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ImportanceFew simplified instruments exist for use in hidradenitis suppurativa (HS) trials.ObjectiveTo assess psychometric properties of the Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA) score using a clinical trial data set.Design, Setting, and ParticipantsThis retrospective analysis of a phase 2 randomized double-blind, placebo-controlled, active-reference arm trial (UCB HS0001) included adults with moderate-to-severe HS.ExposuresTrial participants were randomized at baseline to receive bimekizumab, adalimumab, or placebo.Main Outcomes and MeasuresThe HS-IGA score at prespecified time points up to 12 weeks after randomization.ResultsThe HS-IGA score showed strong convergent validity with IHS4 and HS-PhGA scores at baseline (Spearman correlation, 0.86 [P P P P 2 = 18.45; P 2 = 18.11; P 2 = 20.83; P Conclusions and RelevanceThe HS-IGA score demonstrated good psychometric properties compared with existing measures and may be considered for use as an end point in clinical trials for HS.

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A.To assess patients' ability to self-inject bimekizumab subcutaneously using a 1 mL safety syringe or auto-injector.DV0002 and DV0006 were sub-studies of BE BRIGHT, a multicenter, phase 3 open-label extension study. Patients with moderate to severe plaque psoriasis received bimekizumab 320 mg (2x160 mg injections) every 4 or 8 weeks and were randomized 1:1 to the safety syringe or the auto-injector. The ability of patients to safely and effectively self-inject bimekizumab was assessed at 8 weeks (primary endpoint) and immediately after self-injection training at Baseline (secondary endpoint). Patient experience was evaluated using the pain visual analog scale (VAS; 0ndash;100 mm; 100 being worst pain), and the Self-Injection Assessment Questionnaire (SIAQ; 0ndash;10; 10 being most positive experience).All evaluable patients in DV0002 (n=125) and DV0006 (n=86) safely and effectively self-injected bimekizumab at Week 8. All evaluable patients in DV0002 who used the safety syringe (n=64) and 97.1% (n=66/68) who used the auto-injector, as well as all evaluable DV0006 patients (n=88) also self-injected bimekizumab safely and effectively at Baseline. Median VAS scores were low (range: 7.0ndash;20.0), and median pre-injection and post-injection SIAQ scores were high (range: 5.8ndash;10.0 and 7.1ndash;10.0, respectively) across both devices, sub-studies, and timepoints.Both devices provide a safe and effective option for patients to self-administer bimekizumab. Furthermore, patients reported a positive self-injection experience.NCT03766685 J Drugs Dermatol. 2022;21(2):162-171. doi:10.36849/JDD.6274THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Traumatic brain injury (TBI) is among the leading causes of death and disability all over the globe. TBI is also commonly associated with clinical sequelae of posttraumatic depression, and reports of other subsequent affective distress are common. Similarly, posttraumatic changes in chemoreceptive sensory functions, primarily due to coup-contrecoup injury induced shearing of the olfactory nerve fibers, leading to anosmia and ageusia are also well documented in the literature. However, the current literature is limited in addressing the intersections between said variables. The aim of this study was to provide a focused narrative review of the literature, to address these intersections found in clinical sequelae of TBI. As chemoreceptive sensory deficits are also linked to significant affective distress of their own, this review addresses the bidirectionality between sensory deficit and affective distress. Prevalence, demographics, mechanisms, and clinical implications are presented. Previous research is presented and discussed, in an effort to highlight the importance of consideration for all factors in TBI patient care and future research.

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined.In this phase 3b trial, we randomly assigned patients with moderate-to-severe plaque psoriasis, in a 1:1 ratio, to receive bimekizumab subcutaneously at a dose of 320 mg every 4 weeks or secukinumab subcutaneously at a dose of 300 mg weekly to week 4, followed by every 4 weeks to week 48. At week 16, patients receiving bimekizumab underwent rerandomization, in a 1:2 ratio, to receive maintenance dosing every 4 weeks or every 8 weeks to week 48. The primary end point was 100% reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 16. The primary analysis was first tested for the noninferiority of bimekizumab to secukinumab at a margin of -10 percentage points and then tested for superiority.A total of 1005 patients were screened and 743 were enrolled; 373 patients were assigned to receive bimekizumab and 370 to receive secukinumab. At week 16, a total of 230 patients (61.7%) in the bimekizumab group and 181 (48.9%) in the secukinumab group had a 100% reduction from baseline in the PASI score (PASI 100) (adjusted risk difference, 12.7 percentage points; 95% confidence interval [CI], 5.8 to 19.6); bimekizumab was shown to be noninferior and superior to secukinumab (P0.001 for noninferiority and superiority). At week 48, a total of 250 patients (67.0%) treated with bimekizumab had a PASI 100 response, as compared with 171 patients (46.2%) treated with secukinumab (adjusted risk difference, 20.9 percentage points; 95% CI, 14.1 to 27.7; P0.001). At the week 4 time point, 265 patients (71.0%) in the bimekizumab group had 75% or greater reduction from baseline in the PASI score, as compared with 175 patients (47.3%) in the secukinumab group (adjusted risk difference, 23.7; 95% CI, 17.0 to 30.4; P0.001). Oral candidiasis occurred more often with bimekizumab (72 patients, 19.3%) than with secukinumab (11 patients, 3.0%).In patients with moderate-to-severe psoriasis, treatment with bimekizumab resulted in greater skin clearance than treatment with secukinumab over 16 and 48 weeks but was associated with oral candidiasis (predominantly mild or moderate as recorded by the investigator). Longer and larger trials are required to determine the comparative effect and risks of interleukin-17 inhibitors in psoriasis. (Funded by UCB Pharma; BE RADIANT ClinicalTrials.gov number, NCT03536884.).

