Subcutaneous Etanercept Research Articles

E028 A differential diagnosis for treatment resistant psoriatic arthritis

Abstract Background/Aims This case involves a 45 year old gentleman with established psoriatic arthritis with axial and peripheral joint involvement. His disease was managed with subcutaneous methotrexate and etanercept. Despite improvement in axial symptoms and resolution of symptoms at other peripheral joints, he had ongoing severe monoarthritis of his right knee with significant pain and swelling. Methods In spite of several joint aspirations and intra-articular steroid injections [ten in total], escalation of dose of methotrexate, addition of sulfasalazine and switch of biologic to adalimumab, the patient’s right knee symptoms persisted. Further imaging was performed. An US scan showed chronic synovial hypertrophy with fatty metaplasia and an MRI scan showed frond like synovial thickening, suggestive of lipoma arborescens. Results The patient was referred to the orthopaedic surgeons and underwent excision synovectomy. The histopathology reported fibrofatty tissue with areas of chronic synovitis with presence of lymphoplasmacytic aggregates. The patient’s knee symptoms persisted for five years in total after clinical improvement at other joints; post-synovectomy, his right knee symptoms were improved. Lipoma arborescens is a benign progressive intra-articular lesion characterised by villous lipomatous proliferation of the synovium; it frequently affects the knee joint suprapatellar pouch. Villous proliferation of the synovium occurs, with subsequent replacement of synovial connective tissue by adipocytes. Conclusion Lipoma arborescens has been described occasionally in association with psoriatic arthritis. It is felt to occur as a reactive response to chronic synovial irritation; in this case from an inflammatory affront. Given the rarity of lipoma arborescens, coupled with the patient’s known underlying diagnosis of a seronegative arthritis, there was significant delay in his diagnosis. This case highlights the need to consider other causes of persistent joint pain and swelling when maximal therapeutic options have been unsuccessful. Disclosure A. Jacobs: None. M. Callan: None.

S1934 Acute Colonic Ischemia: A Rare Complication of Stevens-Johnson Syndrome

Introduction: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions characterized by necrotic epidermal detachment and blister formation. Mucosal involvement of oropharyngeal, ocular, and urogenital surfaces is most common, but involvement of the small bowel and colon is distinctively rare. We present a unique case of SJS with colonic involvement resulting in acute colonic ischemia. Case description/methods: A 36 year-old female with systemic lupus erythematosus, hypertension, and asthma presented with one day of fever and emesis after taking ibuprofen for sore throat. On admission, she was febrile to 104°F. Laboratory evaluation was non-diagnostic. A diffuse pink morbilliform rash was noted, which rapidly progressed to widespread erythema, targetoid lesions, and bullae. Skin biopsy was consistent with SJS. A week into hospitalization, she developed respiratory failure requiring intubation and transfer to the intensive care unit. CT of the chest, abdomen, and pelvis revealed multifocal pneumonia but normal small and large bowel. She was treated with broad spectrum antibiotics and one dose of subcutaneous etanercept. The patient then developed worsening abdominal pain and distension. Repeat abdominal CT showed marked diffuse colonic distension with pneumatosis from the cecum to proximal transverse colon (Fig. 1). Abdominal arterial vasculature was patent. Exploratory laparotomy confirmed full thickness colonic ischemia. She underwent right and transverse colectomy with end ileostomy. Histology of the colonic mucosa was consistent with ischemia. She was started on IVIG and IV methylprednisolone therapy. The patient gradually improved. Her recovery was complicated by intra-abdominal and pelvic abscesses requiring percutaneous drainage, along with persistent abdominal pain. Further evaluation of her pain included a normal ileoscopy and upper endoscopy and an abdominal CT demonstrating enteritis which was managed with supportive care. The patient was ultimately discharged to a rehabilitation facility. Discussion: SJS/TEN is a potentially fatal and often drug-induced dermatologic reaction involving mucocutaneous membranes. We present a case of SJS thought secondary to ibuprofen use resulting in acute colonic ischemia, which is infrequently encountered and associated with significant morbidity. Clinicians must maintain high suspicion for gastrointestinal involvement of SJS/TEN to allow for prompt diagnosis and intervention.Figure 1.: Colonoscopy revealing a 5 cm polypoid mass at the hepatic flexure.

