Etanercept In Rheumatoid Arthritis Research Articles

Persistence of biological agents over an eight-year period in rheumatoid arthritis and spondylarthritis patients

ObjectiveTo calculate the persistence, over a period of eight years, the retention rate of first and second-line of treatment with biological agents in patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis and to compare retention rates of the various drugs for each pathology. MethodRetrospective observational study that included patients affected by rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, who started treatment with biological agents between January 2009 and December 2012 and followed until December 2016. Results132, 87 and 33 patients were included in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, respectively. The median retention duration of all biological agents for the first and second-line, was 30.9 months and 14.0 months, respectively for rheumatoid arthritis; 63.06 months and 25.6 months, respectively in spondyloarthritis. Psoriatic arthritis did not reach the median (> 70 months in first-line) (first line p = 0.002). Individual drug survival in first line: the median retention duration of tocilizumab was 58.3 months, followed by etanercept (p = 0.79) in rheumatoid arthritis. For spondyloarthritis, golimumab and etanercept had greater retention than the other drugs (they did not reach the median): adalimumab was 63.0 months and for infliximab was 50.1 months. In psoriatic arthritis, golimumab, infliximab and etanercept not reach the median and they had greater retention than adalimumab (59.4 months). Individual drug survival in second line: tocilizumab was the most persistent drug (median 22.1 months) in rheumatoid arthritis, and golimumab for spondyloarthritis and psoriatic arthritis. ConclusionsTocilizumab and etanercept in rheumatoid arthritis, and golimumab in spondyloarthritis and psoriatic arthritis also, were the most persistent drugs in first-line and second-line treatment.

Validation and predictive capacity of a Dutch version of the FLARE-RA questionnaire within the context of a TNFi-tapering trial.

Flare Assessment in Rheumatoid Arthritis (FLARE-RA) is a self-administered tool aiming to capture current or recent flares in rheumatoid arthritis (RA). We aimed to externally validate the FLARE-RA instrument and its existing cutoffs for flare detection within a bDMARD-tapering context in established RA. Data were analyzed from the Tapering Etanercept in Rheumatoid Arthritis (TapERA) trial, which studied the feasibility of tapering etanercept in patients with established RA in sustained remission. The English FLARE-RA was translated and cross-culturally adapted into Dutch, and internal consistency and test-retest reliability were evaluated with Crohnbach's alpha and intraclass correlation coefficient (ICC). Participants completed the FLARE-RA 3-monthly for 12months. Accuracy and optimal cutoffs of FLARE-RA to detect DAS28-defined flares were assessed using area under the receiver operating characteristic curves (AUC). Association of FLARE-RA scores with current and future flares was studied using logistic generalized estimating equations (GEE). The Dutch FLARE-RA showed excellent internal consistency and test-retest reliability (Cronbach's alpha 0.96; ICC 0.96 [95% CI 0.70-1.00]). Discriminatory capacity of FLARE-RA to detect flares was acceptable (AUC 0.77, 0.80, and 0.72 for global, arthritis, and general symptoms subscales, respectively), with an optimal global score cutoff of 4/10. In GEE-models, higher FLARE-RA scores were associated with increased odds of both current and future flares. We successfully translated and cross-culturally adapted the FLARE-RA into a Dutch version and validated its capacity to detect flares in a bDMARD-tapering context in established RA. Finally, higher FLARE-RA scores might indicate an increased risk of future flares.Trial registration: EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004631-22/BE , EudraCT number 2012-004,631-22. Key Points • Translation and cross-cultural adaptation of the FLARE-RA resulted in a Dutch version with excellent internal consistency and test-retest reliability. • The FLARE-RA is a valid instrument to detect current OMERACT-defined flares within a bDMARD tapering setting, with an optimal global score cutoff of 4/10. • Higher scores on the FLARE-RA are associated with increased risk of future flares, which could be particularly relevant when considering DMARD tapering.

P215 In a treatment-naïve, early rheumatoid arthritis cohort, baseline ultrasound power Doppler synovitis and tenosynovitis are highly associated with remission when treated with first line etanercept + methotrexate (MTX) but not MTX alone

