BACKGROUND:Topical corticosteroids are used with systemic therapies for treatment of plaque psoriasis, but data from randomized clinical trials to document efficacy of combination therapy are lacking.OBJECTIVE:To evaluate efficacy and safety of adding topical corticosteroid therapy from the time that etanercept dosage is reduced from initial label dose [50 mg twice weekly (BIW)] to maintenance dose [50 mg once weekly (QW)].METHODS:In this phase 3b, multicentre, randomized, open-label study, patients with moderate-to-severe plaque psoriasis received etanercept 50 mg BIW for 12 weeks, and then were randomized to etanercept 50 mg BIW or 50 mg QW plus topical agent as needed to achieve static physician global assessment (sPGA) status of clear for 12 weeks. Endpoints included percentage change in Psoriasis Area and Severity Index (PASI) score from week 12 to week 24 (primary endpoint); proportion of patients achieving 50% improvement in (PASI 50), PASI 75 and PASI 90; patients achieving sPGA of clear/almost clear; and change in affected body surface area (BSA).RESULTS:Mean difference [95% confidence interval (CI)] between etanercept arm (n = 140) and etanercept plus topical arm (n = 142) in change in PASI score from week 12 to week 24 was 16.2% (-3.5%, 35.8%). PASI response rates were similar between groups. Percentage (95% CI) of patients achieving sPGA status of clear/almost clear was 40.6% (32.5%, 48.6%) and 45.8% (37.6%, 54.0%) at week 12 for patients in etanercept and etanercept plus topical arms, respectively, and 53.5% (45.3%, 61.7%) and 45.4% (37.2%, 53.6%) at week 24. Difference (95% CI) between groups in change in affected BSA from week 12 to week 24 was 4.9% (-23.4%, 33.2%).CONCLUSION:Patients who received etanercept 50 mg QW at week 12 plus as-needed topical therapy and those who stayed on etanercept 50 mg BIW maintained clinical response through week 24 with no notable differences in PASI responses.

Background Remission (REM) or low disease activity (LDA) are key clinical targets in patients with rheumatoid arthritis (RA).1 The CAMEO study, an open-label trial in RA patients, demonstrated that those with LDA after 6 months of etanercept (ETN) and methotrexate (MTX) therapy had similar clinical outcomes at 12 months whether they continued ETN+MTX or switched to ETN monotherapy at month 6 (M6).2 Conversely, patients who had not achieved LDA at M6 showed reduced response when treated with ETN alone after withdrawing MTX.2 Objectives This post-hoc analysis of the CAMEO study examined the achievement and sustainability of REM or LDA for up to 24 months in patients who continued ETN+MTX or switched to ETN monotherapy following 6 months of combination therapy. Methods TNF inhibitor naïve patients with active RA (≥3 swollen joints, Disease Activity Score [DAS28] ≥3.2), despite MTX therapy (≥15 mg/week or 10 mg/week if intolerant) for >12 weeks, were enrolled. Following 6 months of ETN (50 mg/week SC) + MTX treatment, patients were randomized (1:1) to continue ETN+MTX or to switch to ETN monotherapy for an additional 18 months. DAS28 was assessed at baseline through month 24 (M24). Results A total of 258 patients enrolled (76% female, mean age 54.7±12.5 yrs, disease duration 8.9±8.4 yrs, baseline DAS28 5.4±1.1) and 205 (79%) were randomized at M6 to maintain ETN+MTX (n=107) or to begin ETN alone (n=98). Among patients who achieved REM (DAS28 <2.6) at M6, REM rates were similar at M24 whether on combination or monotherapy (Table 1). Similarly, in patients who achieved M6 LDA (DAS28 <3.2), the proportion of individuals maintaining LDA at M24 was comparable between treatment arms (ETN: 36% vs. ETN+MTX: 40%). In contrast, in subgroups without M6 REM or LDA but who achieved M12 REM or LDA, fewer patients in the ETN arm maintained REM (ETN: 