Concomitant csDMARD Research Articles

Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

The aim of this article is to update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA). We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, two independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to conventional synthetic DMARD (csDMARD). Rituximab with and without concomitant csDMARDs showed similar efficacy to other biological DMARDs (bDMARDs) in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. This systematic review provides latest evidence for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for RA management.

The Evaluation of Effectiveness and Safety of Guselkumab in Patients with Psoriatic Arthritis in a Prospective Multicentre "Real-Life" Cohort Study.

Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a "real-life" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up. Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR. A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6months, a significant reduction of DAPSA was observed (β - 15.47, p = 0.001, 95%CI - 23.15 to - 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs. The "real-life" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs.

Efficacy and Safety of Upadacitinib in Rheumatoid Arthritis: Real-Life Experience from a Prospective Longitudinal Multicentric Study.

We provide the first prospective longitudinal multicenter experience on Upadacitinib efficacy and safety profile in Rheumatoid Arthritis (RA) in a real-life context, focusing on clinimetric and ultrasonographic (US) data. RA patients referred to three Italian tertiary Centers who started Upadacitinib were enrolled as per ACR/EULAR classification criteria and prospectively reviewed. The primary aim of this study was to assess changes in clinimetric and ultrasonographic scores through time (at baseline, after 1 month, 3 months, and 6 months from the beginning of the therapy). Secondary aims were to: (i) estimate the impact of biologic lines of treatment and concomitant therapies on response to therapy; (ii) explore changes in laboratory parameters; and (iii) find potential predictive factors associated with response to therapy. Seventy-one patients (49 Females and 22 Males) were included. Clinimetric scores, including the Disease Activity Score (DAS28-CRP) and Simplified Clinical Disease Activity Index (SDAI), and US findings (synovial hypertrophy and power Doppler) significantly improved (p = 0.029, p = 0.001, p = 0.001, p = 0.001, respectively). Regression analysis revealed a significant association between the concomitant csDMARDs therapy at baseline and the lack of improvement in synovial hypertrophy [OR -4.824, p = 0.010] as well as with DAS28-CRP [OR -0.690, p = 0.045], whereas the presence of increased ESR or CRP at baseline was able to predict a significant improvement in SDAI [OR 8.481, p = 0.003]. No adverse events, such as deep venous thrombosis, pulmonary embolism, or herpes zoster virus infection, were reported during this study observation. Our real-life experience confirms the efficacy of Upadacitinib in terms of clinical and ultrasonographic improvement, as well as displaying a good safety profile.

E072 Real-world single-centre experience of JAK inhibitor use in RA

Abstract Background/Aims The use of Janus Kinase Inhibitors (JAKi) has been gradually increasing overtime in the management of rheumatoid arthritis (RA) and other inflammatory arthritis and these appeal to patients. being oral agents. Nevertheless, rheumatologists have become cautious about their use since recent trials have shown safety concerns about VTEs, MACE and malignancies. Methods We decided to study use of JAKi at our centre in Princess of Wales Hospital Bridgend. The aim was to assess whether appropriate patients were selected (considering cautions about MACE, VTEs and malignancies). We also wanted to see whether all patients had required pre-treatment safety testing and post-treatment monitoring performed. Results These were 70 patients; 59 were females and 11 were males. All of them were diagnosed as RA. Average age was 61.1 years (20—85), average duration of disease 129.9 months (16—340) and average duration of treatment was 58.1 weeks. The most common JAKi being used was baricitinib (84%) followed by tofacitinib (12%) and upadacitinib (4%). 50% patient were on concomitant csDMARDs among whom two-thirds were on methotrexate. Looking at previous biologic use, 9 patients were biologic naïve, 22 had one biologic, 15 had two biologics used in the past. All patients were appropriately selected (severe RA and no significant risk factors for MACE, VTEs and malignancies). All patients had pre-treatment Hepatitis B, Hepatitis C, latent TB, FBC and LFTs checked. All patients had FBC and LFTs monitored post treatment. No patient developed VTE, MACE or cancer on treatment. 84.2% patients had lipids tested before starting JAKi. 22.8% patients had abnormal lipids before Rx initiation and 62.5% of these were on lipid lowering Rx. All patients had lipids tested post treatment, but the timing was quite variable and only 62.5% of patients had lipids tested on the recommended time. There were 2 deaths recorded in this cohort. One of those was an 80-year-old RA patient on baricitinib 2 mg OD, who died due to chest infection on the background of ILD. He was not on steroids or csDMARDs. The second patient was 63 years' old (on baricitinib 4mg OD), and died due to respiratory sepsis, and was also on azathioprine. She had RA with advanced ILD. The reasons for discontinuing JAKi were inefficacy (46%), side effects (39%) and both inefficacy and side effects (15%). 41.4 % of patient experienced side effects due to JAKi. These included infection 28%, deranged lipids 17%, cytopenia 14%, deranged LFTs 14%, GI side effects 10%, skin rash 7% and varicella zoster 3%. Conclusion There has been steady increase in the use of tsDMARDs for RA and other rheumatic conditions. Due to short half-life, these drugs became a popular choice during COVID-19 pandemic but on the other hand safety monitoring became extremely challenging during this time. Disclosure A. Anjum: None. K. Ghanem: None. S. Smale: None. U. Srinivasan: None. S. Duffill: None. C. Jenkins: None.

