0.89 (0.49 – 1.64) JAKi † 0.38 (0.16 – 0.91) * 0.38 (0.16 – 0.91) * 0.53 (0.22 – 1.28) RTX † 0.078 (0.013 – 0.46) ** 0.078 (0.015 – 0.42) ** 0.16 (0.037 – 0.71) * ABA † 0.14 (0.039 – 0.51) ** 0.087 (0.022 – 0.35) *** 0.068 (0.017 – 0.27) *** Interactions § Age:vaccine ‡ 1.04 (1.02 – 1.07) ** 1.02 (0.99 – 1.05) 1.03 (1.0008 – 1.058) * csDMARD:combi 0.12 (0.02 – 0.70) * 0.17 (0.029 – 0.95) * 0.11 (0.023 – 0.56) ** TNFi:combi 0.34 (0.20 – 0.59) *** 0.37 (0.22 – 0.61) *** 0.36 (0.21 – 0.62) *** IL-1/6/17/23i:combi 0.26 (0.09 – 0.78) * 0.25 (0.085 – 0.70) ** 0.20 (0.071 – 0.58) ** JAKi:combi 1.76 (0.33 – 9.44) 1.23 (0.32 – 4.70) 0.95 (0.25 – 3.65) RTX:combi 0.11 (0.01 – 0.87) * 0.095 (0.012 – 0.73) * 0.085 (0.0091 – 0.79) * ABA:combi 1.75 (0.25 – 12.2) 0.74 (0.096 – 5.75) 0.51 (0.073 – 3.62) * p 〈 0.05; ** p 〈 0.01; *** p 〈 0.001; **** p 〈 0.0001; † Medication as monoth. vs no medication ‡ Interaction terms showing how OR of mRNA-1273 (vs BNT162b2) increases with age § Interaction terms with medications: medication in combination th. vs medication as monoth. Conclusion Compared to no medication, some immunomodulatory therapies resulted in markedly lower Ab levels at all timepoints. In IRD patients, a past SARS-CoV-2 infection resulted in strikingly increased immunogenicity, as did mRNA-1273 compared to BNT162b2. Acknowledgements This study is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM thanks the patients for their participation in this study. A list of rheumatology offices and hospitals that contribute to the SCQM registries can be found on www.scqm.ch/institutions . The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors . Disclosure of Interests Catherine Elizabeth Raptis Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Diego Olivier Andrey: None declared, Christos Polysopoulos Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Christoph Berger: None declared, Adrian Ciurea: None declared, Pierre Lescuyer: None declared, Tanja Maletic Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Myriam Riek Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Almut Scherer Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Isabell von Loga Grant/research support from: The study presented in the abstract is investigator-initiated and received independent financial support from Moderna Switzerland GmbH. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found on www.scqm.ch/sponsors , Judith Safford: None declared, Kim Lauper Speakers bureau: Kim Lauper reports consulting fees for Pfizer and speakers fees for Pfizer, Viatris and Celltrion outside of the submitted work., Consultant of: Kim Lauper reports consulting fees for Pfizer and speakers fees for Pfizer, Viatris and Celltrion outside of the submitted work., Burkhard Moeller: None declared, Nicolas Vuilleumier: None declared, Axel Finckh Speakers bureau: Axel Finckh has received consultancies or speaker honoraria for AbbVie, BMS, Eli-Lilly, Gilead, Pfizer, Sanofi, and UCB outside of the submitted work, Consultant of: Axel Finckh has received consultancies or speaker honoraria for AbbVie, BMS, Eli-Lilly, Gilead, Pfizer, Sanofi, and UCB outside of the submitted work, Grant/research support from: Axel Finckh has received research support from AbbVie, Eli-Lilly, Galapagos, and Pfizer outside of the submitted work, Andrea Rubbert-Roth: None declared

