Discontinuation Of Etanercept Research Articles

Distinct long-term disease activity trajectories differentiate early on treatment with etanercept in both rheumatoid arthritis and spondylarthritis patients: a prospective cohort study

To characterize disease activity trajectories and compare long-term drug retention between rheumatoid (RA) and spondylarthritis (SpA) patients initiating tumor necrosis factor inhibitor (TNFi) treatment (etanercept). Prospective observational study of RA, axial (AxSpA) and peripheral SpA (PerSpA) patients initiating etanercept during 2004–2020. Kaplan–Meier plots were used for drug retention comparisons and multivariable Cox regression models for predictors of discontinuation. Long-term disease activity trajectories were identified by latent class growth models using DAS28-ESR or ASDAS-CRP as outcome for RA and AxSpA respectively. We assessed 711 patients (450 RA, 178 AxSpA and 83 PerSpA) with a median (IQR) follow-up of 12 (5–32) months. At 5 years, 22%, 30% and 21% of RA, AxSpA and PerSpA patients, respectively, remained on therapy. Etanercept discontinuation was independent of the diagnosis and was predicted by gender and obesity in both RA and SpA groups. Four disease activity (DA) trajectories were identified from 6th month of treatment in both RA and AxSpA. RA patients in remission-low DA groups (33.7%) were younger, had shorter disease duration, fewer comorbidities and lower baseline disease activity compared to moderate (40.6%) & high DA (25.7%) groups. In AxSpA 74% were in inactive-low DA and they were more often males, non-obese and had lower number of comorbidities compared to higher ASDAS-CRP trajectories. In RA and AxSpA patients, disease activity trajectories revealed heterogeneity of TNFi treatment responses and prognosis. Male gender, lower baseline disease activity and fewer comorbidities, characterize a favourable outcome in terms of disease burden accrual and TNFi survival.

Interval prolongation of etanercept in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a randomized controlled trial

Objective The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering are scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study. Method 160 patients with rheumatoid arthritis (RA), PsA, or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomized controlled trial. The intervention group doubled the dosing interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose for 6 months and doubled the dosing-interval thereafter. The primary outcome was the proportion of patients maintaining MDA at 6 month follow-up. Results At 6 months, MDA status was maintained in 47 patients (63%) in the intervention group and 56 (74%) in the control group (p = 0.15), with comparable results in all rheumatic diseases. And median etanercept concentrations decreased from 1.50 µg/mL (interquartile range 1.06– 2.65) to 0.46 µg/mL (0.28–0.92). In total, 40% discontinued etanercept successfully with maintained MDA for at least 6 months. Conclusion Etanercept tapering can be done without losing efficacy in RA, PsA, and AS patients in sustained MDA. A substantial proportion of patients could stop etanercept for at least 6 months. In many patients, low drug concentrations proved sufficient to control disease activity. However, the risk of minor and major flares is substantial, even in patients continuing standard dosing.

Pulmonary sarcoid-like granulomatosis during etanercept treatment for inflammatory arthritis: A case series and literature review

Rationale: Tumor necrosis factor-alpha (TNF-α) inhibitors have been implicated in the development of sarcoid-like granulomatous inflammation when used for treatment of a variety of immune-related diseases. The mechanisms are not completely understood, and the clinical, radiographic and histologic findings of this condition require further description. The literature surrounding this is largely limited to single case reports. Objectives: The objective of this study was to describe pulmonary sarcoid-like granulomatosis in 5 patients receiving etanercept therapy prescribed for inflammatory arthritis. Methods: We retrospectively reviewed the medical records of 5 patients who developed granulomatous sarcoid-like manifestations while on treatment with etanercept for inflammatory arthritis. Data surrounding clinical features and radiographic and histologic findings, as well as clinical outcomes, were described. Results: Median time from initiation of treatment to development of symptoms was 36 months (range 7-60 months). All patients had radiographic abnormalities on chest imaging, with 4 patients having adenopathy on thoracic imaging, and 2 of the 5 patients having parenchymal involvement. Biopsy evidence of granulomatous inflammation was seen in all patients. Three of 5 patients had discontinuation of etanercept when the diagnosis was made, and all experienced improvement. Of the 2 patients that were continued on etanercept, 1 had spontaneous improvement and the other had stable, asymptomatic radiographic abnormalities. Only 1 patient was treated with corticosteroids. Conclusion: Pulmonary sarcoid-like granulomatosis is incompletely understood and establishing the causal role of these drugs in sarcoid-like lung disease is difficult. We hope that the addition of these 5 cases of etanercept-related pulmonary sarcoid-like granulomatosis will add to our future understanding of this response to etanercept and other anti-TNF-α agents.

