Use Of csDMARDs Research Articles

Trends in New Use of Disease-Modifying Antirheumatic Drugs in Juvenile Idiopathic Arthritis Among Commercially Insured Children in the United States from 2001-2022.

To describe recent trends in DMARD use for children with juvenile idiopathic arthritis (JIA) in the US. We used commercial claims data (2000-2022) to perform a serial cross-sectional utilization study of children ages 1-18 diagnosed with JIA. Initiations of conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs were identified after a ≥12-month baseline and expressed as percentage of all new DMARD initiations per year, by category, class, and individual agent. Trends were evaluated using linear regression. Secondarily, we examined first b/tsDMARDs initiated after csDMARD monotherapy. We identified 20,258 new DMARD use episodes among 13,696 individuals (median age 14 years, 67.5% female). csDMARDs, while most commonly used overall, declined from 89.5% of new use episodes to 43.2% (2001-2022, p<0.001 for trend). In contrast, bDMARD use increased (10.5-50.0%, p<0.001). For tumor necrosis factor inhibitors (TNFi), etanercept peaked at 28.3% (2006) and declined to 4.2% (2022) (p=0.002). Meanwhile, adalimumab use doubled (7.0-14.0%, 2007-2008) after JIA approval, increasing further following a less painful formulation release (20.5%, 2022, p<0.001). However, overall TNFi use has declined with increasing use of other b/tsDMARDs, particularly ustekinumab, secukinumab, and tofacitinib. By 2022, adalimumab was the most common b/tsDMARD initiated first after csDMARDs (77.8%). Among commercially insured children with JIA in the US, new b/tsDMARD use is rising while new csDMARD use declines. For b/tsDMARDs, adalimumab is most used and the predominant b/tsDMARD initiated first after csDMARDs. Patterns in DMARD use for JIA have evolved relative to multiple factors, including regulatory approvals and tolerability.

Four-year effectiveness, safety and drug retention rate of secukinumab in psoriatic arthritis: a real-life Italian multicenter cohort

Objectivesto evaluate over a 48-month follow-up period the: 1) long-term effectiveness and safety; 2) drug retention rate (DRR); 3) impact of comorbidities and bDMARDs line on MDA and DAPSA remission/low disease activity (LDA) of secukinumab in a multicenter Italian cohort of PsA patients.MethodsConsecutive PsA patients receiving secukinumab were followed prospectively in Italian centers between 2016 and 2023. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were recorded. Treatment response was evaluated at 6 and 12 months after initiation, and every year up to 48 months (T48). DRR was assessed according to clinical and demographic features, comorbidities and bDMARDs line. Adverse events (AE) were recorded.ResultsSix hundred eighty-five patients [42.5% male] were enrolled; 32.9% naïve received secukinumab; 74.2% had ≥ 1 comorbidity. Overall, secukinumab yielded improved outcomes at T48: naïve maintained lower disease activity vs. non-naïve [DAPSA 4.0 (1.4–8.1) vs. 6.0 (2.2–10.4);p = 0.04]; 76.9% naïve and 66.2% non-naïve achieved MDA; MDA no comorbidities vs. 1–3 comorbidities 78.8% vs. 73.3% (p < 0.05), and MDA no comorbidities vs. > 3 comorbidities 78.8% vs. 48.7% (p < 0.001). DAPSA-REM and DAPSA-LDA rates were higher in naïve patients, albeit similar between those without comorbidities vs. 1–3 comorbidities, and slightly lower in those with > 3 comorbidities. Treatment was discontinued in 233 patients due to loss of effectiveness, and in 41 due to AE. The overall DRR at T48 was 66%, with differences according to bDMARDs line (p < 0.001), use of combined csDMARDs (p = 0.016), BMI (p = 0.037) and mono/oligoarthritis vs. polyarthritis (p = 0.012).ConclusionsSecukinumab proved safe and effective, and patients achieved sustained remission with a notable drug retention rate at 4 years.

