Multicenter Study of Secukinumab Survival and Safety in Spondyloarthritis and Psoriatic Arthritis: SEcukinumab in Cantabria and ASTURias Study

Objectives: We aimed to evaluate the drug retention rate and safety of secukinumab (SEC) in patients with axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA) in a real clinical setting.Methods: This multicenter retrospective observational study included all AxSpA and PsA patients who received at least one dose of SEC. Adverse events (AE) and the drug retention rate were the main study outcomes. Drug survival was analyzed by Kaplan-Meier curves while predictive factors of discontinuation were evaluated using a Cox regression analysis. The weight of these associations was estimated by hazard ratio (HR) values.Results: We included 154 patients (59 PsA and 95 AxSpA). Mean disease duration was 6.5 years (IQR 2-8). Sixty-one percent of patients were treated with two or more biologics prior to SEC. The 1 and 2-year retention rates for SEC were 66 and 43%, respectively. The main causes of discontinuation were inefficacy (59%) and AE (36%). The factors associated with lower risk of discontinuation were male gender (HR 0.54, 95% CI 0.38-0.78 p = 0.001), obesity (HR 0.53, 95% CI 0.30-0.93 p = 0.027), hypertension (HR 0.55, 95% CI 0.30-0.93 p = 0.008), and diabetes (HR 0.42 95% CI 0.18-0.99 p = 0.047) while number of previous biologics and depression were predictors of discontinuation (HR 1.18, 95% CI 1.04-1.34 p = 0.011 and HR 2.53, 95% CI 1.61-3.96 p < 0.001).Conclusions: SEC showed a good retention rate in a population previously exposed to several biological therapies. As a novelty, cardiometabolic comorbidities were associated with better drug survival.

AB0252 EFFICACY OF A SECOND JANUS KINASE INHIBITOR THAT WAS SWITCHED FOR DIFFICULT-TO-TREAT RA IN CLINICAL PRACTICE

Background:In clinical practice, when refractory rheumatoid arthritis (RA) is present, of which the definition implies previous use of at least two biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)), the next treatment choice often made is a bDMARD of another class (non-TNFis) [1]. However, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARDs treatment reduces their response [2]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis. The choice of therapeutic agents for refractory RA is increasing, and its efficacy is expected. On the other hand, it is also true that some patients discontinued JAKis at a rate that cannot be overlooked because of insufficient efficacy. Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(3)Objectives:To evaluate real world efficacy of approved JAKis switching in patients with D2T RA who were unable to control their disease activity due to insufficient efficacy despite the sequential use of multiple bDMARDs and JAKis, focusing on the drug retention rate.Methods:In our hospital, RA was diagnosed according to the 1987 or 2010 classification criteria, and when two or more bDMARDs (including both TNFis and non-TNFis) were inadequately effective, it was defined as D2T RA. We retrospectively investigated patients who switched to JAKis for D2T RA. The drug retention rate was investigated by the Kaplan-Meier method, and the difference was tested by the Logrank test.Results:The 1-year retention rate of JAKis for D2T RA was 50.8% in TOF 38 cases [28 women, age average 70.2 years, disease duration average 12.4 years, past bDMARDs use average 3.5 drugs, MTX combination 9 cases, DAS28 ESR average 4.11] and 66.3% in BAR 35 cases [26 cases, 73.0 years old, 14.8 years, 4.17 agents, 9 cases, 3.68], and there was no significant difference (P = 0.30). Among them, there were 17 cases [11 cases, 70.6 years old, 13.5 years, 4.18 drugs, 2 cases, 3.65] of switching between JAKis, all of which were switching from TOF to BAR. The 1-year retention rate was 45.8% [reason for discontinuation: insufficient effect in 3 cases, adverse events in 6 cases], which was not significantly different but tended to be lower than 72.7% [reason for discontinuation: insufficient effect in 1 case, adverse event in 2 cases, patient’s convenience in 1 case] in 16 patients [13 cases, 76.3 years old, 17.1 years, 3.19 drugs, 7 cases, 3.69] who received BAR as the first JAKi for D2T RA patients (P = 0.089).Conclusion:Although the number of cases is small in the retrospective survey, it is suggested that the retention rate of BAR switched to D2T RA may be slightly lower in patients with a history of TOF discontinuation due to insufficient efficacy than in JAKi naive patients. It is expected that the number of new JAKi usage cases will increase in the future, and it is necessary to consider switching between other JAKis in addition to switching from BAR to TOF.References:[1]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[2]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[3]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared

