Tumor Necrosis Factor Inhibitor Group Research Articles

Real-world evaluation of persistence, effectiveness and usage patterns of tofacitinib in treatment of psoriatic arthritis in Australia

ObjectivesTo describe treatment patterns and persistence of tofacitinib, interleukin 17 inhibitors (IL-17Ai) and tumour necrosis factor inhibitors (TNFi), in patients with psoriatic arthritis (PsA).MethodsData from adult patients with PsA and who had received at least one prescription of tofacitinib, IL-17Ai or TNFi between May 2019 and September 2021 were sourced from the Australian OPAL dataset. Persistence, analysed via Kaplan–Meier methods, and propensity score matching between tofacitinib and bDMARD (IL-17Ai and TNFi) groups were conducted.ResultsOf 16,692 patients with PsA, 1486 (n = 406 tofacitinib, n = 416 IL-17Ai and n = 664 TNFi) were included. More females were in the tofacitinib group (75.4%) than in the IL-17Ai (61.1%) and TNFi (64.8%) groups. Overall, 19.2% of tofacitinib patients were first line, compared with 41.8% of IL-17Ai and 62.8% of TNFi patients. In the overall population, the median persistence was 16.5 months (95% CI 13.8 to 19.5 months), 17.7 months (95% CI 15.8 to 19.6 months) and 17.2 months (95% CI 14.9 to 20.5 months) in the tofacitinib, IL-17Ai and TNFi groups, respectively. Persistence was similar in the tofacitinib/IL-17Ai matched population; however, in the tofacitinib/TNFi matched population, persistence was longer in the tofacitinib group (18.7 months, 95% CI 15.6 to 21.4 months) compared with the TNFi group (12.2 months, 95% CI 19.9 to 14.9 months).ConclusionsIn this Australian real-world dataset, tofacitinib was more frequently used in later lines and among a slightly higher proportion of female patients than IL-17Ai or TNFi. Overall, treatment persistence was similar for tofacitinib, IL-17Ai and TNFi, but tofacitinib exhibited longer persistence than TNFi in a matched population.Key Points• This is the first, large real-world study from Australia investigating the demographics, treatment patterns and comparative treatment persistence of patients with psoriatic arthritis (PsA) treated with tofacitinib and biologic disease-modifying drugs (bDMARDs).• The study suggests that tofacitinib is an effective intervention in PsA with at least comparable persistence to bDMARDs: tumour necrosis factor inhibitors (TNFi) and interleukin-17 A inhibitors (IL-17Ai).

Reducing cardiovascular risk in immune-mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies-A systematic review and meta-analysis.

Immune-mediated inflammatory disease (IMID) patients including psoriasis, inflammatory arthritides and bowel diseases have a higher risk of developing cardiovascular (CV) diseases compared to the general population. The increased CV risk may be promoted by tumour necrosis factor (TNF)-α-mediated immunological processes, which are present both in the pathomechanism of IMIDs and atherosclerosis. Our objective was to comprehensively investigate the effect of TNF inhibitors (TNFi) on CV risk compared with conventional therapies in IMIDs. The systematic literature search was conducted in three databases (MEDLINE, EMBASE, Cochrane Library) on 14 November 2022. Randomized controlled trials, cohort and case-control studies were eligible for inclusion. Outcomes consisted of the incidence of CV events, with major adverse cardiovascular events (MACE) as a main endpoint. A random-effects meta-analysis was performed by pooling fully adjusted multivariate hazard ratios (HR) and incidence rate ratios (IRR) with a 95% confidence interval (CI) comparing TNFis with conventional systemic non-biologicals (CSNBs). Of a total of 8724 search results, 56 studies were included overall, of which 29 articles were eligible for the meta-analysis, and 27 were involved in the systematic review. Including all IMIDs, the TNFi group showed a significantly reduced risk of MACE compared with the CSNB group (HR = 0.74, 95% confidence interval (CI) 0.58-0.95, p = 0.025; IRR = 0.77, 95% CI 0.67-0.88, p < 0.001). Subgroup analysis of Pso, PsA patients by pooling IRRs also confirmed the significantly decreased risk of MACE in TNFi-treated patients compared with CSNB groups (IRR = 0.79, 95% CI 0.64-0.98). The observational nature of most included studies leading to high heterogeneity represents a limitation. Based on the results, TNFis may reduce the risk of CV events compared to CSNBs. Therefore, earlier use of TNFis compared to conventional systemic agents in the therapeutic sequence may benefit CV risk in IMID patients.