Background Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the tumor necros...

Government agencies, globally, strive to minimize the likelihood and frequency of human death and severe injury on road transport systems. From an engineering design standpoint, the minimization of these road accident effects on occupants becomes a critical design goal. This necessitates the quantification and management of injury risks on the human body in response to several vehicular impact variables and their associated uncertainties for different crash scenarios. In this paper, we present a decision-based, robust design (RD) framework to quantify and manage the impact-based injury risks on occupants for different computational model-based car crash scenarios. The key functionality offered is the designer's capability to conduct robust concept exploration focused on managing the selected impact variables and associated uncertainties, such that injury risks are controlled within acceptable levels. The framework's efficacy is tested for near-side impact scenarios with impact velocity and angle of impact as the critical variables of interest. Two injury criteria, namely, head injury criterion (HIC) and lateral neck injury criteria (Lateral Nij) are selected to quantitatively measure the head and neck injury risks in each crash simulation. Using the framework, a RD problem is formulated to determine the combination of impact variables that best satisfies the injury goals defined. The framework and associated design constructs are generic and support the formulation and decision-based robust concept exploration of similar problems involving models under uncertainty. Our focus in this paper is on the framework rather than the results per se.

Introduction Patients with plaque psoriasis experience a variety of signs and symptoms that can impact daily life, which may not be evaluated by clinician-reported outcomes. This study aimed to develop and assess the content validity of a new patient-reported outcome (PRO) measure to capture patient experiences of the signs, symptoms and impacts of psoriasis and aid integration of the patient perspective in treatment benefit-risk decision-making. Methods The psoriasis symptoms and impacts measure (P-SIM) was developed based on a literature search and interviews with five clinical experts in psoriasis to identify frequent signs, symptoms and impacts of psoriasis. Hybrid concept elicitation, cognitive debriefing and usability testing interviews were conducted with moderate to severe psoriasis patients to evaluate the content validity and patient understanding of the preliminary P-SIM. The preliminary P-SIM was refined using initial quantitative analyses of phase 2b data from psoriasis patients to inform the removal of any items. Results A preliminary 19-item P-SIM was developed for administration on a hand-held electronic tablet device using a 0–10 numerical response scale over a 24-h recall period. Patient interviews and testing demonstrated most patients interpreted the items and responses as intended, would not re-word any items, felt the responses matched the items and rated the device as easy to use. After quantitative testing, five items were removed from the preliminary 19-item measure because of conceptual overlap, floor effects and/or skewed distributions to generate the final 14-item P-SIM. Conclusions The P-SIM questionnaire has good content validity; patients reported it was easy to understand and reflective of their experiences. Following psychometric validation, the P-SIM may be a useful PRO measure for capturing the signs, symptoms and impacts of psoriasis and may support clinician-reported outcomes when assessing treatment benefits in clinical trials. Electronic supplementary material The online version of this article (10.1007/s13555-020-00434-3) contains supplementary material, which is available to authorized users.

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Introduction Plaque psoriasis can significantly impact patients’ quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients’ experiences of signs, symptoms and impacts of psoriasis. Methods Pooled, blinded, 16-week data from 1002 patients in the BE VIVID and BE READY bimekizumab phase 3 trials were analysed. The suitability of the P-SIM missing score rule (weekly scores considered missing if ≥ 4 daily scores were missing) was assessed. Test–retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between P-SIM and relevant patient-reported outcome (PRO) (Dermatology Life Quality Index [DLQI], DLQI item 1 [skin symptoms], Patient Global Assessment of Psoriasis) and clinician-reported outcome (ClinRO) scores (Psoriasis Area and Severity Index [PASI], Investigator’s Global Assessment [IGA]) at baseline and week 16. Known-groups validity was assessed, comparing P-SIM scores between patient subgroups predefined using PASI/IGA scores. Sensitivity to change over 16 weeks was evaluated; responder definition (RD) thresholds were explored. Results The missing score rule used did not impact P-SIM scores. Test–retest reliability analyses demonstrated excellent score reproducibility (ICC 0.91–0.98). Inter-item correlations at baseline and week 16 were strong (> 0.5), apart from “choice of clothing” with “skin pain” and “burning” at baseline (both 0.49). All P-SIM scores were moderately to strongly correlated with other outcomes, demonstrating convergent validity, apart from ClinROs (PASI, IGA) at baseline that had low variability. P-SIM scores discriminated known groups at week 16, confirming known-groups validity. Changes from baseline to week 16 in P-SIM and other clinically relevant outcomes were strongly correlated (> 0.5; weaker with ClinROs), establishing sensitivity to change. Anchor-based RD analyses determined a four-point P-SIM item score decrease as indicative of marked clinically meaningful improvement. Conclusion P-SIM scores demonstrated good reliability, validity and sensitivity to change. A four-point RD threshold could be used to assess 16-week treatment effects. Trial Registration BE VIVID: NCT03370133; BE READY: NCT03410992. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00570-4.