P017 Prescription trends and reasons for discontinuation amongst at-home biological therapies

Abstract Background/Aims Our unit currently follows the 2019 British Society of Rheumatology Guidelines in the prescribing and monitoring of bDMARDs which advocates 3-6 monthly monitoring blood tests in patients prescribed a biologic without a concomitant csDMARD. The guideline acknowledges “there is no evidence on the optimal monitoring requirements for patients receiving biologics”. In particular there is lack of evidence on the extent to which routine blood monitoring in such patients results in the discontinuation of the biologic. Given the costs associated with complying with this aspect of the guideline we devised this project to describe at-home biologic prescribing trends at our unit over the previous 5 years and to identify the rate of biologic discontinuation due to dyscrasias. Methods We retrospectively analysed all at-home biologic prescriptions issued at our unit between 2017 and 2021 to describe temporal trends in biologic prescribing habits. We used this data to identify patients that discontinued biological therapies and then performed a detailed retrospective analysis of electronic case records of patients who discontinued an at-home anti-TNF biologic (adalimumab, etanercept, golimumab, and certolizumab) between 01/01/2017 and 31/12/2018 to describe the reasons for discontinuation of anti-TNF biologics. Blood dyscrasia was defined as: white cell count <3.5 × 109/l; neutrophils <1.6 × 109/l; creatinine increase >30% over 12 months and/or calculated GFR <60 ml/min; unexplained eosinophilia >0.5 × 109/l; ALT and/or AST >100 U/l; platelet count <140 × 109/l; unexplained reduction in albumin <30 g/l. Results Between 2017 and 2021 our unit issued a total of 39,298 prescriptions for at-home biologics. During this timeframe the total number of annual prescriptions at our unit increased by 76.6% (2017: 5240, 2021: 9265) and the number of unique patients prescribed a biological therapy increased by 72.4% (2017: 1018, 2021: 1755). The total number of anti-TNF biologic prescriptions increased by 49.8%, and the number of adalimumab prescriptions increased by 89.8%. Between 1/1/2017 and 31/12/2018 295 patients discontinued an anti-TNF biologic. Reasons for discontinuation included: drug inefficacy: n = 156 (52.9%), treatment de-escalation: n = 15 (5.1%), adverse event (e.g. infection, side effect, intolerance): n = 36 (12.2%), blood dyscrasia: n = 4 (1.4%), patient lost to follow up: n = 43 (14.6%), pregnancy: n = 8 (2.7%), other (e.g. malignancy, heart failure, interstitial lung disease): n = 33 (11.2%). Conclusion Our data suggests that prescription of at-home biological therapies has increased significantly between 2017-2021. Amongst patients taking anti-TNF therapies the number of patients discontinuing therapy due to blood dyscrasia was very low. In view of the increasing number of biologic prescriptions and the associated costs of 3-6 monthly blood monitoring, further data to determine the optimal monitoring requirements for patients on biological therapies is needed. Disclosure M.D.J. Gibson: None. J. Wells: None. S. Subesinghe: None.

Tofacitinib as monotherapy in cutaneous polyarteritis nodosa: a case series.

Cutaneous polyarteritis nodosa (CPAN) is a distinct clinical entity represented by a chronic, relapsing, benign course, with rare systemic involvement. Treatment is with CSs, CYC or other conventional synthetic DMARDs (csDMARDs). In this case series, we aimed to share our varied clinical experience of successfully treating patients with CPAN, with tofacitinib in a refractory/relapsing course or as upfront monotherapy without CSs/csDMARDs. We report this retrospective case series managed at our rheumatology centre in Bangalore from 2019 to 2022. Four patients identified as CPAN on biopsy were able to achieve disease-free remission with tofacitinib as part of their treatment, with no relapse on further follow-up. Our patients presented with subcutaneous nodules and cutaneous ulcers. After systemic evaluation, all the patients underwent skin biopsy, which showed fibrinoid necrosis in the vessel walls of the dermis, with a histopathological impression of CPAN. They were initially treated with a conventional approach of CSs with/without csDMARDs. On experiencing a refractory/relapsing course, tofacitinib was tried in all the patients as either CS sparing or upfront monotherapy without concomitant csDMARDs. Use of tofacitinib resulted in improvement of ulcers and paraesthesia and in gradual healing of skin lesions, albeit with scarring, with no further recurrence or relapse over a follow-up period of 6 months for all the patients. The therapeutic effect of tofacitinib was consistent when used either as CS sparing or as upfront monotherapy, thereby proving the drug to be a promising option that warrants larger trials in future to treat the subset of patients with established CPAN. Tofacitinib could be used for disease-free remission as monotherapy for CPAN either upfront or as CS sparing, even without concomitant csDMARDs, in those patients who are dependent on CSs or multiple DMARDs.

