Line Of Biological Treatment Research Articles

P945 Crohn´s disease response to ustekinumab measured by bowel ultrasound

Abstract Background After the STRIDE-II update for patients with Crohn’s disease (CD) one of the new possible adjunct treatment goals was transmural healing, yet its assessment is still not fully cost/risk-benefit proven. A valuable tool to assess this adjunct goal is bowel ultrasound. For this reason, our aim was to evaluate the bowel ultrasonographic response to ustekinumab at one year. Methods Retrospective, observational, single center study was designed. All adult patients with CD who were treated with ustekinumab and had a bowel ultrasound just before the induction dose with ustekinumab and who repeated the bowel ultrasound one year after it were included. Examination was done by ultrasound machine (Hitachi Avius) with low frequency curved-array (1-5 MHz) and high-frequency linear-array (5-13 MHz) transducers. The measured bowel ultrasonographic variables were: wall thickness, Doppler activity (Limberg index) and fatty striation. Ultrasonographic response was defined as a reduction in wall thickness of at least 25%, 2mm or 1mm plus 1 Doppler sign. Remission was defined as wall thickness less than 3mm plus absent Doppler sign. Patient demographics and disease characteristics were also collected: age, sex, extension of CD, previous biologic treatments and ustekinumab trough levels. Demographic and clinical characteristics were compared using χ2 analysis (or Fisher’s exact test), Student’s t test or Spearman correlation. All statistical analyses were performed using the STATA Statistical Software. Results A total of 41 patients (56.1% female) with a mean age of 57.9 years (SD ±2.7) were included. 63.4% had ileal disease and 36.6% ileocolonic involvement. Ustekinumab was first line of biologic treatment in 7.3%, second line in 61.0%, third line in 29.3% and fourth line in 2.4% of patients. 63.4% of patients were on ustekinumab 90mg subcutaneous every 4 weeks at one year with a median trough level of 8.6 (range 7.9-10.6). The median wall thickness measured by bowel ultrasound before induction was 5.5 mm (range 5.0-6.4) and after one year it was 5.0 mm (4.1-5.7) (p=0.47) Figure 1. Before treatment Limberg index was 3 in 26.8% and after treatment it was 3 in 4.9% (p=0.052). Fatty striation was present in 90.2% of patients at the beginning of treatment and in 63.4% at one year (p=0.013). Ultrasound response was achieved in 36.6% of patients while transmural remission was achieved in 12.2% of patients in the first year. No association between ustekinumab trough levels and response/remission were found (p=0.70/p=0.83) Conclusion Treatment with USK was related with an ultrasonographic response in one third of patients with refractory CD at one year. No association between ustekinumab trough levels and ultrasonographic response/remission were found

Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease.

The effectiveness of canakinumab may change according to the different times it is used after Still's disease onset. This study aimed to investigate whether canakinumab (CAN) shows differences in short- and long-term therapeutic outcomes, according to its use as different lines of biologic treatment. Patients included in this study were retrospectively enrolled from the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to Still's disease. Seventy-seven (51 females and 26 males) patients with Still's disease were included in the present study. In total, 39 (50.6%) patients underwent CAN as a first-line biologic agent, and the remaining 38 (49.4%) patients were treated with CAN as a second-line biologic agent or subsequent biologic agent. No statistically significant differences were found between patients treated with CAN as a first-line biologic agent and those previously treated with other biologic agents in terms of the frequency of complete response (p =0.62), partial response (p =0.61), treatment failure (p >0.99), and frequency of patients discontinuing CAN due to lack or loss of efficacy (p =0.2). Of all the patients, 18 (23.4%) patients experienced disease relapse during canakinumab treatment, 9 patients were treated with canakinumab as a first-line biologic agent, and nine patients were treated with a second-line or subsequent biologic agent. No differences were found in the frequency of glucocorticoid use (p =0.34), daily glucocorticoid dosage (p =0.47), or concomitant methotrexate dosage (p =0.43) at the last assessment during CAN treatment. Canakinumab has proved to be effective in patients with Still's disease, regardless of its line of biologic treatment.