Age-Related Variations in Treatment Patterns for Axial Spondyloarthritis

Aim: This study examines treatment patterns and preferences among patients diagnosed with Axial Spondyloarthritis (AxSpA) across different age groups. Material and Method: Ankara Bilkent City Hospital registry enabled a comprehensive cross-sectional analysis of 2,811 patients stratified into three age groups: 18-40, 41-55, and over 55 years. These groups were compared in terms of their treatments. Results: Our findings indicate an increasing prevalence of female patients and comorbidities with age. Medication usage patterns showed a trend towards increased use of Methotrexate and Colchicine with age, while Sulfasalazine and Leflunomide were more commonly prescribed in older age groups. Notably, the use of biologic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs), including anti-Tumor Necrosis Factor (anti-TNF)", "anti-Interleukin (anti-IL) agents, demonstrated a declining trend with advancing age, though not reaching statistical significance. This trend was also reflected in gender-specific treatment distributions, where no significant difference was found in bDMARDs administration among patients over 55 years, contrasting with a higher usage rate in younger male patients. Conclusion: Our study highlights a shift towards more conservative treatment approaches, such as increased conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) use in older patients, likely due to their safety profile and the specific challenges associated with treating older adults, including higher comorbidity rates and medication side effects. These findings emphasize the need for personalized treatment strategies and suggest potential adjustments in clinical practices to better accommodate the aging population, advocating for ongoing research to optimize treatment efficacy and safety for elderly patients with AxSpA.

Impact of Oral, Selective, Allosteric Tyrosine Kinase 2 Inhibitor, Deucravacitinib, on Psoriasis in Patients with Active Psoriatic Arthritis: Results from a Phase 2 Trial

Introduction: Deucravacitinib (DEUC), an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy. DEUC was superior to apremilast and placebo (PBO) in two phase 3 trials in patients with moderate to severe PsO. DEUC was efficacious on multiple measures of arthritis severity vs PBO in a phase 2 trial in patients with active psoriatic arthritis (PsA) who had ≥1 PsO lesion (≥2 cm). In patients with body surface area (BSA) involvement ≥3% at baseline (80% of patients in this trial), a greater proportion achieved PASI 75 with DEUC (6 mg QD: 42.4%, P=0.01; 12 mg QD: 59.6%, P&lt;0.0001) vs PBO (20.4%) at Week 16. This analysis evaluated the impact of DEUC on PsO in patients with PsA in the phase 2 trial (NCT03881059).&#x0D; Methods: The phase 2 double-blind PsA trial randomized patients (N=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or DEUC 12 mg QD. After Week 16, patients could enroll in an optional, double-blind period until Week 52. DEUC-treated patients achieving minimal disease activity at Week 16 continued DEUC to Week 52. PsO disease activity measurements were assessed.&#x0D; Results: Baseline PsO characteristics were comparable across groups. At Week 16, significant decreases from baseline in mean PASI were observed with DEUC vs PBO in patients with baseline BSA ≥3%-&lt;10% or PASI ≤12 even with very low baseline PASI scores, and also in those with baseline BSA ≥10% and PASI &gt;12. Significant decreases in PASI from baseline were observed with DEUC vs PBO in patients with background csDMARD use (DEUC 6 mg, -4.0 and 12 mg, -4.9 vs PBO, -2.3; both P&lt;0.05) and those without csDMARD use (-3.7 and -4.0 vs -2.5, respectively; both P&lt;0.001). At Week 16, greater proportions of DEUC vs PBO patients achieved PASI ≤1 with baseline BSA ≥3% (DEUC 6 mg: 32.2%; DEUC 12 mg: 44.2%; PBO: 18.5%) and in patients with baseline BSA ≥10% and PASI &gt;12 (23.1%; 28.6%; 0.0%). In patients with baseline BSA ≥3%, decreases in mean PASI at Week 16 were maintained through Week 52 in patients continuing DEUC 6 mg (absolute PASI score, Week 16: 2.39, Week 52: 1.22) and 12 mg (Week 16: 0.64, Week 52: 0.24).&#x0D; Conclusion: DEUC significantly improved PsO in patients with PsA, regardless of baseline PsO severity and background csDMARD use. Improvement was comparable to that observed in the phase 3 POETYK PSO-1 trial.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network.

Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi. Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled. Logistic regression was used to analyze the association between sex and treatment response using low disease activity (LDA) according to the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) (<3.2) at six months as the primary outcome. Analyses were adjusted for age, country, conventional synthetic disease-modifying antirheumatic drug treatment, and TNFi start year. Retention rates were explored using the Kaplan-Meier estimator. We analyzed the treatment response of 7,679 patients with PsA (50% women) with available data on LDA at six months. At baseline, women and men had similar characteristics, including mean DAS28-CRP (women vs men, 4.4 [SD 1.2] vs 4.2 [SD 1.2]), though patient-reported outcome measures were worse in women. At six months, 64% of women and 78% of men had LDA (relative risk [RR] 0.82; 95% confidence interval [CI] 0.80-0.84). This difference was similar after adjustment (RR 0.83; 95% CI 0.81-0.85). TNFi retention rates were evaluated in 17,842 patients with PsA. Women had significantly lower retention rates than men at all time points (women 79%, 64%, and 50% vs men 88%, 77%, and 64% at 6, 12, and 24 months, respectively). Despite comparable disease characteristics at baseline, women with PsA have reduced treatment response and retention rates to their first TNFi, highlighting the need to consider sex differences in PsA research and management.

Abstract 19 — Treat-to-Target in Spondyloarthritis (SpA): Are There Sex-Related Differential Responses?

Background: Studies have reported that female patients with spondyloarthritis have different disease courses and treatment responses compared to male patients. Whether patients’ sex is associated with a different outcome after receiving one-year of tight control, treat-to-target (T2T) strategy remains uncertain. Thus, this study aimed to evaluate the differences in the clinical response between male and female patients from the APLAR SpA Registry. Methods: Patients who fulfilled the CASPAR 2006 classification criteria for PsA and 2009 ASAS classification for axSpA were recruited. They received 1 year of protocolized treatment aiming at 1) MDA or DAPSA-LDA for PsA patients, and 2) ASDAS-LDA for axSpA patients. Patients were assessed every 3-monthly and treatment was escalated if target was not reached. Results: Ninety-one male (age: 45.6±16.1, 43 PsA, 48 axSpA) and 52 female (age: 49.2±13.4, 36 PsA, 16 axSpA) patients were included. There was no significant difference between the 2 sexes at baseline, except a higher ESR and more severe enthesitis in female patients. During the study period, the use of csDMARDs and NSAIDs decreased slightly, whilst the use of bDMARDs significantly increased across both sexes (Fig. 1a). Considering the whole cohort, there were significant improvement in disease activity in PsA after 1-year and disease activity in axSpA remained low. Despite similar bDMARDs use at 1-year, female PsA patients had a lower MDA achievement rate (36% in female vs 51% in male). Female patients also remained to have a higher physician global assessment score (2.61±1.76 in female vs 1.98±1.57 in male, p=0.03), greater functional impairment (HAQ: 0.54±0.57 in female vs 0.32±0.46 in male, p=0.01) and more severe enthesitis (SPARCC: 0.83±1.67 in female vs 0.16±1.09 in male, p=0.005) at 1-year. There was also a trend of higher perceived disease burden and peripheral involvement in female (Fig. 1b). Conclusion: There may be differential treat-to-target responses between male and female SpA patients. The causes of such differential characteristics should be further explored to potentially implement a sex-specific treat-to-target strategy for spondyloarthritis.

Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19.Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes.Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2–46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84–1.40 or 1.09, 0.92–1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01–1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26–1.64; 0.95, 0.36–2.54; and 1.01, 0.53–1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82–1.66; 1.18, 0.78–1.77; and 1.22, 0.92–1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31–2.81; 0.97, 0.25–3.74 and 1.05, 0.44–2.49, respectively) compared to those not using medication.Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.

Chinese Registry of Psoriatic Arthritis (CREPAR): I. Clinical characteristics of Chinese patients with psoriatic arthritis.