Comparative effectiveness of tofacitinib and tumour necrosis factor inhibitors in patients with rheumatoid arthritis in real-world practice: a prospective observational study.

To assess the effectiveness of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in Korean patients with rheumatoid arthritis (RA). The study used data from a single academic referral hospital's registries of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and tofacitinib and examined remission rates based on the disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) after 12 months. Multivariable logistic regression analysis was used to estimate the odds ratio (OR) for achieving remission with tofacitinib compared with TNFi, adjusting for potential confounders. This analysis included 665 patients (200 on tofacitinib and 455 on TNFi) who were followed up for at least 12 months. Of these, 96 patients in the tofacitinib group (48.0%) and 409 patients in the TNFi group (89.9%) were treatment-naïve to bDMARDs. Intention-to-treat analysis revealed no significant difference in the remission rates between the two groups (18.0% vs 19.6%, p = 0.640). Multivariable analysis demonstrated comparable remission rates with tofacitinib and TNFi (OR 1.204, 95% confidence interval [CI] 0.720-2.013). In the subpopulation naïve to JAKi and bDMARD, tofacitinib showed better remission rates than TNFi (OR 1.867, 95% CI 1.033-3.377). Tofacitinib had more adverse events (AEs) but similar rates of serious AEs (SAEs) to TNFi. In real-world settings, there was no significant difference in remission rates at 12 months between the tofacitinib and TNFi groups. In terms of safety, tofacitinib exhibited a higher incidence of AEs compared with TNFi, while the occurrence of SAEs was comparable between the groups. ClinicalTrials.gov, NCT02602704.

Comparison of Incidence or Recurrence of Anterior Uveitis in Patients with Ankylosing Spondylitis Treated with Tumor Necrosis Factor Inhibitors

Background: Anterior uveitis (AU) is a significant concern in patients with ankylosing spondylitis (AS), and the choice of tumor necrosis factor inhibitors (TNFi) as a treatment modality raises questions regarding its effects on AU. We compared the effects of TNFi on AU in patients with AS. Methods: Patients diagnosed with AS and treated with at least one TNFi, including anti-TNFα antibodies (adalimumab and infliximab) or a soluble TNF receptor molecule (etanercept), between January 2010 and December 2022, were retrospectively reviewed. We compared the recurrence rate of AU in patients with a history of uveitis and the incidence of new-onset AU in those without a history of uveitis among the three TNFi groups. We also compared the effects of two different TNFi agents in patients who underwent TNFi switching. Results: Within two years of treatment initiation, there was no significant difference in AU recurrence among the three TNFi groups. However, the incidence of new-onset AU was significantly higher in the etanercept group than in the adalimumab group (26.4% vs. 6.3%; p = 0.024). After two years, the AU recurrence rate was significantly lower in the adalimumab group than in the other groups (p &lt; 0.001). Among patients who underwent anti-TNFi switching, adalimumab treatment was associated with a significantly lower incidence of uveitis than etanercept (p = 0.023). Conclusion: In the short-term period following TNFi therapy, etanercept induced new-onset AU more frequently than adalimumab in patients with AS. Adalimumab recipients experienced fewer AU recurrences during the subsequent long-term period compared to other TNFi recipients.

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

Retention rate of tumor necrosis factor inhibitors, anti-interleukin 17, and anti-interleukin 12/23 drugs in a single-center cohort of psoriatic arthritis patients.

The objective of this study was to evaluate biological disease-modifying anti-rheumatic drugs (bDMARDs) survival in several therapy courses of patients affected by psoriatic arthritis (PsA) and to compare tumor necrosis factor inhibitors (TNFi) and non-TNFi retention rates. A total of 241 bDMARD therapy courses (155 TNFi drugs, 65 anti-interleukin (IL)-17 drugs, and 21 anti-IL12/23) were analyzed. Bivariate analyses were performed to assess the presence of demographic and clinical features, as well as comorbidities, associated with bDMARD discontinuation in TNFi and non-TNFi groups. In the bivariate analyses of TNFi and non-TNFi groups, we found a lower age at the start of TNFi therapy in the former group [46 years, interquartile range (IQR) 45-54 vs 50.5 years, IQR 42-61; p=0.004] as well as a lower proportion of patients with skin psoriasis (65.8% vs 88.4%; p<0.001). Survival analysis showed no significant differences between TNFi and non-TNFi groups. Cox regression found fibromyalgia as a predictor of drug failure [hazard ratio (HR) 3.40, confidence interval (CI) 1.92-6.03; p<0.001] and first-line bDMARDs as a protective factor (HR 0.46, CI 0.25-0.88; p=0.019). Lastly, among TNFi courses, fibromyalgia was associated with drug suspension (HR 6.52, CI 3.16-13.46; p<0.001), while only a trend of significance for skin psoriasis as a risk factor for drug failure was shown (HR 2.38, CI 1.00-5.66, p=0.05). This study provides information about clinical and demographic factors associated with retention rates of bDMARDs from a real-life, single-center cohort of PsA patients.