POS0088 EFFICACY OF JANUS KINASE INHIBITORS FOR DIFFICULT-TO-TREAT RA IN CLINICAL PRACTICE

Background:In 20-30% of rheumatoid arthritis (RA) patients, the first biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)) is ineffective, and among the patients who do respond to therapy, 20% is faced with secondary ineffectiveness within the first 2 years of treatment [1]. In practice, when refractory RA is present, of which the definition implies previous use of at least two bDMARDs (generally TNFis), the next treatment choice often made is a bDMARD of another class (non-TNFis) [2]. On the other hand, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARD treatment reduces their response [3]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis.Objectives:Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(4). We evaluated real world efficacy of approved JAKis and factors that may help to continue them in patients with D2T RA.Methods:Patients who had inadequate response to two or more bDMARDs (including both TNFis and non-TNFis) at our hospital by December 2019 were defined as D2T RA, and patients who switched to JAKis were retrospectively investigated. The drug retention rate was determined by Kaplan-Meier method, and the difference was tested by Logrank test. Multiple regression analysis was used as the statistical method to predict continuation of JAKis for more than 1 year, with patient background (age, gender, during the disease, number of bDMARDs used, with or without methotrexate and/or glucocorticoids, disease activity score assessing 28 joints using erythrocyte sedimentation rate’ presence of rheumatoid factor/anti-CCP antibody, matrix metalloproteinase 3 value, Health Assessment Questionnaire disability index) at the time of initiation as an explanatory variable.Results:A total of 915 bDMARDs had been administered to 394 RA patients. The retention rate of bDMARDs and the number of bDMARDs used were 89.3% and 1.48 bDMARDs at 1 year, 67.7% and 2.27 bDMARDs at 5 years, and 52.0% and 3.15 bDMARDs at 10 years, respectively. The retention rate of JAKis at 1 year was 60.2% in 65 patients with tofacitinib (TOF) and 67.2% in 70 patients with baricitinib (BAR) (P=0.38). Among them, the drug retention rate in D2T RA patients was 50.8% in 38 TOF patients and 66.3% in 35 BAR patients with no significant difference (P=0.30). There were no patient background factors that significantly predicted continuation at 1 year for any JAKis.Conclusion:Despite the limited number of patients and the retrospective nature of the study, TOF and BAR were shown to be effective options for D2T RA, regardless of patient background such as disease activity or number of bDMARDs used. Other JAKis and switches between JAKis need to be investigated in the future.References:[1]Schaeverbeke T, Truchetet ME, Kostine M et al. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology 2016;55:210_20.[2]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[3]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[4]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared

Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) differences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); p<0.01). At T24, group A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

A retrospective analysis of the relationship between anti-cyclic citrullinated peptide antibody and the effectiveness of abatacept in rheumatoid arthritis patients

This study aimed to evaluate the effectiveness of abatacept (ABA) by anti-cyclic citrullinated peptide (ACPA) status on disease activity as well as radiographic progression in patients with rheumatoid arthritis (RA) in clinical settings. A retrospective cohort study was conducted using data from a multicenter registry. Data from a total of 553 consecutive RA patients treated with intravenous ABA were included. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between the ACPA-negative (N = 107) and ACPA-positive (N = 446) groups. ‘ACPA positive’ was defined as ≥ 13.5 U/mL of anti-CCP antibody. Baseline characteristics between groups were similar. The proportion of patients who achieved low disease activity (LDA; SDAI ≤ 11) at 52 weeks was significantly higher in the ACPA-positive group. Multivariate logistic regression analysis identified ACPA positivity as an independent predictor for achievement of LDA at 52 weeks. Drug retention rate at 52 weeks estimated by the Kaplan–Meier curve was significantly higher in the ACPA-positive group. Achievement rate of structural remission (ΔmTSS ≤ 0.5) at 52 weeks was similar between groups. ABA treatment demonstrated a significantly higher clinical response and higher drug retention rate in ACPA-positive patients. Progression of joint destruction was similar between the ACPA-negative and ACPA-positive groups. Close attention should be paid to joint destruction even in patients showing a favorable response to ABA, especially when the ACPA status is positive.

Long-Term Effectiveness of Secukinumab in Patients with Axial Spondyloarthritis

Objectives. The primary aim of our study was to evaluate long-term efficacy of secukinumab (SCK) in patients with axial spondyloarthritis (axSpA); secondary aims were to evaluate drug retention rate and to identify differences in the clinical and laboratory assessment according to axSpA clinical features, dosage administered, and biologic treatment lines. Patients and Methods. We collected clinical, demographical, and treatment data from 39 patients affected by axSpA consecutively treated with SCK. Laboratory assessment was based on inflammation parameters; clinical assessment was performed with the Ankylosing Spondylitis Disease Activity Score- (ASDAS-) CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were recorded at baseline and every 3 months for the first year and then every 6 months in the second year. Results. Twelve males and 27 females were enrolled; both BASDAI and ASDAS-CRP showed a statistically significant reduction during the observation period (p<0.0001 and p<0.0001, respectively). C-reactive protein significantly decreased (p=0.006), with significant reduction at the post hoc analysis between baseline and both 6-month evaluation (p=0.02) and 24-month visit (p=0.036). No statistical significance was observed in BASDAI and ASDAS-CRP improvement (p=0.482 and p=0.164, respectively) between different dosages administered. No significant differences emerged in the BASDAI and ASDAS-CRP variations between biologic-naïve patients and subjects previously failing to tumour necrosis factor (TNF) inhibitors (p=0.53 and p=0.148, respectively). At the end of our observation, 7 out of 39 patients discontinued SCK. The global retention rate at the end of the study period was 78.2%, without any significant differences between biologic-naïve and anti-TNF-failure patients (p=0.619) or between subjects administered with different SCK dosages (p=0.614). No adverse events were reported. Conclusions. In our cohort, SCK has proved a remarkable effectiveness regardless biologic treatment line and dosages employed. As suggested by the notable drug retention rate, SCK has been able to maintain its effectiveness over a considerable long period of treatment.