Psoriasis is a chronic disease requiring long-term management; understanding the long-term safety profiles of psoriasis treatments, such as bimekizumab, is important.To evaluate the 2-year safety profile of bimekizumab in patients with moderate to severe plaque psoriasis.Safety data were pooled from a cohort of patients from 4 phase 2 randomized clinical trials (BE ABLE 1, BE ABLE 2, PS0016, and PS0018) and 4 phase 3 randomized clinical trials (BE VIVID, BE READY, BE SURE, and BE BRIGHT) to include 2 years of study treatment. Data were obtained on adults with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index level ≥12, ≥10% body surface area affected by psoriasis, and an Investigator's Global Assessment score ≥3 on a 5-point scale) who were eligible for systemic psoriasis therapy and/or phototherapy.Included patients received 1 or more doses of bimekizumab during the phase 2 or phase 3 trials.Treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs leading to treatment discontinuation are reported using exposure-adjusted incidence rates (EAIRs) per 100 person-years.A total of 1789 patients (1252 [70.0%] men; mean [SD] age, 45.2 [13.5] years) were treated with 1 or more doses of bimekizumab across the phase 2/3 trials and were included in these analyses; total bimekizumab exposure was 3109.7 person-years. TEAEs occurred at an EAIR of 202.4 per 100 person-years and did not increase with longer duration of bimekizumab exposure. The 3 most frequently reported TEAEs were nasopharyngitis (19.1 per 100 person-years; 95% CI, 17.4-20.9 per 100 person-years), oral candidiasis (12.6 per 100 person-years; 95% CI, 11.3-14.0 per 100 person-years), and upper respiratory tract infection (8.9 per 100 person-years; 95% CI, 7.8-10.1 per 100 person-years). Most oral candidiasis events were mild or moderate; 3 events led to discontinuation. The EAIRs of inflammatory bowel disease (0.1 per 100 person-years; 95% CI, 0.0-0.3 per 100 person-years), adjudicated suicidal ideation and behavior (0.0 per 100 person-years; 95% CI, 0.0-0.2 per 100 person-years), and adjudicated major adverse cardiac events (0.5 per 100 person-years; 95% CI, 0.3-0.8 per 100 person-years) were low.In these pooled analyses of data from a cohort of patients from 8 randomized clinical trials, bimekizumab was well tolerated aside from an increased incidence of mild to moderate oral candidiasis. No safety signals were observed compared with previous reports, and there was no increased risk of AEs with longer duration of bimekizumab exposure.

Introduction This analysis assessed the psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), a novel patient-reported outcome (PRO) tool designed to capture patient experiences of the signs, symptoms and impacts of psoriasis. Methods Blinded data from the BE RADIANT phase 3b trial of bimekizumab were analysed. In BE RADIANT, patients were randomised 1:1 to bimekizumab 320 mg every 4 weeks (Q4W) or secukinumab 300 mg (weekly until Week 4, then Q4W). Three items (itching, skin pain and scaling) of the P-SIM were electronically assessed throughout the trial and were scored from 0 to 10 (none to very severe signs/symptoms/impacts). Test–retest reliability was determined using intraclass correlations. Convergent validity was assessed between P-SIM and other relevant PRO and clinician-reported outcome (ClinRO) scores. Known-groups validity was assessed by comparing mean P-SIM item scores between patient subgroups based on the Psoriasis Area and Severity Index (PASI)/Investigator’s Global Assessment (IGA) scores. Responsiveness was assessed via correlations between changes from baseline in P-SIM item scores and other relevant PRO and ClinRO scores. Anchor-based responder analyses and empirical cumulative distribution function (eCDF) curves determined responder thresholds. Results The three P-SIM items yielded high intraclass coefficients (> 0.70). By Week 48, the three P-SIM items had moderate (> 0.30 and ≤ 0.50) to strong (> 0.50) correlations with other PROs and weaker correlations with ClinROs, demonstrating good convergent validity. For almost all known-group comparisons, statistically significant between-subgroup score differences were seen across all three P-SIM items. Changes from baseline in the P-SIM and other relevant outcomes were above the acceptable threshold of ≤ 0.30, demonstrating sensitivity to change. Anchor-based analyses determined a ≥ four-point reduction from baseline to indicate marked clinically meaningful improvement for the P-SIM. Conclusion These results support the validity, reliability and sensitivity to change of the P-SIM in assessing key symptoms (itching, skin pain and scaling) in patients with moderate to severe plaque psoriasis. Trial registration NCT03536884. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01836-1.

The protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) plays a critical role in acute leukemias with translocations of the MLL1 gene or with mutations in the nucleophosmin 1 (NPM1) gene. As a step toward clinical translation of menin-MLL1 inhibitors, we report development of MI-3454, a highly potent and orally bioavailable inhibitor of the menin-MLL1 interaction. MI-3454 profoundly inhibited proliferation and induced differentiation in acute leukemia cells and primary patient samples with MLL1 translocations or NPM1 mutations. When applied as a single agent, MI-3454 induced complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia, including patient-derived xenograft models, through downregulation of key genes involved in leukemogenesis. We also identified MEIS1 as a potential pharmacodynamic biomarker of treatment response with MI-3454 in leukemia, and demonstrated that this compound is well tolerated and did not impair normal hematopoiesis in mice. Overall, this study demonstrates, for the first time to our knowledge, profound activity of the menin-MLL1 inhibitor as a single agent in clinically relevant PDX models of leukemia. These data provide a strong rationale for clinical translation of MI-3454 or its analogs for leukemia patients with MLL1 rearrangements or NPM1 mutations.