Efficacy and safety of ixekizumab in patients with active psoriatic arthritis with and without concomitant conventional disease-modifying antirheumatic drugs: SPIRIT-P1 and SPIRIT-P2 3-year results

Introduction/objectivesTo evaluate the three-year efficacy and safety of ixekizumab with and without concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use in patients with active psoriatic arthritis (PsA).MethodPatients with PsA who were biologic-naïve (SPIRIT-P1, NCT01695239) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2, NCT02349295) were randomized to receive 80-mg ixekizumab every four weeks after receiving 160-mg ixekizumab at baseline. Efficacy, safety, and immunogenicity were evaluated in this post-hoc analysis in three subgroups: (1) ixekizumab monotherapy, (2) ixekizumab and methotrexate (MTX), (3) ixekizumab and any csDMARD (including MTX). Missing data were imputed using multiple imputation for continuous variables and modified non-responder imputation for categorical variables.ResultsEfficacy was similar across the three subgroups with 59.1%, 67.0%, and 66.1% of ixekizumab-treated patients achieving 20% improvement in the American College of Rheumatology scale score at week 156. Radiographic progression of structural joint damage (SPIRIT-P1 only) was similarly inhibited across the three subgroups with several outliers. No new safety signals were reported, and 91.0%, 84.1%, and 83.2% in the three subgroups reported ≥ 1 treatment-emergent adverse event. At week 156, 15.9%, 13.1%, and 11.0% in the three subgroups had antidrug antibodies; most had low titer status.ConclusionsIxekizumab showed sustained efficacy in treating patients with PsA for up to three years in monotherapy or in combination with MTX or any csDMARD. The three subgroups had similar safety and immunogenicity profiles, which supports that the use of concomitant MTX or csDMARDs does not seem to impact the benefit/risk profile of ixekizumab.Key Points• Ixekizumab treatment led to improved clinical responses over time when used as monotherapy or in combination with concomitant MTX or any concomitant csDMARD (including MTX) in patients with active PsA.• Ixekizumab monotherapy has similar radiographic efficacy as ixekizumab with MTX or ixekizumab with other csDMARDs (including MTX); similar inhibition of radiographic progression was observed between the subgroups of patients receiving ixekizumab monotherapy or ixekizumab with MTX or other csDMARDs.• The long-term safety profile of ixekizumab used as monotherapy or in combination with MTX or any other csDMARDs is consistent with what has been previously reported. The addition of MTX or any csDMARD to ixekizumab treatment did not negatively impact the favorable long-term safety profile of ixekizumab.

P274 The effect of ixekizumab versus adalimumab on individual components of the ACR composite score, with and without concomitant methotrexate or other conventional synthetic DMARDs, at 52 weeks in patients with psoriatic arthritis

Abstract Background/Aims It is useful to evaluate individual American College of Rheumatology (ACR) components in large trials for active psoriatic arthritis (PsA) because individual patient domains may influence treatment choice. SPIRIT-H2H showed superiority of ixekizumab (IXE) over adalimumab (ADA) in patients with PsA and inadequate response (IR) to conventional synthetic disease modifying antirheumatic drugs (csDMARDs). This analysis describes the effect of IXE and ADA on individual ACR components at week (Wk) 52, with and without concomitant methotrexate (MTX) and csDMARDs. Methods Patients from SPIRIT-H2H (NCT03151551, 52 Wk randomized multicenter study) who met Classification Criteria for Psoriatic Arthritis (CASPAR) (N = 566), were randomized (1:1, stratified by baseline concomitant csDMARDs and moderate-to-severe PsO) to IXE or ADA on-label PsA or PsO dosing. Patients were bDMARD-naïve with IR to csDMARDs, active PsA (≥3 tender joints [TJC] and ≥3 swollen joints [SJC]) and had psoriasis (PsO) ≥3% BSA (body surface area). Patient’s Global Assessment (PtGA) and Physicians Global Assessment (PGA), Health Assessment Questionnaire-Disability Index (HAQ-DI), and joint pain were assessed by visual analog scale, and TJC and SJC as well as C-reactive protein (CRP) were analyzed. All post-hoc analyses were performed on the intent-to-treat (ITT) population. Change from baseline (CFB) in individual ACR components was analyzed using an Analysis of Covariance (ANCOVA) model, for overall as well as with and without concomitant therapies (e.g., MTX or csDMARD). Least square mean (LSM) and standard error (SE) are presented. Missing data were imputed using modified baseline observation carried forward (mBOCF). Nine patients with active PsO and BSA≥3% were assessed as Psoriasis Area and Severity Index (PASI)=0 at baseline, a medical inconsistency that was resolved using medical judgment. These patients were considered PASI100 responders if PASI=0 and BSA=0 at post baseline visits. Results A total of 566 patients received either IXE (N = 283) or ADA (N = 283). Baseline values for individual ACR components were balanced between IXE and ADA. At Wk 52, IXE demonstrated efficacy across all individual ACR components in the ITT population, specifically in PGA, PtGA and Joint Pain; ADA also demonstrated numerical efficacy. Improvements from baseline for IXE were observed across ACR components, with or without MTX or csDMARD. The effect of MTX (with or without) was notably different between IXE and ADA in TJC68, PGA, Joint Pain, and PtGA. Conclusion In this analysis, there was improvement with IXE in all components of the ACR composite score at Wk 52, irrespective of MTX or csDMARD use (with or without). In the ITT population, IXE showed comparable efficacy to ADA at Wk 52 in all components of ACR, demonstrating improvement across musculoskeletal domains. These results may provide further confidence of the clinical benefits of ixekizumab across musculoskeletal domains in patients with PsA, regardless of MTX or csDMARD use. Disclosure A. Kiprianos: None. E. Husni: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, and UCB Pharma. S. Kamat: Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly and Company, and Exogen. K. Stenger: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. T. Holzkaemper: Shareholder/stock ownership; Eli Lilly and Company. C.C. Helt: Shareholder/stock ownership; Eli Lilly and Company. S. Park: Shareholder/stock ownership; Eli Lilly and Company. J.R. Lisse: Shareholder/stock ownership; Eli Lilly and Company. L. Idolazzi: Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly and Company, and Janssen.