Gastrointestinal Adverse Drug Reaction Profile of Etanercept: Real-world Data From Patients and Healthcare Professionals.

We aimed to describe the nature and frequency of gastrointestinal adverse drug reactions (GI-ADRs) of etanercept (ETN) using patient-reported and healthcare professional (HCP)-registered data and compared this frequency with the GI-ADR frequency of the widely used tumor necrosis factor-α inhibitor adalimumab (ADA). Reported GI-ADRs of ETN for rheumatic diseases were collected from the Dutch Biologic Monitor and DREAM registries. We described the clinical course of GI-ADRs and compared the frequency with ADA in both data sources using Fisher exact test. Out of 416 patients using ETN for inflammatory rheumatic diseases in the Dutch Biologic Monitor, 25 (6%) patients reported 36 GI-ADRs. In the DREAM registries 11 GI-ADRs were registered for 9 patients (2.3%), out of 399 patients using ETN, with an incidence of 7.1 per 1000 patient-years. Most GI-ADRs consisted of diarrhea, nausea, and abdominal pain. GI-ADRs led to ETN discontinuation in 1 patient (4%) and dose adjustment in 4 (16%) in the Dutch Biologic Monitor. Eight GI-ADRs (73%) led to ETN discontinuation in the DREAM registries. The frequency of GI-ADRs of ETN did not significantly differ from GI-ADRs of ADA in both data sources (Dutch Biologic Monitor: ETN 8.7% vs ADA 5.3%, P = 0.07; DREAM: ETN 2.8% vs ADA 4.7%, P = 0.16). Most GI-ADRs associated with ETN concerned gastrointestinal symptoms. These ADRs may lead to dose adjustment or ETN discontinuation. The frequency of ETN-associated GI-ADRs was comparable to the frequency of ADA-associated GI-ADRs. Knowledge about these previously unknown ADRs can facilitate early recognition and improve patient communication.

Re-treatment with etanercept is as effective as the initial firstline treatment in patients with juvenile idiopathic arthritis

ObjectivesTo determine (i) correlates for etanercept (ETA) discontinuation after achieving an inactive disease and for the subsequent risk of flare and (ii) to analyze the effectiveness of ETA in the re-treatment after a disease flare.MethodsData from two ongoing prospective registries, BiKeR and JuMBO, were used for the analysis. Both registries provide individual trajectories of clinical data and outcomes from childhood to adulthood in juvenile idiopathic arthritis (JIA) patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs (csDMARDs).ResultsA total of 1724 patients were treated first with ETA treatment course (338 with second, 54 with third ETA course). Similar rates of discontinuation due to ineffectiveness and adverse events could be observed for the first (19.4%/6.2%), second (18.6%/5.9%), and third (14.8%/5.6%) ETA course. A total of 332 patients (+/−methotrexate, 19.3%) discontinued ETA after achieving remission with the first ETA course. Younger age (hazard ratio (HR) 1.08, p < 0.001), persistent oligoarthritis (HR 1.89, p = 0.004), and shorter duration between JIA onset and ETA start (HR 1.10, p < 0.001), as well as good response to therapy within the first 6 months of treatment (HR 1.11, p < 0.001) significantly correlated to discontinuation with inactive disease. Reoccurrence of active disease was reported for 77% of patients with mean time to flare of 12.1 months. We could not identify any factor correlating to flare risk. The majority of patients were re-treated with ETA (n = 117 of 161; 72.7%) after the flare. One in five patients (n = 23, 19.7%) discontinued ETA again after achieving an inactive disease and about 70% of the patients achieved an inactive disease 12 months after restarting ETA.ConclusionThe study confirms the effectiveness of ETA even for re-treatment of patients with JIA. Our data highlight the association of an early bDMARD treatment with a higher rate of inactive disease indicating a window of opportunity.