Abstract Background/Aims Clinical remission is the treatment target in rheumatoid arthritis (RA). In a treatment-naïve, early RA trial (VEDERA: ‘Very early Etanercept and Methotrexate versus Methotrexate with/without Delayed Etanercept in RA’), we previously reported the presence of ultrasound power Doppler synovitis (PDUS) at diagnosis that improved in the majority with treatment. For this study, we aimed to investigate specifically for an association of baseline PDUS and PD tenosynovitis (PDTS) with subsequent clinical remission (DAS28ESR ≤ 2.6) in VEDERA, also comparing the two treatment groups. Methods The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to either first-line etanercept+methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) regime with escalation to ETN+MTX if not in DAS28ESR remission at week 24. Clinically symptomatic and dominant hand (MCP 1-5, wrist, flexor tendons 1-5 and extensor carpii ulnaris tendon) ultrasound assessments were completed at baseline, weeks 12, 24 and 48. PDUS and PDTS were assessed semi-quantitatively and converted to dichotomous (absent = total score 0, present = total score ≥ 1) for this logistic regression analysis. Results At baseline, 68% (81/120) demonstrated PDUS and 68% also demonstrated PDTS overall. In the MTX-TT group, 63% (38/60) had PDUS and 62% (37/60) had PDTS at baseline. In ETN+MTX group, 72% (43/60) had PDUS and 75% (45/60) had PDTS at baseline. As per randomised trial, there were no differences in baseline demographics, DAS28ESR and HAQ between the groups. Overall, baseline PDUS was associated with week 24 remission and baseline PDTS was associated with week 24 and 48 remission (table 1). Baseline PDUS was particularly associated with week 24 remission in the ETN+MTX group, with a high OR (95% CI) of 6.83(1.2 - 38.91) compared to the MTX-TT group [1.75(0.5 - 6.14)]. Baseline PDTS was also associated with a high OR for week 48 remission in the ETN+MTX group (OR [95% CI] 9.13[1.77 - 47.02]) in contrast to an absence of association in the MTX-TT group. Conclusion Baseline PDUS and PDTS are associated with remission in early RA patients treated with TNF-inhibitor treatment. These measures may be useful to stratify patients early for TNF bDMARD to attain the target of clinical remission in RA. Disclosure R. Shukla: None. R. Hum: Other; R.H holds an Academic Clinical Fellowship funded by the National Institute for Health Research (NIHR) through the Integrated Academic Training (IAT) Programme. P. Ho: None. R.J. Wakefield: None. P. Emery: None. M.H. Buch: None.

P214 Classifiable early RA shows heterogeneous imaging features and potential means of stratification

Abstract Background/Aims Synovitis and tenosynovitis (TS) are key findings seen in patients with rheumatoid arthritis (RA) on musculoskeletal ultrasound (MSUS). Both power Doppler TS (PDTS) and power Doppler synovitis (PDUS) have also been reported in preclinical-RA. We aimed to describe the prevalence of PDTS and PDUS in a treatment-naïve, new-onset RA trial cohort and their association with clinical and disease activity data. Methods The VEDERA (Very early Etanercept and Methotrexate versus Methotrexate with/without Delayed Etanercept in RA) trial recruited 120 treatment-naïve, new-onset RA patients fulfilling ACR-EULAR 2010 classification criteria with at least moderate DAS28-ESR to either first-line etanercept + methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT), and included clinical and dominant hand (MCP 1-5, wrist, flexor tendons 1-5 and extensor carpii ulnaris tendon) MSUS assessments. Joint Grey scale (GS), PDUS and PDTS were assessed semi-quantitatively and converted to dichotomous scale (absent = total score 0; present = total score ≥ 1). Patients were categorised in one of four groups based on presence of PDUS and/or PDTS: no PDUS or PDTS (PDUS-PDTS-), PDTS alone (PDUS-PDTS+), PDUS alone (PDUS+PDTS-) and both PDUS and PDTS (PDUS+PDTS+). Clinical and GS features are described for these groups. Results At time of diagnosis, 17% (20/120) were PDUS-PDTS-, 16% (19/120) PDUS-PDTS+, 15% (18/120) PDUS+PDTS- and 53% (63/120) PDUS+PDTS+. Table 1 details demographic, clinical and disease activity data. GS was present in 60% (12/20) and 74% (14/19) of PDUS-PDTS- and PDUS-PDTS+ groups respectively, while all patients with PDUS + (PDUS+PDTS- and PDUS+PDTS+ groups) demonstrated GS (table 1). The PDUS+PDTS+ group had the shortest symptom duration. PDUS-PDTS- group had lower DAS28ESR, tender/swollen joint counts (28 joints), CRP and pain. The two groups with PDTS + (with/without PDUS) had higher visual analogue pain scores. Conclusion Heterogeneous imaging features of classifiable, new-onset RA likely reflect different rates of progress along the continuum and presentation, and timing in capturing PDUS and PDTS. Severe clinical and imaging features associate with more rapid presentation. A minor proportion show no clear features of PDUS or GS yet are classifiable as RA indicating other contributors to diagnosis. MSUS features may offer a means of stratifying patients and tailoring treatment approaches. Disclosure R. Shukla: None. R. Levy: None. P. Ho: None. K. Mankia: None. R.J. Wakefield: None. P. Emery: None. M.H. Buch: None.