P188 Baricitinib effectiveness after a previous inadequate response to an alternative JAK inhibitor: results from the Swiss rheumatoid arthritis register

Abstract Background/Aims Previous research has suggested that switching between b/tsDMARDs with different mode of action may be more effective than switching agents within the same mechanism of action. Limited data exists about the impact of an inadequate response to a previous JAK-inhibitor (JAKi) on subsequent JAKi effectiveness. Methods This is a nested study within the Swiss Clinical Quality Management (SCQM) registry of RA patients. All patients initiating baricitinib treatment courses (BARI) between 01-09-2017 and 01-06-2020, with at least one follow-up visit, were included. We compared the time to treatment discontinuation, as a measure of drug effectiveness, of BARI with a previous history of an inadequate response (IR) to tofacitinib (“BARI-post-TOFA”) or without (“BARI-initial”). Tofacitinib IR was defined as previous tofacitinib treatment discontinuation for adverse events or for ineffectiveness. Baseline characteristics were compared using t-tests or χ2. We used Kaplan-Meier curve to display crude time to discontinuation and a Cox model to estimate adjusted hazard ratio (HR). Cox model was adjusted for potential confounding factors: age, BMI, concomitant csDMARD, concomitant steroid usage, baseline CDAI, disease duration, smoking status, line of therapy, gender and seropositivity to RF/ACPA. Results Of the 273 included BARI, 72 were initiated in patients with a history of a previous tofacitinib IR (Table 1). No differences were found between the “BARI-post-TOFA” and the “BARI-initial” groups in terms of time-to-discontinuation, as demonstrated by both the unadjusted Kaplan-Meier survival analysis (Log-rank p = 0.44) and the fully adjusted Cox analysis (Hazard Ratio BARI-post-TOFA vs BARI-initial = 0.76 (95% IC [0.42 - 1.34]; p = 0.34). Other covariates significantly associated with drug maintenance were active smoking (p = 0.03) and CDAI score (p < 0.01). Conclusion In this preliminary analysis, a history of prior tofacitinib IR did not appear to significantly impact subsequent drug maintenance of baricitinib. Disclosure B.T.P. Gilbert: Other; Invited speaker for Lilly Symposium SGR Congress Lausanne (2021). D.S. Courvoisier: None. D. Mongin: None. K. Lauper: None. V.A. Guimaraes: Other; Clinical Research Scientist Immunology at Eli Lilly (Suisse) S.A. R.B. Mueller: None. A. Finckh: Grants/research support; Invited speaker and consultant for Eli Lilly. Has received research grant from Eli Lilly.