One-year results after transitioning from etanercept originator to biosimilar in a setting promoting shared decision-making in rheumatology.

ObjectiveThe aim was to study the effect of non-mandatory transitioning from etanercept originator to etanercept biosimilar on retention rates in a setting promoting shared decision-making.MethodsIn 2016, all patients treated with etanercept originator and stable disease at the Rheumatology department in Bernhoven were offered transitioning to etanercept biosimilar by an opt-in approach. A historical cohort of patients treated with etanercept originator in 2015 was identified as the control group. Etanercept discontinuation was compared between the cohorts using Cox regression. To study the nocebo effect, reasons for discontinuation were categorized into objective reasons (e.g. laboratory abnormalities, increase in swollen joint count, allergic reaction) and subjective health complaints (symptoms perceptible only to the patient, e.g. tiredness, arthralgia). An adjusted Kaplan–Meier curve for retention of the etanercept biosimilar was made, censoring subjective health complaints as the reason for discontinuation.ResultsSeventy of the 79 patients eligible for transitioning agreed to transition (89%). The 1-year crude retention rate of etanercept in the transition cohort was 73% (95% CI: 0.62, 0.83), compared with a retention rate of 89% (95% CI: 0.81, 0.95) in the historical cohort (P = 0.013). This resulted in a higher risk of treatment discontinuation in the transition cohort (adjusted hazard ratio = 2.73; 95% CI: 1.23, 6.05, P = 0.01). After adjusting for the nocebo effect, the cohorts had comparable retention rates (86 vs 89%, P = 0.51).ConclusionNon-mandatory transition from etanercept originator to its biosimilar using an opt-in approach in a setting promoting shared decision-making resulted in a higher discontinuation of etanercept compared with the historical cohort. This could be attributed largely to the nocebo effect.

OP0209 INTERVAL PROLONGATION IN ETANERCEPT-TREATED PATIENTS WITH RHEUMATOID ARTHRITIS, ANKYLOSING SPONDYLITIS OR PSORIATIC ARTHRITIS: AN OPEN-LABEL, RANDOMISED CONTROLLED TRIAL

Background:The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering is scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Dose reductions can potentially reduce blood drug levels too much, resulting in loss of effect.Objectives:We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study.Methods:160 consecutive patients with rheumatoid arthritis (RA), PsA or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomised controlled trial. The intervention group doubled the dosing-interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose up to 6 months, after which the dosing-interval was doubled. Primary outcome was the proportion of patients maintaining MDA after 6 months follow-up.Results:At 6 months, MDA status was maintained in 47 (63%) patients in the intervention group and 56 (74%) in the control group (p=0.15), with comparable results in all rheumatic diseases. Median etanercept concentrations decreased from 1.50 µg/mL (25-75thpercentile 1.06-2.65) to 0.46 µg/mL (0.28-0.92) after 6 months of interval prolongation (figure 1). In total, 40% discontinued etanercept successfully with maintained MDA for at least 6 months.Figure 1.Median (with Q1 to Q3 boxplots) etanercept concentrations (per protocol) during the first 6 months of follow-up in the intervention group (prolongation; gray boxplots) and the control group (continuation; white boxplots), separated by disease (RA, PsA, AS). Bars represent 10-90 percentile and outliers are shown separately (dots).Conclusion:As observed in RA, etanercept tapering can be safely attempted in PsA and AS patients in sustained MDA. A substantial proportion of patients could stop etanercept for at least 6 months. In many patients low drug concentrations proved sufficient to control disease activity. However, the risk of minor and major flares is substantial, even in patients continuing standard dosing.

Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry.

This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry. This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model. Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis. Although ETA demonstrated a high persistence in biologic-naïve RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.

Efficacy and retention rate of adalimumab in rheumatoid arthritis and psoriatic arthritis patients after first-line etanercept failure: the FEARLESS cohort.

