Etanercept Treatment Research Articles

SAT0389 FREQUENCY OF DISEASE FLARES UNDER LONG-TERM ANTI-TNF THERAPY IN PATIENTS WITH EARLY AXIAL SPONDYLOARTHRITIS: RESULTS FROM THE ETANERCEPT VERSUS SULFASALAZINE IN EARLY AXIAL SPONDYLOARTHRITIS TRIAL

Background:Disease flares in axial spondyloarthritis (axSpA) might occur even in patients with otherwise stable disease receiving highly effective anti-inflammatory therapy such as TNF inhibitors. The frequency of disease flares, especially in patients with axSpA receiving long-term stable therapy, and factors associated with flares are not sufficiently investigated.Objectives:The objective was to assess the frequency of disease flares and to identify factors associated with flares in patients with early axSpA receiving continuous long-tem (up to 10 years) treatment with a TNF inhibitor etanercept.Methods:In the ESTHER (etanercept versus sulfasalazine in early axial spondyloarthritis trial), patients with early axSpA (symptom duration ≤5 years) were treated with ETN (n=40) versus sulfasalazine (n=36) for 48 weeks [2]. After one year all patients were treated continuously with etanercept (n=17 patients temporarily interrupted treatment in the 2nd year to assess time to flare and were then (re-)treated with etanercept, except 4 patients who completed the study in sustained remission) for up to 10 years in total. Only patients who were continuously treated with etanercept for at least 6 months were included in the current analysis. The disease flare was defined as a worsening of the ASDAS by ≥0.9 as compared to the value obtained at the previous visit. Univariate and multivariable cox-regression analyses were performed to analyze the predictors of flares.Results:Out of 76 patients who entered the study at baseline, 62 patients (n=32 with radiographic (r-) axSpA and n=30 with non-radiographic (nr-) axSpA) fulfilled the criterion of the continuous etanercept treatment. A total of 22 patients (35%) experienced at least one flare over the entire treatment period 10 patients (31.3%) in the r-axSpA and 12 patients (40%) in the nr-axSpA subgroup) - figure. A total of 81 flares occurred (33 and 48 in the r- and nr-axSpA subgroups, respectively) in the 10 years of follow-up. None of the documented disease flares resulted in a direct study withdrawal. The majority of flares occurred within first 4 years of treatment (figure). There were also no statistically significant differences between nr- and r-axSpA in the time until the first flare (p=0.4, Log-rank test). In the multivariable Cox regression analysis normal CRP values (≤5mg/l), HLA-B27 negativity, higher physician global assessment, a longer symptom duration at study entry, higher spinal ankylosis and higher fatty degeneration in the sacroiliac joints but lower spinal osteitis scores and lower ankylosis scores in the sacroiliac joints at baseline MRI were associated with a higher risk for flares.Conclusion:Disease flares according to the ASAS definition of clinically important worsening in axSpA based on ASDAS occurred ~1/3 of patients with early axSpA who received a treatment with etanercept for up to 10 years without major differences between r- and nr- forms of axSpA. HLA-B27 negativity, normal CRP, higher spinal ankylosis scores, higher fatty degeneration scores but lower ankylosis scores in the SIJ´s at baseline MRI were associated with a higher risk for flares.Figure 1.Baseline characteristics of all patients with with continous ETC treatment.all≥1 flareno flarepatientsn (%)62 (100)22 (35.5)40 (64.5)malen (%)38 (61.3)16 (72.7)22 (55)agemean (SD)34.1 (8.3)32.6 (7.8)35 (8.6)BASDAImean (SD)2.7 (2)1.8 (1.8)3.2 (1.9)ASDASmean (SD)1.6 (0.8)1.3 (0.7)1.7 (0.8)Figure 2.Kaplan-Meier curves indicating time to first flare and flare free survival propability.Acknowledgments:The ESTHER study was supported by an unrestricted research grant from Pfizer. Murat Torgutalp’s (MT) work at Charité - Universitätsmedizin was supported by an award from the Scientific and Technological Research Council of Turkey (TUBITAK).Disclosure of Interests:Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Murat Torgutalp: None declared, Anja Weiß: None declared, Mikhail Protopopov Consultant of: Novartis, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Kay Hermann: None declared, Christian Althoff: None declared, Olaf Behmer Employee of: Pfizer Pharma GmbH, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB

Efficacy of needle-knife combined with etanercept treatment regarding disease activity and hip joint function in ankylosing spondylitis patients with hip joint involvement

