Abstract: An alert regarding about the tolerance of Interleukin 17 (IL-17) inhibitors has been issued from data of randomized controlled trials showing cases of de novo inflammatory bowel diseases (IBD). In a recent analysis of pooled data from 21 clinical trials, cases of IBD events (including Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU)) were uncommon (1). Yet, real-world data are lacking. Objectives: To describe real-world data about patients treated by IL-17 inhibitors developing new onset IBD (CD or UC). Methods: A French national registry called MISSIL was started in February 2018 to collect the cases of patients treated by IL-17 inhibitors developing new onset IBD. This registry is conducted by rheumatologist, dermatologist and gastroenterologist learned societies specialized on immune-mediated inflammatory diseases. In France, secukinumab (SEK) has been granted market authorization since June 2016 and ixekizumab since April 2018. Results: 24 cases under SEK were reported between February 2018 and January 2020: 3 patients with psoriasis and 21 patients with spondylwoarthritis. There were 20 patients with new onset CD and 4 with UC. Mean age was 51.7 ± 15.7 years old and 12/24 were female; 10 presented an axial spondyloarthritis, 5 a peripheral spondyloarthritis and 6 both,13/17 were HLA-B27 positive,7/19 had a radiographic sacroiliitis and 11/17 a MRI sacroiliitis. Only 2 were biological Disease-modifying antirheumatic drug (bDMARD)-naïve. Crohn’s disease was mainly located at the ileum, colon and rectum. The median time to onset of symptoms was 2 (1-6) months. The main symptoms were diarrhea, nausea and vomiting and loss of weight. Median CRP at the onset of symptoms was 68 mg/L (41-140.5); 21 patients underwent biopsies, 12 were in favor of CD. IL-17 inhibitors were consistently stopped. Patients were treated by corticosteroids (16/24), mesalazine (7/24), methotrexate (3/24), thiopurines (2/24), infliximab (9/243), adalimumab (3/24), golimumab (2/24), ustekinumab (5/24). The evolution was favorable under treatment with complete resolution (4/24), improvement (11/24) or stabilization (5/24). 3 patients worsened under treatment and 1 died (massive myocardial infarction). Conclusion: IBD flare in patients treated with IL-17 inhibitors are rare and lead to discuss the potential iatrogenic role of IL-17 inhibitor drugs. Further cases are needed to better characterize this complication. A case-control study will be conducted to identify patients at risk to develop IBD under IL-17 inhibitor. References: [1]Reich et al. Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials. Ann Rheum Dis. 2019;78:473-479 Disclosure of Interests: Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Benjamin Pariente: None declared, Delphine Staumont-Sallé Speakers bureau: Lilly, Novartis, Philippe Goupille Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Lilly, Janssen, Medac, MSD France, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Stephane Varin: None declared, Sylvain Lanot: None declared, Emmanuelle Dernis Speakers bureau: Lilly, Novartis, Tristan Pascart Speakers bureau: Novartis, Lilly, Beatrice Banneville Speakers bureau: Lilly, Novartis, Pauline Baudart: None declared, Bruno Gombert: None declared, Elodie BAUER: None declared, Laurianne Plastaras: None declared, Sébastien Barbarot: None declared, Renaud FELTEN: None declared, Loïc Le Dantec: None declared, Nathalie Sultan-Bichat: None declared, Céline Girard: None declared, Arnaud Constantin Grant/research support from: Study was sponsored by Sanofi Genzyme, Consultant of: Consulting fees from Abbvie, BMS, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, Daniel Wendling: None declared, Philippe Gaudin Speakers bureau: Lilly, Denis Jullien Speakers bureau: Lilly, Novartis, Thao Pham Speakers bureau: Novartis, Janssen, Lilly, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly

Abstract: The impact of immunosuppressants on COVID-19 vaccination response and durability in patients with immune-mediated inflammatory diseases (IMID) is yet to be fully characterized. Humoral response may be attenuated in these patients especially those on B cell depleting therapy and higher doses of corticosteroids, but data regarding other immunosuppressants are scarce. Objectives We aimed to investigate antibody and T cell responses and durability to SARS-CoV-2 mRNA vaccines (BNT162b and/or mRNA 1273) in IMID patients on immunomodulatory maintenance therapy other than B-cell depleting therapy and corticosteroids. Methods This prospective observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with IMIDs (psoriatic arthritis, psoriasis, inflammatory bowel disease and rheumatoid arthritis) with or without maintenance immunosuppressive therapies (anti-TNF, methotrexate/azathioprine [MTX/AZA], anti-TNF + MTX/AZA, anti IL12/23, anti-IL-17, anti-IL23) compared to healthy controls. Automated ELISA for IgGs to spike trimer, spike receptor binding domain (RBD) and the nucleocapsid (NP) and T-cell release of 9 cytokines (IFNg, IL2, IL4, IL17A, TNF) and cytotoxic molecules (sFasL, GzmA, GzmB, Perforinin) in cell culture supernatants following stimulation with spike or NP peptide arrays were conducted at 4 time points: T1=pre vaccination, T2=median 26 days after dose 1, T3=median 16 days after dose 2 and T4=median 106 days after dose 2. Neutralization assays against four SARS-CoV-2 variants (wild type, delta, beta and gamma) were conducted at T3. Results We followed 150 subjects: 26 healthy controls and 124 IMID patients: 9 untreated, 44 on anti-TNF, 16 on anti-TNF with MTX/AZA, 10 on anti-IL23, 28 on anti-IL12/23, 9 on anti-IL17, 8 on MTX/AZA (Table 1). Most patients mounted antibody and T cell responses with increases from dose 1 to dose 2 (100% seroconversion at T3) and some decline by T4, with variability within groups. Antibody levels and neutralization efficacy was lower in anti-TNFgroups (anti-TNF, anti-TNF + MTX/AZA) compared to controls and waned by T4 (Figure 1). T cell responses were not consistently different between groups. Pooled data showed a higher antibody response to mRNA-1273 compared to BNT162b. Table 1. Baseline characteristics of study participants Control untreated IMID Anti- TNF Anti- TNF +MTX/AZA Anti-IL-23 Anti -IL-12/23 Anti -IL-17 MTX/AZA n=26 n=9 n=44 n=16 n=10 n=28 n=9 n=8 p-value IMID* N/A  IBD 9 30 10 0 27 0 4  Psoriasis 1 3 1 8 1 2 2  PA 0 7 3 2 1 7 2  AS 0 8 3 0 0 1 0  RA 1 1 0 0 0 1 1 Age  median years [IQR] 36 [26-46] 33 [27-41] 38 [30-51] 53 [44-59] 48 [45-61] 34 [28-47] 49 [46-61] 42 [31-55] 〈 0.001^ Sex  male (%) 16 (62) 5 (56) 18 (41) 8 (50) 5 (50) 13 (46) 6 (67) 4 (50) 0.772~ BMI median kg/m2 [IQR] 25 [23-28] 26 [22-27] 22 [24-26] 26 [24-28] 27 [24-35] 22 [21-24] 32 [26-34] 26[25-33] 0.001^ Vaccine interval  median days [IQR] 74 [35-84] 54 [31-64] 60 [45-69] 64 [50-72] 74 [35-84] 62 [49-69] 65 [52-75] 58 [21-97] 0.372^ *multiple IMIDs per patient possible Figure 1. Antibody responses (A) Anti spike and anti RBD IgG levels at indicated time points. Blue line represents median ratio in convalescent patients. The red line is the seropositivity threshold: the median antibody level of those that pass both a 1% false positive rate and show ≥3SD from the log means of the negative controls. (B) Relative ratio of RBD, spike and NP across time. Black and gray lines indicate median and mean values, respectively. *p≤0.05, **p≤0.01, ***p≤0.001, ****p≤0.0001 Conclusion Following 2 doses of mRNA vaccination there is 100% seroconversion in IMID patients on maintenance therapy. Antibody levels and neutralization efficacy in anti-TNF group are lower than controls, and wane substantially by 3 months after dose 2. These findings highlight the need for third dose in patients undergoing treatment with anti-TNF therapy and continued monitoring of immunity in these patient groups, taking into consideration newer variants and additional vaccine doses. Acknowledgements This work was funded by a donation from Juan