To describe the clinical characteristics of Chinese patients with psoriatic arthritis (PsA) using the data recorded in the Chinese Registry of Psoriatic Arthritis (CREPAR). This is a cross-sectional study based on the CREPAR registry, which is a prospective registry founded in December 2018. Data regarding clinical characteristics and treatment of patients were collected during every visit. Data recorded at enrollment were extracted, analyzed, and compared with data in other registries or cohorts. A total of 1074 patients were registered from December 2018 to June 2021. Of these, 929 (86.5%) patients had a history of peripheral arthritis, and 844 patients (78.6%) had peripheral arthritis at enrollment, of which polyarthritis is the most common subtype. Axial involvement was present in 39.9% of patients, and 50 (4.7%) patients had axial involvement only. More than half of the patients (55.4%) had at least two musculoskeletal presentations at enrollment. The prevalence of low disease activity and remission according to DAPSA were 26.4% and 6.8%, respectively. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs were used in 64.9% and 29.1% of patients, respectively. Among patients with different musculoskeletal presentations, patients with dactylitis had the highest proportion of nonsteroidal anti-inflammatory and csDMARD use. The proportion of patients receiving bDMARDs was highest in axial PsA. The CREPAR registry has provided information on Chinese patients with PsA. Compared with data in other registries or cohorts, the disease activity of patients in CREPAR was higher, and the proportion of bDMARD use was lower.

HPR144 Coverage of Biologics for Rheumatoid Arthritis in Canada

In Canada, there is a need for consistent access to medications across the country to ensure health care equity and the optimal management of patients. In 2015, private drug plans implemented a national standard for coverage of biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), which includes a prior trial of dual conventional synthetic DMARDs (csDMARDs). The aims of this study were to acquire an understanding of current bDMARD listing status and coverage criteria across jurisdictions, review the clinical evidence and guideline recommendations regarding the use of csDMARDs and bDMARDs, determine the current utilization of csDMARDs and bDMARDs across jurisdictions, and estimate the budgetary impact if jurisdictions harmonized the time to bDMARD initiation in RA.

E075 Predictive factors for successful biologic disease-modifying anti-rheumatic drugs dose tapering in rheumatoid arthritis

Abstract Background/Aims Use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionised the management of rheumatoid arthritis (RA). However, their use is not without side effects including infection and malignancy risk. Recent EULAR and ACR guidelines support consideration of dose tapering in patients in sustained remission. This study looks at identifying predictive factors for successful bDMARD dose tapering, to help select patients who may benefit from it, whilst minimising the risk of flare. Methods We searched our local biologic database retrospectively for RA patients who were dose tapered in line with our local guideline, between June 2015 and December 2021. 91 patients were identified, 17 patients were excluded due to death or cessation of bDMARD for unrelated reasons. Clinical and demographic data collected included: age, gender, rheumatoid factor and/or anti-cyclic citrullinated peptide antibody positivity, biologic choice, concurrent use of conventional synthetic DMARD (csDMARD), number of previous bDMARDs, and overall annual cost-saving. Incidence of flares after tapering and outcome after resuming original dose of biologic were noted. Results Of the 74 patients included, 39 (53%) were on rituximab, 14 (19%) were on etanercept , 11 (15%) were on certolizumab pegol, 9 (12%) were on adalimumab, and 1 (1%) was on tocilizumab. The incidence of flare is highest in the first 6 months after being tapered (47%; n = 18). Of those who flared (n = 38), 84% regained control following re-introduction of original dose. After tapering, 67% (n = 18/27) of patients aged 70-89 remained in remission whilst more than 50% (n = 29/47) flared in younger age groups. Patients on rituximab were more likely to remain in remission. There were no notable differences in gender, seropositivity and concurrent csDMARD use. Despite reduced cost of biologics through use of biosimilars, we are estimated to save £68,783 per annum from dose tapering. Conclusion We find that patients in older age group or on rituximab have a higher chance of remaining in remission following bDMARD dose tapering. The risk of flare is not affected by gender, seropositivity or concurrent csDMARDs use. If patients were to flare post dose tapering, this is more likely to occur within the first 6 months after tapering. Disclosure M. Loh: None. C.J. Jones: Other; Received payment from Fresenius Kabi for participation in a focus group regarding publication of NICE TA 715. A. Peall: None. J. Trickey: None.