Discontinuation of tofacitinib and TNF inhibitors in patients with rheumatoid arthritis: analysis of pooled data from two registries in Canada

ObjectivesThe similarity in retention of tumour necrosis factor inhibitors (TNFi) and tofacitinib (TOFA) was previously reported separately by the Ontario Best Practices Research Initiative and the Quebec cohort Rhumadata. However,...

Tumor necrosis factor inhibitors and methotrexate are associated with decreased COVID-19-related hospitalization: Follow up of “Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors and methotrexate”

Tumor necrosis factor inhibitors and methotrexate are associated with decreased COVID-19-related hospitalization: Follow up of “Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors and methotrexate”

Factors associated with selection of targeted therapy in patients with rheumatoid arthritis.

Deciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice. We selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis. 145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01-1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95-1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01-0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01-0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51-2.38) and previous tacrolimus use (OR 2.05, CI 1.20-3.51) were factors suggesting selection of JAKis than TNF inhibitors. Age, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea.

The effect of targeted rheumatoid arthritis therapeutics on systemic inflammation and anemia: analysis of data from the CorEvitas RA registry

BackgroundTo evaluate the effects of tumor necrosis factor inhibitors (TNFi), interleukin-6 receptor inhibitors (IL-6Ri), and Janus kinase inhibitors (JAKi) on hemoglobin (Hb) and C-reactive protein (CRP) levels in adults enrolled in CorEvitas (formerly Corrona), a large US rheumatoid arthritis (RA) registry.MethodsPatients who initiated TNFi, IL-6Ri, or JAKi treatment during or after January 2010, had Hb and CRP measurements at baseline and 6-month follow-up (± 3 months) and had continued therapy at least until that follow-up, through March 2020, were included in the analysis. Changes in Hb and CRP were assessed at month 6. Abnormal Hb was defined as < 12 g/dL (women) or < 13 g/dL (men); abnormal CRP was ≥ 0.8 mg/dL. Differences in Hb and CRP levels were evaluated using multivariable regression.ResultsOf 2772 patients (TNFi, 65%; IL-6Ri, 17%; JAKi, 17%) evaluated, 1044 (38%) had abnormal Hb or CRP at initiation; an additional 252 (9%) had both abnormal Hb and CRP. At month 6, the IL-6Ri group had a greater Hb increase than the TNFi (mean difference in effect on Hb: 0.28 g/dL; 95% CI 0.19–0.38) and JAKi (mean difference in effect on Hb: 0.47 g/dL; 95% CI 0.35–0.58) groups, regardless of baseline Hb status (both p < 0.001). The CRP decrease at month 6 was greater with IL-6Ri compared with TNFi and JAKi, regardless of baseline CRP status (both p < 0.05).ConclusionThese real-world results align with the mechanism of IL-6R inhibition and may inform treatment decisions for patients with RA.

Tumor necrosis factor (TNF) inhibitors for juvenile idiopathic arthritis-associated uveitis.