This study aimed to assess the efficacy of needle-knife (NK) combined with etanercept (NKCE) in attenuating pain, inflammation, disease activity, and improving hip joint function in ankylosing spondylitis (AS) patients with hip joint involvement.Totally, 90 patients with active AS involving unilateral hip joint were enrolled and randomly assigned in 1:1:1 ratio to receive NKCE, NK or conventional drugs (control). The ESR, CRP, hip joint pain Visual Analogue Scale (VAS) score, bath ankylosing spondylitis disease activity index (BASDAI), bath ankylosing spondylitis functional index (BASFI), modified Harris hip score (mHHS), and range of motion (ROM) of affected hip joint were assessed at baseline (W0), after 1-week treatment (W1) and after 24-week treatment (W24).ESR and CRP were decreased in NKCE group compared with NK and control groups, while was not attenuated in NK group compared with control group. Regrading pain and disease activity, NKCE group presented a reduction in hip pain VAS score and BASDAI compared with NK and control groups, and NK group showed a decrease in hip pain VAS score and BASDAI compared with control group. Besides, BASFI was lowered in NKCE and NK groups compared with control group, but similar between NKCE and NK groups. mHHS and hip ROM were raised in NKCE and NK groups compared with control group, but similar between NKCE and NK groups.NKCE decreases hip pain, inflammation, disease activity and improves hip joint function in AS patients with hip joint involvement.

Association between C-reactive protein gene variant and treatment efficacy of etanercept in ankylosing spondylitis patients receiving hip arthroplasty.

BackgroundC‐reactive protein (CRP) level is one of the most widely used parameters to assess ankylosing spondylitis (AS), since CRP is associated with poor radiographic progression of AS patients. Recent studies have investigated the association between CRP gene variants and AS risk, but with conflicting findings.Material and MethodsWe enrolled 232 AS cases and 314 controls in this case‐control study. Next, we assessed the association of CRP gene rs3091244 polymorphism with the efficacy of etanercept for AS. Genotyping was done using a custom‐by‐design 48‐Plex SNP scanTM Kit.ResultsCRP gene rs3091244 polymorphism was associated with an increased risk of AS in this Chinese population. Clinical indicators of AS patients including morning stiffness time, Bath AS function index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Visual Analogue Scale (VAS), erythrocyte sedimentation rate (ESR), and CRP were significantly decreased after 12 weeks of etanercept treatment. Furthermore, AA genotype carriers showed higher values of VAS, BASDAI, BASFI, and CRP before etanercept treatment. AA genotype or A allele of rs3091244 polymorphism was associated with Ankylosing Spondylitis Assessment Study group response criteria 20 scores (ASAS20) and Assessment in SpondyloArthritis international Society 40 response (ASAS40) improvement. In addition, AA genotype carriers showed significantly higher CRP levels compared with genotype GG carriers (16.3 vs 8.8 mg/L).ConclusionCRP gene rs3091244 polymorphism is associated with an increased risk of AS. Additionally, rs3091244 polymorphism could serve as a biomarker for good response to etanercept treatment in AS.

P55 Carcinoid syndrome on etanercept and subsequent treatment with secukinumab in a patient with psoriatic arthritis

Abstract Background Psoriatic arthritis requires early recognition and treatment for prevention of disease progression. Conventional disease modifying drugs are first-line agents followed by biologic DMARDs for patients with active disease. TNF-alpha blockers are first line biologic agents in the UK. Th17 inhibitors are used since the elucidation of Th17 pathway. Safety and efficacy profiles of biologic agents inhibiting the Th17 pathway, including secukinumab (IL-17A) and ustekinumab (IL-12/23p40) have been studied. Methods We report a case of carcinoid syndrome in a lady on etanercept for psoriatic arthritis, carcinoid as a potential TNF alpha side effect. We also report safety of Th17 (secukinumab) inhibitors in the patient to date (>1 year). Results A female with a history of acne rosacea, was diagnosed with psoriatic arthritis in 2000 age 32. Initial sulphasalazine failed, then received methotrexate until 2011, when her arthritis flared. She was commenced on etanercept which proved effective. After 4 years of etanercept and methotrexate, her liver profile became deranged. Investigations off treatment included ultrasound abdomen demonstrating a liver mass, which resembled focal nodular hyperplasia on magnetic resonance imaging. Further screening revealed high urinary 5HIAA (527 umol/24h) and raised chromogranin A & B levels (1574 pmol/L and 373 pmol/L respectively). She had no symptoms suggestive of carcinoid, although facial flushing could have been camouflaged by her rosacea. Octreotide scan was positive, CT enterogram showed a distal ileal neuroendocrine tumour with adjacent lymphadenopathy. She underwent right hemihepatectomy and hemicolectomy. Her liver profile deteriorated again on methotrexate, leflunomide was ineffective. In November 2017 she was started on ustekinumab, which was ineffective and was withdrawn after 8 months. There was no alteration in carcinoid blood markers and no CT changes. In July 2018, she was commenced on secukinumab, which has allowed reduction in steroids. The patient is aware of lack of safety data in her circumstances. Regular surveillance has shown no recurrence of carcinoid with serial negative 5HIAA and chromogranin levels. There are no progressive CT changes at 1 year. Conclusion This is a case of carcinoid tumour occurring on TNF-alpha blockers and may represent a rare complication. Screening biomarkers including 5HIAA and chromogranin levels can be useful if disease is suspected. We could not find other similar case reports to guide further management. Within time limited data available - ustekinumab had no effect on the carcinoid. Th17 inhibitors can be safe options for treating psoriatic arthritis and psoriasis with highly sustained efficacy and favourable safety profile seen in large clinical trials. In this case, after > one year of secukinumab treatment - there is no adverse effect on carcinoid syndrome. Disclosures A.S.F. Sheikh None. S.G. Srivastva None. F. Wood None.

