BackgroundIn rheumatoid arthritis (RA), the patient global assessment (PGA) is influenced by a multitude of factors that may vary over time and in relation to certain disease characteristics [1]. The inclusion of the PGA in the definition of remission and the cut-offs that better guarantee good functional and structural outcomes remain therefore uncertain [2,3].ObjectivesAim of our study was to investigate the thresholds of the PGA capable of identifying sustained suppression of inflammation and functional integrity in patients with early RA in relation to the autoantibody status.MethodsData were retrieved from a prospective monocentric cohort of 810 patients with early RA (<12 months of symptoms at inclusion) with an observation period of 24 months after treatment institution with methotrexate aimed at the achievement of low disease activity. Patients were evaluated for the achievement of Boolean 3-variable (3-v) remission (swollen joint count, tender joint count, and C-reactive protein all ≤1) at any time-point in the first 12 months. The thresholds of the PGA at the time of 3-v remission that best predicted persistence of 3-v remission after 6 months, and normal function (health Assessment Questionnaire, HAQ, ≤0.5) after 12 months were investigated through receiver operating curve (ROC) analyses in autoantibody-positive and –negative patients separately.ResultsA total of 749/810 (92.5%) patients had follow-up data available until month 24. Of them, 390 (52.1%) achieved 3-v remission in the first year of observation after a median (IQR) of 6 (2-9) months. Autoantibody-positive patients showed a trend for earlier 3-v remission (adjusted HR [95% CI] 1.21 [0.99-1.48]). Among patients achieving 3-v remission, 193 (49.5%) maintained 3-v remission after 6 months, without significant differences in relation to the autoantibody status. Normal function after 12 months characterized slightly more autoantibody-positive than –negative patients (91.2% vs 83.3%, p=0.15). The best cut-off values of the PGA capable of predicting persistence of 3-v remission and normal function in autoantibody-positive patients were ≤9 (AUC 0.76) and ≤13 (AUC 0.73), respectively (Table 1). The corresponding thresholds in autoantibody-negative patients were ≤20 (AUC 0.75) and ≤21 (AUC 0.69).Table 1.Performance of PGA thresholds for predicting persistence of remission and normal functionAb-posAb-negPersistence of 3-v remissionCriterionSens95% CISpec95% CI+LR-LRCriterionSens95% CISpec95% CI+LR-LR≤976.166.1-84.475.865.9-843.140.32≤2084.275.6-90.762.852.6-72.12.260.25Normal function≤1381.774-87.968.841.3-892.610.27≤2166.757.4-75.174.255.4-88.12.580.45ConclusionIncreasing the threshold of the PGA to ≤20 in patients with early RA is associated with sustained suppression of inflammation and good functional outcomes in autoantibody-negative patients. In contrast, in autoantibody-positive patients, a stringent threshold of ≤10 remains optimal.References[1]Bugatti S et al. Ann Rheum Dis 2022; doi: 10.1136/annrheumdis-2022-222436.[2]Studenic P et al. Ann Rheum Dis 2020; doi: 10.1136/annrheumdis-2019-216529.[3]Ferreira RJO et al. Ann Rheum Dis 2020; doi: 10.1136/annrheumdis-2020-217171.Acknowledgements:NIL.Disclosure of InterestsLudovico De Stefano: None declared, Bernardo D’Onofrio: None declared, Elena Marazzi: None declared, MIchele Di Lernia: None declared, Emanuele Cassione Bozzalla: None declared, Antonio Manzo: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Novartis, Pfizer, Sandoz, Janssen, Serena Bugatti Speakers bureau: AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Novartis, Pfizer.

BackgroundThe management of rheumatoid arthritis (RA) has substantially improved during the last few decades; despite that, a significant proportion of patients remain refractory to conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), as well as to one or more biologic/target-synthetic (b/ts) DMARDs. It is estimated the overall proportion of refractory RA is around 3-17%. Refractory disease has been defined among patients with established, long-standing, RA. However, at present time, it is not known whether early diagnosis, prompt institution of DMARD within the window of opportunity and treatment steered-to-target are efficacious to prevent multidrug failure in patients with new-diagnosed RA.ObjectivesFirst, to assess if an Early Arthritis Clinic (EAC) background – early diagnosis and treatment within the “window of opportunity”, disease management according to treat-to-target (T2) strategy – reduces the risk of being DMARDs refractory; secondly, to detect possible predictors of refractoriness in patients escalated to b/tsDMARDs.MethodsData were retrieved from a prospective monocentric cohort of 810 patients with early RA (symptoms duration <12 months at inclusion) diagnosed between 2005-2017 and treated with csDMARDs (methotrexate in 90.4% of the cases) according to a T2T strategy in the setting of an EAC. The population of interest included all patients escalated to b/tsDMARDs because of inefficacy/intolerance to csDMARDs. The frequency and factors associated with failure to first and second b/tsDMARDs were analysed by logistic regression.ResultsA total of 135/816 (16.5%) early RA patients required treatment escalation to a b/tsDMARDs after a median (IQR) of 18.5 (11-39) months from diagnosis; of them, 117 had follow-up visits available for a median (IQR) of 96 (37-122.5) months after treatment initiation. Fifty-six patients (50.4%) failed the first b/tsDMARD after a median (IQR) of 14 (7.3-44.3) months