Uveitisis the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by intraocular inflammation. Current treatment for JIA-associated uveitis (JIA-U) is largely based on physician experience, observational evidence and consensus guidelines, resulting in considerable variations in practice. OBJECTIVES: To evaluate the effectiveness and safety of tumor necrosis factor (TNF)inhibitors used for treatment of JIA-U. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We last searched the electronic databases on 3 February 2022. We included randomized controlled trials (RCTs) comparing TNF inhibitors with placebo in participantswith a diagnosis of JIA and uveitis who were aged 2 to 18 years old. We used standard Cochrane methodology and graded the certainty of the body of evidence for seven outcomes using the GRADE classification. We included three RCTs with 134 participants. One study conducted in the USA randomized participants to etanercept or placebo (N = 12). Two studies, one conducted in the UK (N = 90) and one in France (N = 32), randomized participants to adalimumab or placebo. All studies were at low risk of bias.Initial pooled estimates suggested that TNF-inhibitors may result in little to no difference on treatment success defined as 0 to trace cells on Standardization of Uveitis Nomenclature (SUN)-grading; or two-step decrease in activity based on SUN grading (estimated risk ratio (RR) 0.66; 95% confidence interval (CI) 0.21 to 2.10; 2 studies; 43 participants;low-certainty evidence) or treatment failure defined as a two-step increase in activity based on SUN grading (RR 0.31; 95% CI 0.01 to 7.15; 1 study; 31 participants;low-certainty evidence). Further analysis using the individual trial definitions of treatment response and failure suggested a positive treatment effect of TNF inhibitors; a RR of treatment success of 2.60 (95% CI 1.30 to 5.20; 3 studies; 124 participants; low-certainty evidence), and RR of treatment failure of 0.23 (95% CI 0.11 to 0.50; 3 studies; 133 participants). Almost all the evidence was on adalimumab and the evidence on etanercept was very limited. For secondary outcomes, one study suggests that adalimumab may have little to no effect on risk of recurrence after induction of remission at three months (RR 2.50, 95% CI 0.31 to 20.45; 90 participants; very low-certainty evidence) and visual acuity, but the evidence is very uncertain; mean difference in longitudinal logMAR score change over six months was -0.01 (95% CI -0.06 to 0.03) and -0.02 (95% CI -0.07 to 0.03) using the best and worst logMAR measurement, respectively (low-certainty evidence). Low-certainty evidence from one study suggested that adalimumab treatment results in reduction of topical steroid doses at six months (hazard ratio 3.58; 95% CI 1.24 to 10.32; 74 participants who took one or more topical steroid per day at baseline). Adverse events, including injection site reactions and infections, were more common in the TNF inhibitor group. Serious adverse events were uncommon. Adalimumab appears to increase the likelihood of treatment success and decrease the likelihood of treatment failure when compared with placebo. The evidence was less conclusive about a positive treatment effect with etanercept. Adverse events from JIA-U trials are in keeping with the known side effect profile of TNF inhibitors. Standard validated JIA-U outcome measures are required to homogenize assessment and to allow for comparison and analysis of multiple datasets.

Comparative safety of Janus kinase inhibitors and tumor necrosis factor inhibitors in patients undergoing treatment for rheumatoid arthritis.

Since 2010, biological disease-modifying antirheumatic drugs (bDMARDs) have been the dominant mode of treatment for rheumatoid arthritis (RA). However, the safety of DMARDs, such as tumor necrosis factor inhibitors (TNFis) and Janus kinase inhibitors (JAKis), in treating patients with RA is a concern. We compared the safety outcomes of JAKis and TNFis in RA patients in clinical settings. Patients diagnosed with RA between 2015 and 2017 were identified from the Taiwan National Health Insurance Research Database and followed till 2018. Propensity score stabilized weighting was used to balance the baseline characteristics of the JAKis and TNFis groups. The incidences of safety outcomes, namely cardiovascular (CV) events, tuberculosis (TB), total hip replacement (THR), total knee replacement (TKR), and all-cause mortality, were compared between the 2 study groups. A total of 3179 patients with RA who were administered JAKis (n=822) and TNFis (n=2357) were included in this study. The mean follow-up duration was 2.02 years in the JAKis group and 2.10 in the TNFis group. All-cause mortality had the highest incidence rate, followed by TKR, THR, CV events, and TB. A lower incidence rate of the study outcomes was observed in the JAKis group than in the TNFis group but without statistical significance. Comparable safety issues and mortality rates were observed for JAKis and TNFis in RA patients treated in real-world settings.

Efficacy of Abatacept Versus Tumor Necrosis Factor Inhibitors in Anti-citrullinated Protein Antibody-Positive Patients with Rheumatoid Arthritis: Results from a Korean Nationwide Biologics Registry.