Safety update of etanercept treatment for moderate to severe plaque psoriasis

ABSTRACTIntroduction: Conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) for patients with psoriasis are often linked to inadequate outcomes and risk of multiple adverse effects. Biologic agents such as etanercept (ETN) have revolutionized the therapeutic management of psoriasis, allowing the treatment of most difficult cases, and fragile patients.Areas covered: The authors searched PubMed using the term ‘psoriasis,’ ‘etanercept,’ and ‘safety.’ Articles considered by the authors to be most relevant, such as randomized controlled studies, cohort studies, and review articles placing emphasis on studies of efficacy and safety were selected. Case reports and letters relating to safety were also included. The main sources of data referenced by these articles were also included in the review. Besides, to get the relevant studies, the reference lists were examined to identify the potentially available studies. The aim of this review is to describe the safety profile of ETN, used for psoriasis treatment, focusing on related clinical implications.Expert opinion: ETN has a favorable safety profile, and its use should be largely considered in psoriatic patients. Caution should be recommended in case of chronic heart failure, autoimmune disease, previous malignancies, familial history of demyelinating diseases, latent TBC infection, chronic HBV and HCV infection or HIV.

Efficacy of an anti-TNF-alpha agent in refractory livedoid vasculopathy: a retrospective analysis

Background Livedoid vasculopathy is a recurrent thrombo-occlusive vasculopathy of cutaneous blood vessels and its standard or first-line therapy is still controversial. Besides hypercoagulability, inflammatory factors may also play a secondary role in the pathogenesis of this disease. Monotherapy of thrombolytics cannot achieve satisfactory results because of concomitant inflammation. Objective This pilot study aimed to determine the efficacy of an anti-TNF-alpha agent in patients with refractory livedoid vasculopathy. Methods We studied five patients with livedoid vasculopathy who were resistant to steroids, antiplatelets, or danazol therapy, and were treated with etanercept 25–50 mg once a week for 12 consecutive weeks. We assessed clinical characteristics, laboratory findings, and etanercept’s efficacy on skin lesions, pain, and quality of life. Results Etanercept therapy resulted in fast relief of pain in a mean time of 2 weeks. The median duration for the disappearance of erythema and ulcer healing was 8.8 weeks and 10.6 weeks, respectively. There was a reduction in pain by 34.3% after 12 consecutive weeks of etanercept treatment. Disease severity and quality of life significantly improved. Conclusions In refractory livedoid vasculopathy patients, etanercept therapy is efficient for skin lesions and pain, and improvement of quality of life, especially in rapid relief of pain.

Drug survival in patients with psoriasis is associated with the availability of biologic medications.

Drug survival rates in patients with psoriasis had been described extensively. Different survival rates of TNF-α inhibitors (TNFIs), ustekinumab and secukinumab were reported. To investigate drug survival rates of TNFIs, ustekinumab and secukinumab, with particular emphasis on the difference between ustekinumab and secukinumab. Survival analysis was performed in patients with moderate-to-severe psoriasis who received adalimumab, infliximab, etanercept, ustekinumab and secukinumab treatment in 2002-2018, using the Clalit Health Services database. Stratified analysis was performed according to biologic treatment lines. Multivariate analysis was performed adjusting for demographic variables, calendar year, metabolic syndrome, psoriatic arthritis, biologic treatment line, biologic naivety, co-administration of oral treatments and previous oral systemic treatment exposure. Among 1459 patients treated with 3070 biologic medication courses, ustekinumab had a significantly higher crude survival as compared with TNFIs and secukinumab. The mean drug survival of ustekinumab, adalimumab, etanercept, infliximab and secukinumab was 43.5 (CI: 39.7-47.2), 38.2 (CI: 34.8-41), 33.9 (CI: 30.8-37.1), 28.2 (CI: 22.5-33.8) and 17.1 (CI: 15.6-18.6) months, respectively, with significant statistical differences for all comparisons (P<0.001). The differences between ustekinumab and secukinumab were not significant following adjustment to factors that included treatment line (hazard rate 1.16, CI: 0.93-1.43). Different drug survival rates between ustekinumab and secukinumab are determined by the treatment line and calendar year, reflecting the availability of biologic medications, and not only by the biologic attributes of each medication.