Abstract: To compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi. Methods SWITCH-RA was a prospective, global, observational, real-life study. Patients non-responsive or intolerant to a single TNFi were enrolled ≤4 weeks after starting rituximab or a second TNFi. Primary end point: change in Disease Activity Score in 28 joints excluding patient's global health component (DAS28-3)–erythrocyte sedimentation rate (ESR) over 6 months. Results 604 patients received rituximab, and 507 an alternative TNFi as second biological therapy. Reasons for discontinuing the first TNFi were inefficacy (n=827), intolerance (n=263) and other (n=21). A total of 728 patients were available for primary end point analysis (rituximab n=405; TNFi n=323). Baseline mean (SD) DAS28-3–ESR was higher in the rituximab than the TNFi group: 5.2 (1.2) vs 4.8 (1.3); p 〈 0.0001. Least squares mean (SE) change in DAS28-3–ESR at 6 months was significantly greater in rituximab than TNFi patients: −1.5 (0.2) vs −1.1 (0.2); p=0.007. The difference remained significant among patients discontinuing the initial TNFi because of inefficacy (−1.7 vs −1.3; p=0.017) but not intolerance (−0.7 vs −0.7; p=0.894). Seropositive patients showed significantly greater improvements in DAS28-3–ESR with rituximab than with TNFi (−1.6 (0.3) vs −1.2 (0.3); p=0.011), particularly those switching because of inefficacy (−1.9 (0.3) vs −1.5 (0.4); p=0.021). The overall incidence of adverse events was similar between the rituximab and TNFi groups. Conclusions These real-life data indicate that, after discontinuation of an initial TNFi, switching to rituximab is associated with significantly improved clinical effectiveness compared with switching to a second TNFi. This difference was particularly evident in seropositive patients and in those switched because of inefficacy.

Abstract: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. Methods An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item. Results The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3–6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations. Conclusions These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.

Abstract: The development of RA is described by a preclinical phase of autoimmunity, that precedes clinical disease. This autoimmune phase is characterized by the presence of anti-modified protein antibodies that recognize citrullinated proteins (ACPA). A subset of individuals with ACPA develops RA, i.e. those with imaging signs of subclinical inflammation in the joints. As T cell mediated B cell activation is a key step in developing autoimmunity and RA, interventions that target this process may be useful for preventing the onset of RA. In this context, abatacept seems being an attractive therapeutic tool as it interrupts the activation of T cells and has a favourable safety profile in the treatment of RA. Objectives To test whether treatment of abatacept, as compared to placebo, delays the onset of RA in ACPA positive individuals with a high risk to develop RA. Methods ARIAA is an international, randomized double-blinded placebo-controlled multi-center study in RA-at risk individuals, being ACPA positive and showing MRI signs of inflammation. The study was composed of a 6 months treatment phase with either abatacept s.c. 125 mg weekly or placebo and a 12 months observation phase with no treatment. Primary endpoint was the improvement of MRI inflammation after 6 months, secondary endpoints were the progression to RA after 6 and 18 months. The primary analysis was done on the ITT population and missing values were classified as treatment failures. Results Between November 2014 and December 2019 139 RA-at risk individuals were included into ARIAA by 14 study sites (11 in Germany, 1 in the Czech Republic and 2 in Spain). Of them, 100 patients were randomized to receive either abatacept or placebo. Two patients were excluded and 98 patients could be evaluated for efficacy and safety. The primary endpoint was met: 61% of abatacept and 31% of placebo treated individuals (p=0.0043) improved in MRI inflammation. Furthermore, only 4 patients (8.2%) in the abatacept group but 17 patients in the placebo group (34.7%) progressed to RA after 6 months (p= 0.0025). Even 1 year after cessation of treatment (18 months after inclusion) the number of patients progressing to RA was lower in the