5,6-Diaminoacenaphthylene was synthesized in four steps from acenaphthene. This seemingly simple molecule provides unique synthetic challenges because it is relatively difficult to reduce the nitro groups and the molecule contains a particularly reactive double bond. It was determined that the only feasible sequence for the synthesis was to nitrate acenaphthene, then brominate, eliminate, and finally selectively reduce. Several reduction methods were attempted before finding one that would completely reduce both nitro groups while leaving the double bond intact.

Objective The aim was to assess the long-term safety and efficacy of certolizumab pegol over 4 years of continuous treatment in patients with axial spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA. Methods RAPID-axSpA was a phase 3 randomized trial, double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Patients had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis international Society (ASAS) criteria, and had active disease. The assessed outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores, along with selected measures of remission. Further patient-reported outcomes, peripheral arthritis, enthesitis, uveitis and quality-of-life measures are also reported. Results Two hundred and eighteen of 325 patients randomized (AS: 121; nr-axSpA: 97) received certolizumab pegol from week 0. Of these, 65% remained in the study at week 204 (AS: 67%; nr-axSpA: 63%). Across all outcomes, for AS and nr-axSpA, sustained improvements were observed to week 204 [week 204 overall axSpA: ASAS20: 54.1% (non-responder imputation); 83.7% (observed case, OC); ASAS40: 44.0% (non-responder imputation); 68.1% (OC); ASDAS inactive disease: 32.1% (last observation carried forward); 31.4% (OC)]. In the safety set (n = 315), there were 292.8 adverse events and 10.4 serious adverse events per 100 patient-years. No deaths were reported. Conclusion In the first study to evaluate the efficacy of an anti-TNF across both axSpA subpopulations, improvements in clinical and patient-reported outcomes at 24 and 96 weeks were sustained through 4 years of treatment, with no new safety signals. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01087762.

Small exoplanets of nearby M dwarf stars present the possibility to find and characterize habitable worlds within the next decade. TRAPPIST-1, an ultracool M dwarf star, was recently found to have seven Earth-sized planets of predominantly rocky composition. The planets e, f, and g can have a liquid water ocean on their surface given appropriate atmospheres of N2 and CO2. Particularly, climate models have shown that the planets e and f can sustain a global liquid water ocean, for >=0.2 bar CO2 plus 1 bar N2, or >=2 bars CO2, respectively. These atmospheres are irradiated by ultraviolet emission from the star's moderately active chromosphere, and the consequence of this irradiation is unknown. Here we show that chemical reactions driven by the irradiation can produce and maintain more than 0.2 bar O2 and 0.05 bar CO if the CO2 is >=0.1 bar. The abundance of O2 and CO can rise to more than 1 bar under certain boundary conditions. Because of this O2-CO runaway, habitable environments on the TRAPPIST-1 planets entail an O2- and CO-rich atmosphere with coexisting O3. The only process that would prevent the runaway is direct recombination of O2 and CO in the ocean, a reaction that is facilitated biologically. Our results indicate that O2, O3, and CO should be considered together with CO2 as the primary molecules in the search for atmospheric signatures from temperate and rocky planets of TRAPPIST-1 and other M dwarf stars., ApJ accepted

9105 Background: Immune checkpoint inhibitor (ICI) therapy has become a mainstay of non-small cell lung cancer (NSCLC) treatment. However, not all patients (pts) benefit with a subset paradoxically experiencing accelerated tumor growth while on ICI. Hyperprogression (HP) refers to accelerated tumor growth on ICI with worsening clinical status. Various gene alterations may be associated with HP including MDM2/MDM4 amplifications, EGFR alterations, and STK11/LKB1 mutations. Kato et al. (doi: 10.1158/1078-0432.CCR-16-3133 ) showed HP in 6/6 pts with MDM2/MDM4 amplification and in 2/10 pts with EGFR alterations. This report describes HP in pts with NSCLC treated with ICIs in a large health system. Methods: Pts with NSCLC treated with ICIs from Jan 2012 to Jan 2021 at Advocate Aurora Health were reviewed after IRB approval. Pts with NSCLC histology (ICD diagnosis codes and/or manual chart review), ICI treatment, and molecular testing were identified via the real world data integrated within the Syapse Learning Health Network platform. Additional chart review to ascertain HP was performed, and molecular results were analyzed. HP criteria include: 1) time-to-treatment failure < 2 months (from start to discontinuation of ICI for any reason), 2) > 50% increase in tumor burden by RECIST, 3) spread of the disease to a new organ between baseline and first radiologic evaluation or clinical deterioration, and 4) ECOG PS ≥ 2 during the first 2 months of treatment. Based on the number of criteria fulfilled, HP = > 3, Progression = 1-2, and non-progressor = 0. Pts with and without HP were compared using Chi-squared and Fisher Exact tests. T-tests were performed for continuous variables. Results: Out of 7,078 NSCLC pts, 1,389 (20%) were treated with ICI including atezolizumab (40 pts, 3%), durvalumab (17 pts, 1%), nivolumab (167 pts, 12%), pembrolizumab (190 pts, 14%), and multiple ICIs (12 pts, 1%). Of those pts treated with ICIs, molecular testing was performed in 427 (31%). 98 of 427 pts (23%)had HP and an additional 86 pts (20%) had progressive disease without meeting the definition of HP. Biomarker associations with HP are shown in the table. By tumor gene alterations, HP was seen in pts with: EGFR (20/60), STK11/LKB1 (16/25); and MDM2/4 (4/7). Conclusions: EGFR, STK11/LKB1, and MDM2/4 gene alterations were all statistically significantly associated with HP. Clinical and molecular predictors of HP need to be explored in order to optimize selection of pts for ICI therapy.[Table: see text]