Paradoxical pulmonary sarcoidosis under etanercept treatment: a case report and review of the literature

Tumor nekroz faktoru inhibitoru (TNFi) tedavileri gunumuzde bircok romatizmal hastalikta en onemli tedavi basamaklarindan birini olusturmaktadir. Bununla birlikte, bu ajanlarin kullaniminin bircok paradoksal otoimmun hastaligin gelisimi ile iliskili oldugu gosterilmistir. Bu vaka sunumunda etanersept tedavisi altinda paradoksal sarkoidoz gelisen hastayi guncel literatur esliginde tartismayi amacladik. Psoriatik artrit (PsA) tanisi ile 3 yildir etanercept (50 mg/hafta subkutan) kullanan 40 yasindaki erkek hastanin akciger goruntulemesinde mediastinal lenfadenopati ve her iki akciger alaninda santral yerlesimli noduller saptandi. Lenf bezi biopsi sonucu non kazeifiye granulomatoz inflamasyon saptandi. Asemptomatik paradoksal sarkoidoz olarak kabul edilen hastanin etanersept tedavisi sonlandirildi. Hastanin 6. ay takibinde PsA klinik aktivite skorlarinda artis saptandi. Bu nedenle hastaya Interlokin 17A inhibitoru (anti-IL17A) olan sekukinumab tedavisi baslandi. Hastanin birinci yil takibinde mediastinal lenf nodlarinda tama yakin regresyon izlendi. TNFi tedavisi sirasinda paradoksal sarkoidoz gelisen hastalarda mevcut TNFi tedavisinin kesilmesinin ve sekukinumab (anti-IL-17A) veya diger TNFi tedavilere gecilmesinin uygun olacagini dusunmekteyiz.

Anaphylactic Reaction to a Change in the Route of Administration of Abatacept: A Case Study

The incidence of anaphylactic reaction after the long-term use of abatacept has not been reported until now. Herein, we present a case of rheumatoid arthritis (RA) in which the patient experienced an anaphylactic reaction one year after initiation of treatment with abatacept. A 75-year-old woman visited our hospital with symptoms of bilateral knee pain and swelling. She was initially treated with methotrexate (6 mg/week increased to 8 mg/week). Two months later, because of inadequate response, self-injections of abatacept (subcutaneous; 125 mg every two weeks) were prescribed. However, 6 months later, because of frequent stomatitis, the methotrexate dose was decreased to 6 mg/week, which resulted in worsening of RA. We changed the route of abatacept administration from subcutaneous injection to intravenous infusion (500 mg/month as a drip). After 30 min of starting the drip, the patient experienced itchiness and drop in vital signs, which were managed using methylprednisolone (2 doses, 125 mg each), dopamine hydrochloride (8 mg/h), and oxygen therapy (flow decreased from 3 L/min to 1 L/min). Wheals and redness were treated with oral antihistamines. Six hours after the onset of the anaphylactic reaction, the vital signs were stabilized. On the subsequent day, the patient’s general state was confirmed to be normal. One month later, etanercept (25 mg) treatment was initiated. The patient is currently in remission. We recommend caution when changing the route of administration and dosage of abatacept in anti-cyclic citrullinated peptide antibody-positive patients or those with a history of mild infusion-related reaction.

The role of non-invasive scores in determining the liver fibrosis in NAFLD and psoriatic patients.

According to recent data, psoriatic patients have an increased prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome, compared with the general population. In some published studies, the severity and presence of psoriasis disease were correlated with the severity of NAFLD. In the current study, we aimed to compare the sensibility and specificity of the non-invasive scores and liver biopsy in determining fibrosis in patients with NAFLD and moderate to severe psoriasis. We performed the scientific research from June 2014–December 2017 and we included 71 patients: 40 patients with NAFLD and 31 patients with moderate to severe psoriasis according to Psoriasis Area and Severity Index (PASI) score and NAFLD, who received Etanercept treatment for at least one year. Based on the clinical and laboratory data, we calculated the following scores for fibrosis: body mass index (BMI), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, diabetes (BARD) score, Fibrosis-4 (FIB-4) score, and NAFLD fibrosis score (NFS). For liver biopsy, we used the Menghini technique. By calculating Kendall’s test, we also observed a strong direct correlation between the degree of fibrosis and FIB-4 (tau=0.558) and NFS (tau=0.490) scores, with a critical statistical impact, and the lack of a correlation with the BARD score (tau=0.095; p=0.332). The hepatic biopsy allowed the more accurate establishment of the role of the non-invasive tests in the diagnosis of the lesions of steatosis, steatohepatitis, and hepatic fibrosis. The non-invasive tests are most useful for the exclusion of the evolution lesions and for the confirmation of the advanced stages of the disease. Among these, the NFS score proved a high statistically significant correlation (p<0.0001) with the fibrosis histological lesions.

Sacroiliitis associated with familial Mediterranean fever in childhood: a case series and review of literature.