Introduction To compare the efficacy of abatacept and tumor necrosis factor inhibitor (TNFi) in patients with anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and identify those who benefit most from abatacept over TNFi.MethodsThis observational study identified RA patients who were ACPA-positive and initiated abatacept or TNFi from the Korean College of Rheumatology Biologics and Targeted therapy registry. Propensity score (PS) matching was performed to balance baseline confounding in abatacept- or TNFi-treated patients. The major endpoints were changes in Clinical Disease Activity Index (CDAI) and achievement of CDAI remission/low disease activity after 1 year of treatment. Subgroup analysis was mainly performed stratified by prior biologics use.ResultsA total of 291 PS-matched, ACPA-positive RA patients who initiated abatacept (n = 97) and TNFi (n = 194) were included. From baseline CDAI scores of 26.52 in the abatacept group and 26.38 in the TNFi group, the mean changes after 1 year were − 16.78 and − 13.61, respectively (difference − 3.17, p = 0.020). The proportion of patients achieving CDAI remission/low disease activity was 68.0% with abatacept and 52.6% with TNFi (p = 0.013). In the subgroup analysis, patients that were biologics-naïve had better improvement in CDAI after treatment with abatacept than TNFi (difference − 3.35, p = 0.021).ConclusionsThis real-world study suggests that abatacept may have better clinical response compared to TNFi in patients with established ACPA-positive RA, especially in those that were biologics-naïve.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00467-4.

OP0135 RISK OF CARDIOVASCULAR EVENTS UNDER JANUS KINASE INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS: OBSERVATIONAL DATA FROM THE GERMAN RABBIT REGISTER

BackgroundIn 2021, the European and US-American regulatory agencies EMA and FDA issued warnings about the cardiovascular (CV) safety of the Janus kinase inhibitor (JAKi) tofacitinib and required changes in labelling. These actions were based on results of the post-authorisation safety trial Oral Surveillance(1).ObjectivesTo analyse major cardiovascular events (MACE) under treatment with JAKi, tumor necrosis factor inhibitors (TNFi) or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs - bionaive) in patients with rheumatoid arthritis (RA) observed in daily rheumatological care.MethodsData from patients enrolled in the biologics register RABBIT with treatment episodes from 01/2017 - 04/2021 were included. Incidence rates (IR) of MACE per 100 patient-years (PY) with 95% confidence intervals (CI) and adjusted risk ratios (RR) were calculated for all and for high-risk patients (age ≥ 50 years and ≥ 1 CV risk factor). Poisson regression analysis was adjusted for age, sex, smoking, disease activity, prior therapies, glucocorticoids and comorbidities.ResultsStarting from 2017, 2030 JAKi, 2338 TNFi and 871 csDMARD initiations were documented. Patients with a JAKi start were slightly older, more often women and had a longer RA disease duration (Table 1). The proportion with positive autoantibodies was higher than in the TNFi and csDMARD group, the physical function was lower, and they had received more previous biologic treatments. Characteristics of high-risk patients are also given in the Table 1.Table 1.Patient characteristics at the start of a JAKi, TNFi or csDMARD.ALL PATIENTSHIGH RISK PATIENTS*JAKiTNFicsDMARDJAKiTNFicsDMARD# treatment starts2030233887112151254508Age59.9 ± 11.657.6 ± 13.059.5 ± 12.764.3 ± 8.963.5 ± 8.964.4 ± 9.2Women1573 (77.5)1707 (73.0)627 (72.0)907 (74.7)864 (68.9)355 (69.9)Disease duration12.6 ± 9.68.9 ± 8.55.7 ± 6.613.3 ± 9.99.7 ± 9.16.0 ± 7.0Rheumatoid factor/ ACPA positive1531 (79.2)1672 (74.2)548 (66.3)917 (79.7)890 (73.7)321 (66.5)# previous bDMARDs2.0 ± 1.80.7 ± 1.202.0 ± 1.80.7 ± 1.20DAS28-ESR4.2 ± 1.44.5 ± 1.44.2 ± 1.34.4 ± 1.54.7 ± 1.34.3 ± 1.3Percentage of full physical function63.3 ± 24.168.6 ± 22.472.3 ± 21.960.3 ± 24.264.4 ± 23.369.6 ± 22.7Glucocorticoids ≥10 mg/d170 (17.5)239 (21.5)49 (12.4)112 (18.6)142 (22.3)23 (10.0)BMI &gt;30 kg/m2565 (28.2)631 (27.4)271 (31.7)383 (31.8)413 (33.3)180 (36.0)Sum of comorbidities2.9 ± 2.52.6 ± 2.42.2 ± 2.23.7 ± 2.63.5 ± 2.53.1 ± 2.3Current smokers461 (26.3)617 (28.5)274 (33.5)355 (33.5)466 (39.5)202 (42.3)Previous smokers551 (31.4)692 (31.9)230 (28.1)300 (28.3)338 (28.6)114 (23.9)Values are given as mean ± standard deviation or number (percentage). *Age ≥50 years and ≥ 1 CV risk factor (hypertension, coronary heart disease, diabetes, hyperlipoproteinaemia, current smoking)In total, 28 incident MACE were reported. Patients under treatment with JAKi, TNFi and csDMARD showed comparable IR for MACE between 0.26 and 0.41 events per 100 PY (Figure 1). High-risk patients showed higher IRs. The median time under treatment was 10 months on JAKi and TNFi, and 12 months on csDMARDs. The majority of events were reported in the first year after treatment start. In the adjusted analyses, JAKi (RR 0.94 [95% CI 0.39; 2.28]) and csDMARDs (RR 0.85 [0.25; 2.88]) did not show a significantly increased risk for MACE compared with TNFi in unselected patients, and also not in high-risk patients (JAKi: RR 0.90 [0.37; 2.17]; csDMARDs: RR 0.61 [0.16; 2.28]).Figure 1.Incidence rates of MACE per 100 patient years by treatment group.ConclusionIR of MACE in patients receiving JAKi in a real-world setting was lower than the IR reported for tofacitinib in the Oral Surveillance study. We found no evidence of an increased risk of MACE with JAKi compared to TNFi, although patients in the JAKi group were older and had longer disease duration.