abatacept group (35%) than in the placebo group (57%; p=0.0421). With respect to safety, 12 serious adverse events (each one gastritis, cellulitis, pneumonia, tendinitis calcificans, rotator cuff syndrome, cholelithiasis, peripheral artery disease, idiopathic pain syndrome, prostate cancer, penile neoplasm; trabeculectomy, cataract surgery) were reported, with only one (pneumonia) being considered to be related to treatment. Conclusion Abatacept significantly reduces subclinical joint inflammation and delays the development of RA in at-risk individuals. Table 1. ABA PBO All N 49 49 98 Females, N (%) 31 (63.3) 39 (79.6) 70 (71.4) Age (ys); mean (±SD) 51.3 (±10.8) 48.5 (±12.6) 49.9 (±11.7) SJC (N); mean (±SD) 0 0 0 TJC (N); mean (±SD) 3.06 (± 3.75) 3.51 (± 4.42) 3.29 (±4.08) VAS Pain (mm) mean (±SD) 42.2 (± 27.1) 42.8 (± 33.2) 42.5 (± 30.2) VAS PG (mm) mean (±SD 42.2 (±28.7) 43.0 (± 33.8) 42.6 (± 31.2) MRI improvement, N (%) 30 (61.2) 15 (30.6) 45 (45.9) RA at 6 months, N (%) 4 (8.2) 17 (34.7) 21 (21.4) RA at 18 months, N (%) 17 (34.7) 28 (57.1) 45 (45.9) Acknowledgements The study was supported by BMS according to the items outlined in the IIS contract and the IMI funded project RTCure. Disclosure of Interests Jürgen Rech Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB, Consultancy: Biogen, BMS, Chugai, GSK, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Sobi, Novartis, Arnd Kleyer Consultant of: BMS, Pfizer, Sanofi, Abbvie, Janssen, Medac, Novartis, Lilly Deutschland GmbH, Gilead, Amgen, Grant/research support from: Novartis, Lilly Deutschland GmbH, Mikkel Østergaard: None declared, Melanie Hagen: None declared, Larissa Valor: None declared, Koray Tascilar: None declared, Gerhard Krönke: None declared, Verena Schönau: None declared, Stefan Kleinert: None declared, Xenofon Baraliakos: None declared, Juergen Braun: None declared, Martin Fleck: None declared, Andrea Rubbert-Roth: None declared, Frank Behrens: None declared, Martin Feuchtenberger: None declared, Michael Zaenker: None declared, David M Kofler: None declared, Reinhard Voll: None declared, Cornelia Glaser: None declared, Axel Hueber: None declared, Eugen Feist: None declared, Gerd Rüdiger Burmester: None declared, Kirsten Karberg: None declared, Johannes Strunk: None declared, Juan de Dios Cañete: None declared, Ladislav Šenolt: None declared, Esperanza Naredo: None declared, Georg Schett: None declared.

Abstract: The phase 3 SELECT-CHOICE trial of patients with rheumatoid arthritis (RA) and prior inadequate response to biologic DMARD(s) (bDMARD-IR) demonstrated superiority of the JAK inhibitor upadacitinib (UPA) vs abatacept (ABA) in the mean change from baseline (BL) in DAS28(CRP) and in the proportion achieving DAS28(CRP) 〈 2.6 at week (wk) 12, with higher incidence of serious adverse events reported in the UPA treatment group. Objectives To evaluate the impact of UPA vs ABA on individual components of composite measures of disease activity in SELECT-CHOICE. Methods In SELECT-CHOICE, a double-blind phase 3 trial, bDMARD-IR patients were randomly assigned to UPA 15 mg once daily or ABA, each with background conventional synthetic DMARDs, for 24 wks. For this post hoc analysis, the proportions of patients achieving improvement from BL through wk 24 in ACR core variables (including SJC, TJC, Patient Global Assessment [PtGA], Physician Global Assessment [PhGA] , pain, HAQ-DI, and hsCRP) and Boolean remission criteria were evaluated. Differences in the cumulative distributions of CDAI, DAS28(hsCRP), SDAI, and ACR-n (the lowest of percent change in TJC, percent change in SJC, or median of the other 5 ACR components) were determined using the Kolmogorov-Smirnov test and are reported as observed. For all other variables, non-responder imputation was applied for missing data. Nominal P values are provided throughout. Results A total of 616 bDMARD-IR