Familial Mediterranean fever (FMF) is an autosomal-recessive auto-inflammatory disorder characterized by recurrent episodes of fever with serositis. Sacroiliitis associated with FMF is very rare, especially in children. We aimed to describe the demographic, clinical, laboratory features, and treatment responses of pediatric patients with FMF -related sacroiliitis. The study consisted of seven pediatric patients younger than 16 years, diagnosed with sacroiliitis associated with FMF between 2010 and 2017. Medical records of patients were retrospectively evaluated. Sacroiliitis was diagnosed based on magnetic resonance imaging. We also reviewed previous studies of FMF related sacroiliitis. Five of the seven patients (male:female ratio of 5:2) had a M694V (homozygous) mutation, one patient had a M694V (heterozygous) mutation, and one patient had a V726A (heterozygous) mutation. All patients were HLA-B27 negative. One of the cases achieved remission with colchicine plus non-steroidal anti-inflammatory drug treatment, and one patient`s symptoms were managed by the addition of sulfasalazine. Four patients responded to etanercept treatment, and one patient`s symptoms were suppressed with canakinumab. Sacroiliitis can be seen in pediatric FMF patients suffering with inflammatory back pain. This manifestation generally occurs in FMF patients who have M694V mutation. Etanercept could likely show a beneficial effect in patients who are resistant to disease modifying anti-rheumatic drugs and non-steroidal anti-inflammatory drugs. In addition, canakinumab treatment should be considered as a successful alternative therapy in this rare group of patients.

Assessing the Association of Formulary Copayment Changes with Real-World Treatment Patterns in Patients with Rheumatoid Arthritis on Etanercept.

Rheumatoid arthritis (RA) is a chronic disease that requires long-term treatment to improve or maintain stable disease activity. Tumor necrosis factor inhibitors (TNFi), a class of biologic disease-modifying antirheumatic drugs (bDMARD), are effective at treating symptoms and inhibiting joint progression. Although treatment changes are not recommended in patients with stable disease, health plans have recently enacted formulary changes with higher copayments that could disrupt patient access to TNFis. To assess the association of formulary copayment changes with real-world treatment patterns, treatment effectiveness, and health care costs among bDMARD-naive patients with RA receiving the TNFi etanercept. This retrospective observational cohort analysis used the IBM Watson Health MarketScan Commercial Claims and Encounters Database. Adult patients with RA with 6 months of stable etanercept use (no refill gap ≥ 45 days) from January 1, 2013, through December 31, 2015, were selected and the index date was set to the first fill date after the stable-use period. Average etanercept copayment was calculated at the drug-plan level. Copayment change was defined as a monthly increase of at least $40 to account for copayment changes attributable to etanercept wholesale acquisition costs between 2014 and 2015. This amount also corresponded to the 90th percentile of average plan-level changes in etanercept copayments in the database, representing an average change in copayment by a payer. Patients were followed ≥ 12 months before and after the index date to track etanercept treatment changes and ≥ 12 months after a treatment change to track costs after etanercept copayment changes. Etanercept persistence, bDMARD switching, refill gaps, and treatment effectiveness (using a validated effectiveness algorithm) were described for patients with or without copayment change during the 12 months post-index or postchange. We also assessed the mean total of all-cause and RA-related expenditure during the 12-month post-index (or postchange) period. 1,970 stable patients met study inclusion criteria (mean [standard deviation] age: 50.3 [9.5] years; 77.8% female) and were evaluated. Of these, 133 (6.8%) patients had a copayment change ≥$40 during follow-up. Overall, most patients (60.3%) persisted on etanercept for the 12-month follow-up period, while 13.0% switched from etanercept, and 8.1% discontinued (refill gap of ≥ 45 days). Nearly half (48.0%) of all patients were considered effectively treated according to a validated algorithm. Compared with patients without a copayment change, those with a copayment change were more likely to switch biologics (19.5% vs. 12.6%; P = 0.021). Although statistical significance was not reached, patients with a copayment change were less likely to be persistent (54.1% vs. 60.7%; P = 0.135), and less likely to be effectively treated (42.1% vs. 48.4%; P = 0.161) than patients without a copayment change. All-cause and RA-related expenditures at baseline and post-copayment change were similar between patients with and without a copayment change. Changing formulary copayment of etanercept was associated with higher switching without difference in costs or health care utilization between copayment and no copayment change groups. This study was sponsored by Amgen. Bonafede, Manjelievskaia, and Lopez-Gonzalez are employees of IBM Watson Health, which received funding from Amgen to conduct this study. Oko-osi, Collier, and Stolshek are employees and shareholders of Amgen. Gharaibeh was an employee of Amgen at the time of study execution and manuscript drafting. The authors have no other relationships that present a potential conflict of interest. Data pertaining to this study were presented in a poster at the 2018 ACR/ARHP Annual Meeting; October 19-24, 2018; Chicago, IL.

Measurement of circulating miRNA-125a exhibits good value in the management of etanercept-treated psoriatic patients.