e21047 Background: Patients (pts) with lung cancer and other cancers treated with immune checkpoint inhibitors (ICI) may experience immune related adverse events (irAE). These can present with variable severity and with single- or multi-organ involvement including pneumonitis, colitis, hepatitis, and myocarditis/pericarditis. The incidence of myocarditis has been reported between 0.06% and 2.4% and is associated with a high mortality (25% to 50%). This retrospective review of real-world data (RWD) investigates myocarditis as a high-grade adverse event in pts with lung cancer treated with ICIs. Methods: Pts were identified and characterized using RWD in the Syapse Learning Health Network platform from 2010 to 2020 at Advocate Aurora Health Care. Eligible pts included: ≥18 years old; histologically confirmed NSCLC; and myocarditis diagnosis by ICD codes. Additional chart review was performed to confirm timing of ICI treatment and myocarditis. All pts identification and review were performed after IRB review. Results: 12,686 pts with non-small cell lung cancer were eligible for review. The median age at diagnosis was 70; 54% were female; 86% were White and 12% were Black; 1,975 (15.6%) were treated with an ICI and of those 4 cases (0.2%) of myocarditis were identified. All 4 pts were White females, ages 46, 59, 65, and 74 years. Pathology included lung adenocarcinoma (3) and an undifferentiated lung carcinoma (1). All pts had metastatic disease, and none had a prior history of cardiac disease. ICIs were pembrolizumab (2), durvalumab (1), and nivolumab (1). Median time from initial dose of ICI to diagnosis of myocarditis was 62 days [range: 42-185]. All 4 pts presented with chest pain and elevated troponin T [median 0.07 ng/ml (range: 0.06-0.08)]. All pts had echocardiography at the time of diagnosis, and 2 pts had cardiac MRI that confirmed myocarditis. 3 pts were treated with a prednisone taper. 1 pt died of recurrent congestive heart failure and ventricular tachycardia despite rescue attempt with high dose corticosteroids. 2 pts had additional concomitant irAEs of hypothyroidism/colitis, and thyroiditis/pneumonitis, respectively. Conclusions: Many irAEs are reversible. This RWD analysis confirms that clinically evident myocarditis is a rare but serious adverse event of ICI therapy. Early consideration, diagnosis, and intervention may help prevent poor outcomes. Termination of ICI therapy along with initiation of corticosteroids constitute the current standard of management. Further research is warranted to better identify high risk groups, surveillance measures, and improved management of ICI associated myocarditis.