Few studies have compared the efficacy of switching from etanercept to adalimumab in the real-life setting in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This study evaluated the 2-year retention rate and 12-month efficacy of adalimumab in RA and PsA patients, previously treated with etanercept. RA and PsA patients from 11 Italian Rheumatology Units received adalimumab after first-line etanercept failure. Two-year adalimumab retention rate was calculated by the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of drug persistence. Univariate and multivariate logistic regression analyses were developed to examine potential predictors of 12-month DAS-28 remission. The study population included 117 RA (disease duration of 10.1 ± 7.7years and baseline DAS28-ESR of 4.97 ± 1.3) and 102 PsA (disease duration of 7.1 ± 5.1years and baseline DAPSA of 24.6 ± 11.8). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients. Concomitant methotrexate treatment was not associated with increased drug survival in both groups. Similarly, cause of etanercept discontinuation or treatment duration was not associated with retention rate. 12-month remission and low disease activity were achieved, respectively, in 27.3% and 23.9% of RA patients and 27.4% and 23.5% PsA of patients. In multivariate models, etanercept discontinuation due to inefficacy (OR 0.27, 95% CI 1.03-0.73; p = 0.009) and baseline DAS-28 (OR 0.45, 95% CI 0.29-0.69; p < 0.001) remained significant negative predictors of remission in RA patients. No variable was associated with remission in PsA patients. Adalimumab after etanercept failure was highly effective and safe in both RA and PsA patients.

Longterm Drug Survival of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis.

To evaluate longterm drug survival (proportion of patients still receiving treatment) and discontinuation of etanercept (ETN), infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP), and golimumab (GOL) using observational data from patients with rheumatoid arthritis (RA). Following a systematic literature review, drug survival at 12 and 12-24 months of followup was estimated by summing proportions of patients continuing treatment and dividing by number of studies. Drug survival at ≥ 36 months of followup was estimated through Metaprop. There were 170 publications included. In the first-line setting, drug survival at 12 months with ETN, IFX, or ADA was 71%, 69%, and 70%, respectively, while at 12-24 months the corresponding rates were 63%, 57%, and 59%. In the second-line setting, drug survival at 12 months with ETN, IFX, or ADA was 61%, 69%, and 55%, respectively, while at 12-24 months the corresponding rates were 53%, 39%, and 43%. Drug survival at ≥ 36 months with ETN, IFX, or ADA in the first-line setting was 59% (95% CI 46-72%), 49% (95% CI 43-54%), and 51% (95% CI 41-60%), respectively, while in the second-line setting the corresponding rates were 56% (95% CI 52-61%), 48% (95% CI 40-55%), and 41% (95% CI 36-47%). Discontinuation of ETN, IFX, and ADA at 36 months of followup was 38-48%, 42-62%, and 38-59%, respectively. Data on CZP and GOL were scarce. After > 12 months of followup, more patients with RA receiving ETN remain on treatment compared with other tumor necrosis factor inhibitors.

Real-World Experience with Etanercept Therapy and the Switching Pattern among Korean Patients with Psoriasis after Withdrawal of Etanercept.

BackgroundThe efficacy and safety of etanercept in the treatment of psoriasis has been proven, and the drug was approved for the treatment of moderate to severe psoriasis. However, there have been few studies that have presented real-world data focused on concomitant treatment during etanercept treatment, and the switching pattern after discontinuation of etanercept.ObjectiveTo reveal the real-world treatment pattern of etanercept-based psoriasis treatment and to investigate the switching pattern after withdrawal of etanercept.MethodsWe enrolled 66 patients with psoriasis who were treated with etanercept. We collected data regarding the demographic characteristics of the patients, etanercept treatment schedules, and other treatments administered during the etanercept treatment period. We also investigated the treatment pattern after the discontinuation of etanercept with emphasis on the drug-free interval and the administered treatment modalities.ResultsThe mean treatment duration was 22.7±26.1 months and the mean number of etanercept injections was 21.5±27.9. Thirty-six patients were administered concomitant systemic medication or phototherapy. After discontinuation of etanercept, 54 patients were followed up and 34 of these patients were administered other systemic medication or phototherapy; phototherapy and cyclosporine was the most commonly administered treatment modality and 27.4% of treatments used biologics.ConclusionThe treatment schedule for etanercept was modified according to the severity of psoriasis and concomitant treatment was administered to improve the effectiveness of treatment in the patients enrolled in the study. We also found that most patients required other treatment modalities to control psoriasis during the period of etanercept treatment.