POS0110 INCIDENCE OF MAJOR ADVERSE CARDIOVASCULAR EVENTS STRATIFIED BY GEOGRAPHIC REGION AND BASELINE CARDIOVASCULAR RISK: A POST HOC ANALYSIS OF ORAL SURVEILLANCE

BackgroundORAL Surveillance was a post-authorisation safety study of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in patients (pts) with rheumatoid arthritis (RA) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor and an inadequate response to methotrexate (MTX).ObjectivesTo examine associations between major adverse CV events (MACE) and the geographic region and baseline (BL) CV risk profile of pts in ORAL Surveillance.MethodsPts on stable MTX were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID) or a TNFi (adalimumab 40 mg every 2 weeks in North America [NA] or etanercept 50 mg once weekly in the rest of the world [RoW]). Incidence rates (IRs; pts with first events/100 pt-yrs) were evaluated for adjudicated MACE, as well as myocardial infarction (MI) and stroke. MACE was defined as CV death (excluding CV death due to pulmonary embolism), non-fatal MI and non-fatal stroke. IRs were stratified by geographic region (NA vs RoW) and BL CV risk profile: pts were first categorised by history of coronary artery disease (HxCAD); pts without a HxCAD were then categorised by 10-yr risk of MACE (high [≥20%], intermediate [≥7.5–&lt;20%], borderline [≥5–&lt;7.5%] and low [&lt;5%] risk), per the ASCVD-pooled cohort equations calculator1 with a 1.5 multiplier applied.2ResultsOverall, 4362 pts were included in the study (tofacitinib 5 mg BID, n=1455; tofacitinib 10 mg BID, n=1456; TNFi, n=1451). Across treatments, a higher proportion of pts in NA vs RoW had a HxCAD (Table 1). In pts without a HxCAD, across treatments, higher percentages of pts had a high 10-yr risk of MACE in NA vs RoW (Table 1). Across treatments, overall MACE IRs were higher in pts in NA vs RoW (Figure 1). Incidence and risk of MACE were higher with tofacitinib vs TNFi in both NA and RoW (Figure 1). In NA, MACE IRs were higher for tofacitinib 5 mg BID vs TNFi in pts with a HxCAD, and tofacitinib 10 mg BID vs TNFi for pts with a high 10-yr risk of MACE; pts with low or borderline 10-yr MACE risk had no MACE across tofacitinib groups (Figure 1). Compared with NA, similar trends for MACE were generally observed across treatments in RoW, particularly for intermediate, borderline and low CV risk categories (Figure 1).Table 1.Percentages of pts in NA and RoW with a HxCAD and pts without a HxCAD categorised by 10-yr risk of MACE, per ASCVD-pooled cohorts equation risk calculator1 with a 1.5 multiplier applied2NAaRoWTofacitinib 5 mg BID (N=402)Tofacitinib 10 mg BID (N=409)TNFib (N=432)Tofacitinib 5 mg BID (N=1053)Tofacitinib 10 mg BID (N=1047)TNFib (N=1019)HxCAD, n (%)58 (14.4)64 (15.6)81 (18.8)103 (9.8)108 (10.3)83 (8.1)No HxCAD: 10-yr risk of MACE, n (%)High (≥20%)97 (24.1)108 (26.4)113 (26.2)177 (16.8)195 (18.6)183 (18.0)Intermediate (≥7.5–&lt;20%)131 (32.6)144 (35.2)137 (31.7)359 (34.1)372 (35.5)368 (36.1)Borderline (≥5–&lt;7.5%)49 (12.2)31 (7.6)31 (7.2)151 (14.3)143 (13.7)124 (12.2)Low (&lt;5%)60 (14.9)54 (13.2)65 (15.0)253 (24.0)218 (20.8)250 (24.5)Missing data7 (1.7)8 (2.0)5 (1.2)10 (0.9)11 (1.1)11 (1.1)HxCAD was defined as any history of MI, coronary heart disease, stable angina pectoris or coronary artery procedures. aUnited States, Puerto Rico and Canada. bFor pts randomised to the TNFi group, adalimumab and etanercept were administered in NA and RoW, respectivelyn, number of pts with specified characteristics; N, number of evaluable ptsConclusionThis post hoc analysis of data from ORAL Surveillance suggests that differences in MACE IRs across geographic regions are largely driven by HxCAD and high BL CV risk scores in NA vs RoW. Results should be interpreted with caution due to low pt and event numbers, particularly restricting the evaluation of tofacitinib vs TNFi in NA and RoW. Noting this limitation, these findings emphasise the importance of assessing and addressing BL CV risk when treating pts with RA.