This study aimed to explore the correlation of miR-125a with risk and severity of psoriasis, and further investigate the potential of miR-125a for predicting response to etanercept (ETN) treatment in psoriatic patients. Moderate to severe plaque psoriatic patients (n=126) about to undergo ETN treatment for 6months were recruited. Their plasma samples were obtained, and Psoriasis Area and Severity Index (PASI) scores and PASI-75 response rate were assessed at baseline (M0), and at 1 (M1), 3 (M3) and 6months (M6) of treatment. Referring to PASI-75 response status at M6, patients were categorized as PASI-75 responders and PASI-75 non-responders. Healthy controls (HC, n=120) were also enrolled and their plasma samples were collected. In addition, plasma miR-125a was determined by quantitative polymerase chain reaction. miR-125a was decreased in psoriatic patients compared with HC; further, the receiver-operator curve (ROC) exhibited that miR-125a was of good value in differentiating psoriatic patients from HC with an area under the curve (AUC) of 0.802. In psoriatic patients, miR-125a was negatively associated with PASI score to some extent. Interestingly, baseline miR-125a was lower in PASI-75 responders than PASI-75 non-responders; further, ROC showed it predicted PASI-75 response at M6 to some extent with AUC of 0.672. Multivariate logistic regression also revealed that miR-125a was an independent predictive factor for worse PASI-75 response at M6. Furthermore, miR-125a expression was gradually increased during the treatment in PASI-75 responders, but unchanged in PASI-75 non-responders. Measurement of circulating miR-125a exhibits good value in the management of ETN-treated psoriatic patients.

Treatment with etanercept and low monocyte concentration contribute to the risk of invasive aspergillosis in patients post allogeneic stem cell transplantation

Invasive aspergillosis (IA) is a life-threatening complication among allogeneic hematopoietic stem cell transplant (alloSCT) recipients. Despite well known risk factors and different available assays, diagnosis of invasive aspergillosis remains challenging. 103 clinical variables from patients with hematological malignancies and subsequent alloSCT were collected. Associations between collected variables and patients with (n = 36) and without IA (n = 36) were investigated by applying univariate and multivariable logistic regression. The predictive power of the final model was tested in an independent patient cohort (23 IA cases and 25 control patients). Findings were investigated further by in vitro studies, which analysed the effect of etanercept on A. fumigatus-stimulated macrophages at the gene expression and cytokine secretion. Additionally, the release of C-X-C motif chemokine ligand 10 (CXCL10) in patient sera was studied. Low monocyte concentration (p = 4.8 × 10−06), severe GvHD of the gut (grade 2–4) (p = 1.08 × 10−02) and etanercept treatment of GvHD (p = 3.5 × 10−03) were significantly associated with IA. Our studies showed that etanercept lowers CXCL10 concentrations in vitro and ex vivo and down-regulates genes involved in immune responses and TNF-alpha signaling. Our study offers clinicians new information regarding risk factors for IA including low monocyte counts and administration of etanercept. After necessary validation, such information may be used for decision making regarding antifungal prophylaxis or closely monitoring patients at risk.

Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients.

BackgroundPsoriasis is associated with metabolic, liver and cardiovascular comorbidity. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin‐17A, has shown significant and sustained efficacy in the treatment of moderate to severe psoriasis.ObjectivesThis was an exploratory post hoc analysis of pooled data from three phase 3 studies in plaque psoriasis patient populations. The objective was to show the course of metabolic and liver parameters under secukinumab, etanercept or placebo treatment over time. A further objective was to assess the impact of selected comorbidities and metabolic characteristics on high‐sensitivity C‐reactive protein (hs‐CRP), as a surrogate marker of systemic inflammation.MethodsData from the phase 3 randomized controlled trials [FIXTURE (NCT01358578), ERASURE (NCT01365455) and SCULPTURE (NCT01406938); n = 3010] were included in this analysis. Patients were treated with secukinumab 150 mg or 300 mg, placebo or etanercept 50 mg (FIXTURE only) as active comparator. A set of metabolic and liver parameters was longitudinally assessed over 52 weeks. Multivariate regression analyses assessed the impact of selected comorbidities and metabolic characteristics on hs‐CRP levels at baseline and under treatment.ResultsSecukinumab treatment reduced hs‐CRP levels. Body weight and uric acid levels tended to decrease over 52 weeks with secukinumab. Secukinumab showed a neutral effect on fasting plasma glucose, lipid parameters and liver enzymes. Psoriatic arthritis, metabolic syndrome, obesity, impaired glucose metabolism, and hyperuricemia were each associated with increased hs‐CRP levels at baseline. Concomitant obesity attenuated the decline in hs‐CRP under treatment.ConclusionsThese analyses suggest neutral to favourable long‐term trends in metabolic and liver parameters under secukinumab treatment. Metabolic comorbidities were associated with increased hs‐CRP levels, reflecting the role of systemic inflammatory processes in their pathophysiology.