Efficacy of Etanercept in the Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

It has been suggested that the use of etanercept for treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) might provide improved mortality benefit and decreased skin healing times. This retrospective study compared the use of single-dose subcutaneous etanercept to intravenous immunoglobulin (IVIG) and supportive care alone. Thirteen patients were treated with a single dose (50 mg) of subcutaneous etanercept. Results of this study support the use of etanercept as a potentially beneficial agent in the treatment of SJS/TEN.

Mitochondrial targeted therapy with elamipretide (MTP-131) as an adjunct to tumor necrosis factor inhibition for traumatic optic neuropathy in the acute setting

Traumatic optic neuropathy (TON) can occur following blunt trauma to the orbit and can lead to permanent vision loss. In this study, we investigated the effectiveness of elamipretide (MTP-131), a small mitochondrially-targeted tetrapeptide, in conjunction with etanercept, a tumor necrosis factor (TNF) inhibitor, as neuroprotective agents of retinal ganglion cells (RGCs) after optic nerve trauma with sonication-induced TON (SI-TON) in mice. Treatment with intravitreal MTP-131 and subcutaneous etanercept and MTP-131 showed a 21% increase (p < 0.01) in RGC survival rate compared to PBS-treated control eyes. Subcutaneous etanercept and MTP-131 had an 11% increase (p < 0.05) in RGC survival compared to controls. Subcutaneous etanercept only group showed 20% increase (p < 0.01) in RGC survival compared to controls, while subcutaneous MTP-131 alone showed a 17% increase (p < 0.01). Surprisingly, we did not observe a synergistic effect between the two drugs in the group receiving both etanercept and MTP-131. One possible explanation for the absence of a synergistic effect is that MTP-131 and etanercept may be acting on different portions of the same pathway.

6. The Stillness after the storm: a challenging diagnostic and therapeutic case of adult-onset Still’s disease

6. The Stillness after the storm: a challenging diagnostic and therapeutic case of adult-onset Still’s disease

Personalized rheumatic medicine through dose reduction reduces the cost of biological treatment – a retrospective intervention analysis

Objective: The effects of a dose-reduction intervention of biological disease-modifying anti-rheumatic drugs (bDMARDs) in patients in remission were analysed with epidemiology and health economics strategies. The aims were to analyse changes in bDMARD dosage, evaluate potential disease worsening, and estimate cost reduction.Method: This uncontrolled single-centre observational study analysed bDMARD-treated patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthritis (SpA). bDMARD expenditure constituted a proxy for bDMARD doses, which enabled group-level analysis. Interrupted time-series regression was used to analyse changes in treatment cost due to the dose reduction. Disease activity and treatment durations were monitored to investigate disease worsening.Results: In total, 997 biological treatment cases were analysed. This involved 527 bDMARD patients, where an unknown fraction of patients was given reduced doses. Disease activity of RA and PsA patients decreased from 2001 to 2009 and remained stable after that, while disease activity for SpA patients was unchanged, indicating no disease worsening from the intervention. The dose tapering resulted in decreased bDMARD expenditure, indicating a decrease in bDMARD consumption, which led to an accumulated cost reduction of 4 178 000 EUR.Conclusions: The results suggest that dose reduction can be safely performed in patients in treatment remission on a group level without compromising treatment efficacy. Subcutaneous bDMARDs, including abatacept, adalimumab, and etanercept, were observed to be well suited to customizing dosage. This study highlights the potential for individualized and personalized rheumatic medicine by providing dose reduction to individual patients, while monitoring disease activity.

Etanercept and Methotrexate as Monotherapy or in Combination for Psoriatic Arthritis: Primary Results From a Randomized, Controlled Phase III Trial