and Stefania Speck and by grants VR-1 172711, VS1-175545, FDN-143250, GA1- 177703 and GA2- 177716, from Canadian Institutes of Health Research and COVID Immunity task force and by Sinai Health Foundation Disclosure of Interests Naomi Finkelstein: None declared, Roya M. Dayam: None declared, Jaclyn Law: None declared, Rogier Goetgebuer: None declared, Gary Chao: None declared, Kento T. Abe: None declared, Mitchell Sutton: None declared, Joanne M. Stempak: None declared, Daniel Pereira: None declared, David Croitoru: None declared, Lily Acheampong: None declared, Saima Rizwan: None declared, Klaudia Rymaszewski: None declared, Raquel Milgrom: None declared, Darshini Ganatra: None declared, Nathalia V. Batista: None declared, Melanie Girard: None declared, Irene Lau: None declared, Ryan Law: None declared, Michelle Cheung: None declared, Bhavisha Rathod: None declared, Julia Kitaygorodsky: None declared, Reuben Samson: None declared, Queenie Hu: None declared, Nigil Haroon: None declared, Robert Inman Consultant of: AbbVie, Janssen, Lilly, Novartis., Grant/research support from: AbbVie, Novartis, Vincent Piguet Consultant of: AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin Co. Ltd, LEO Pharma, Novartis, Pfizer, Sanofi, UCB, and Union Therapeutic, Grant/research support from: Unrestricted educational grants from AbbVie, Bausch Health, Celgene, Janssen, LEO Pharma, Lilly, L’Oréal, NAOS, Novartis, Pfizer, Pierre-Fabre, Sandoz, and Sanofi, Mark Silverberg Speakers bureau: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Consultant of: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Grant/research support from: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Anne-Claude Grigras: None declared, Tania H. Watts: None declared, Vinod Chandran Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Eli-Lilly.

Abstract: The heterogeneity and complexity of the chronic autoimmune diseases systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) necessitate comprehensive person-centred management, including non-pharmacological approaches. Recommendations for non-pharmacological management are currently lacking. Objectives To perform a systematic literature review to inform the EULAR task force for recommendations/points to consider for the non-pharmacological management of adult patients with SLE and SSc. Among research questions formulated by the task force, we aimed at identifying (i) non-pharmacological interventions that have been evaluated and (ii) their target health domains or organ systems. Methods We searched the Medline, Embase, Web of Science Core Collection and CINAHL for articles published between January 2000 and June 2021. From the initial search (n=15,803), 2 researchers independently performed the article selection. Conflicts were discussed until consensus with 2 additional researchers. Subsequent data extraction from the selected articles was performed by 4 researchers, with an overarching guidance by 2 additional researchers. Risk of bias assessment was performed according to Joanna Briggs Institute Critical Appraisal Checklists. Results A total of 111 articles for SLE and 75 for SSc were selected for analysis. Non-pharmacological interventions identified for SLE included physical exercise (n=34), psychological support (n=21), dietary therapy and nutrition (n=15), patient education and self-management (n=14), photoprotection (n=5), medication adherence interventions (n=5), complementary and alternative medicine (CAM) e.g., Chinese medicine (n=5), multidisciplinary care (n=4), and phototherapy/laser modalities (n=4). Interventions identified for SSc included physical exercise e.g., hand, oral and general exercise (n=21), phototherapy/laser modalities or shockwave therapy (n=15), patient education and self-management (n=10), CAM (n=8), hand-bathing e.g., in paraffin (n=5), manual therapy e.g., osteopathic manipulative treatment (n=5), dietary therapy and nutrition (n=5), oral hygiene (n=2), hyperbaric oxygen or