Early Quantification of Systemic Inflammatory Proteins Predicts Long-Term Treatment Response to Tofacitinib and Etanercept

The application of machine learning to longitudinal gene-expression profiles has demonstrated potential to decrease the assessment gap, between biochemical determination and clinical manifestation, of a patient’s response to treatment. Although psoriasis is a proven testing ground for treatment-response prediction using transcriptomic data from clinically accessible skin biopsies, these biopsies are expensive, invasive, and challenging to obtain from certain body areas. Response prediction from blood biochemical measurements could be a cheaper, less invasive predictive platform. Longitudinal profiles for 92 inflammatory and 65 cardiovascular disease proteins were measured from the blood of psoriasis patients at baseline, and 4-weeks, following tofacitinib (janus kinase-signal transducer and activator of transcription-inhibitor) or etanercept (tumor necrosis factor-inhibitor) treatment, and predictive models were developed by applying machine-learning techniques such as bagging and ensembles. This data driven approach developed predictive models able to accurately predict the 12-week clinical endpoint for psoriasis following tofacitinib (area under the receiver operating characteristic curve [auROC] = 78%), or etanercept (auROC = 71%) treatment in a validation dataset, revealing a robust predictive protein signature including well-established psoriasis markers such as IL-17A and IL-17C, highlighting potential for biologically meaningful and clinically useful response predictions using blood protein data. Although most blood classifiers were outperformed by simple models trained using Psoriasis Area Severity Index scores, performance might be enhanced in future studies by measuring a wider variety of proteins.

The effect of methotrexate on tumour necrosis factor concentrations in etanercept-treated rheumatoid arthritis patients.

Recently, we demonstrated that early low concentrations of circulating, adalimumab-bound TNF in RA patients treated with adalimumab was associated with future anti-drug antibody formation. Furthermore, low TNF was associated with less frequent baseline MTX use. This is remarkable, because of the anti-inflammatory effects of MTX and a potential inhibiting effect on cytokine production. We hypothesized an indirect effect of non-MTX use on low TNF concentrations via immunogenicity. To investigate the effect of MTX on TNF concentrations independent of anti-drug antibody formation, we measured TNF in RA patients treated with etanercept, a drug with low immunogenicity. TNF was quantified in 186 consecutive etanercept-treated RA patients at baseline and at weeks 4, 16 and 28. The dynamics of TNF during etanercept treatment were compared with dynamics recently published for adalimumab. We demonstrated that TNF concentrations at week 4 did not associate with baseline MTX or remission after 28 weeks. Furthermore, median (interquartile range) TNF increased from <112 (<112-<112) pg/ml at baseline to 548 (344-688) pg/ml at week 4 and remained stable at week 16 and 28 [598 (442-756) and 568 (444-755) pg/ml, respectively]. Circulating TNF did not associate with MTX usage in etanercept-treated patients. This implies that MTX does not have a direct effect on TNF concentrations in circulation and that the association between early low TNF and non-use of MTX for adalimumab is thus most likely due to anti-drug antibody formation.

Successful treatment in a child with enthesitis-related arthritis involving the sternoclavicular joint: a case report

BackgroundAlthough the sternoclavicular joint (SCJ) may be involved in ankylosing spondylitis, rheumatic arthritis, and Behçet’s disease and participates in the systemic inflammatory process of arthritis, it is often neglected during routine rheumatologic clinical examinations. To the best of our knowledge, this is the first study to report etanercept treatment in juvenile idiopathic arthritis (JIA) with SCJ involvement.Case presentationIn this study, we describe an unusual case of a child with juvenile idiopathic arthritis with an initial presentation of sternoclavicular mass. The patient (age, 14 years 10 months) presented with an insidious onset atraumatic swelling of the left SCJ and complained of right hip and bilateral ankle tenderness without an apparent cause. Initial ultrasonography indicated a heterogeneous mass in the left SCJ, while computed tomography identified mild swelling of the left SCJ with a thickened synovial lining, mild bone erosion, and some turbid fluid. The patient ultimately underwent left SCJ arthrotomy, during which tapping of the SCJ revealed 2 cc of yellowish fluid, inflammation and necrosis of tissues within the SCJ. A clear yellow joint fluid was aspirated, and testing revealed a negative culture result. The patient was diagnosed with JIA. The joint tenderness improved and erythrocyte sedimentation rate decreased after administering anti-tumor necrosis factor etanercept. An additional ultrasonography demonstrated that the initial imaging findings have been resolved. At the end of a 2-year follow-up period, the patient was completely symptom-free.ConclusionsJIA with SCJ involvement is an uncommon presentation in adolescents. Etanercept may be a beneficial treatment for SCJ involvement in patients with JIA. The upper limbs showed no signs of limited range of motion during the follow-up period. Further studies are warranted to elucidate the efficacy of etanercept in JIA with sternoclavicular joint involvement.

BACTRIM-RESPONSIVE HIGHLY SUSPECTED PNEUMOCYSTIS PNEUMONIA IN ETANERCEPT-TREATED RHEUMATOID ARTHRITIS PATIENT WITH CHRONIC ADRENAL INSUFFICIENCY: CASE REPORT