ObjectiveTo examine the efficacy of methotrexate monotherapy relative to etanercept monotherapy and the value of combining methotrexate and etanercept for the treatment of patients with psoriatic arthritis (PsA).MethodsIn this double‐blind study, 851 patients with PsA were randomized to 1 of 3 treatment arms, as follows: oral methotrexate (20 mg) plus subcutaneous placebo given weekly (n = 284), subcutaneous etanercept (50 mg) plus oral placebo given weekly (n = 284), or subcutaneous etanercept (50 mg) plus oral methotrexate (20 mg) given weekly (combination therapy; n = 283). The American College of Rheumatology 20% improvement (ACR20) response and Minimal Disease Activity (MDA) response at week 24 were the primary end point and key secondary end point, respectively. Other measures of inflammatory arthritis, radiographic progression, and nonarticular disease manifestations were also assessed.ResultsPatients with PsA had a mean ± SD age of 48.4 ± 13.1 years, and the mean ± SD duration of PsA was 3.2 ± 6.3 years (median 0.6 years). ACR20 and MDA response rates at week 24 were significantly greater in patients who received etanercept monotherapy compared with those who received methotrexate monotherapy (ACR20, 60.9% versus 50.7% of patients [P = 0.029]; MDA, 35.9% versus 22.9% of patients [P = 0.005]), and both were significantly greater in the combination therapy group compared with the methotrexate monotherapy group at week 24 (ACR20, 65.0% versus 50.7% of patients [P = 0.005]; MDA, 35.7% versus 22.9% of patients [P = 0.005]). Other secondary outcomes (ACR50 and ACR70 response rates, proportions of patients achieving a Very Low Disease Activity score, and PsA disease activity scores) showed between‐group differences that were consistent with the primary and key secondary end point results. Furthermore, patients in both etanercept treatment arms showed less radiographic progression at week 48 compared with patients who received methotrexate monotherapy. Outcomes were similar in the combination therapy and etanercept monotherapy groups, except for some skin end points. No new safety signals were seen.ConclusionEtanercept monotherapy and combination therapy with etanercept and methotrexate showed greater efficacy than methotrexate monotherapy in patients with PsA, according to the ACR and MDA response rates and extent of radiographic progression at follow‐up. Overall, combining methotrexate and etanercept did not improve the efficacy of etanercept.

Treatment persistence of subcutaneous TNF inhibitors among Australian patients with immune-mediated rheumatic disease (IMRD).

IntroductionTo describe the persistence of treatment with subcutaneous tumor necrosis factor inhibitors (TNFi) adalimumab, etanercept, and golimumab in immune-mediated rheumatic disease (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) by treatment sequence (first-line treatment, second-line or further lines of treatment).MethodsA retrospective cohort analysis was conducted using the Australian Commonwealth Department of Human Services Pharmaceutical Benefits Scheme 10% sample data from January 1, 2010, to June 30, 2016. Pharmaceutical Benefits Scheme indications were used to identify patient prescriptions for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A patient was considered persistent until a 3-month gap period where a prescription was not dispensed. The 3-month gap interval was chosen because only 1% of all discontinuations occurred beyond this 3-month period.ResultsData from 2,612 first-line patients were included. Treatment discontinuation among first-line patients treated with etanercept or adalimumab was not significantly different from those treated with golimumab (HR 1.10, 95% CI 0.95–1.28, P=0.22; HR 1.06, 95% CI 0.93–1.22, P=0.39; respectively). Among the 1,276 patients in the second-line cohort (etanercept=41%, adalimumab=41%, golimumab=18%) discontinuation was significantly higher for patients on etanercept compared with golimumab (HR 1.24, 95% CI 1.03–1.50, P=0.03); but not for adalimumab compared with golimumab (HR 1.11, 95% CI 0.91–1.34, P=0.31). In the third-line setting, treatment persistence with etanercept was longer than golimumab (HR 0.75, 95% CI 0.59–0.96, P=0.02), but there was no difference between golimumab and adalimumab. Similar findings occurred in the propensity score matched population.ConclusionOur study shows there is variance in real-world persistence to TNFi in patients with immune-mediated rheumatic disease by line of therapy, with the time on therapy decreasing by line. Australian persistence has been reported at lower overall rates than international evidence.

Sorafenib Reveals Anti-Arthritic Potentials in Collagen Induced Experimental Arthritis Model.

This study aims to examine the effects of sorafenib on a collagen-induced arthritis model. The study included 50 randomly selected female Wistar-albino rats (8-10-week-old, weighing between 200 g to 250 g). The rats were divided into five equal groups as control, arthritis, etanercept, sorafenib high-dose, and sorafenib low-dose groups, respectively. Arthritis was induced by injecting mixed intradermal chicken type II collagen and incomplete Freund's adjuvant. Twenty-four hours after the advent of arthritis; rats in group 3 were injected subcutaneous etanercept (6 mg/kg/week), while those in groups 4 and 5 were given sorafenib (10 or 30 mg/ kg/day) orally until they were sacrificed on the 34th day. The rat claws and trunk bloods were carefully examined to note perisynovial inflammation and cartilage/bone injury through histopathology. Tissue vascular endothelial growth factor (VEGF) and VEGF receptor levels were carefully checked using western blot analysis. Analysis of the experimental data showed that collagen-induced arthritis decreased in treatments groups after 12-13 days and 34th day in contrast with the arthritis group. Histopathological examination revealed broad perisynovial inflammation and cartilage/bone break down in the arthritis group. Compared to the control group, tissue VEGF and VEGF receptor levels increased in the arthritis group. Sorafenib and etanercept decreased tissue VEGF and VEGF receptor levels, perisynovial inflammation, damage of cartilage/bone. Our findings indicate that sorafenib treatment ameliorates collagen-induced arthritis with anti-VEGF effectiveness.