Effectiveness of SB4 Transition from Originator Etanercept in Rheumatoid Arthritis and Axial Spondyloarthritis: A Subgroup Analysis from the BENEFIT Study.

The pan-European BENEFIT study of patients with stable rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who transitioned from reference etanercept to SB4 found no clinically meaningful changes in disease control after transition. The analysis aims to illustrate the peculiarities of the Italian cohort of patients compared with the whole population to provide a more real-life approach to the data for the Italian rheumatologists, ruling out possible local confounding factors. A prospective study for up to 6 months following transition was conducted. Outcome measures of interest include clinical characteristics at time of transition and disease activity scores (Disease Activity Score-28 [DAS28] for RA, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] for axSpA) over time and safety. One-hundred and eleven subjects (out of the 557 in total enrolled in the study) were derived from 8 Italian sites, including 79 with RA and 32 with axSpA. In both cohorts, the efficacy was maintained at 3 months and 6 months from the transition to the biosimilar with no significant change in mean DAS28 and BASDAI scores: at the end of the 6 months of observation the mean DAS28 and BASDAI was similar to baseline (confidence interval [CI] -0.22, 0.22), while the mean variation of the BASDAI was -0.14. Of note, 100.0% (95% CI 89.1, 100.0) in the axSpA and 90.8% (95% CI 81.5, 95.5) in the RA cohort of patients continued to receive SB4 at month 6 (binary variable with 95% Clopper-Pearson CI). Italian patients with stable RA or axSpA who transitioned from originator Etanercept to SB4 maintained clinical response at 6 months post-transition. Both the cohorts are representative of typical patients with long-standing established diagnoses. Most of the patients transitioned to the same dose regimen of biosimilar as that received for the originator, and the regimen remained unchanged at 6 months, supporting the effectiveness of the transition.

Restoration of Default Blood Monocyte-Derived Macrophage Polarization With Adalimumab But Not Etanercept in Rheumatoid Arthritis.

IntroductionWe previously reported a specific defect of rheumatoid arthritis (RA) monocyte polarization to anti-inflammatory M2-like macrophages related to increased miR-155 expression in all RA patients except those receiving adalimumab (ADA). In this longitudinal study, we examined whether different tumor necrosis factor inhibitors were able to restore monocyte polarization to M2-like macrophages and their effect on the transcriptomic signature.MethodsM2-like polarization induced by human serum AB was studied in 7 healthy donors and 20 RA patients included in the ABIRA cohort before and 3 months after starting ADA or etanercept (ETA). The differential gene expression of M2- and M1-related transcripts was studied in macrophage-derived monocytes after differentiation.ResultsAt baseline, RA monocytes showed a defect of polarization to M2-like macrophages as compared with healthy donor monocytes, which was negatively correlated with disease activity. M2-like polarization from circulating monocytes was restored only with ADA and not ETA treatment. The transcriptomic signature demonstrated downregulation of M2-related transcripts and upregulation of M1-related transcripts in active RA. In patients receiving ADA, the transcriptomic signature of M2-related transcripts was restored.ConclusionThis longitudinal study demonstrates that ADA but not ETA is able to restore the M2-like polarization of monocytes that is defective in RA.

Effectiveness of Etanercept in Rheumatoid Arthritis: Real-World Data from the German Non-interventional Study ADEQUATE with Focus on Treat-to-Target and Patient-Reported Outcomes.

BackgroundFor rheumatoid arthritis (RA), the treat-to-target concept suggests attaining remission or at least low disease activity (LDA) after 12 weeks.ObjectivesThis German, prospective, multicenter, non-interventional study aimed to determine the proportion of patients with RA who achieved their treat-to-target aim after 12 and 24 weeks of etanercept (ETN) treatment in a real-life setting, as opposed to patients achieving their therapeutic target at a later timepoint (week 36 or 52).MethodsA total of 824 adults with a confirmed diagnosis of RA without prior ETN treatment were included. Remission and LDA were defined as DAS28 < 2.6 and DAS28 ≤ 3.2, respectively.ResultsThe proportion of patients achieving remission was 24% at week 12 and 31% at week 24. The proportion of patients achieving LDA was 39% at week 12 and 45% at week 24. The proportion of patients achieving remission or LDA further increased beyond week 24 up to week 52. Improvement in pain and reduction in concomitant glucocorticoid treatment were observed. Improvements in patient-reported outcomes were also seen in patients who did not reach remission or LDA. No new safety signals were detected.ConclusionsA considerable proportion of patients with RA attained the target of remission or LDA after 12 weeks of ETN treatment. Even beyond that timepoint, the proportion of patients achieving treatment targets continued to increase up to week 52.Trial RegistrationClinicalTrials.gov Identifier: NCT02486302.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00418-5.