Interstitial lung disease in rheumatoid arthritis: incidence, prevalence and related drug prescriptions between 2007 and 2020

ObjectiveTo investigate prevalence, incidence and medication of interstitial lung disease (ILD) among German individuals with rheumatoid arthritis (RA).MethodsNationwide BARMER claims data from 2007 to 2020 were used. RA-ILD was identified...

Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)

ObjectiveTo assess whether rituximab (RTX) is associated with worse COVID-19 outcomes among patients with rheumatoid arthritis (RA). MethodsWe used the National COVID Cohort Collaborative (N3C), the largest US cohort of COVID-19 cases and controls, to identify patients with RA (International Classification of Diseases (ICD)-10 code, M05.X or M06.X). Key outcomes were COVID-19-related hospitalization, intensive care unit (ICU) admission, 30-day mortality, and World Health Organization (WHO) classification for COVID-19 severity. We used multivariable logistic regression models to assess the association between RTX use and the odds of COVID-19 outcomes compared with the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adjusting for demographics, medical comorbidities, smoking status, body mass index, US region and COVID-19 treatments. ResultsA total of 69,549 patients met our eligibility criteria of which 22,956 received a COVID-19 positive diagnosis between 1/1/2020 and 9/16/2021. Median (IQR) age of the cohort was 63 (52–72) years, 76% of the cohort was female, 68% was non-Hispanic/Latinx White, and 73% was non-smokers. Prior to their first COVID-19 diagnosis, 364 patients were exposed to RTX. Compared to the use of csDMARDs, RTX use was associated with an increased odds of COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.1, 95% confidence interval 1.5–3.0), ICU admission (aOR 5.2, 1.8–15.4) and invasive ventilation (aOR 2.7, 1.4–5.5). Results were confirmed in multiple sensitivity analyses. ConclusionOur findings can guide patients, providers, and policymakers regarding the increased risks associated with RTX use during the COVID-19 pandemic. These results can help risk stratification and prognosis-assessment.

The Economic Benefit of Remission for Patients with Rheumatoid Arthritis.

IntroductionIn patients with rheumatoid arthritis (RA), attaining remission or low disease activity (LDA), as recommended by the treat-to-target approach, has shown to yield improvement in symptoms and quality of life. However, limited evidence from real-world settings is available to support the premise that better disease control is associated with lower healthcare costs. This study fills in evidence gaps regarding the cost of care by RA disease activity (DA) states and by therapy.MethodsThis retrospective cohort study linked medical and prescription claims from Optum Clinformatics Data Mart to electronic health record data from Illumination Health over 1/1/2010–3/31/2020. Mean annual costs for payers and patients were examined, stratifying on DA state and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics, and targeted synthetic (ts)DMARDs. Subgroup analysis examining within-person change in costs pre- and post-initiation of new therapy was also performed. Descriptive statistics, means, and boot-strapped confidence intervals were analyzed by DA state and by RA therapy. Furthermore, multivariate negative binomial regression analysis adjusting for key baseline characteristics was conducted.ResultsOf 2339 eligible patients, 19% were in remission, 40% in LDA, 29% in moderate DA (MDA), and 12% in high DA (HDA) at baseline. Mean annual costs during follow-up were substantially less for patients in remission ($40,072) versus those in MDA ($56,536) and HDA ($59,217). For patients in remission, csDMARD use was associated with the lowest mean annual cost ($25,575), tsDMARD was highest ($75,512), and tumor necrosis factor inhibitor (TNFi) ($69,846) and non-TNFi ($57,507) were intermediate. Among new TNFi (n = 137) and non-TNFi initiators (n = 107), 31% and 26% attained LDA/remission, respectively, and the time to achieve remission/LDA was numerically shorter in TNFi vs. non-TNFi initiators. For those on biologics, mean annual within-person medical and inpatient costs were lower after achieving LDA/remission, although pharmacy costs were higher.ConclusionsCost of care increased with increasing DA state, with patients in remission having the lowest costs. Optimizing DA has the potential for substantial savings in healthcare costs, although may be partially offset by the high cost of targeted RA therapies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00473-6.