CLINICAL EXPERIENCE WITH ETANERCEPT IN THE TREATMENT OF PATIENTS WITH ANKYLOSING SPONDYLITIS

Etanercept (ETC), a soluble tumor necrosis factor-α (TNF-α) receptor, was registered for the treatment of spondyloarthritis in the Russian Federation in 2009. By now, results of prolonged treatment with this drug have been obtained in patients with ankylosing spondylitis (AS). Objective: to evaluate the efficiency and tolerability of long-term therapy with ETC in patients with AS. Subjects and methods. The follow-up included 60 patients with a documented diagnosis of AS (the 1984 New York criteria) and/or axial spondyloarthritis (the 2009 ASAS criteria), high activity (BASDAI >4), who received long-term (at least a year) regular therapy with subcutaneous ETC 50 mg weekly. Its effect was evaluated using the ASAS criteria. Results and discussion. ETC was the first TNF-α inhibitor used in 29 (48%) patients, including 22 (76%) patients who achieved partial remission; 7 (24%) patients who showed ASAS40 improvement. One patient was observed to have hepatotoxicity (alanine aminotransferase elevation to 72 U/l), therefore the drug was discontinued. 31 (52%) patients were switched to ETC after infliximab (n=24) or adalimumab (n=7) due to their poor tolerance and/or loss of effect. At the same time, ETC became the second anti-TNF-α drug in 21 (35%) patients and the third one in 10 (17%). During the therapy, 21 (68%) patients switched to ETC were noted to have ASAS40 improvement; 9 (29%) patients had partial remission. The insufficient effect of the drug was observed only in one patient (3%), in whom ETC was the third TNF-α inhibitor. The tolerability of ETC was generally satisfactory after switching from anti-TNF-α monoclonal antibodies (mAbs). Three patients developed de novo psoriasis that required therapy discontinuation in one patient; another male patient developed uveitis for the first time. In one female patient with AS associated with Crohn’s disease with loss of mAb effect, ETC became the third anti-TNF-α drug, during therapy with which there was no exacerbation of Crohn’s disease. The drug was well tolerated and highly effective in 8 patients, in whom ETC treatment was initiated at the age of 60 years and older: 6 (75%) achieved partial remission, 2 (25%) had ASAS40 improvement. Nine patients with previous and/or latent tuberculosis had no exacerbation of this disease during ETC therapy. Conclusion. During regular therapy with ETC, more than half of patients (52%) achieved partial remission according to the ASAS criteria, while this was more frequently achieved when the drug was used for the first time (76%) than when mAbs were switched to ETC (29%). Discontinuation of the latter due to adverse events was required only in 2 (3%) patients.

Cost-effectiveness analysis of secukinumab for the treatment of active psoriatic arthritis: a Canadian perspective

Objective: The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective.Methods: A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150 mg and 300 mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses.Results: Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses indicated the results were most sensitive to variation in PsARC response rates, change in HAQ, and utility values in both populations.Conclusions: Secukinumab is either dominant or cost-effective vs all licensed biologics for the treatment of active PsA in biologic-naive and biologic-experienced populations in Canada.

Randomised, placebo-controlled trial to evaluate clinical efficacy and structure modifying properties of subcutaneous etanercept in patients with erosive inflammatory hand osteoarthritis

Randomised, placebo-controlled trial to evaluate clinical efficacy and structure modifying properties of subcutaneous etanercept in patients with erosive inflammatory hand osteoarthritis

Tumor necrosis factor-alpha blockade with etanercept improves autonomic dysfunction in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease associated with autonomic neuropathy. There is no specific treatment recommendation for autonomic neuropathy (AN) in rheumatic diseases. In addition, there is no study demonstrating therapeutic efficacy of TNF-inhibitor (TNFi) etanercept on autonomic neuropathy in RA. This is the first reported observation of improvement in AN with blockade of TNFi-etanercept in RA. We report a case of a 46-year-old female with severe disease activity treated with subcutaneous etanercept 50mg once a week along with methotrexate 15 mg/week. A significant improvement in cardiovascular autonomic neuropathy and sudomotor function was noted after 6 weeks of treatment.