2% vs. ETN+MTX: 6%; Table 1) or LDA (ETN: 0% vs. ETN+MTX: 10%) to M24. For patients without M6 REM, completion rates at M24 were 45% and 70% in the ETN and ETN+MTX arms, respectively; in patients achieving M6 REM, completion rates were 65% in the ETN arm and 70% in the ETN+MTX arm. Conclusions This analysis demonstrates that a substantial proportion of patients who achieve LDA/REM at M6 sustain LDA/REM through M24 whether on combination or monotherapy. These results suggest that ETN monotherapy may be considered in those patients who achieve LDA/REM after 6 months of combination therapy. References Smolen JS, et al. Ann Rheum Dis. 2010;69:631-637. Pope JE, et al. Ann Rheum Dis. 2013 August [Epub ahead of print]. Acknowledgements Amgen Canada Inc. oversaw the design, conduct, and data collection and assisted in the analysis and interpretation of data. Disclosure of Interest : J. Pope Grant/research support: Abbott/AbbVie, Amgen, Actelion, AstraZeneca Pharmaceuticals, Bristol-Meyers Squibb, Glaxo-Smith Kline, Hoffmann-LaRoche, Janssen, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, UCB, Consultant for: Abbott/AbbVie, Amgen, Actelion, AstraZeneca Pharmaceuticals, Bristol-Meyers Squibb, Glaxo-Smith Kline, Hoffmann-LaRoche, Janssen, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, UCB, B. Haraoui Grant/research support: Abbott/AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Pfizer, Roche, UCB, Consultant for: Abbott/AbbVie, Amgen, Bristol-Meyers Squibb, Merck, Pfizer, Roche, UCB, J. C. Thorne Grant/research support: Amgen, Pfizer, Abbott/AbbVie, Bristol-Myers Squibb, Centocor, Merck, Roche, UCB, Consultant for: Amgen, Pfizer, Abbott/AbbVie, Bristol-Myers Squibb, Centocor, Merck, Roche, UCB, K. Phan-Chronis Employee of: Amgen Canada, M. Poulin-Costello Employee of: Amgen Canada, A. Vieira Employee of: Amgen Canada (Former employee), E. Keystone Grant/research support: Abbott/AbbVie, Amgen, AstraZeneca Pharmaceuticals, Bristol-Meyers Squibb, Centocor, F. Hoffmann-LaRoche, Genzyme, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, UCB, Genentech, Janssen, Consultant for: Abbott/AbbVie, Bristol-Meyers Squibb, F. Hoffmann-LaRoche, Merck, Pfizer Pharmaceuticals, UCB, Janssen DOI 10.1136/annrheumdis-2014-eular.1054

BackgroundPatients with psoriasis (PsO) and psoriatic arthritis (PsA) have functional disability, pain and emotional problems, and experience lower quality of life (QoL) than patients with PsO alone.ObjectivesExamine effectiveness of etanercept (ETN) in patients with PsO alone, and with PsA, and determine whether PsA patients on ETN experience rapid QoL improvement.MethodsData from three phase III trials using ETN in adults with moderate-to-severe PsO were pooled. Patients with (n=523) and without (n=1330) PsA received ETN 25mg once weekly to 50mg twice weekly or placebo for 12-24weeks. Assessments included Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), EuroQoL-5D (EQ-5D), Study 36-item Short Form Health Survey (SF-36) and Hamilton Depression Rating Scale (HAM-D).ResultsBaseline PASI, EQ-5D and SF-36 physical component summary scores were worse for PsA patients. With ETN, PASI for PsA and non-PsA groups improved as early as week 2. Scores for both groups converged by week 12. EQ-5D and SF-36 physical component improved faster in PsA patients, with EQ-5D scores converged by week 2. For total DLQI and most components, both groups had similar baseline scores and improved over 24weeks on ETN. While the PsA group had more depressed patients at baseline, after 24weeks on ETN it showed a greater reduction in the number of depressed patients than the non-PsA group.ConclusionsIn patients with PsO involving 10% of body surface area, skin disease and QoL are worse in PsA patients. With ETN, QoL improved rapidly in PsA patients.