Clinical and radiologic analysis of on-demand use of etanercept for disease flares in patients with rheumatoid arthritis for 2 years: The RESUME study: A case-control study.

To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we evaluated the efficacy of repeated etanercept (ETN) discontinuation and restarting in rheumatoid arthritis (RA) patients in a case–control study.Thirty-one bDMARD-naive RA patients with moderate to high disease activity received ETN until low disease activity (LDA) was achieved, after which ETN was discontinued. Upon flaring, ETN was readministered with observation every 2 months for 2 years, and radiographically evaluated in comparison with a historical control group treated continuously with ETN. Statistical methods including Fisher exact test, analysis of variance (ANOVA), Kruskal–Wallis test, multiple regression analysis, and Student t test were conducted as appropriate.Thirteen patients with inadequate response to ETN were withdrawn from the study, and 5 had no flare-up after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand to maintain LDA. Multivariate analysis revealed that MTX was significantly correlated with ETN. All 13 patients achieved LDA at final follow-up. Although joint damage progressed in patients using ETN on-demand, structural damage progression in the on-demand group was not significantly different from that in controls.On-demand use of ETN for flaring reduced disease activity but not structural damage in 50% of patients (though not significantly). However, inhibition of joint damage was achieved in 50% of patients after 2 years, supporting on-demand use of ETN as a treatment option for patients with RA who cannot afford bDMARD or targeted synthetic DMARD therapy.

Long-term etanercept retention patterns and factors associated with treatment discontinuation: a retrospective cohort study using Canadian claims-level data.

To examine 12-month retention rates over 6years of etanercept patients in Canada, and to identify factors associated with treatment discontinuation. A retrospective cohort study was conducted using longitudinal prescription drug claims data from IQVIA Private Drug Plan database (PDP), Ontario Public Drug Plan database (OPDP), and Régie de l'assurance maladie du Québec database (RAMQ). Between 07/2008 and 06/2010, bio-naïve patients who initiated etanercept were identified and followed for 72months. Twelve-month retention rates were estimated in one-year increments and factors associated with time to discontinuation over the 72-month period were identified using a Cox proportional hazards regression model. The study identified 4528 etanercept patients (61% female, 85% rheumatic diseases, and 15% psoriasis). Twelve-month etanercept retention rates increased significantly for patients following their first year on therapy (p < 0.0001), with 66% of patients retained at year 1 vs. 79, 82, 84, 83, and 79% at years 2, 3, 4, 5, and 6, respectively. 17.1% (n = 771) of patients were retained for the entire 72-month study. Patients with psoriasis were at increased risk (HR 1.199; p < 0.0001); while public drug coverage plan patients (OPDP HR 0.721; p < 0.0001 and RAMQ HR 0.537; p < 0.0001) were at decreased risk of treatment discontinuation. Twelve-month etanercept retention rates increased significantly for patients following their first year on therapy. Indication and drug coverage plan were associated with patients' time to etanercept discontinuation. With a better understanding of factors associated with retention, programs can be designed to address the specific needs of at-risk groups while supporting patients stable on therapy.

Clinical aspects of the use of etanercept in treatment of rheumatoid arthritis.