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials

Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89·7%; [effect size 87·4% (97·5% CI 82·9-91·8) vs placebo; 48·1% (41·2-55·0) vs etanercept]) and 336 (87·3%; [80·0% (74·4-85·7) vs placebo; 33·9% (27·0-40·7) vs etanercept]) patients; in the ixekizumab every 4 weeks group, by 269 (77·5%; [75·1% (69·5-80·8) vs placebo; 35·9% (28·2-43·6) vs etanercept]) and 325 (84·2%; [76·9% (71·0-82·8) vs placebo; 30·8% (23·7-37·9) vs etanercept]) patients; in the placebo group, by four (2·4%) and 14 (7·3%) patients; and in the etanercept group by 149 (41·6%) and 204 (53·4%) patients (all p<0·0001 vs placebo or etanercept). In the ixekizumab every 2 weeks group, sPGA 0/1 was achieved by 292 (response rate 83·2%; [effect size 80·8% (97·5% CI 75·6-86·0) vs placebo; 47·2% (39·9-54·4) vs etanercept]) and 310 (80·5%; [73·8% (67·7-79·9) vs placebo; 38·9% (31·7-46·1) vs etanercept]) patients; in the ixekizumab every 4 weeks group by 253 (72·9%; [70·5% (64·6-76·5) vs placebo; 36·9% (29·1-44·7) vs etanercept]) and 291 (75·4%; [68·7% (62·3-75·0) vs placebo; 33·8% (26·3-41·3) vs etanercept]) patients; in the placebo group by four (2·4%) and 13 (6·7%) patients; and in the etanercept group by 129 (36·0%) and 159 (41·6%) patients (all p<0·0001 vs placebo or etanercept). In combined studies, serious adverse events were reported in 14 (1·9%) of 734 patients given ixekizumab every 2 weeks, 14 (1·9%) of 729 given ixekizumab every 4 weeks, seven (1·9%) of 360 given placebo, and 14 (1·9%) of 739 given etanercept; no deaths were noted. Both ixekizumab dose regimens had greater efficacy than placebo and etanercept over 12 weeks in two independent studies. These studies show that selectively neutralising interleukin 17A with a high affinity antibody potentially gives patients with psoriasis a new and effective biological therapy option. Eli Lilly and Co.

Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence and dosing patterns in Germany.

ObjectiveTo obtain detailed real-world data on persistence and dosing patterns in the utilisation of the TNF inhibitors adalimumab, etanercept, and infliximab in rheumatoid arthritis (RA) patients treated in Germany.MethodsIn this retrospective observational study claims data of a major German health insurance fund between 2005 and 2008 were analysed. Patients receiving at least one prescription of adalimumab, etanercept or infliximab were identified and categorised as “TNF inhibitor naive" or “TNF inhibitor continuing”. For the calculation of TNF inhibitor persistence a survival analysis with the Kaplan–Meier estimator was used. A Cox regression was used to analyse, if any relevant factors were influencing persistence. Dosage increase rates were analysed for adalimumab, etanercept and infliximab. Sensitivity analyses based on variations in gap length were conducted.ResultsA total of 2,201 RA patients were identified. 1,468 of these patients were TNF inhibitor naive patients and 733 were defined as TNF inhibitor continuing patients. There were no significant differences in the treatment persistence rates between adalimumab, etanercept and infliximab for TNF inhibitor naive and continuing patients. The persistence rate after three years was 22.47% for adalimumab, 24.27% for etanercept and 21.49% for infliximab naive patients. For continuing patients, the persistence rate after three years was 32.88% for adalimumab, 30.95% for etanercept, and 33.90% for infliximab, respectively. Gender, medication and Charlson Comorbidities Index did not influence the persistence significantly. Dosage increase occurred in 7.3% adalimumab, 1.4% etanercept, and 17.2% infliximab naive patients and 5.8%, 1.1% and 11.9% respectively in the continuing patients.ConclusionsIn this study, there were no significant differences in persistence among adalimumab, etanercept and infliximab treated patients. Consistent with previous research, there was a higher dose escalation for infliximab than for the two subcutaneous treatments, adalimumab or etanercept.