Free Papers Compiled

Background:Schizophrenia (SCZ) and rheumatoid arthritis (RA) may remain as co-morbid diseases in clinical setting. In research it has been reported that one will influence the outcome of other disease. Hence, the psychiatrist should be aware of the interactions between immunomodulatory drugs and antipsychotics for better treatment outcomes.Aim:To understand clinically important drug-drug interaction and challenges in management of two middle aged females diagnosed with chronic rheumatoid arthritis and co-morbid schizophrenia.Result:We report 2 cases of RA with co morbid SCZ. The first case was maintaining on prednisolone and etanercept for RA and showed poor reponse to risperidone due to interaction with anti-rheumatoid drugs. The patient then improved on clozapine. The second case was being treated with methotrexate and olanzapine was initiated which showed improvement in schizophrenic as well as pain symptoms associated with RA.Conclusion:The metabolism of Risperidone can be increased when combined with Etanercept leading to reduced serum antipsychotic level and failure of treatment as found in this case. Also, olanzapine has unique pharmacological properties which can act as an adjunct to other pain medications prescribed for relief in RA patients. In the present cases, clozapine and olanzapine were beneficial respectively and therefore may be preferred over risperidone for management of schizophrenic patients with RA.

Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial

Objective In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. Method Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28–C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. Results Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0–6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. Conclusions Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.

Correlation of Ultrasound Synovitis Joint Count with Disease Activity and Its Longitudinal Variation with Treatment Response to Etanercept in Rheumatoid Arthritis

More research is needed into rheumatoid arthritis (RA), and ultrasound (US) synovitis is a promising factor for assisting in the management of RA; however, related research is extremely limited. The goal of this study was to evaluate the correlation of US synovitis joint count with clinical features, and its longitudinal changes with treatment response to etanercept in RA. We consecutively enrolled 117 people with active RA being treated with etanercept. US synovitis joint count was evaluated in 28 joints at baseline (W0), week 4 (W4), week 12 (W12) and week 24 (W24) after initiation of etanercept treatment. The mean (±standard deviation), median, inter-quartile range, and total range of the US synovitis joint count at W0 were 9.3 ± 4.0, 9.0, 7.0–11.0 and 2.0–21.0, respectively. US synovitis joint count was positively associated with tenderness joint count, swollen joint count, erythrocyte sedimentation rate, 28-joint Disease Activity Score based on erythrocyte sedimentation rate and Health Assessment Questionnaire–Disability Index score. Then participants were categorized into response and non-response groups according to their response status at W24. Further analyses showed that US synovitis joint count gradually decreased from W0 to W24, and displayed a more notable declining trend in the response group compared with the non-response group. In addition, US synovitis joint count at W0 and W4 was similar between groups, but at W12 and W24 it was markedly decreased in the response group compared with the non-response group. In conclusion, US synovitis joint count correlates with disease activity, and its longitudinal decrease is associated with treatment response to etanercept in RA.

Using cardiovascular magnetic resonance to define mechanisms of comorbidity and to measure the effect of biological therapy: the CADERA observational study