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Background Disease Activity Index for Psoriatic Arthritis (DAPSA) 1 and the minimal disease activity (MDA) criteria 2 are instruments recommended for evaluating disease activity in psoriatic arthritis (PsA). The RAPID-PsA trial (NCT01087788) has demonstrated the sustained efficacy of certolizumab pegol (CZP) across the spectrum of PsA symptoms. 3,4 Objectives To report the proportion of CZP-treated patients (pts) achieving DAPSA remission (REM), DAPSA low disease activity (LDA), MDA (fulfilling ≥5/7 MDA criteria), and very low disease activity (VLDA; fulfilling 7/7 MDA criteria) over 216 weeks (wks) in RAPID-PsA. Methods RAPID-PsA was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label (OL) to Wk216. Pts had active PsA and had failed ≥1 disease modifying anti-rheumatic drug. Data for pts randomised to CZP at Wk0 (200 mg every 2 wks or 400 mg every 4 wks, following a 400 mg loading dose at Wks0, 2, 4), who continued their assigned dose in the OL period, are presented as observed case and with imputation (figure 1). Outcomes reported are DAPSA (the sum of tender and swollen joint counts [TJC 68; SJC 66], pt global and pain assessment [10 cm visual analogue scale], and C-reactive protein levels [mg/dL]), and pts achieving: 1) DAPSA LDA (DAPSA>4 and≤14); 2) DAPSA REM (DAPSA≤4); 3) MDA (fulfilling ≥5/7 MDA criteria); and 4) VLDA (fulfilling 7/7 MDA criteria), to Wk216. Pts withdrawing from the study between scheduled visits had their final observed assessment values assigned to the next scheduled visit timepoint. Results Of 409 pts randomised; 273 received CZP from Wk0, of whom 248 (90.8%) completed Wk24, 237 (86.8%) completed Wk48, and 183 (67.0%) completed Wk216. The mean (SD) baseline DAPSA was 44.8 (22.9). Of pts completing Wk24, 29.7% (74/249) achieved LDA; 25.3% (63/249) REM; 38.2% (95/249) MDA; and 14.9% (37/249) VLDA. At Wk216, 31.9% (59/185) achieved LDA; 44.3% (82/185) REM; 57.8% (107/185) MDA; and 29.0% (58/183) VLDA (figure 1). Conclusions A substantial proportion of pts who completed the 4 year study achieved disease inactivity targets:~75% achieved DAPSA LDA or REM, almost 60% achieved MDA, and half of those also achieved VLDA. References [1] Schoels MM. Ann Rheum Dis2016;75(5):811–18. [2] Coates LC. Ann Rheum Dis2010;69(01):48–53. [3] Mease PJ. Ann Rheum Dis2016;75:608. [4] FitzGerald O. JAAD2017;76(6):AB264. Acknowledgements This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. Editorial services were provided by Costello Medical. Disclosure of Interest D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, UCB Pharma, Employee of: Director of Imaging Rheumatology B.V., A. Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, Consultant for: Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Janssen, Pfizer, Consultant for: AbbVie, Celgene, Amgen, Eli Lilly, Janssen, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Pfizer, UCB Pharma, R. Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, MSD Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Aventis, D. Gladman Grant/research support from: Abbott, Amgen, Bristol-Myers Squibb, Celgene, Johnson and Johnson, MSD, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Bristol-Myers Squibb, Celgene, Johnson and Johnson, MSD, Novartis, Pfizer, UCB Pharma, A. Gottlieb Grant/research support from: Abbott, Aclaris, Actelion, Akros, Amiscus, Amgen, Astellas, Baxalta, Beiersdorf, Bristol-Myers Squibb, Canfite, Catabasis, Celgene, Coronado, Crescendo Bioscience, CSL Behring Biotherapies for Life, Dermipsor, Dermira, Eli Lilly, Genentech, GlaxoSmithKline, Incyte, Janssen, Karyopharm, KinetaOne, KPI Therapeutics, Levia, Meiji Seika Pharma Co., Merck, Mitsubishi Tanabe, Novartis, Novo Nordisk, Pfizer, Reddy, Takeda, TEVA, UCB Pharma, Vertex, Xenoport, Consultant for: Abbott, Aclaris, Actelion, Akros, Amiscus, Amgen, Astellas, Baxalta, Beiersdorf, Bristol-Myers Squibb, Canfite, Catabasis, Celgene, Coronado, Crescendo Bioscience, CSL Behring Biotherapies for Life, Dermipsor, Dermira, Eli Lilly, Genentech, GlaxoSmithKline, Incyte, Janssen, Karyopharm, KinetaOne, KPI Therapeutics, Levia, Meiji Seika Pharma Co., Merck, Mitsubishi Tanabe, Novartis, Novo Nordisk, Pfizer, Reddy, Takeda, TEVA, UCB Pharma, Vertex, Xenoport, L. Coates Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Prothena, Sun Pharma, UCB Pharma, B. Hoepken Employee of: UCB Pharma, L. Bauer Employee of: UCB Pharma, L. Peterson Employee of: UCB Pharma, M. Khraishi Grant/research support from: Abbott, Amgen, Pfizer, Consultant for: Abbott, Amgen, Pfizer, P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Sun, UCB Pharma, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Sun, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma

Background Certolizumab pegol, an Fc‐free, PEGylated, anti‐tumour necrosis factor (TNF) biologic, has demonstrated favourable results in three ongoing, phase 3, randomized, double‐blinded, placebo‐controlled trials in adults with psoriasis. Objective Data were pooled from the ongoing trials to investigate efficacy in selected subgroups and add precision to estimates of treatment effects during the initial 16 weeks of treatment. Methods In each trial, patients ≥18 years with moderate‐to‐severe chronic plaque psoriasis for ≥6 months were randomized to receive certolizumab 400 mg, certolizumab 200 mg or placebo every 2 weeks for 16 weeks. Coprimary endpoints for the pooled analysis were responder rates at Week 16, defined as ≥75% reduction in psoriasis area and severity index (PASI 75) and physician global assessment (PGA) of 0/1 (‘clear’/‘almost clear’ with ≥2‐category improvement). Safety was assessed by treatment‐emergent adverse events. Results A total of 850 patients treated with certolizumab 400 mg (N = 342), certolizumab 200 mg (N = 351) or placebo (N = 157) were included in the pooled analysis. At Week 16, PASI 75 and PGA 0/1 responder rates were 80.1% and 63.7% in the certolizumab 400 mg group, 74.5% and 54.6% in the certolizumab 200 mg group, and 7.5% and 2.8% in the placebo group (P