Background The majority of patients with rheumatoid arthritis (RA) initiating biologics have moderate disease activity (MDA)1 and achieve better outcomes than those with severe disease activity (SDA).2 The PRESERVE trial reported similar rates of low disease activity/remission (LDA/REM) at 88 weeks in MDA patients reaching LDA/REM after 36 weeks of etanercept(ETN)+methotrexate(MTX), whether they had continued full or half dose of ETN+MTX.3 PRESERVE did not address if patients would have done equally well on ETN vs. ETN+MTX. Objectives The open-label CAMEO trial sought to determine if withdrawing MTX is as effective as continuing ETN+MTX in MDA and SDA after 6 months of ETN+MTX.4 This pre-specified post-hoc analysis assessed month 12 response in MDA (3.25.1) patients. Methods TNF inhibitor naive, RA patients with active disease [≥3 swollen joints, DAS28≥3.2] despite MTX (≥15mg/wk, or 10mg/wk if intolerant) for >12 weeks were enrolled. Patients received ETN(50mg/wk sc)+MTX for 6 months. At month 6, patients were randomized to continue ETN+MTX or switch to ETN alone for 18 more months. Here we present DAS28 from month 6 to 12 by MDA or SDA at baseline (BL). Results 258 patients were enrolled (female: 76%; mean disease duration: 8.9±8.4 yrs; mean # prior DMARDS: 2.7±1.0; prior oral prednisone: 52%). 205 were randomized at month 6, 121(59.0%) with BL SDA vs 84(41.0%) with BL MDA. Nearly twice as many with MDA vs. SDA patients reached LDA/REM(DAS28<3.2) at month 6 (61.3%(49/80) vs. 35.8%(43/120); OR[95%CI]=2.5[1.38-4.41]). MDA patients maintained stable DAS28 to month 12 whether continuing ETN+MTX (mean DAS28 [95% CI]=3.10[2.66-3.53]) or on ETN alone (mean DAS28[95% CI]=3.06[2.59-3.52]). In contrast, patients with SDA continued to improve to month 12 when maintaining ETN+MTX (mean DAS28[95% CI]=3.39[3.02-3.76]) but not on ETN alone (mean DAS28[95% CI]=4.31[3.85-4.76])[Fig1]. Image/graph Conclusions It may be possible to withdraw MTX in a relatively high proportion of patients initiating treatment with MDA after 6 months of combination ETN+MTX, as more of these patients maintain LDA/REM. Patients with initial SDA, however, may need to continue combination therapy. This analysis provides important information on the disease state required to make a therapeutic adjustment in order to achieve and maintain LDA/REM. References PincusT, et al.Arthritis Rheum.2005;52:1009-1019; MaderR, et al.J Rheumatol Suppl.2007;80:16-24; Smolen JS, et al.Lancet.2013.Published Online; PopeJ, et al.Arthritis & Rheum.2012;64(S10):S566 Acknowledgements Amgen Canada Inc. oversaw the design, conduct, & collection of data in the study & assisted in the analysis/interpretation of data. Disclosure of Interest E. Keystone Grant/research support from: Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Centocor Inc, F. Hoffmann-LaRoche Inc, Genzyme, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, UCB, Genentech Inc, Nycomed, Speakers bureau: Abbott Laboratories, Bristol-Myers Squibb, F. Hoffmann-LarRaoche Inc, Merck, Pfizer Pharmaceuticals, UCB, B. Haraoui Grant/research support from: Abbott, Amgen, Bristol-Meyers Squibb, Merck, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Bristol-Meyers Squibb, Merck, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Bristol-Meyers Squibb, Merck, Pfizer, Roche, UCB, C. Thorne Grant/research support from: Amgen, Pfizer, Abbott, Bristol-Myers Squibb, Roche, UCB, Merck, Centocor, Consultant for: Amgen, Pfizer, Abbott, Bristol-Myers Squibb, Roche, UCB, Merck, Centocor, M. Poulin-Costello Employee of: Amgen Canada, E. Trottier Employee of: Amgen Canada, A. Vieira Employee of: Amgen Canada, J. E. Pope Grant/research support from: Abbott, Amgen, Actelion, AstraZeneca, Bristol-Meyers Squibb, Glaxo-Smith Kline, Hoffmann-LaRoche, Janssen, Novartis, Pfizer, UCB, Consultant for: Abbott, Amgen, Actelion, AstraZeneca, Bristol-Meyers Squibb, Glaxo-Smith Kline, Hoffmann-LaRoche, Janssen, Novartis, Pfizer, UCB

Placental growth factor (PIGF) plays a role in angiogenesis and neuroprotection. It has been suggested that angiogenesis and blood–brain barrier damage are involved in the pathophysiology of epilepsy. In this study, we investigated the PIGF expression in the temporal neocortices of 11 patients with pharmaco-resistant temporal lobe epilepsy (TLE) and 6 non-epileptic controls, using double immunofluorescence labeling, immunohistochemistry and Western blotting. We also assessed PIGF expression pattern in a rat model of TLE induced by lithium chloride-pilocarpine. We found that PIGF expression was significantly elevated in patients with TLE than in control. TLE patients with initial injuries had significantly higher PIGF level than those without initial injuries. In the TLE rat model, PIGF upregulation started at 6 h after status epilepticus and maintained at significant high level for up to 60 days. These results suggest that the augmentation of brain PIGF is associated with development of epilepsy.