Background. Maintaining of a favourable response of tumour necrosis factor inhibitors is one of the most challenging to rheumatologist. Only limited data have been published addressing this field. The aim of our study was investigate efficacy of etanercept (ETN) and evaluate maintaining response after ETN discontinuation in patients who have achieved remission or low disease activity (REM/LDA) of rheumatoid arthritis (RA). Methods. Patients with high disease activity (n = 29) received ETN 50 mg injection and methotrexate 10-20 mg once weekly were included in analysis. Frequency of REM/LDA scoring by DAS 28-joint counts and C-reactive protein level (DAS28-CRP), changes from baseline in DAS28-CRP, Health Assessment Questionnaire (HAQ), global assessment of disease activity by patient and provider (PtGA and PrGA) were evaluated. We assessed persistent of achieved REM/LDA after the ETN discontinued. Results. We saw fast decreasing of active flare already after first month: HAQ (1.4 ± 0.6 vs 2.0 ± 0.6, p = 0.048), PtGA (49.5 ± 17.9 vs 75.6 ± 14.9, p = 0.016) and PrGA (46.6 ± 14.7 vs 77.0 ± 12.3, p = 0.014). DAS28-CRP changes from baseline become significant after second month (3.9 ± 1.1 vs 6.2 ± 0.6, р = 0.005). After 6 months 82.6% patients had DAS28-CRP &lt; 3.2 and 41.4% patients had HAQ &lt; 0.5. Maintenance of REM/LDA lasted 3 month after ETN discontinuation. Conclusion. ETN+MTX is very effective combination in treat to target strategy of RA treatment. In patients who have achieved REM/LDA maintained stable condition during three months after ETN withdrawn. It might be consider in a number of patients in case of accidental or necessary treatment interruption.

Exertional Dyspnea and New Onset Pulmonary Nodules in a 62-Year-Old Female With Seronegative Rheumatoid Arthritis

SESSION TITLE: Student/Resident Lung Pathology SESSION TYPE: Student/Resident Case Report Slide PRESENTED ON: Monday, October 30, 2017 at 03:15 PM - 04:15 PM INTRODUCTION: Tumor necrosis factor alpha (TNFα) inhibitors are important target therapies for inflammatory mediated diseases but they are not without adverse effects. CASE PRESENTATION: A 68 year-old Caucasian female with lichenoid dermatitis, psoriasis, rheumatoid variant psoriatic arthritis, COPD, and a former smoker was referred to Thoracic Medicine in 2016 for peripheral lung nodules (Fig 1) noted incidentally on a chest CT performed for a 3-month history of worsening dyspnea on exertion. In 2015 she had a negative quantiferon gold assay in preparation to start TNFα inhibitor therapy for recalcitrant psoriatic arthritis with which she struggled since 2013. After almost a year of increasing doses of methotrexate, it was discontinued for worsening gastrointestinal side effects. She further did not tolerate a 4-month course of sulfasalazine, 6-months of adalimumab, or a dose of infliximab. Finally, she was placed on golimumab- the newest TNFα inhibitor and in less than 6 months had near resolution of her arthritic symptoms. All serum calcium during this time was normal; there were no ACE levels available for review. Her exam was remarkable only for mild tenderness of the MCP joints and scattered deep-seated rose-colored papules coalescing into plaques over the hands. In office EKG was positive for new 1st degree heart block. Pulmonary function testing was consistent with restrictive lung disease and transthoracic echocardiogram was normal. An endoscopic bronchoscopy with biopsy of a right lung nodules was positive for non-caseating granulomas consistent with sarcoidosis (Fig 2). Golimumab was immediately discontinued and abatacept started. While her arthritic symptoms have started to worsen, her dyspnea has completely resolved. DISCUSSION: Sarcoidosis is a multisystem infiltrative granulomatous disease of unclear etiology. The paradoxical effect of TNFα inhibitors to both cause and treat sarcoidosis is not understood. The earliest reported occurence of sarcoidosis with a TNFα inhibitor is 6 months1-3. In this case, the newest TNFα inhibitor Golimumab, is not only associated with a new onset asymptomatic AV node block but also biopsy proven sarcoidosis with resolution of symptoms after the drug is discontinued. CONCLUSIONS: Clinicians should be aware of this rare but clinically significant association of Golimumab with pulmonary and possible cardiac sarcoidosis. Reference #1: Baughman RP, Drent M, & Kavuru M (2006) Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 174(7):795-802. Reference #2: Daïen, et al. (2009) Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases.” Rheumatology 48(8):883-886. Reference #3: Harney S, Haroon M, & Ryan JG (2011) Development of sarcoidosis 6-month post discontinuation of etanercept: coincidence or real association? Clinical Rheumatology. 30(8):1095-1098. DISCLOSURE: The following authors have nothing to disclose: Kimberley Youkhana, Ibrahim Ismail-Sayed, Muhammad Younus, Sudheer Penupolu No Product/Research Disclosure Information