Predicting Probability of Response to Tumor Necrosis Factor Inhibitors for Individual Patients With Ankylosing Spondylitis

Tumor necrosis factor inhibitors (TNFis) have revolutionized the management of ankylosing spondylitis (AS); however, the lack of notable clinical responses in approximately one-half of patients suggests important heterogeneity in treatment response. Identifying patients likely to respond or not respond to TNFis could provide opportunities to personalize treatment strategies. To develop models of the probability of short-term response to TNFi treatment in individual patients with active AS. This is a retrospective cohort study using data of the TNFi group (ie, treatment group) from 10 randomized clinical trials (RCTs) of TNFi treatment among patients with active AS, conducted from 2002 to 2016. Participants were adult patients with active AS who failed nonsteroidal anti-inflammatory drugs. Included RCTs were phase 3 and 4 studies that assessed the efficacy of an originator TNFi at week 12 and/or week 24, either compared with placebo or an antirheumatic drug. The cohort was divided into a training and a testing set. Data analysis was conducted from July 1, 2019, to November 30, 2020. All included patients received an originator TNFi for at least 12 weeks. Outcomes included major response and no response based on the change of AS Disease Activity Score at 12 weeks. Machine learning algorithms were applied to estimate the probability of having major response and no response for individual patients. The study included 1899 participants from 10 trials. The training set included 1207 individuals (mean [SD] age, 39 [12] years; 908 [75.2%] men), of whom 407 (33.7%) had major response and 414 (34.3%) had no response. In the reduced logistic regression models, accuracy was 0.74 for major response and 0.75 for no response. The probability of major response increased with higher C-reactive protein (CRP) level, patient global assessment (PGA), and Bath AS Disease Activity Index (BASDAI) question 2 score and decreased with higher body mass index (BMI) and Bath AS Functional Index (BASFI) score. The probability of no response increased with age and BASFI score, and decreased with higher CRP level, BASDAI question 2 score, and PGA. In the testing set (692 participants; mean [SD] age, 38 [11] years; 533 [77.0%] men), models demonstrated moderate to high accuracy. In this cohort study, the probability of initial response to TNFi was predicted from baseline variables, which may facilitate personalized treatment decision-making.

Persistence, effectiveness and safety of ustekinumab compared to TNF inhibitors in psoriatic arthritis within the Italian PsABio cohort.