Background The VEDERA (Very Early vs. Delayed Etanercept in Rheumatoid Arthritis) randomised controlled trial compared the effect of conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy with biologic DMARD (bDMARD) therapy using the tumour necrosis factor inhibitor etanercept in treatment-naive, early rheumatoid arthritis patients. The CADERA (Coronary Artery Disease Evaluation in Rheumatoid Arthritis) trial was a bolt-on study in which VEDERA patients underwent cardiovascular magnetic resonance imaging to detect preclinical cardiovascular disease at baseline and following treatment. Objectives To evaluate whether or not patients with treatment-naive early rheumatoid arthritis have evidence of cardiovascular disease compared with matched control subjects; whether or not this is modifiable with DMARD therapy; and whether or not bDMARDs confer advantages over csDMARDs. Design The VEDERA patients underwent cardiovascular magnetic resonance imaging at baseline and at 1 and 2 years after treatment. Setting The setting was a tertiary centre rheumatology outpatient clinic and specialist cardiovascular magnetic resonance imaging unit. Participants Eighty-one patients completed all assessments at baseline, 71 completed all assessments at 1 year and 56 completed all assessments at 2 years. Patients had no history of cardiovascular disease, had had rheumatoid arthritis symptoms for ≤ 1 year, were DMARD treatment-naive and had a minimum Disease Activity Score-28 of 3.2. Thirty control subjects without cardiovascular disease were approximately individually matched by age and sex to the first 30 CADERA patients. Patients with a Disease Activity Score-28 of ≥ 2.6 at 48 weeks were considered non-responders. Interventions In the VEDERA trial patients were randomised to group 1, immediate etanercept and methotrexate, or group 2, methotrexate ± additional csDMARD therapy in a treat-to-target approach, with a switch to delayed etanercept and methotrexate in the event of failure to achieve clinical remission at 6 months. Main outcome measures The primary outcome measure was difference in baseline aortic distensibility between control subjects and the early rheumatoid arthritis group and the baseline to year 1 change in aortic distensibility in the early rheumatoid arthritis group. Secondary outcome measures were myocardial perfusion reserve, left ventricular strain and twist, left ventricular ejection fraction and left ventricular mass. Results Baseline aortic distensibility [geometric mean (95% confidence interval)] was significantly reduced in patients (n = 81) compared with control subjects (n = 30) [3.0 × 10–3/mmHg (2.7 × 10–3/mmHg to 3.3 × 10–3/mmHg) vs. 4.4 × 10–3/mmHg (3.7 × 10–3/mmHg to 5.2 × 10–3/mmHg), respectively; p &lt; 0.001]. Aortic distensibility [geometric mean (95% confidence interval)] improved significantly from baseline to year 1 across the whole patient cohort (n = 81, with imputation for missing values) [3.0 × 10–3/mmHg (2.7 × 10–3/mmHg to 3.4 × 10–3/mmHg) vs. 3.6 × 10–3/mmHg (3.1 × 10–3/mmHg to 4.1 × 10–3/mmHg), respectively; p &lt; 0.001]. No significant difference in aortic distensibility improvement between baseline and year 1 was seen in the following comparisons (geometric means): group 1 (n = 40 at baseline) versus group 2 (n = 41 at baseline): 3.8 × 10–3/mmHg versus 3.4 × 10–3/mmHg, p = 0.49; combined groups 1 and 2 non-responders (n = 38) versus combined groups 1 and 2 responders (n = 43): 3.5 × 10–3/mmHg versus 3.6 × 10–3/mmHg, p = 0.87; group 1 non-responders (n = 17) versus group 1 responders (n = 23): 3.6 × 10–3/mmHg versus 3.9 × 10–3/mmHg, p = 0.73. There was a trend towards a 10–30% difference in aortic distensibility between (group 1) responders who received first-line etanercept (n = 23) and (group 2) responders who never received etanercept (n = 13): 3.9 × 10–3/mmHg versus 2.8 × 10–3/mmHg, p = 0.19; ratio 0.7 (95% confidence interval 0.4 to 1.2), p = 0.19; ratio adjusted for baseline aortic distensibility 0.8 (95% confidence interval 0.5 to 1.2), p = 0.29; ratio fully adjusted for baseline characteristics 0.9 (95% confidence interval 0.6 to 1.4), p = 0.56. Conclusions The CADERA establishes evidence of the vascular changes in early rheumatoid arthritis compared with controls and shows improvement of vascular changes with rheumatoid arthritis DMARD therapy. Response to rheumatoid arthritis therapy does not add further to modification of cardiovascular disease but, within the response to either strategy, etanercept/methotrexate may confer greater benefits over standard methotrexate/csDMARD therapy. Trial registration Current Controlled Trials ISRCTN89222125 and ClinicalTrials.gov NCT01295151. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 4. See the NIHR Journals Library website for further project information. Pfizer Inc. (New York, NY, USA) supported the parent study, VEDERA, through an investigator-sponsored research grant reference WS1092499.

Comparison of efficacy of Infliximab and Etanercept on Rheumatoid Arthritis patients

This study aimed to compare the efficacy of infliximab and etanercept in rheumatoid arthritis (RA) patients to help clinicians select the most effective treatment options. This was a cross sectional study conducted in Urmia, Iran, from March 21, 2017, to February 20, 2018. Data was collected by checklists from RA patients referred to the Rheumatology Clinic of Urmia Imam Khomeini Hospital who were receiving either infliximab or etanercept. Inclusion criteria were a diagnosis of RA according to the revised 2016 criteria of the American College of Rheumatology (ACR)/European League Against Rheumatism, aged over 18, consent to participate in the study, and poor response to other drugs. Both genders were included. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count (TJC), swollen joint count (SJC), and disease activity score (DAS) (28 scores) were analyzed before and after treatment. In a total of 44 eligible patients, 13 patients received infliximab and 31 received etanercept. The mean age was 53.92 ± 10.94 and 52.8 ± 64.13 years in the infliximab and etanercept groups, respectively. No significant differences were reported concerning ESR (p value = 0.97) or CRP (p value = 0.96), while a significant decrease in the infliximab group compared to the etanercept group was demonstrated in terms of DAS28 scores (p value = 0.028), global health (GH)1 (p value = 0.005), SJC (p value = 0.008), and TJC (p value = 0.01). This study demonstrated a significant difference between the two groups in the DAS scores 28, SJC, TJC, and GH.