Effectiveness of etanercept in children with plaque psoriasis in real practice: a one-year multicenter retrospective study

Background: Etanercept is licensed for the treatment of moderate-to-severe plaque psoriasis in children.Objectives: The aim of this analysis was to investigate effectiveness, tolerability, and reasons for discontinuation of etanercept in a real-life cohort of children and adolescents with moderate to severe plaque psoriasis.Methods: Data collected from a number of centers belonging to the ‘Pediatric Dermatology Group’ of the Italian Society of Dermatology (SIDeMaST) were examined in patients (age ≤17 years) who started treatment with etanercept from 2011 to 2015. A group of 23 patients were identified. Efficacy assessment was defined as the proportion of patients with a ≥50% and ≥75% improvement in Psoriasis Area Severity Index (PASI) at weeks 12, 24, and 52. Safety was evaluated on adverse event reporting. Reasons for discontinuation were classified as ineffectiveness, adverse events, remission, or other reasons.Results: At week 12, 56.5% of patients achieved PASI 75, 86.9% achieved PASI 50. Efficacy was sustained through week 52. In 15 patients etanercept was still ongoing at the time of data collection. In three patients the therapy was suspended due to inefficacy. The medication was overall well tolerated.Conclusions: Etanercept was an effective and well-tolerated treatment in this real-life cohort of patients.

Possible predictors for relapse from etanercept discontinuation in ankylosing spondylitis patients in remission: a threeyears' following-up study.

The aim of this study is to assess the recurrence probability and the possible predictors in patients with ankylosing spondylitis from etanercept discontinuation in a 3-year observational cohort ( ClinicalTrials.gov : NCT02915354). A cohort of 35 patients who achieved an ASAS 20 response at the end of a randomized controlled trial underwent a 3-year follow-up evaluation. The primary end point was clinical relapse defined as the BASDAI score going back to 80% of its initial level at the beginning of the trial. Prognostic factors of relapse were analyzed using the Cox regression. Median duration of clinical remission was 15.0months (interquartile range, 3.7-26.3months). The cumulative probabilities of relapse at 1, 2, and 3years were 45.7, 57.1, and 60.0%, respectively. The proportion of recurrence was not significantly different between placebo group and etanercept group by Kaplan-Meier analysis (placebo vs. etanercept: 61.11 vs. 58.82%, P=0.890). Two independent factors associated with increasing risk of relapse were (1) age of patients (25years or older with risk of 3.07, 95% confidence interval, 1.19-7.97, P=0.021); (2) onset age (younger than 24years with risk of 3.12, 95% confidence interval, 1.24-7.83, P=0.016). No correlation was observed in the present study between the time of relapse and the duration of the treatment with etanercept in AS patients who achieved the ASAS 20 response after receiving the treatment. The older age and younger onset age of patients seems to be important factors associate with an increasing risk of relapse.

Real-world Effectiveness of Biologic Disease-modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis After Etanercept Discontinuation in the United Kingdom, France, and Germany