Objective.The product of physician’s global assessment and body surface area (PGA×BSA) to assess psoriasis severity has previously been investigated in patients with psoriasis, with the aim of assessing PGA×BSA as an alternative to the time-consuming Psoriasis Area and Severity Index (PASI). Here, we investigate PGA×BSA as an alternative to PASI in patients with psoriatic arthritis (PsA).Methods.Analyses used data from the double-blind, placebo-controlled, RAPID-PsA trial (NCT01087788) that investigated the efficacy of certolizumab pegol (CZP) in patients with PsA. Outcomes assessed whether the PGA×BSA and PASI results were comparable, and whether these outcomes correlated with one another or with the Dermatology Life Quality Index (DLQI).Results.For CZP-treated patients, both PGA×BSA and PASI demonstrated similar sensitivities to treatment between baseline and Week 24, with mean improvements of 77.4% and 69.0%, respectively. Similar improvements were also seen with placebo (PGA×BSA: 3.2%, PASI: 6.1%). Achievement of 75% response criterion in PGA×BSA and PASI was attained by similar proportions of patients with CZP (PGA×BSA75: 59.0%, PASI75: 61.4%) and placebo (PGA × BSA75: 15.1%, PASI75: 15.1%). Cross tabulations showed high concordance between achievement of response outcomes in PGA×BSA and PASI (79.6–95.2%). Spearman correlations revealed strong correlations between PGA×BSA and PASI at baseline (r = 0.78; n = 225) and percentage improvement to Week 24 (r = 0.85; n = 186). Both outcomes were only moderately correlated with DLQI (r = 0.41–0.50; n = 179–249).Conclusion.PGA×BSA is sensitive to changes in skin manifestations in patients with PsA treated with CZP. Further, PGA×BSA correlates strongly with PASI, and achievement of 75% improvement was similar for PGA×BSA and PASI.

Background Certolizumab pegol, the only Fc-free, PEGylated anti–tumor necrosis factor biologic, demonstrated clinically meaningful improvements suggestive of a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis. Objective Assess certolizumab efficacy and safety versus placebo in phase 3 studies. Methods Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks. At week 16, certolizumab-treated patients achieving a 50% reduction in Psoriasis Area and Severity Index continued treatment through week 48. Coprimary endpoints were week 16 responder rates, defined as a 75% reduction in Psoriasis Area and Severity Index and Physician's Global Assessment 0/1 (clear/almost clear) and ≥2-point improvement. Safety was assessed by treatment-emergent adverse events. Results Week-16 endpoints were significantly greater for both doses of certolizumab versus placebo, and the responses were maintained through week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified. Limitation There was no active comparator. Conclusion Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant and clinically meaningful improvements in moderate-to-severe psoriasis. The 400-mg dose could provide additional clinical benefit. The safety profile was consistent with the therapeutic class.

Introduction Le certolizumab pegol (CZP), un anti-TNFα, a montre des ameliorations cliniques et un profil de tolerance coherent avec sa classe chez des adultes souffrant de psoriasis en plaques (PSO) chronique. Les donnees poolees des 3 etudes du CZP dans le PSO ont permis d’evaluer le maintien de la reponse clinique initiale de la semaine(S)16 jusqu’a S48. Materiel et methodes Les donnees des 3 etudes de phase III de CZP (CIMPASI-1/2 et CIMPACT) ont ete poolees. Les patients souffraient de PSO modere a severe depuis ≥ 6 mois (PASI ≥ 12, BSA ≥ 10 %, PGA ≥ 3/5) et etaient randomises pour recevoir CZP 400 mg/2S, CZP 200 mg/2S (apres une dose de charge de 400 mg a S0/2/4), un placebo (PBO) pendant 16S ou de l’etanercept 50 mg 2×/S pendant 12S (CIMPACT). A S16, les repondeurs PASI 50 de CIMPASI-1/2 recevant du CZP 200 mg/2S ou du CZP 400 mg/2S poursuivaient leur traitement a la meme dose jusqu’a S48. Dans CIMPACT, les repondeurs PASI75 a S16 etaient rerandomises pour recevoir des doses de CZP 400 mg/2S, CZP 200 mg/2S ou PBO/2S jusqu’a S48. Cette analyse poolee incluait uniquement les patients repondeurs PASI 75 a S16 et qui avaient recu la meme dose de CZP de S0 a S48. Les patients recevant du PBO, ont ete rerandomises pour recevoir une dose de CZP differente et les non-repondeurs PASI75 a S16 etaient exclus. Les patients non repondeurs PASI 50 a S32 ou apres, etaient sortis de l’etude dans CIMPASI-1/2 ou passaient a 400 mg de CZP/2S dans CIMPACT ; ces patients etaient classes comme non-repondeurs lors des evaluations ulterieures. Nous rapportons la reponse PASI 75 a S48 chez les patients repondeurs PASI 75 a S16 et la reponse PASI 90 a S48 chez les patients repondeurs PASI 90 a S16. Les donnees sont presentees avec les donnees manquantes imputees (methode Markov Chain Monte Carlo [MCMC]). Les analyses de sensibilite ont ete menees avec une imputation des non-repondeurs (NRI). Resultats Sur les 3 etudes, 180 patients recevant CZP 400 mg/2S et 173 patients recevant CZP 200 mg/2S avaient atteint une reponse PASI 75 a S16 ; 98,0 % des patients traites par du CZP 400 mg/2S et 86,1 % des patients traites par du CZP 200 mg/2S avaient egalement atteint une reponse PASI 75 a S48 (MCMC). Une proportion elevee de patients ayant atteint une reponse PASI 90 a S16 avaient egalement atteint cette reponse a S48. Cent seize patients recevant du CZP 400 mg/2S et 100 patients recevant du CZP 200 mg/2S avaient atteint une reponse PASI 90 a S16 ; respectivement 89,0 % et 80,1 % avaient egalement atteint une reponse PASI 90 a S48 (MCMC). Les analyses de sensibilite montraient des tendances similaires, a la fois pour les reponses PASI 75 et PASI 90. Conclusion Les patients dans les 2 groupes de doses de CZP ont montre un maintien de leur reponse initiale PASI 75 et PASI 90 de S16 jusqu’a S48. Un plus long maintien a ete observe chez les patients recevant du CZP 400 mg/2S, 98,0 % des patients ayant obtenu une reponse PASI 75 a S16 rapportaient encore cette reponse a S48.