patients with moderate to severe RA were randomized in SELECT-CHOICE (UPA 15 mg, n=303; ABA, n=309). BL demographic and disease characteristics were generally comparable between treatment groups, with a mean disease duration of approximately 12 years and mean CDAI of 39.6. At wk 12, more patients receiving UPA vs ABA achieved ≥50% improvements from BL in TJC68, PtGA, and hsCRP, with comparable proportions observed between UPA and ABA for the remaining ACR components (Figure 1). At wk 24, similar proportions of patients receiving UPA and ABA achieved ≥50% improvements in all but the hsCRP component. Overall, 15% and 26% of patients on UPA compared with 6% and 15% on ABA demonstrated ≥50% improvements across all ACR components at wks 12 and 24, respectively. At wks 12 and 24, Boolean remission was achieved by 6% and 14% of patients on UPA vs 2% and 10% of patients on ABA, respectively; the proportion of patients in both treatment groups achieving the individual Boolean components were also reported (Table 1). While comparable at BL, cumulative distributions of CDAI, SDAI, DAS28(hsCRP), and ACR-n were improved on UPA vs ABA at wk 12 (all nominal P 〈 0.05); differences persisted for most measures at wk 24. Table 1. Proportions of Patients Achieving Boolean Remission and Its Components at Week 12 and 24 (NRI) Week 12 Week 24 n (%) UPA 15 mg ABA UPA 15 mg ABA (N=303) (N=309) (N=303) (N=309) Boolean Remission 19 (6)*** 5 (2) 42 (14)* 30 (10)  PtGA ≤10 54 (18)*** 29 (9) 80 (26)* 66 (21)  TJC ≤1 89 (29)*** 64 (21) 134 (44)* 115 (37)  SJC ≤1 127 (42)** 106 (34) 169 (56)* 152 (49)  hsCRP ≤1 mg/dL 257 (85)*** 209 (68) 244 (81)*** 199 (64) Nominal *** P 〈 .001, ** P 〈 .01, * P 〈 .05 for UPA vs ABA. ABA, abatacept; PtGA, Patient’s Global Assessment of disease severity; UPA, upadacitinib. Conclusion In this post hoc analysis of bDMARD-IR RA patients, improvements in components of disease measures were reported for both UPA and ABA through 24 weeks, with numeric differences noted for several components. Nominally higher attainment of Boolean remission and its components were observed for UPA over ABA. References [1]Rubbert-Roth A, et al. N Engl J Med 2020; 383:1511-21. Acknowledgements AbbVie and the authors thank the patients, study sites, and investigators who participated in these clinical trials. AbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Matthew Eckwahl, PhD, of AbbVie. Disclosure of Interests Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer, UCB, Grant/research support from: Research: BMS, GSK, UCB; Educational programs: MSD, Pfizer, Roche, Andrea Rubbert-Roth Speakers bureau: AbbVie, Pfizer, Sanofi, UCB, BMS, Lilly, Gilead, Roche, Consultant of: AbbVie, Gilead, Lilly, BMS, Sanofi, R-Pharm, Stephen Hall Consultant of: AbbVie, BMS, Lilly, Janssen, Pfizer, UCB, Novartis, Grant/research support from: AbbVie, BMS, Lilly, Janssen, Pfizer, UCB, Novartis, Ricardo Xavier Consultant of: AbbVie, Amgen, BMS, Lilly, Janssen, Novartis, Pfizer, UCB, Anna Shmagel Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie, Employee of: AbbVie, Samuel Anyanwu Shareholder of: AbbVie, Employee of: AbbVie, Vibeke Strand Consultant of: AbbVie, Amgen, Arena, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Chemocentryx, BMS, Celltrion, Lilly, Genentech/Roche, Gilead, GlaxoSmithKline, Ichnos, Inmedix, Janssen, Kiniksa, Lilly, Merck, Myriad Genetics, Novartis, Pfizer, Regeneron Pharmaceuticals, Rheos, R-Pharma, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sorrento, Spherix, UCB

Abstract: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. Methods A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. Results The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still’s disease, Castleman’s disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. Conclusions The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.