P282 ANA seroconversion during prior anti-TNF therapy abolishes anti-CCP antibody positivity as a predictor of abatacept retention in rheumatoid arthritis

Abstract Background/Aims Few long-term drug survival analyses have been reported for patients with rheumatoid arthritis (RA) treated with abatacept. Here we report a machine learning approach to investigate drug-survival of abatacept over 5 years in RA patients. Methods We performed a retrospective observational study on a tertiary hospital dataset of RA patients who started abatacept between January 2008 and December 2020. Time to abatacept discontinuation over 5 years was estimated using Kaplan-Meier survival analyses. A multivariate cox-proportional hazard model to predict abatacept discontinuation was chosen by random survival forest and partial least regression. Results A total of 112 RA patients (81% female, mean age 58.1 [SD 13.5] years) received abatacept. Mean disease duration was 18.3 months (SD 13.6). More than half (65/112) were co-prescribed at least one conventional synthetic DMARD (csDMARD). Methotrexate was the most frequently concomitant csDMARD (n = 37), followed by hydroxychloroquine (n = 23), sulfasalazine (n = 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (intermittent or continuous) with abatacept. Abatacept was mostly used as 4th (n = 29) and 3rd line (n = 24) bDMARD, but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive (≥1:80) in 25 patients (pre-biologics) and 18 seroconverted to previously exposed anti-TNF (ANA seroconversion group). Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years. Multivariate cox-proportional hazard model revealed that ACPA positivity was associated with reduced risk of abatacept discontinuation with HR of 0.56 (95% CI 0.32-0.95,p=0.03) compared to the ACPA-negative group. In contrast, the ANA seroconversion group demonstrated worse retention of abatacept with HR of 2.67 (95% CI 1.39-5.16, p = 0.0033) compared to ANA-negative patients. Kaplan-Meier analysis demonstrated that in the ANA seroconversion group, retention of abatacept was significantly inferior to pre-anti-TNF ANA positive patients (p = 0.0084) and ANA-negative patients (p = 0.0041). ACPA positivity was associated with better survival only in the non-ANA seroconverted group with HR of 0.54 (95% CI 0.29-0.92, p = 0.041), after adjusted by propensity score. Combining abatacept with any csDMARDs reduced the risk of abatacept discontinuation with HR of 0.57 (95% CI 0.33-0.98, p = 0.043) after adjusting by propensity score. No statistical difference was found between first-line, second-line, or any subsequent chronology of use of abatacept. Conclusion Our data suggest that previous ANA seroconversion occurring whilst on anti-TNF therapy reduces subsequent abatacept retention and cancels out the protective effect of anti-CCP positivity. The mechanism through which this occurs is unclear and further prospective and mechanistic studies are needed to validate these findings. Disclosure J. Kimpton: None. M. Shipa: Grants/research support; MS is funded by Versus Arthritis. S. Yeoh: Grants/research support; SY is funded by the Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities, and Versus Arthritis. E. Hawkins: None. M. Ehrenstein: Grants/research support; ME is supported (in part) by the University College London Hospital Biomedical Research Centre.

Real-Life Retention Rates and Reasons for Switching of Biological DMARDs in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis.

Aims: To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data.Methods: Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients (n = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated “biologics” clinic in a tertiary hospital; the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences. The effect of covariates on switching risk was analysed by a conditional risk-set Cox proportional-hazards model. Treatment retention data was compared to a historical analysis (2002–2008).Results: The proportions remaining on treatment (retention) were similar, throughout follow-up, for the first, second and third b/tsDMARDs across all patients (p = 0.46). When compared to RA patients, the risk of b/tsDMARD failure was halved in PsA patients [Hazard Ratio (HR) = 0.50], but no different in AS patients (HR = 1.0). The respective restricted mean (95%CI) treatment durations, estimated at 5 years of follow-up, were 3.1 (2.9, 3.4), 4.1 (3.7, 4.6), and 3.3 (2.8, 3.9) years, for RA, PsA, and AS, respectively. Age, gender, disease duration, smoking status and the use of concomitant csDMARDS were not associated with the risk of bDMARD failure. The most common reasons for switching in the first and subsequent years were secondary (n = 62) and primary (n = 35) failure. Comparison with historical data indicated no substantive differences in switching of the first biologic for RA and PsA.Conclusion: Similar retention rates of the second and third compared to the first b/tsDMARD in RA, PsA, and AS support a strategy of differential b/tsDMARDs use informed by patient presentation. Despite greater availability of b/tsDMARDs with differing mechanisms of action, retention rates of the first b/tsDMARD remain similar to previous years.

Impact of using concomitant conventional DMARDs on adherence to biologic DMARD treatment in rheumatoid arthritis: Multi-centre, population-based cohort study