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.

AB0891 Deucravacitinib Efficacy in Psoriatic Arthritis by Baseline DMARD Use: Exploratory Analysis From a Phase 2 Study

BackgroundPsoriatic arthritis (PsA) treatment guidelines recommend that patients (pts) inadequately responding to conventional synthetic DMARDs (csDMARDs) can be treated with targeted synthetic DMARDs with or without background use of csDMARDs. Deucravacitinib (DEUC) is a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2) that binds to the unique TYK2 regulatory domain, thereby suppressing signaling of key cytokines (eg, IL-23) involved in PsA pathogenesis. In a Phase 2 trial in pts with active PsA, DEUC was well tolerated and significantly more efficacious than placebo (PBO) after 16 weeks of treatment.1ObjectivesThis analysis further evaluated the effect of DEUC in this Phase 2 trial in pts treated with and without background csDMARDs for 16 weeks.MethodsThis double-blind trial (NCT03881059) enrolled pts with active PsA who had either failed or were intolerant to ≥1 nonsteroidal anti-inflammatory drug, corticosteroid, csDMARD, and/or 1 TNF inhibitor (TNFi; up to 30%). Pts were randomised 1:1:1 to DEUC 6 mg once daily (QD) or 12 mg QD, or PBO. A post hoc subgroup analysis in pts with and without background csDMARD use assessed improvements in select clinical outcomes (ACR 20 response, and change from baseline in ACR components, Psoriasis Area and Severity Index total score, and Psoriatic Arthritis Disease Activity Score) at Week 16.ResultsBaseline (BL) demographics, clinical characteristics, and disease activity were generally similar among pts with and without background csDMARD use. At BL, background csDMARD use was 64.3%, 64.2%, and 66.7% and methotrexate use was 50.0%, 55.2%, and 59.1% in the DEUC 6 mg QD, 12 mg QD, and PBO groups, respectively. Pts with and without background csDMARD use showed similar improvements at Week 16 with DEUC treatment versus PBO on most clinical measures, pt-reported outcomes, and composite measures (Table 1 and Figure 1). No clinically meaningful differences in adverse events (AEs) were observed in pts with or without background csDMARD use.Table 1.Adjusted mean (SE) change from baseline at Week 16 in clinical outcomes by csDMARD usePBO w/o csDMARD (n=22)PBO w csDMARD (n=44)DEUC 6 mg QD w/o csDMARD (n=25)DEUC 6 mg QD w csDMARD (n=45)DEUC 12 mg QD w/o csDMARD (n=24)DEUC 12 mg QD w csDMARD (n=43)Swollen joint count-4.7 (1.4)-5.0 (0.9)-7.4 (1.4)-6.8 (0.9)-8.4 (1.3)-7.7 (1.0)Tender joint count-5.3 (2.2)-6.6 (1.3)-6.4 (2.2)-11.3 (1.3)-11.5 (2.0)-11.6 (1.4)Physician’s Global Assessment of Disease Activity-20.6 (5.6)-20.6 (3.7)-29.1 (5.8)-32.6 (3.5)-30.1 (5.3)-32.1 (3.9)Patients’ Global Assessment of Disease Activity-14.9 (5.8)-13.4 (3.9)-23.0 (5.9)-28.4 (3.8)-28.2 (5.4)-24.9 (4.2)Pain-14.7 (5.6)-14.6 (3.9)-22.7 (5.7)-26.2 (3.7)-25.5 (5.3)-25.5 (4.2)HAQ-DI-0.23 (0.11)-0.04 (0.09)-0.31 (0.11)-0.38 (0.08)-0.48 (0.10)-0.34 (0.09)hsCRP12.0 (5.3)-4.4 (2.1)-10.1 (5.3)-13.3 (2.0)-4.9 (4.9)-10.0 (2.2)PASI total score2.5 (1.4)-2.3 (0.7)-3.7 (1.4)-4.0 (0.6)-4.0 (1.3)-4.9 (0.7)PASDAS-0.9 (0.4)-1.2 (0.3)-1.8 (0.4)-2.1 (0.2)-2.2 (0.3)-2.1 (0.3)The number of patients with data available for individual endpoints may vary.csDMARD, conventional synthetic disease-modifying antirheumatic drug; DEUC, deucravacitinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; hsCRP, high-sensitivity C-reactive protein; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area and Severity Index; PBO, placebo; QD, once daily; SE, standard error; w, with; w/o, without.ConclusionThese analyses demonstrate that the efficacy of DEUC for the treatment of PsA was similar in pts with and without background csDMARD use. The AE profile of DEUC treatment with and without csDMARD use was consistent with findings from the overall Phase 2 PsA trial population.