To compare real-world persistence, effectiveness and tolerability of ustekinumab versus TNF inhibitors (TNFi) in psoriatic arthritis (PsA). One-year data from Italian subjects enrolled in the PsABio study (PsA patients receiving 1st- to 3rd-line treatment with ustekinumab or TNFi) were evaluated. Treatment persistence was analysed using Kaplan-Meier curves; hazard ratios (HR) of stopping treatment, and the corresponding 95% confidence intervals (CI), were computed through Cox regression models. Proportions of patients reaching clinical effectiveness endpoints were analysed using logistic regression, including propensity score (PS) adjustment for imbalanced baseline covariates, and non-response imputation if treatment was stopped/switched. Among 222 participants with follow-up data (effectiveness set), 101 received ustekinumab and 121 TNFi. In the ustekinumab group, 74.3% continued treatment up to 12±3 months compared to 63.6% in the TNFi group. Ustekinumab showed better persistence than TNFi, overall and in specific subgroups (females, monotherapy without methotrexate, BMI <25 or >30 kg/m2, patients receiving ustekinumab as 2nd-line treatment instead of a second TNFi). Overall, the PS-adjusted HR of treatment discontinuation was 0.46 (95% CI: 0.26-0.82) for ustekinumab vs. TNFi. cDAPSA LDA/remission was achieved in 43.5% of ustekinumab and 43.6% of TNFi-treated patients, while MDA was achieved in 24.2% and 28.0% of patients, respectively. After PS adjustment, odds ratios of clinical effectiveness did not differ significantly. Both treatments showed an acceptable safety profile. This prospective, real-life study found a better persistence of ustekinumab than TNFi in PsA patients. At 1 year, both treatments showed similar effectiveness.

Comparison of the efficacy and risk of discontinuation between non-TNF-targeted treatment and a second TNF inhibitor in patients with rheumatoid arthritis after first TNF inhibitor failure.

Objectives:Despite improved care for rheumatoid arthritis (RA) patients, many still experience treatment failure with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs [tsDMARDs; typically Janus kinase inhibitors (JAKi)], and eventually switch to other agents. We compared the efficacy of a second tumor necrosis factor inhibitor (TNFi) and non-TNF-targeted treatment as the second-line treatment in patients showing an insufficient response to the first TNFi.Methods:Patients were included if they had received at least one prescription for a TNFi, and at least one follow-up prescription for a second TNFi or non-TNF-targeted treatment after discontinuation of the first drug. In total, 209 patients were analyzed, including 69 with a second TNFi and 140 with a non-TNF-targeted treatment (106 non-TNFi biologics and 34 JAKi). Cox regression was used to estimate the hazard ratio (HR) for discontinuation.Results:The mean follow-up period after switching was 28.0 (range: 0–80) months and 24.4% of the 209 patients switched or discontinued the second drug. In multivariate Cox proportional hazard analysis, the non-TNF-targeted treatment group had a lower likelihood of discontinuing their treatment than the second TNFi group [HR = 0.326, 95% confidence interval (CI): 0.170–0.626, p = 0.001]. When analyzed separately, the risk of discontinuation was significantly lower in both the non-TNFi biologic (HR = 0.318, 95% CI: 0.160–0.633, p = 0.001) and JAKi (HR = 0.356, 95% CI: 0.129–0.980, p = 0.046) groups than in the second TNFi group.Conclusion:Our study supported switching to a non-TNF-targeted treatment instead of TNF cycling in patients with RA showing an inadequate response to initial TNFi.

Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines.

To analyse the role of body mass index (BMI) in the clinical response to biologic dis-ease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). To per-form an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment. This study involved 105 patients with RA starting tumour necrosis factor inhibitors (TNFi) or tocilizumab (TCZ). Patients were classified ac-cording to BMI as normal-weight and overweight/obesity. The clinical response to treatment was as-sessed by Clinical Disease Activity Index (CDAI) 6 months after initiation of bDMARDs. Serum adi-pokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples ob-tained before initiation of bDMARDs and after 6 months of treatment. A correlation was observed between BMI and disease activity and between BMI and serum adipokines. Sixty percent of patients achieved low disease activity (LDA)/remission: 45 patients in TNFi group (64.2%) and 18 (51.4%) in TCZ group. In TNFi group, patients who did not attain LDA/remission had a higher BMI (kg/m2) ([28.7±5.1] vs. [24.5±4.6], p=0.001) and baseline CDAI (26.3 [17.4-33.9] vs. 19.8 [14.0-28.8], p<0.03). However, no differences in BMI or baseline CDAI were observed between patients who achieved LDA after 6 months in TCZ group. Obesity influences the extent of LDA/remission in patients treated with TNFi, but not in patients treated with TCZ, probably because of underlying pathophysiological mechanisms intrinsic to the production of proinflammatory adi-pokines. Therefore, therapeutic strategies with a mechanism of action other than TNF inhibition would be more suitable for obese patients.

Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.

The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.