BENEFIT: real-world effectiveness of SB4 after transition from reference etanercept in rheumatoid arthritis and axial spondyloarthritis

The objective of this non-interventional study was to evaluate the effectiveness and safety of the etanercept biosimilar SB4 (BenepaliTM) following transition from reference etanercept in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). Data were collected from clinical records of adult patients with stable RA or axSpA, in France, Germany, Italy and Spain. Key outcomes included the change from transition to 3 and 6 months in Disease Activity Score 28 (DAS28) for RA or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for axSpA. In total, 358 patients with RA and 199 patients with axSpA were enrolled. The mean individual change in disease score from transition was -0.02 (95% confidence interval [CI] -0.11, 0.08) at 3 months and 0.01 (95% CI -0.09, 0.11) at 6 months for DAS28, and -0.01 (95% CI -0.24, 0.21) at 3 months and -0.11 (95% CI -0.31, 0.10) at 6 months for BASDAI. In the RA cohort, 19 (5.3%) and 5 patients (1.4%) reported adverse events and serious adverse events (SAEs), respectively. In the axSpA cohort, 12 (6.0%) and 2 patients (1.0%) reported adverse events and SAEs, respectively. One SAE of pneumonia (RA cohort) was considered to be related to SB4 administration. At 6 months post-transition, the SB4 retention rate was 90.8% (95% CI 87.2%, 93.4%) in the RA cohort and 92.4% (95% CI 87.5%, 95.4%) in the axSpA cohort. Transition from reference etanercept to SB4 is effective and safe in patients with stable RA and axSpA.

P137 Growing up on biologics: a case report of development of NMDAr encephalitis in a young person with JIA on abatacept

Abstract Background A 12-year-old female with JIA on biologic medication (IV abatacept every three weeks) presented with a first generalised tonic-clonic seizure on background of preceding headache and fatigue. The seizure self-terminated but disorientation and encephalopathy ensued. MRI brain demonstrated lesions with high signal intensity in the left periventricular and right occipital regions. The clinical picture and radiological imaging suggested a broad differential diagnosis including CNS infection, JC virus associated progressive multifocal leucoencephalomalacia (PML), acute disseminated encephalomyelitis (ADEM) and Anti-N-methyl-d-aspartate receptor (NMDAr) encephalitis. She was commenced on IV ceftriaxone, acyclovir and clarithromycin. All bloods including inflammatory markers and infection serology were unremarkable. CSF was acellular and JC virus PCR negative. NMDAr encephalitis was initially considered unlikely (pre-existing immunosuppression, abnormal MRI brain and no evidence of ovarian teratoma on abdominal MRI pelvis). However more classical clinical features developed including further seizures, significant movement disorder, cognitive dysfunction, sleep and speech dysfunction. Anti-NMDAr antibodies in both serum and CSF were positive. She made a good recovery following IV steroids, plasmapheresis and rituximab and was discharged home after a 10-week admission. NMDAr encephalitis developed three years after commencing abatacept treatment. Previous immune modulating treatment included methotrexate (since age 2 years), Etanercept (age 5-8 years) and Tocilizumab (aged 8-10 years). Flares of disease following a period of control necessitated the changes in therapy. Methods A literature review was conducted to explore the relationship between NMDAr encephalitis and biologic medication. A yellow card report and information request to abatacept manufacturer were also submitted. Results No previous cases of NMDAr encephalitis in patients on abatacept or paediatric cases related to biologic therapy are described. There are reports of adults developing NMDAr encephalitis on Adalumimab for Crohn’s disease and etanercept for rheumatoid arthritis. NMDAr encephalitis has also been described in patients on immune checkpoint inhibitors for malignant melanoma (nivolumab and ipilimumab). Known triggers of production of anti-NMDA receptor antibodies include tumours (ovarian teratoma; rarely associated in patients under 12 years) and viral infections. Developing autoimmune disorders on biologic medication is well reported, most notably psoriasis and inflammatory bowel disease. In relation to abatacept specifically, the development of anti-nuclear antibodies (ANA) and psoriasis have been described. However, patients with autoimmune disorders are known to be of increased risk for additional immune disease. A new cohort of patients are emerging who have received multiple biologic medications and the development of autoimmune conditions despite immunosuppression needs to be considered. Conclusion We describe the first case of NMDAr encephalitis occurring in a child on abatacept therapy, and the first case in JIA. We are unable to determine what contribution a history of autoimmune disease or immunomodulating therapy has made on its development in this case. Disclosures R. Close: None. P. Bale: None. K. Gallagher: None. G. Ambegaonkar: None. T. Rossor: None. N. Abbassi: None. K. Armon: None.