POS0652 LONG-TERM EFFECTIVENESS OF ULTRA-LOW DOSES OF RITUXIMAB IN RHEUMATOID ARTHRITIS

BackgroundThe optimal rituximab (RTX) dose for the treatment of rheumatoid arthritis remains unclear. RTX treatment of 1000mg per 6 months and 2000mg per 6 months were shown to be similarly efficacious (1). The REDO trial showed comparable the 6-month efficacy of continued treatment with 500mg and 200mg compared to 1000mg, though formal non-inferiority could not be established (2).ObjectivesTo assess the long-term effects of ultra-low dose RTX (1×500mg and 1×200mg) in RA patients previously responding well to conventional low dose RTX (1×1000mg).MethodsPatients from the REDO trial were invited to participate in this study. Treatment decisions were left at the discretion of the rheumatologist and patient. Disease activity (DAS28-CRP), and medication use (b/tsDMARD, csDMARD, gluccocorticoids [GC]) were collected from start of the trial to censoring in April 2021. The primary outcome was disease activity, secondary outcomes were RTX persistence, RTX doses and intervals, and use of comedication.Disease activity was analyzed using a longitudinal mixed model with random intercepts to account for intra-patient correlations, in two ways: 1. By original randomization and stratification factors (RF/ACPA and csDMARD use). 2. By time-varying total RTX dose received in the year preceding each disease activity measurement, adjusted for current csDMARD or GC use, and RF/ACPA. The original DAS28-CRP non-inferiority (NI) margin of 0.6 was used.Results118 out of 142 REDO patients were included in current analyses (Table 1) Reasons for exclusion were: continuing treatment elsewhere (n=3), no informed consent (n=9) and data yet to be collected in 2 study centers (n=12). Mean follow up was 3.2 years (total of 377 patient-years), with 7 patients switching to another b/tsDMARD (Figure 1) upon which they were censored from disease activity analyses.Table 1.Patient characteristics by original randomization1000mg (n=24)500mg (n=48)200mg (n=46)Age (years)65 (9)64 (11)64 (12)Female15 (63%)28 (58%)34 (74%)Meeting ACR1987 or ACRU/EULAR 2010 RA criteria22 (92%)47 (98%)43 (93%)Disease duration (years)14 (9-24)14 (7-21)13 (8-20)RF or ACPA positive22 (92%)44 (92%)40 (87%)Duration of rituximab use (years)3.0 (1.6-5.5)2.0 (1.0-5.5)3.7 (2.0-5.7)Concomitant csDMARD17 (71%)29 (60%)27 (59%)Previous number of b/tsDMARDs used2 (2-2)2 (1-3)2 (1-2)Previous number of csDMARDs used3 (1-3)2 (1-4)3 (1-3)Oral GC use at baseline3 (13%)8 (17%)5 (11%)Baseline DAS28-CRP2.3 (0.9)2.3 (0.9)2.5 (1.1)Data are n (%), mean (SD), or median (IQR).Figure 1.Rituximab treatment persistence during follow up.Disease activity in both ultra-low dose groups was non-inferior to the 1000mg group, with a mean DAS28-CRP (95% CI) during follow-up of 2.2 (2.0-2.4) in the 1000mg group, 2.2 (2.1-2.4) in the 500mg group and 2.3 (2.2-2.5) in the 200mg group.Analyzed by received RTX dose, lower RTX dose was significantly associated with a higher DAS28-CRP: 0.15 (95% CI: 0.04-0.26) points higher per 1000mg more RTX. The upper limit for relevant RTX doses was below the prespecified NI margin, excluding a relevant effect of RTX dose on disease activity.Median (IQR) yearly RTX dose was 978mg (704mg-1425mg). Final RTX dose per infusion was 200mg in 37 patients (31%), 500mg in 47 (40%) and 1000mg in 34 (29%), with a median (IQR) final interval between infusions of 6.0 (5.7-6.5), 6.2 (6.0-7.4) and 6.4 (6.0-9.6) months respectively. The rate of GC injections was 0.38 (95% CI: 0.32-0.44) per patient-year and initiation rate of oral GC was 0.05 (0.03-0.08) per patient-year.ConclusionA majority of patients treated with ultra-low dose RTX remained on ultra-low doses for up to 4 years, while disease activity remained low and did not relevantly differ between RTX doses, either according to original randomization or by received dose. Switching to other b/tsDMARDS or use of GC was rarely required.