ozone therapy (n=2) and multidisciplinary care (n=2). Target health domains and organ systems identified within SLE included (in descending order) (i) disease activity, (ii) health-related quality of life (HRQoL), (iii) depression/anxiety, (iv) fatigue, (v) organ damage, (vi) inflammatory markers, (vii) psychological stress, (viii) pain, (ix) body composition/anthropometry, and (x) aerobic capacity. Intervention targets in SSc included (i) functional impairment e.g., hand mobility, (ii) skin sclerosis including microstomia, (iii) HRQoL, (iv) pain, (v) circulation e.g., Raynaud’s phenomena and telangiectasias, (vi) skin ulcers, (vii) oral hygiene, (viii) fatigue, (ix) digestion, and (x) depression/anxiety. Conclusion Physical exercise was a frequently researched non-pharmacological intervention within both SLE and SSc. While psychological support and dietary therapy/nutrition were frequently investigated in SLE, phototherapy modalities were common in SSc. Patient education and self-management was advocated in both SLE and SSc literature. HRQoL was a frequent target domain in both diseases; while disease activity and psychosocial domains emerged as important targets in SLE, functional impairment and skin-related aspects constituted predominant targets in SSc. Efficacy of interventions varied considerably across studies. Current evidence is limited by the overall small study populations, and the lack of large RCTs. Table 1. Studies categorised by design. Study design SLE SSc Meta-analysis of RCTs 5 1 RCT (including long-term follow-up or post-hoc analysis) 41 28 Non-randomised longitudinal controlled/cohort studies 28 7 Retrospective cohort study, cross-sectional or case-control study 16 2 Case series or open pilot studies 21 37 Acknowledgements The authors would like to thank the members of the EULAR task force for recommendations/points to consider for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis (in alphabetical order by family name) i.e., Helene Alexanderson, Laurent Arnaud, Oliver Distler, Andrea Domján, Els van den Ende, Kim Fligelstone, Agnes Kocher, Maddalena Larosa, Martin Lau, Alexandros Mitropoulos, Mwidimi Ndosi, Gunilla von Perner, Janet Poole, Anthony Redmond, Valentin Ritschl, Yvonne Sjöberg, Tillmann Uhlig, Cecília Varjú, Joke Vriezekolk, Elisabet Welin, and Rene Westhovens, for their contribution to the formulation of the research questions together with IP, CG, TS and CB. Disclosure of Interests None declared

Abstract: Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX) as anchor therapy in combination with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). However, its tolerability is challenging with a significant proportion of patients not adhering to their prescribed MTX regimen following b/tsDMARD initiation. Rates of MTX tapering and withdrawal have been reported elsewhere but Canadian data are lacking. Objectives This multi-centre, retrospective chart-based cohort study assessed the frequency of MTX withdrawal or tapering following initiation of a b/tsDMARD in Canadian adults with RA. Methods Patients were eligible if they received MTX for ≥3 months before initiation of a b/tsDMARD that was then prescribed continuously for ≥18 months and was initiated in combination with MTX. Patients taking oral prednisone or equivalent at a dose 〉 10 mg per day, and those whose b/tsDMARD was prescribed prior to 2014, were excluded. Results Data from 889 patients were included in the analysis. Mean age was 50.6 years and 72.6% were female. Mean time since diagnosis was approximately 8 years. Of the 46.1% of patients with a documented assessment of disease status at baseline, 62.7% of patients had high disease activity. Baseline mean (SD) MTX dose was 18.9 (6.63) mg/week, administered orally (57.4%), subcutaneously (41.3%), or intramuscularly (1.2%). Overall, 270 (30.4%) patients either tapered (123, 13.8%) or discontinued (147, 16.5%) their MTX within 2 years of initiating the b/tsDMARD. Methotrexate dose was