Repeat exchange transfusion for treatment of severe babesiosis

We report a case of severe babesiosis presenting with 43% parasitemia in a 73-year-old splenectomized woman on etanercept for rheumatoid arthritis. She initially was treated aggressively with clindamycin and quinine and exchange transfusion. Despite a post-exchange drop in parasitemia to 7.6%, it rebounded to 11.4% on hospital day 5 accompanied by new onset high fevers and hypoxia. She improved after a second exchange transfusion and ultimately resolved her infection after 12 weeks of antibabesial antibiotics. Although exchange transfusion is commonly used in immunocompromised hosts, there is a dearth of information about repeat exchange transfusion, including the risk for and outcome of repeat exchange. We performed a literature search for other cases of repeat exchange transfusion for severe Babesia microti infection and compared our case with those in other published reports.

IL-1β, IL-17A, CRP and biologics history might serve as potential markers for clinical response to etanercept in rheumatoid arthritis patients.

This study aimed to explore the predictive value of 10 serum cytokines for clinical response to etanercept (ETN) in rheumatoid arthritis (RA) patients. Totally 128 active RA patients were enrolled, and their serum cytokines levels were detected by enzyme-linked immune sorbent assay at baseline. All patients received ETN treatment for 24weeks, and clinical response to ETN was assessed at week 4 (W4), week 12 (W12) and week 24 (W24). There were 40 (31.3%), 74 (57.8%) and 94 (73.4%) patients who achieved clinical response at W4, W12 and W24, respectively. Based on the clinical response status at W24, patients were divided into responders and non-responders. Baseline levels of interleukin (IL)-1β and IL-17A were higher in responders, while baseline levels of tumor necrosis factor (TNF)-α, IL-6, 1L-8, IL-21, IL-23, intercellular cell adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) were similar in responders compared with non-responders. Responders had less of a history of biologics, and higher baseline level of C-reactive protein (CRP) compared with non-responders. Further analysis revealed that CRP and IL-1β were independent factors predicting increased clinical response. Subsequent receiver operating characteristics (ROC) curve analysis illustrated that the combination of CRP and IL-1β (AUC: 0.730, 95% CI 0.636-0.824) well distinguished responders from non-responders. In conclusion, IL-1β, IL-17A, CRP and biologics history would serve as potential markers for clinical response to ETN in RA patients.

Efficacy and Safety of Etanercept in Elderly Patients with Rheumatoid Arthritis: A Post-Hoc Analysis of Randomized Controlled Trials.

Elderly individuals are disproportionately affected by rheumatoid arthritis (RA), but few studies have addressed the efficacy and safety of treatments in this population. Our objective was to assess the efficacy and safety of etanercept in elderly patients (aged ≥ 65years) with RA. The efficacy analysis was a post hoc analysis of data from the open-label period of three phase IV clinical trials of etanercept for RA. Least squares (LS) change from baseline (cfb) in 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and modified Total Sharp Scores (mTSS) were analyzed by age (< 65 vs. ≥ 65years) for each study. The safety analyses were of data pooled from the double-blind, placebo-controlled periods of 19 phase I-IV randomized studies of etanercept in patients with RA. The percentage occurrence of adverse events (AEs) in placebo- and etanercept-treated patients was analyzed by age (< 65 vs. ≥ 65years). There were no significant differences in LS mean cfb in DAS28 or mTSS between the two age groups. LS mean cfb in HAQ-DI scores was consistently lower in elderly than in non-elderly patients, although significant differences were not observed in all trials. Overall,AE occurrence was higher in elderly than non-elderly patients, regardless of treatment. In etanercept-treated patients, there were small yet statistically significant increases in the occurrence of congestive heart failure, serious infections, and non-melanoma skin cancers in elderly versus non-elderly patients. For most AEs, occurrence did not significantly differ between elderly and non-elderly patients. Overall, there were no substantial differences in the efficacy or safety of etanercept between elderly and non-elderly patients with RA.