PurposeTo evaluate the impact of concomitant use of conventional synthetic DMARDs (csCMARD) on adherence, switching and dose of biologic disease modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis (RA) patients treated with bDMARDs. Patients and methodsThis was a population-based cohort study conducted in five provinces of Canada (Alberta, Manitoba, Ontario, Quebec, and Saskatchewan), and one American database (IBM® MarketScan® Databases). Adult RA patients entered the study after a 3-month initiation period of bDMARDs between 1 January 2007, and 30 March 2014. Concomitant csDMARD exposure was compared to non-csDMARD exposure on the following outcomes: discontinuation of bDMARD therapy, switching of bDMARDs, and percent change in dose of bDMARD compared to initial dose. The effect of the time-varying changes in csDMARD exposure was analyzed using marginal structural models. Dose change was analyzed using linear regression. Results from each participating site were combined using likelihood ratio meta-analysis. ResultsThe study population comprised 20,221 new users of bDMARDs: adalimumab (7609), etanercept (9809), abatacept (1024), infliximab (1779). Concomitant use of csDMARD therapy was not significantly associated with reduced discontinuation of bDMARD treatment (hazard ratio 0.90, 95% intrinsic confidence interval 0.79 to 1.02) or reduced switching of bDMARDs (hazard ratio 0.95, 95% intrinsic confidence interval 0.80 to 1.11), but was associated with a small increase in bDMARD dose compared to the mean dose over the first three months of treatment (mean percentage change in dose +0.56% mg/day, 95% intrinsic confidence interval +0.14% to +0.97%). ConclusionIn this large study of RA patients using bDMARDs in Canada and the United States, we found no clear evidence that patients who received concomitant csDMARD therapy were less likely to discontinue, switch or increase their dose of bDMARD.

POS0601 DIFFERENCES IN DRUG SURVIVAL BETWEEN ORIGINATOR AND BIOSIMILAR PRODUCTS AMONG FIRST USERS OF EACH MOLECULE

Background:Biosimilar products of biological disease-modifying antirheumatic drugs (bDMARDs) entered the Swedish market in 2015, with regulatory approvals based on head to head trials of limited duration. Longer-term comparative drug survival, in clinical practice, remains less well documented.Objectives:To compare survival on drug between biosimilars and their originator products among first starters of etanercept, infliximab, adalimumab and rituximab.Methods:Data from the Swedish Rheumatology Quality register (SRQ) was used to identify and follow patients who started a first ever treatment with etanercept since April 2015 (originator=ETA,biosimilar= SB4), infliximab since March 2014 (originator=IFX,biosimilar= CT-P13), adalimumab since January 2018 (originator=ADA biosimilars=SB5, ABP501), or rituximab since January 2018 (originator=RIT,biosimilar= GP2013), through December 31st, 2019, date of first discontinuation of the drug, or death. Discontinuation was defined as lack of effectiveness or adverse events, while other reasons for interruption of the drug (including non-medical switch) were considered censoring events. Descriptive characteristics were collected from the SRQ and tabulated. Hazard ratios (HR) of discontinuation were estimated using Cox regression, with each drug analyzed separately, adjusted for age,sex,indication,line of treatment,disease duration,year of treatment start,region and concomitant use of csDMARD.Results:9274 patients started etanercept(49% SB4), 3609 started infliximab(64% CT-P13), 3117 started adalimumab(27% SB5, 14% ABP 501), and 763 started rituximab(39% GP2013), Table 1. Patients starting CT-P13 and GP2013 were less likely to be biologics-naïve compared to those starting the originator product. Initiators of SB5,ABP501 and GP2013 were more likely,and those starting CT-P13 were less likely,to be on concomitant csDMARDs compared to those starting the originator products. Patients characteristics of ETA and SB4 were similar.The introduction of a biosimilar was typically followed by a decrease in the uptake of the originator, but for ETA a change in pricing in 2018 later led to a reversal of this pattern (Figure 1).For IFX,ADA,and RIT, survival on drug was similar for the originator and its biosimilar(s). For ETA,risk of discontinuation was somewhat lower for the biosimilar than for the originator(adjusted HR:0.87,95% confidence interval:0.79-0.95), Table 1.Table 1.Hazard ratios of discontinuation and descriptive characteristics of biosimilar vs. originator among first starters of each molecule, until 31st December 2019.EtanerceptInfliximabAdalimumabRituximabOriginatorSB4OriginatorCT-P13OriginatorSB5ABP 501OriginatorGP2013N47214553130823011834852431465298Discontinuation12891236582878399139805726Adjusted hazard ratios*Ref0.87 (0.79-0.95)Ref1.14 (0.99-1.31)Ref1.02 (0.83-1.26)1.16 (0.88-1.52)Ref1.12 (0.68-1.85)Age, mean years (std)51 (16)51 (15)49 (16)49 (16)48 (15)52 (15)51 (15)59 (15)60 (15)Female, %67%65%61%64%62%64%65%75%76%RA, %46%48%39%35%33%42%43%61%76%Bionaïve, %72%72%76%69%45%52%43%53%38%Disease duration, mean years (std)11 (12)11 (11)11 (11)11 (11)12 (13)12 (11)14 (15)14 (19)15 (11)DAS28, mean4.0 (1.3)4.0 (1.4)4.1 (1.4)4.1 (1.4)3.7 (1.4)3.8 (1.3)4.0 (1.3)4.5 (1.4)4.7 (1.4)Concomitant csDMARDs, %45%47%57%48%37%49%42%36%43%Abbreviations: RA=rheumatoid arthritis. csDMARDs=conventional synthetic DMARD, std=standard deviation.Figure 1.Number of starts of biosimilars compared to the originator during the follow-up time, by moleculeConclusion:Despite their identical indications and therapeutic positioning, there are some differences in the baseline characteristics between patients who start ADA, IFX and RIT and their biosimilars. There are no differences in drug survival between originator and biosimilar with the possible exception of etanercept although the observed difference should be interpreted in light of possible unmeasured or residual channeling.Disclosure of Interests:Daniela Di Giuseppe: None declared, Hannah Bower: None declared, Bénédicte Delcoigne: None declared, Thomas Frisell: None declared, Katerina Chatzidionysiou Consultant of: Eli Lilly, AbbVie and Pfizer, Ulf Lindström: None declared, Christopher Sjowall: None declared, Elisabet Lindqvist: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB,