PurposeThe purpose of this study was to assess the real-world effectiveness of patients with rheumatoid arthritis (RA) who discontinued etanercept treatment and subsequently received another tumor necrosis factor α (TNF-α) inhibitor or a non–TNF-α biologic in the United Kingdom, France, and Germany. MethodsMedical record data of patients with RA were collected from a panel of rheumatologists in the United Kingdom, France, and Germany. Patients were required to have a diagnosis of RA, be ≥18 years old, and have initiated use of another TNF-α inhibitor (adalimumab, certolizumab pegol, golimumab, or infliximab) or a non–TNF-α biologic (abatacept or tocilizumab) between January 2014 and May 2015 after discontinuing use of etanercept. Reasons for discontinuing use of etanercept and selecting a second biologic disease-modifying antirheumatic drug (DMARD) were described. Study outcomes included European League Against Rheumatism (EULAR) response and change in Clinical Disease Activity Index (CDAI) score. The study outcomes were compared among treatment groups (ie, TNF-α inhibitors and non–TNF-α biologics) using descriptive and multivariable-adjusted analyses. As a secondary analysis, the study outcomes were also descriptively compared between each of the TNF-α inhibitors. Because adalimumab is one of the most commonly used TNF-α inhibitor to treat RA, a secondary analysis was conducted to compare the outcomes among adalimumab, other TNF-α inhibitors, and non–TNF-α inhibitors. FindingsPatient characteristics before initiating treatment with a second DMARD were similar across treatment groups (all TNF-α inhibitors [n = 296] and non–TNF-α biologics [n = 276]). The most common reasons for discontinuing etanercept treatment were inadequate response, adverse effects, and patient preference. After etanercept, TNF-α inhibitors overall were associated with a significantly lower EULAR good response rate (56.0% vs. 64.4%, P < 0.05) and smaller CDAI score change (−6.3 vs −7.3, P = .06) relative to non–TNF-α biologics. However, the proportion of patients achieving an EULAR good response was numerically higher for adalimumab versus other TNF-α inhibitors (61.1% vs 51.6%, P = 0.11) and comparable versus non–TNF-α biologics (61.1% vs 64.4%, P = 0.52). Adalimumab was also associated with a CDAI score change significantly greater than that of other TNF-α inhibitors (−7.1 vs −5.8, P < 0.05) and comparable to that of non–TNF-α biologics (−7.1 vs −7.3, P = 0.79). The results were consistent in the multivariable-adjusted analysis and secondary analysis. ImplicationsIn this retrospective analysis of patients with RA in the United Kingdom, France, and Germany, after discontinuation of etanercept treatment, TNF-α inhibitors as a class were overall less effective as second biologic DMARDs relative to non–TNF-α biologics; however, adalimumab was more or as effective as other TNF-α inhibitors and non–TNF-α biologics.

Spontaneous regression of Epstein-Barr virus-associated lymphoproliferative disorder in a juvenile idiopathic arthritis patient after the discontinuation of methotrexate and etanercept.

A case of a 16-year-old female with polyarticular juvenile idiopathic arthritis (JIA) since the age of 4 years is reported here. This patient also suffered from multiple congenital anomalies. On long-term treatment with oral methotrexate (MTX) and etanercept, multiple subcutaneous nodules were detected, which were accompanied by increased lactate dehydrogenase and uric acid levels. A biopsy of the largest nodule revealed Epstein-Barr (EB) virus-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified as clinical stage IIIA due to a mediastinal lesion. Immunosuppressive treatment was discontinued immediately, which led to regression of the remaining nodules and normalization of the lactate dehydrogenase levels. The patient was considered to have an iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the World health organization (WHO). To our knowledge, this is the first case report of a JIA patient with EBV-positive DLBCL following the administration of etanercept and methotrexate and spontaneous regression of lymphoproliferation after the discontinuation of antirheumatic treatment.

PARADOXICAL CROHN’S DISEASE – MYTH OR REALITY?

We report the clinical case of an emergent Crohn’s disease (CD) as a paradoxical effect after 24 months of successfully treatment with etanercept for active ankylosing spondylitis in a young women. Despite rapid and sustained response of articular disease (remission achieved as soon as three months and maintained through the entire period of administration), new onset intestinal manifestations developed during biological therapy. A complex assessment comprising clinical, endoscopic and histopathologic evaluation, associated with high levels of fecal calprotectin confirmed drug-induced inflammatory bowel disease (IBD) compatible with CD. Although optimal treatment strategy is not yet validated, discontinuation of putative etanercept and cycling to a monoclonal anti-TNF antibody (adalimumab) demonstrated positive outcomes for both articular and IBD. New onset CD may be considered as an immune-mediated injury induced etanercept and should be considered in any patient with spondylarthritis in whom IBD develops with a clear temporal relationship with TNF inhibitors, especially etanercept.