P387 Different rate of transmural remission between first and second line of biologic treatment in Crohn's disease

Abstract Background Transmural remission in Crohn’s disease (CD) has been associated with improved long-term clinical outcomes including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. Albeit transmural remission rate (TRR) in CD patients treated with anti-TNF drugs in first line has been well explored, data on TRR using vedolizumab (VDZ) or ustekinumab (UST) as second-line therapy for CD are still scarce. The aim of this study was to evaluate the TRR in CD patients in maintenance treatment, comparing adalimumab (ADA) in first line with VDZ/UST in second line. Methods From 2018 to 2021 we performed a real world observational longitudinal study evaluating the TRR in all consecutive CD patients in a 2-years maintenance treatment with ADA in first line compared with those treated by VDZ or UST in second line. HBI, fecal calprotectin (FC), SES-CD, and bowel wall thickness (BWT) at ultrasound were analyzed in all patients at the baseline (T0) and after 2 years of maintenance treatment (T1). Clinical remission was defined when HBI was <4. Endoscopic remission was defined when SES-CD was <2. Transmural remission was defined when BWT was <3 mm at a “per-patient” analysis. In accordance with recent literature, laboratory remission was defined when FC was <94 ug/gr. Results One hundred and forty-one CD patients (78 ADA, 31 VDZ, 32 UST) were included in the study. At T1, transmural remission rate was recorded in 39.7% of CD patients treated in first line with ADA, and in 22.5% and 18.7% for VDZ and UST, respectively, in second line (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.7). Endoscopic remission rate was 50% for patients treated in first line with ADA, and 32.2% and 31.2% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.9). Laboratory remission rate was 53.8% for patients treated in first line with ADA, and 29% and 37.5% for VDZ and UST in second line, respectively (ADA vs VDZ/UST: p<0.05; VDZ vs UST: p 0.4). Clinical remission rate was 58.9% for patients treated in first line with ADA, and 45.1% and 40.6% for second line VDZ and UST, respectively (ADA vs VDZ/UST: p=0.057; VDZ vs UST: p=0.7). Conclusion Our findings showed that in CD patients in maintenance treatment with biologics, ADA in first line showed a higher TRR compared with VDZ/UST in second line. Moreover, VDZ and UST showed similar TRR and other outcomes when used in second line.

One-Year Treatment Outcomes of Secukinumab Versus Tumor Necrosis Factor Inhibitors in Spondyloarthritis: Results From Five Nordic Biologic Registries Including More Than 10,000 Treatment Courses.

To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj ] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score <2.1, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] <40 mm, crude/LUNDEX-adjusted, adjusted logistic regression analyses with odds ratios [ORs]) stratified by line of biologic treatment (first, second, and third plus). In total, 10,853 treatment courses (842 secukinumab and 10,011 TNFi, of which 1,977 were adalimumab) were included. The proportions of patients treated with secukinumab during the first, second, and third-plus lines of treatment were 1%, 6%, and 22%, respectively). Extraarticular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a 1-year retention comparable to adalimumab as a first or second line of treatment but poorer as a third-plus line of therapy (secukinumab 56% [95% confidence interval (95% CI) 51-61%] versus adalimumab 70% [95% CI 64-75%]; HRadj 1.43 [95% CI 1.12-1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score <2.1 OR 0.56 [95% CI 0.35-0.90]; BASDAI <40 mm OR 0.62 [95% CI 0.41-0.95]). Treatment outcomes varied across the 5 TNFi. Secukinumab was mainly used in biologics-experienced patients with SpA. Secukinumab and adalimumab performed similarly in patients who had failed a first biologic, although with increasing prior biologic exposure, adalimumab was superior.

Effectiveness and safety of secukinumab in axial spondyloarthritis: a 24-month prospective, multicenter real-life study.

Objectives:To evaluate, in a multicentric Italian cohort of axial spondyloarthritis (axSpA) patients on Secukinumab (SEC) followed for 24 months: (1) the long-term effectiveness and safety of SEC; (2) the drug retention rate and low disease activity (LDA) measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4/Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1 and very low disease activity (VLDA) measured as BASDAI < 2/ASDAS < 1.3; (3) any differences in outcomes according to line of biological treatment (naïve/non-naïve), gender (male/female), subtype of axSpA [radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)].Methods:Consecutive axSpA patients treated with SEC 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 over-time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug discontinuation and LDA at T6. Infections and adverse events were recorded.Results:A total 249 patients (47.8% male; median age 51) were enrolled; 40.9% had HLA-B27; 53.8% had r-axSpA, and 46.2% nr-axSpA. SEC was prescribed in 28.9% naïve and in 71.1% non-naïve patients. SEC effectiveness was shown as an improvement in several outcomes, such as ASDAS [T0 = 3.5 (2.9–4.4) versus T24 = 1.9 (1.2–2.4); p = 0.02] and BASDAI [T0 = 6.5 (5.0–7.5) versus T24 = 2.8 (1.8–4.0); p = 0.03]. At T24, naïve patients showed better physical functioning and lower disease activity than non-naïve. After 24 months of treatment, 90.7% of naïve and 75.3% of non-naïve patients achieved LDA (BASDAI < 4). Treatment was discontinued in 24.5% patients, mainly due to primary/secondary loss of effectiveness, and in 6.8% due to adverse events. Retention rate at T24 was 75% in the whole population, with some difference depending on gender (p = 0.002).Conclusion:In a real-life clinical setting, SEC proved to be safe and effective in axSpA, mainly in naïve-patients, with a notable drug retention rate. No differences were observed between r-axSpA and nr-axSpA.