Serum drug concentrations to optimize switching from adalimumab to etanercept in rheumatoid arthritis

Objectives: Inadequate response to adalimumab can be caused by insufficient blockade of the target tumour necrosis factor (TNF) at low serum concentrations. In such cases, patients may respond to another TNF inhibitor. We investigated whether the serum adalimumab concentration is related to the efficacy of a second TNF inhibitor, etanercept, in rheumatoid arthritis (RA).Methods: Patients with RA starting etanercept treatment were prospectively observed in the Reade Rheumatology Registry. In patients previously on adalimumab, serum concentrations were determined before treatment discontinuation. According to this concentration, three subgroups were formed: < 0.5 μg/mL, 0.5–5.0 μg/mL, and ≥ 5.0 μg/mL. The European League Against Rheumatism (EULAR) good/moderate response rate after 52 weeks of etanercept was compared between the switcher subgroups and biologic-naive patients.Results: In total, 449 consecutive patients were included, of whom 69 switched from adalimumab (15%) and 380 were biologic naive (85%). EULAR good or moderate response was achieved by 74% of the biologic-naive patients and by 72%, 50%, and 52% of switchers with adalimumab concentration < 0.5 μg/mL, 0.5–5.0 μg/mL, and ≥ 5.0 μg/mL, respectively (p = 0.15). Patients with an adalimumab concentration ≥ 0.5 μg/mL were significantly less likely to achieve EULAR good/moderate response on etanercept compared to biologic-naive patients, whereas patients with a concentration < 0.5 μg/mL did not significantly differ from patients starting etanercept without prior biologic treatment.Conclusion: RA patients with an inadequate response to adalimumab, in the presence of sufficient drug concentrations, benefit less from switching to another TNF inhibitor, etanercept.

The Latent Tuberculin Test after 1-year Therapy with Anti-TNF in Babylon, Iraq

Background: Rheumatoid arthritis (RA) patients receiving receive anti-TNF agents are at increased risk of reactivation of latent tuberculosis infection (LTBI). The tuberculin skin test (TST) is widely used to screen LTBI and providing preventive treatment, in an effort to meet the WHO target of a 90% reduction in TB by 2035.&#x0D; Objectives: To determine the proportion of TST conversion among RA patients after 1 year of anti-TNF treatment and association of positive TST result with patients’ socio-demographic characteristics and medical history.&#x0D; Methods: This community-based cross-sectional study was conducted at the Department of Rheumatology of Marjan Teaching Hospital in Iraq, for a period of 1 year. Patients with RA/and spondyloarthropathy, and who received anti-TNF therapy for &gt;1 year, underwent TST. Their demographic data and medical history were also obtained. All statistical analysis was performed using SPSS (Version 20) and, p &lt; 0.05 was considered as a sign. Data from the baseline and 1 year follow-up was subjected to the Kolmogorov-Smirnov test to determine whether they were normally distributed. Chi-Square test used to test significance of TST among etanrecept and infliximab at the end of the study.&#x0D; Results: A total of 96 patients were enrolled, including 55 (57.3%) males and 41 (42.3%) females with an average age of 41.1, and mostly 68 (70.8%) from Babylon Governorate of Iraq. A total of 40 (41.7%) patients had rheumatoid arthritis alone, and the remaining 56 (58.3%) had a comorbidity of spondyloarthropathy. Majority of the patients 65 (67.7%) received the biological agent infliximab, while 31 (32.3%) patients received Etanercept for RA for a period of 1 year. There was a statistically significant decreasing in the median ESR and disease activity from the baseline to the end of the study (p-value &lt;0.01). There was no significant difference in TST results based on gender or age. Both infliximab and etanercept were significantly associated with a decreasing in ESR and disease activity&#x0D; Conclusion: This study has shown that there was very low TST conversion among RA patients after 1 year of anti-TNF treatment and, age and gender were not associated with TST.

Quartz crystal microbalance as an assay to detect anti-drug antibodies for the immunogenicity assessment of therapeutic biologics.

Because of their biological origins, therapeutic biologics can trigger an unwanted deleterious immune response with some patients. The immunogenicity of therapeutic biologics can affect drug efficacy and patient safety by the production of circulating anti-drug antibodies (ADA). In this study, quartz crystal microbalance (QCM) was developed as an assay to detect ADA. Etanercept (Enbrel®) was covalently grafted to dextran-modified QCM surfaces. Rabbits were immunized with etanercept to generate ADA. Results showed the QCM assay could detect purified ADA from rabbits at concentrations as low as 50ng/mL, within the sensitivity range of ELISA. The QCM assay could also assess the ADA isotype. It was shown that the ADA were composed of the IgG isotype, but not IgM, as expected. Furthermore, it was shown that QCM surfaces that had been used to detect ADA could be regenerated in glycine-HCl solution and reused. The QCM assay was also demonstrated to detect ADA in crude serum samples. Serum was collected from the rabbits and analyzed before and after etanercept immunization. ADA were clearly detected in serum from rabbits after immunization, but not in serum before immunization. Serum from patients administered with etanercept for rheumatoid arthritis (RA) treatment was also analyzed and compared to serum from healthy donors. Sera from 10 RA patients were analyzed. Results showed one of the RA patient serum samples may have ADA present. In conclusion, QCM appears to be a viable assay to detect ADA for the immunogenicity assessment of therapeutic biologics.