COVID-19 susceptibility and clinical outcomes in autoimmune inflammatory rheumatic diseases (AIRDs): a systematic review and meta-analysis.

This meta-analysis aims to assess the susceptibility to and clinical outcomes of COVID-19 in autoimmune inflammatory rheumatic disease (AIRD) and following AIRD drug use. We included observational and case-controlled studies assessing susceptibility and clinical outcomes of COVID-19 in patients with AIRD as well as the clinical outcomes of COVID-19 with or without use of steroids and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Meta-analysis including three studies showed that patients with AIRD are not more susceptible to COVID-19 compared to patients without AIRD or the general population (OR: 1.11, 95% CI: 0.58 to 2.14). Incidence of severe outcomes of COVID-19 (OR: 1.34, 95% CI: 0.76 to 2.35) and COVID-19 related death (OR: 1.21, 95% CI: 0.68 to 2.16) also did not show significant difference. The clinical outcomes of COVID-19 among AIRD patients with and without csDMARD or steroid showed that both use of steroid (OR: 1.69, 95% CI: 0.96 to 2.98) or csDMARD (OR: 1.35, 95% CI: 0.63 to 3.08) had no effect on clinical outcomes of COVID-19. AIRD does not increase susceptibility to COVID-19, not affecting the clinical outcome of COVID-19. Similarly, the use of steroids or csDMARDs for AIRD does not worsen the clinical outcome.

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.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR).

The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts. Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts. In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use. Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

Increased remission with fewer corticosteroids and more biologics in rheumatoid arthritis at 7-year follow-up in real-life conditions

Remission in rheumatoid arthritis (RA) is an important therapeutic target that is not easy to achieve in real-life conditions. Some prognostic factors have been identified but the literature is variable. The objectives of this study were to evaluate the remission rate and the maintenance of remission in patients with RA over 7 years of follow-up in real-life conditions and to identify prognostic factors of long-term remission. Patients with RA seen at the Poitiers University Hospital were identified and clinical and biological data were collected. Data were analysed after 1 year and 7 years. Twice as many patients were in remission at 7 years than at 1 year of follow-up. 48.6% of patients who were not in remission at 1 year obtained remission at 7 years of follow-up. Patients achieving remission were more often receiving coprescription of csDMARDs and bDMARDs. Patients not in remission at 7 years were given more corticosteroids at higher doses. After 7 years of follow-up, low initial disease activity and use of csDMARDs and bDMARDs appeared to be independent positive predictive factors. Once obtained at one year, remission was maintained for 76% of our patients. As a conclusion, modern management of RA, whatever disease duration, leads to remission rates similar to those of early RA after 7 years of follow-up.