Management of adult-onset Still\u2019s disease with interleukin-1 inhibitors: evidence- and consensus-based statements by a panel of Italian experts

BackgroundAdult-onset Still’s disease (AOSD) is a rare inflammatory condition characterized by fever, rash, and arthritis. Because of its rarity, clinical trials are inherently small and often uncontrolled. Our objective was to develop recommendations for the use of interleukin (IL)-1 inhibitors in the management of patients with AOSD, based on the best evidence and expert opinion.MethodsA panel of 10 experts (9 rheumatologists and 1 pediatrician) was established. The first step was dedicated to a comprehensive literature review and development of statements. Two separate literature searches were performed on the MEDLINE (Pubmed), EMBASE, and BIOSIS databases through April 2018 to identify (1) differences and similarities between AOSD and pediatric Still’s disease (systemic juvenile idiopathic arthritis [SJIA]) and (2) the efficacy and safety of IL-1 inhibitors in AOSD treatment. In the second step, the statements were submitted in a Delphi process to a panel of 67 rheumatologists. Consensus threshold was set at 66%: positive, > 66% of voters selected scores 3 to 5; negative, > 66% of voters selected scores 1 or 2. In the third step, the voting results were analyzed, and the statements were finalized.ResultsEleven statements were developed. Forty-six of 67 rheumatologists (72%) participated in the Delphi process. A positive consensus was reached after the first round of voting and was full (> 95%) on the majority of statements. A large consensus was achieved in considering AOSD and SJIA as the same disease. The use of anti-IL-1 therapies in refractory patients was considered quite safe and effective both as the first and as a subsequent line of biologic treatment, especially in systemic patients. Because of the lack of head-to-head comparisons, a different profile of efficacy among IL-1 inhibitors could not be established. There was a large consensus that failure of the first IL-1 inhibitor does not preclude response to another one. The lack of studies comparing early versus late treatment did not allow to draw conclusions; however, data from SJIA suggest a better response in early treatment.ConclusionsThe Delphi method was used to develop recommendations that we hope will help clinicians in the management of patients with AOSD refractory to conventional therapies.

PSY55 TREATMENT OF PSORIASIS: ANALYSIS OF REAL-WORLD EVIDENCE

Psoriasis is one of the most common skin dermatoses affecting 2-3% of the Central European population. For the treatment of psoriasis (L40), the conventional, the local and the biological treatment are available in the Czech Republic. Due to increasing use of biological treatments and biosimilars in recent years, analysis of real-world evidence (RWE) was conducted. The aim of the study was to analyze the use of treatments in rea world settings, to determine the time to biological treatment, describe the treatment sequences, using biosimilars and to determine whether biological treatment prescriptions in the Czech Republic are exploited to their full potential. The patient level data on prescriptions connected with L40 diagnosis was collected from General Health Insurance Company of the Czech Republic, which represents approximately 60 % of patients in the Czech Republic. The data were processed by SQL and extrapolated to all Czech population. There are almost 100 thousand patients treated with psoriasis in the Czech Republic every year. Most of them are treated by local therapy, only 1.5 % of patients uses biological treatment. The patient takes on average more than 3 years and almost 5 treatment molecules from the first treatment before getting to the biological treatment. Since patients get the biological treatment they remain on this treatment – 70 % of patients have only one line of biological treatment. Biosimilars replace original biological treatment very slowly. The biological treatment is highly effective but much more expensive therapy. Only small number of patients uses biological treatment in psoriasis, and it takes long time to get on it. The entry of new biosimilars (infliximab and etanercept) did not bring huge change in number of patients or switching to cheaper drug. The additional analysis should be conducted in the future with new adalimumab biosimilars.

Long-Term Retention Rate of Anakinra in Adult Onset Still’s Disease and Predictive Factors for Treatment Response

Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission.Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission.Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed.Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043–1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058–0.863).Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.