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Pneumocystis pneumonia (PCP) is a life-threatening infection that mainly occurs in immunocompromised patients. Etanercept inhibits tumor necrosis factor-alpha (TNFα) and has FDA approval to treat inflammatory arthritis including rheumatoid arthritis (RA). There are only a few cases of PCP have been reported in association to etanercept-treated RA. We report a patient with etanercept-treated RA who likley developed PCP that responded to Bactrim. CASE PRESENTATION: A 50 year old Caucasian woman with polysubstance abuse history, chronic adrenal insufficiency on hydrocortisone, and rheumatoid arthritis (RA) treated with etanercept presented from a rehabilitation facility with lethargy and sepsis. HIV was negative. Urinalysis showed 15 WBC, 4+ bacteria and + nitrite and chest X-ray (CXR) showed right lower lobe (RLL) opacities compatible with aspiration pneumonia. She was treated with IV fluids, stress dose hydrocortisone, metronidazole, and ceftriaxone and etanercept was put on hold. Blood cultures showed no bacterial growth and the urine culture grew pan-sensitive E.coli. Her lethargy improved, and sepsis resolved by day-4 of admission. On day-5, she started to have episodes of shortness of breath and became hypoxic. Arterial blood gas (ABG) on room air showed PaO2 of 46 mmHg. CXR showed worsening infiltrates. Chest computed tomography angiography showed three small peripheral pulmonary emboli, extensive bilateral interstitial infiltrates and RLL airspace disease. She was started on IV heparin. 2D echocardiogram was unremarkable. Azithromycin was added without improvement. On day-8, LDH was 277 U/L; Bactrim and prednisone were initiated and the other antibiotics were discontinued. On day-11, CXR revealed partial resolution of the bilateral infiltrates and the patient underwent bronchoscopy with bronchial washings, which were inconclusive. The patient refused a repeat diagnostic bronchoscopy. She continued to clinically improve and was discharged on day-20 on Bactrim. DISCUSSION: Patients with RA receiving biological antirheumatic drugs are at risk for developing life-threatening pulmonary fungal infections. In our case, the clinical and radiographic findings were highly suggestive of PCP despite having an inconclusive BAL, which could be explained by a low burden of organisms, inadequate specimen, and/or prior treatment. Although the patient had multiple small peripheral pulmonary embolisms, it did not explain the degree of her hypoxia and the fact that she improved with Bactrim making the diagnosis of PCP more likely. CONCLUSIONS: PCP should be suspected in hypoxic patients on etanercept therapy. In such cases coverage with Bactrim (sulfamethoxazole/trimethoprim) should be initiated on suspicion and etanercept should be discontinued. Reference #1: Tanaka M, Sakai R, Koike R, et al. Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rheumatoid arthritis: a retrospective review of 15 cases and analysis of risk factors. Mod Rheumatol. 2012;22(6):849-858. Reference #2: Galli M, Antinori S, Atzeni F, et al. Recommendations for the management of pulmonary fungal infections in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2017;35(6):1018-1028. DISCLOSURES: No relevant relationships by Muhammad Hammami, source=Web Response No relevant relationships by ahmad irshad, source=Web Response No relevant relationships by Navneet Kaur, source=Web Response No relevant relationships by Levonti Ohanisian, source=Web Response

P29 Etanercept and IBD: can we identify at risk patients?

Poster presentation Tuesday 8 October Background We present four cases of patients on etanercept treatment for juvenile idiopathic arthritis (JIA) subsequently diagnosed with inflammatory bowel disease (IBD). We hypothesise that there may be identifiable characteristics of these patients which makes them more identifiable to the physician. Etanercept is a recombinant dimer of human tumour necrosis factor (TNF) receptor proteins bound to human IgG1. It is an effective second line treatment option in JIA for those who have failed, or are intolerant to, methotrexate, and an effective first line treatment option in those who have axial disease at diagnosis. Anti-TNF treatments are effective in IBD, however etanercept in particular does not have therapeutic benefit, and in one trial there was a non-significant trend towards worsening of disease. Methods Please refer to the Results section. Results Four cases, in a 15 year old male, 11 year old female, 10 year old female and 11 year old female, have been identified at our site. The time from etanercept initiation and diagnosis of IBD was between 2 weeks and 2 years 1 month. None of the cases had gastrointestinal symptoms at JIA diagnosis. All four were ANA negative, and in the two with information, both were HLA-B27 negative. Three out of four had hip arthritis involvement. There was a family history of IBD (ulcerative colitis) in only one of the cases. Aside from non-steroidal anti-inflammatory medications, there were no other immunomodulatory medications concurrently being taken in any of the cases while on etanercept. All four were anaemic (Hb &lt; 120g/L) at diagnosis of IBD. Only one had raised ESR (43mm/hr) while all had normal CRP. Albumin was low in two (17g/L and 29g/L). Following gastroenterology review and endoscopy, two cases were diagnosed with Crohn’s disease and two with ulcerative colitis. Conclusion It remains unclear whether etanercept plays a role in the development of IBD in these patients, whether it unmasks subclinical disease, or whether there is no association and it is simply a coincidence. However, there continue to be case reports and series suggesting an association between the two. We hope to identify further cases similar to these from sources such as the UK Biologics Registry and via surveys from teams at paediatric rheumatology centres throughout the UK. Further to the identification of cases, a retrospective review of patient characteristics will be carried out. This may allow for further determination of identifiable characteristics for these patients, and therefore suggest a subgroup of JIA patients with a higher risk of developing IBD, in which case caution when considering etanercept treatment would be advised. Conflicts of Interest The authors declare no conflicts of interest.