unchanged for 582 (65.5%) subjects and increased for 37 (4.2%) subjects. The prescribed b/tsDMARD was most often a tumor necrosis factor inhibitor (TNFi,52.1%), followed by a Janus kinase inhibitor (JAKi, 18.3%), other modes of action (OMA) which included abatacept and rituximab (17.7%) and interleukin-6 inhibitor (IL-6i, 11.9%). The b/tsDMARD type with the highest frequency of MTX Taper or Discontinued was IL-6i (37 patients, 34.9%) followed by TNFi (144 patients, 31.1%), JAKi (47 patients, 28.8%) and OMA (44 patients, 28.0%). In the MTX Discontinued group, the most common reasons for MTX discontinuation were patient decision (27.2%) and adverse events (24.5%). In the MTX Tapered group, the most common reasons for MTX dose change were planned tapering (36.6%) and adverse events (29.3%). In the MTX Increased group, insufficient clinical response (73.0%) was the most common reason provided for MTX dose change. Baseline factors associated with MTX dose discontinuation and tapering by multiple logistic regression were a shorter time since diagnosis (Odds ratio [OR]: 0.981; 95% confidence interval [CI] : 0.964 – 0.999. P=0.0401), use of non-DMARD medications excluding steroids (OR: 0.683; 95%CI: 0.503 – 0.929. P=0.0150) and a greater number of comorbidities (OR: 1.054; 95%CI: 1.001 – 1.110. P=0.0444). The mean (SD) weekly MTX dose at the end of the data extraction period was 14.13 (4.81) mg for the MTX Tapered group, with 109 (88.6%) subjects taking a weekly MTX dose ≥10 mg. In the MTX Increased group the mean (SD) weekly MTX dose was 22.3 (3.74) mg. Interpretation of the effect of MTX dose on disease activity, fatigue, pain and functional status is challenging due to missing data, but most patients in all 4 groups transitioned to low disease activity or remission during the study period. Conclusion Methotrexate withdrawal or tapering occurred in 30.4% of Canadians with RA within two years following b/tsDMARD initiation. There was no evidence of worsening disease activity in these patients. These proportion of Canadian RA patients who reduce or discontinue MTX after the initiation of a ts/bDMARD are generally consistent with those reported in other regions of the world. Acknowledgements AbbVie Corp. funded the research for this study and provided writing support for this abstract. AbbVie participated in the study design; study research; collection, analysis, and interpretation of data; and writing, reviewing, and approving this abstract for submission. All authors had access to the data; participated in the development, review, and approval of the abstract; and agreed to submit this abstract to EULAR 2022. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. Medical writing support was provided by John Howell PhD of McDougall Scientific and funded by AbbVie, Inc. Disclosure of Interests Louis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, Consultant of: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, Brandusa Florica Speakers bureau: AbbVie, Amgen, Lilly, Pfizer, Janssen, Novartis, Merck, Consultant of: AbbVie, Amgen, Lilly, Pfizer, Janssen, Novartis, Merck, Grant/research support from: AbbVie, Amgen, Lilly, Pfizer, Janssen, Novartis, Merck, Pierre-André Fournier Shareholder of: AbbVie, Employee of: AbbVie, Tanya Girard Shareholder of: AbbVie, Employee of: AbbVie, Latha Naik Speakers bureau: AbbVie, Consultant of: AbbVie, Grant/research support from: AbbVie, Dalton Sholter Speakers bureau: AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, UCB, Philip Baer Speakers bureau: Abbvie, Amgen, Lilly, Pfizer, Janssen, Teva, Fresenius Kabi, Viatris, Opticann, Novartis, Organon, Gilead, Celltrion, Astra Zeneca, GSK, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Janssen, Teva, Fresenius Kabi, Viatris, Opticann, Novartis, Organon, Gilead, Celltrion, Astra Zeneca, GSK, Grant/research support from: Abbvie, Amgen, Lilly, Pfizer, Janssen, Teva, Fresenius Kabi, Viatris, Opticann, Novartis, Organon, Gilead, Celltrion, Astra Zeneca, GSK