due to inefficacy/side effects. The rates of failure of the second and third b/tsDMARD were 20.5% and 19.7%. Thirteen patients (11.1%) could be defined D2T, having failed a median (IQR) number of 2 (2-3) b/tsDMARDs with different mechanisms of action, and 3 (2.8-4) different b/tsDMARDs in general. By logistic regression, significant predictors of first b/tsDMARD failure were disease duration ≤24 months and autoantibody-negativity (respectively HR 1.89, 1.01-4.12, p=0.03; HR 1.66, 1.00-3.15, p=0.04). The latter confirms to be a significant predictor of second b/tsDMARD failure as well (HR 2.13, 1.08-4.17, p=0.03). At univariable analysis, significant predictors of D2T were concomitant diagnosis of fibromyalgia, autoantibody-negative status and lower doses of methotrexate. At bivariate logistic regression, fibromyalgia and autoantibody-negative RA maintained independent association with adjusted ORs (95% CI) of 3.6 (1.02-16.4) and 4.3 (1.01-24.1), respectively.ConclusionEarly diagnosis, prompt initiation of methotrexate and management according to T2T strategy have substantially improved RA outcomes, and only about 16% of patients require escalation to second-line therapies. However, in those refractory to csDMARD, EAC setting seems not to ameliorate treatment persistence, as retention rates of b/tsDMARDs are similar to those observed in established disease. Early methotrexate inefficacy and autoantibody-negative disease appear to be predictive of first b/tsDMARD failure; moreover, patients with autoantibody-negative disease maintain a higher risk of failure of subsequent lines of therapies. Collectively, our findings suggest the need for a more tailored approach to refractory RA patients, especially to autoantibody-negative ones.Reference[1]Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021;80(1):31-35. doi:10.1136/annrheumdis-2020-217344.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundRituximab (RTX) achieved high remission-induction and sustained maintenance rates for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [1], [2]. However, RTX is an expensive medication, which may potentially lead to serious side effects. Defining the best dose regimen for maintenance in AAV is still an unmet need.ObjectivesThe aim of the present study is to compare the effects of ultra-low dose RTX (500 mg or 1000 mg once per year) to standard low dose RTX (500 or 1000 mg twice per year) as remission-maintenance therapy in AAV patients.MethodsWe included consecutive AAV patients (classified as GPA and MPA [3]) referring to four different Rheumatology centers in Italy. We assessed all AAV patients who successfully achieved disease remission (BVASv3=0) with conventional RTX or cyclophosphamide regimens and have been subsequently treated with RTX for maintenance of remission. All included patients received at least three maintenance infusions with either 1000 mg or 500 mg, twice per year (standard low dose) or once per year (ultra-low dose). After a period of 18 months, we assessed the remission rate, damage (VDI), glucocorticoids intake, ANCA status, B-cells depletion and serum IgG levels.ResultsFrom January 2011 to December 2021, 83 AAV patients (mean age 51±16, 49.4% female, 95.2% ANCA positive, 65.8% anti PR3, 34.2% anti MPO), 61 classified as GPA and 22 MPA, achieved complete disease remission with conventional RTX induction regimen. After 7 [6-9] months, 29.9% patients started maintenance treatment with ultra-low dose RTX (once per year), while 70.1% patients with standard low dose (twice per year), for 18 months. No significant differences at baseline were noted between patients receiving ultra-low dose when compared to those treated with conventional low-dose.At the end of observation period, a disease flare was observed in 22.7% of the low-dose group, and 21.2% in those treated with the standard dose (p=0.881). Relapse-free survival was comparable between the two group (log-rank p=0.818, Figure 1).Figure 1.When comparing AAV patients treated with ultra-low dose regimen to those treated with low-dose, no differences were noted in negative ANCA rate (72.2% vs 67.1%, p=0.262), ANCA titer (0 [0-7.8] vs 0 [0-50] UI/mL, p=0.232), B-cells depletion rate (70.6% vs 75%, p=0.725), mean serum IgG (811 [146-922] vs 680 [429-861] mg/dL, p=0.367), mean daily glucocorticoid dosage (2.5 [0-5] vs 3.75 [0-5] mg/d, p=0.647), VDI (4 [1-5] vs 2 [1-4], p=0.098), hypogammaglobulinaemia rate (31.8% vs 36.5%, p=0.697) and deaths (4.5% vs 5.8%, p=0.831).Although not significant, patients treated with ultra-low dose had lower severe infection rate (10.5% vs 26.8%, p=0.154). Notably, in the all cohort 5 deaths were related to COVID19 pneumonia.ConclusionReduced exposure to RTX was not associated with an impaired efficacy of maintenance therapy in patients with AAV. Remission maintenance with ultra-low dose RTX is a safe and more cost-effective option.References[1]B. Terrier et al., “ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance,” Press. Medicale, vol. 49, no. 3, 2020, doi: 10.1016/j.lpm.2020.104031.[2]S. V. Moiseev, N. M. Bulanov, A. S. Zykova, and P. I. Novikov, “Rituximab in ANCA-associated vasculitis: Fewer infusions or ultra low-dose maintenance therapy,” Ann. Rheum. Dis., vol. 78, no. 9, pp. 1–2, 2019, doi: 10.1136/annrheumdis-2018-213873.[3]J. C. Jennette et al., “2012 Revised International Chapel Hill consensus conference nomenclature of vasculitides,” Arthritis Rheum., vol. 65, no. 1, pp. 1–11, 2013, doi: 10.1002/art.37715.Disclosure of InterestsNone declared