Etanercept: A Review of Its Use in Autoimmune Inflammatory Diseases

With its approval more than 15 years ago, subcutaneous etanercept (Enbrel(®)) was the first biological disease-modifying antirheumatic drug (bDMARD) and the first tumour necrosis factor inhibitor to be approved for use in rheumatic diseases. Etanercept remains an important cost-effective treatment option in adult patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or plaque psoriasis, and in paediatric patients with juvenile idiopathic arthritis or plaque psoriasis. In all of these populations, etanercept (with or without methotrexate) effectively reduced signs and symptoms, disease activity and disability, and improved health-related quality of life, with these benefits sustained during long-term treatment. The safety profile of etanercept during short- and long-term treatment was consistent with the approved product labelling, with adverse events being of a predictable and manageable nature. The introduction of etanercept and other bDMARDs as therapeutic options for patients with autoimmune rheumatic diseases and spondyloarthropathies revolutionized disease management and these agents continue to have a central role in treatment strategies. This article reviews the extensive clinical experience with etanercept in these patient populations.

SAT0076 Effectiveness of RA BIOLOGICS in the Two Years following Initiation Using A Validated Claims-Based Algorithm

BackgroundBiologic disease modifying antirheumatic drugs (DMARD) are a mainstay of Rheumatoid Arthritis (RA) treatment. A validated claims-based RA biologic effectiveness algorithm was developed1, allowing administrative claims data to be used...

AB0385 A Randomized Controlled Clinical TRIAL to Evaluate the Efficacy of Recombinant Human Tumor Necrosis Factor-α Receptor II Fusion Protein in Juvenile Idiopathic Arthritis

ObjectivesResearch the Recombinant Human Tumor Necrosis Factor-α Receptor type II fusion protein antibody (Etanercept)for Treatment of juvenile idiopathic arthritis (JIA).A randomized controlled clinical trial was conducted, so as to provide...

Dose REduction strategy of subcutaneous TNF inhibitors in rheumatoid arthritis: design of a pragmatic randomised non inferiority trial, the DRESS study

BackgroundPreliminary, mostly uncontrolled studies suggest that dose reduction or discontinuation of tumour necrosis factor blockers can be achieved in a relevant proportion of patients with RA without loss of disease control. However, long term safety, cost effectiveness and feasibility in clinical practice remain uncertain.Methods/DesignThis study is a 18-months pragmatic, non-inferiority, cost minimalisation, randomized controlled trial on dose reduction and discontinuation of the subcutaneous tumour necrosis factor (TNF) blockers adalimumab and etanercept in RA patients with low disease activity. 180 RA patients with low disease activity (DAS28 < 3.2 or clinical judgment of the rheumatologist) are randomized 2:1 to either increased spacing and eventually discontinuation after 6 months of the TNF blocker, and usual care. Implementation is done in routine daily care, using treat to target and feedback implementation in both treatment arms. The primary outcome is non-inferiority (NI margin 20%) in cumulative incidence of persistent (> 3 months) RA flare, according to a recently validated DAS28 based flare criterion (DAS28 change > 1.2, or DAS28 increase of 0.6 and current DAS28 ≥ 3.2). Secondary outcomes include mean disease activity, function, radiographic progression, safety and cost effectiveness. Cost per quality adjusted life year (QALY) differences between groups are expressed as a decremental cost effectiveness ratio (DCER), i.e. saved costs divided by (possible) loss in QALY.DiscussionThe design of this study targeted several clinical and methodological issues on TNF blocker dose de-escalation, including how to taper the TNF blockers, the satisfactory control condition, how to define flare, implementation in clinical practice, and the choice of the non-inferiority margin. Pragmatic cost minimalisation studies using non-inferiority designs and DCERs will become more mainstream as cost effectiveness in healthcare gains importance.Trial registrationDutch Trial Register NTR3216, The study has received ethical review board approval (number NL37704.091.11)

AB0942 Efficacy and safety of subcutaneous anti-TNF alpha, etanercept and adalimumab, in elderly patients affected by psoriasis and psoriatic arthritis: An observational long term study

BackgroundPsoriasis (Pso) and psoriatic arthritis (PsA) are chronic and disabling inflammatory diseases, characterized by a chronic-relapsing and unpredictable course. Traditional systemic therapies for these conditions are limited by lack of...