First line of biological drugs in rheumatoid arthritis: a medication persistence analysis

ABSTRACTObjectives: To evaluate the persistence of biological drugs used as the first line of biological treatment in patients diagnosed with rheumatoid arthritis. The predictors associated with persistence have also been verified.Methods: We evaluated a historical cohort composed of users of the Brazilian National Health System in the period between 2006 January and 2014 December. The endpoint was the medication persistence at 12 months.Results: A population composed of 66,787 individuals started the first line of biological drug. Out of such individuals, 34,595 (51.80%) persisted in the treatment at 12 months. Abatacept was the drug that presented higher persistence, followed by golimumab, tocilizumab, etanercept, and adalimumab and, with lower persistence certolizumab and infliximab. Younger individuals, living in regions with higher social inequality by Gini coefficient, using certolizumab and infliximab in comparison with adalimumab presented a higher risk of non-persistence to treatment. Individuals from the Southeastern region were more persistent than Northeastern, Central-western, Northern and Southern regions.Conclusion: The medication persistence was different between biological drugs. The rigorous follow-up of patients, by a multidisciplinary team, is important to enable the development of strategies for the adequate use of such drugs.

Golimumab in real-life settings: 2 Years drug survival and predictors of clinical outcomes in rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis.

To assess the drug survival of golimumab, and predictors thereof, in patients affected with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) in a prospective observational cohort. This is a non-interventional, longitudinal study on RA, SpA, and PsA patients starting treatment with golimumab. Endpoints were the 2 years persistence rate of golimumab and predictors of therapy discontinuation. Drug retention was analyzed using Kaplan-Meier and Cox models. Hazard ratios (HR) of golimumab discontinuation were estimated by Cox-regression hazard models. Of 416 patients starting golimumab, 171 biologic-naïve and 245 inadequate responders to prior biologic drugs, 88 had RA, 147 SpA, and 181 PsA. Global 2 years drug retention was 70.2%, with no different hazard of discontinuation among diseases or line of biologic treatment. The strongest predictor of golimumab discontinuation was female gender (HR = 1.95). Golimumab monotherapy was associated with higher risk drug interruption (HR = 1.67). Within SpA, predictors of golimumab discontinuation were female sex (HR = 4.19), and absence of extra-articular manifestations (HR = 4.60). In PsA, duration of disease was negatively associated to drug interruption (HR = 0.93), whereas golimumab monotherapy was positively (HR = 2.21) associated. Interestingly, failing to achieve a good EULAR response at 3 months was the only predictor of golimumab discontinuation for RA patients (HR = 3.03). This study provided evidence that golimumab has high retention rate in real-life settings. SpA male patients with extra-articular manifestations, PsA patients on co-therapy with DMARDs, and RA patients attaining an early clinical response had the highest probability to continue golimumab over 2 years.

PMS26 - Tocilizumab Monotherapy As The First Line of Biological Treatment In Rheumatoid Arthritis: Budget Impact Analyses From The Perspective of Brazilian Public Healthcare System (SUS)

PMS26 - Tocilizumab Monotherapy As The First Line of Biological Treatment In Rheumatoid Arthritis: Budget Impact Analyses From The Perspective of Brazilian Public Healthcare System (SUS)

Gammaglobulins, autoantibodies, therapeutic antibodies and anti-drug antibodies in rheumatoid arthritis.

Gammaglobulins, autoantibodies, therapeutic antibodies and anti-drug antibodies in rheumatoid arthritis.

FRI0542 Course of Biotherapies in A Large Cohort of Juvenile Idiopathic Arthritis at Adulthood

BackgroundFew studies focused on the course of biotherapies in juvenile idiopathic arthritis (JIA). Results of these studies showed that anti-TNFalpha drug survival was comparable to adult rheumatoid arthritis. However, these...

AB0448 Drug Survival of A Patients Cohort with Chronic Inflammatory RHEUMATISM Treated with Abatacept

ObjectivesThe persistence in therapy is an important assessment tool of therapy efficacy in patient with chronic disease. The aim of this study was to evaluate drug survival (DS) of a...

SAT0340 Infliximab Levels and Anti-Infliximab Antibodies Comparison between Two Comercial ELISA Versions in Patients with Ankylosing Spondylitis

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease which can result in invalidating deformities of the joints and spine at an early age. The introduction of tumor necrosis factor (TNF)...

A1.26 Establishing cut-off of infliximab levels and anti-infliximab antibodies by commercial elisa in patients with rheumatoid arthritis

IntroductionIn patients with rheumatoid arthritis (RA) the reasons for failure or loss of response to infliximab (IFX) are controversial, so far both IFX serum levels and the presence of anti-IFX...