AB0141 THE DYNAMICAL TRAJECTORY OF GLUCOCORTICOIDS TAPERING AND DISCONTINUATION IN RHEUMATOID ARTHRITIS PATIENTS COMMENCING GLUCOCORTICOIDS WITH CSDMARDS: A REAL-WORLD DATA FROM 2009 TO 2020

Background:Glucocorticoids (GC) are currently recommended as bridging therapy in combination with csDMARDs in rheumatoid arthritis (RA) and should be tapered as rapidly as clinically feasible for safety concerns about their long-term use [1-3].Objectives:To unravel the dynamical trajectory and characteristics of GCs tapering and discontinuation in RA patients commencing GCs with concomitant csDMARDs.Methods:We used data from longitudinal real-world TARRA (Treat-to-TARget in RA) cohort in Peking University First Hospital. RA patient who started GCs and contaminant csDMARDs therapy over 1-year follow-up were included. The changes in GCs dose and disease activity in the context of csDMARDs were evaluated. GCs discontinuation rate was analyzed using Kaplan-Meier analysis. The relapse profiles within 6 months after GCs discontinuation were also analyzed.Results:A total of 207 RA patients were included. During a median follow-up duration of 38.6 months, 124 (59.9%) patients discontinued GC. The median oral prednisolone dose of 10 (5-10) mg/d at initiation was reduced by 50% in the first 6 months and then more slowly reduced, finally to zero by 48 months. The cumulative probability of GCs discontinuation was 26.6% at year 1, 48.0% at year 2, 58.6% at year 3, with calculated median time of 27 months (Figure 1). Of the 124 patients who discontinued GCs, add of other csDMARDs or increment of current csDMARDs was required in 29.0% of them. Approximately half of 124 patients were in clinical remission at the time point of GCs discontinuation. Within 6 months after GCs withdrawal, 79.1% (91/115) of participants maintained relapse-free.Figure 1.Kaplan-Meier curve with cumulative probability of glucocorticoids discontinuation in RA patients who start glucocorticoids with concomitant csDMARDs during the follow-up period. csDMARDs: conventional synthetic disease modifying antirheumatic drugs.Conclusion:In RA patients commencing GCs in addition to csDMARDs, GCs are feasibly discontinued with favorable control of disease activity in real-life setting, mostly without short-term flare. Adding targeted therapies are sometimes required to attain GCs discontinuation within the time frame of 3 months in current guidelines.

Dynamical trajectory of glucocorticoids tapering and discontinuation in patients with rheumatoid arthritis commencing glucocorticoids with csDMARDs: a real-world data from 2009 to 2020

ObjectiveTo unravel the dynamical trajectory and features of glucocorticoids (GC) tapering and discontinuation in patients with rheumatoid arthritis (RA) commencing GC with concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).MethodsWe used...

Efficacy, retention, and safety of tofacitinib in real-life: Hur-bio monocentric experience

Background/aimTo assess the real-life efficacy, retention rate, and safety data of tofacitinib in rheumatoid arthritis (RA) patients.Materials and methodsWe analyzed all patients registered in the HURBİO database who received at least 1 dose of tofacitinib. Patients who received at least one dose were included in retention analysis; patients with at least 1 control visit were included in efficacy and safety analysis. Factors predicting good response at the last follow-up visit were analyzed by logistic regression analysis. Drug retention rates were calculated using the Kaplan–Meier method and predictors of drug retention were determined by Cox proportional hazard model. Adverse events, reasons for switching, and discontinuation were also determined.Results Two hundred and forty-seven (210, 85.0% female) patients were included in the study. The median duration of tofacitinib treatment was 10.2 (20.2) [med, (IQR)] months. Two hundred and four (82.6%) patients were included in safety and efficacy analysis; 45.6% of patients were in low-disease activity (LDA) state (DAS28-CRP ≤ 3.2). Predictors of LDA were being biologic-naïve [aOR 2.53 (1.31–4.88); 95% CI] and RF negativity [aOR 2.14 (1.12–4.07); 95% CI]. At 1 year, the overall tofacitinib retention rate was 63.9% with no relevant predicting factor. Response and retention rates of tofacitinib were similar in patients with and without concomitant csDMARDs. Treatment failure was the most common cause of discontinuation. The most common infectious and laboratory adverse events were herpes zoster infection (3.9 per 100 patient-years) and elevation in ALT (x3UNL: 9.7 per 100 patient-years), respectively.ConclusionTofacitinib is effective as monotherapy or in combination with csDMARDs. It is a well-tolerated treatment option in Turkish RA patients.

Effectiveness and safety of baricitinib in rheumatoid arthritis: a monocentric, longitudinal, real-life experience

Baricitinib is a Janus-kinase (JAK) 1/2 inhibitor, approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). We report the first real-life experience with baricitinib in a monocentric cohort of unselected RA patients. We enrolled consecutive RA patients starting baricitinib. At baseline and after 4, 12, 24 and 48 weeks we assessed the disease activity by composite indices (SDAI, CDAI and DAS28CRP) and ultrasonography, and we recorded any adverse events. The primary endpoint was the percentage of patients achieving SDAI remission at week 4. We enrolled 59 patients [(F:M = 50:9, median age 58.1 years (IQR 12.8), median disease duration 144 (IQR 150) months] treated with baricitinib in combination with a csDMARD (52.5%) or monotherapy (47.5%) for a median follow-up of 24 weeks (IQR 36). The 12-month drug retention rate was 74%. At weeks 4, 12, 24 and 48 we observed a significant reduction of DAS28, CDAI and SDAI, global health and pain (p<0.001 for all). After 4 weeks of treatment, 12% of patients achieved SDAI remission. Concomitant csDMARDs, previous biological DMARDs, gender, seropositivity and BMI did not affect the efficacy of baricitinib. Baricitinib allowed a significant reduction in prednisone dose after 12 and 24 weeks and a rapid and sustained ultrasound improvement. No serious adverse events, serious infections or cardiovascular events were recorded. Our study confirms the efficacy and safety profile and rapid onset of the effect of baricitinib in RA patients in a real-life setting.

Efficacy and Safety of Ixekizumab with or Without Methotrexate in Biologic-Naïve Patients with Psoriatic Arthritis: 52-Week Results from SPIRIT-H2H Study.

IntroductionIn the SPIRIT-H2H (ClinicalTrials.gov: NCT03151551) trial in biologic-naïve patients with active psoriatic arthritis (PsA), ixekizumab (IXE) was superior to adalimumab (ADA) at week 24 in terms of achieving a combined endpoint of ≥ 50% improved response in the American College of Rheumatology scale score (ACR50) and 100% improvement in the Psoriasis Areas and Severity Index (PASI100), and was non-inferior in terms of achieving ACR50. IXE resulted in similar improvements of PsA manifestations irrespective of the use of concomitant conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while ADA response was higher with concomitant csDMARD use. The aim of this study was to determine the efficacy and safety of treatment with IXE and ADA with or without methotrexate (MTX), the most commonly use csDMARD, through week 52 in patients with PsA.MethodsIn the open-label, rater-blinded, head-to-head SPIRIT-H2H trial, randomization of patients was stratified by concomitant use of csDMARD and moderate-to-severe plaque psoriasis involvement. In the post-hoc subgroup analysis presented here, subgroups were defined as with/without concomitant MTX use at baseline. Treatment group effects within subgroups were tested using Fisher’s exact test. Missing data were imputed using non-responder imputation.ResultsBy week 52, IXE provided similar improvements in the combined ACR50 and PASI100 endpoint, ACR50, and other PsA-related domains regardless of whether IXE was used with or without MTX, while ADA efficacy appeared to be improved with concomitant MTX use. When used without concomitant MTX, IXE resulted in significantly higher response versus ADA in terms of the combined ACR50 and PASI100 (p = 0.002) endpoint, minimal disease activity (p = 0.016), and very low disease activity (p = 0.037). The safety of both agents was consistent with their known safety profiles regardless of concomitant MTX use.ConclusionIn PsA patients with inadequate control of the disease, IXE delivers consistent efficacy in several clinical domains of the disease regardless of concomitant MTX use. The efficacy of ADA is increased by the concomitant use of MTX. These findings can inform treatment decisions when considering the need for concomitant MTX use with IXE or ADA at initiation or for long-term maintenance.Electronic supplementary materialThe online version of this article (10.1007/s40744-020-00250-3) contains supplementary material, which is available to authorized users.

Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52

ObjectivesSPIRIT head-to-head (H2H) is a 52-week (Wk) trial comparing ixekizumab (IXE) with adalimumab (ADA) for simultaneous American College of Rheumatology (ACR)50 and Psoriasis Area and Severity Index (PASI)100 responses in...

Introduction and switching of biologic agents are associated with antidepressant and anxiolytic medication use: data on 42 815 real-world patients with inflammatory rheumatic disease

ObjectivesDepression and anxiety are linked bi-directionally with inflammatory rheumatic diseases (IRDs) activity, which in turn, depends on subjective patient reported outcomes that can be distorted by comorbid mood disorders. We...