Introduction Le certolizumab pegol (CZP) est un anti-TNFα sans fragment Fc. Dans les etudes de phase III, CZP a montre des ameliorations cliniques rapportees par les patients atteints de psoriasis en plaques chronique (PSO), et qui se sont maintenues pendant 48 semaines, avec un profil de tolerance coherent avec sa classe. Nous avons ici evalue l’efficacite du CZP chez des patients ne repondant pas a l’etanercept (ETN). Materiel et methodes Dans l’etude de phase III en cours CIMPACT ( NCT02346240 ), les patients (âges ≥ 18 ans, avec un PSO modere a severe ≥ 6 mois, un score d’etendue et de severite du psoriasis (PASI) ≥ 12, une surface corporelle atteinte ≥ 10 %, une evaluation globale par le medecin (PGA) ≥ 3 sur une echelle a 5 points) ont ete randomises pour recevoir du CZP 400 mg toutes les 2 semaines (/2S), du CZP 200 mg/2S apres une dose de charge de 400 mg a S0, S2, S4, un placebo/2S pendant 16S ou de l’ETN 50 mg ×2/S pendant 12S. A S16 et apres une periode de washout de 4S, les patients avec une reponse inadequate a l’ETN (amelioration du score PASI Resultats Sur les 159 patients randomises pour recevoir de l’ETN encore dans l’etude a S16, 35 n’avaient pas atteint de reponse PASI 50 a S12 et etaient entres dans le bras d’echappement avec du CZP 400 mg/2S a la semaine 16. A S32, apres 16S de traitement par CZP, 60,0 % de ces patients obtenaient une reponse PASI 75, 25,7 % une reponse PASI 90 et 42,9 % une reponse PGA. A S48, apres 32 semaines de traitement par CZP, 62,9 % atteignaient une reponse PASI 75, 51,4 % une reponse PASI 90 et 57,1 % une reponse PGA. Conclusion Chez des patients souffrant de PSO n’ayant pas repondu a un traitement par ETN, des ameliorations ont ete observees apres le passage au CZP, plus de la moitie des patients atteignant une amelioration de 75 % de leur maladie apres 16S de traitement par CZP et plus de la moitie obtenant une amelioration de 90 % de leur maladie apres 32S de traitement par CZP. Ces donnees montrent que le CZP pourrait etre un traitement approprie chez les patients non repondeurs a ETN.

The following study envisions the modern history of the Palestinian- Israeli conflict through the application of previously underutilized theoretical frames. Beginning with the unprecedented political and social upheaval wrought upon the Middle East after the end of World War I, the article unfolds in three distinct sections. The first section provides an historical introduction to the global, transnational forces that guided the developing infrastructure of political conflict within the region. The second section articulates the ideological parameters of the international political and economic forces (“neoliberalism”) that connect the past and present of political conflict in the region as well as the local (state and non-state) and non-local actors involved in its contemporary manifestation. The third and final section reconceptualizes the Palestinian-Israeli conflict not exclusively as a territorial dispute or as a nebulous clash of cultures, but rather as a deliberate, operational casualty enduring in the service of an aggressive, transnational, and indeed historical force whose trajectory spans the length of the twentieth and early twenty-first centuries: neoliberalism. In each sphere in which the neoliberal ideal has been applied – one, an historical fait accompli, another, a contemporary situation en cours – an important, connective element persists: the distinctly non-local origin of both the historical forces and the contemporary economic manifestations under examination.

Background Extra-articular manifestations (EAMs) of psoriatic arthritis (PsA) include nail psoriasis, dactylitis, and enthesitis, which can significantly impact patients9 (pts9) quality of life. 1 In the RAPID-PsA trial (NCT01087788), certolizumab pegol (CZP) improved the signs and symptoms of EAMs in pts with PsA over 96 weeks (wks). 2 Objectives To report improvements in EAMs of PsA in pts treated with CZP over 4 years, both with and without prior anti-TNF exposure. Methods The RAPID-PsA trial was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label (OL) to Wk216. Pts had active PsA and had failed ≥1 DMARD. Pts originally randomized to CZP (200mg Q2W or 400mg Q4W, following 400mg loading dose at Wks0, 2, 4) continued their assigned dose in the OL period. We present EAM data for those pts originally randomized to CZP, with involvement of the particular EAM at baseline (BL), and both with and without prior anti-TNF exposure. EAMs assessed include nail psoriasis (modified Nail Psoriasis Severity Index [mNAPSI], BL involvement = BL mNAPSI >0), enthesitis (Leeds Enthesitis Index [LEI], BL involvement = BL LEI >0), and dactylitis (Leeds Dactylitis Index [LDI], BL involvement = ≥1 digit affected with a difference in circumference ≥10% compared to the opposite digit). Also presented are the proportions of pts with BL involvement of each EAM who achieved total resolution of the respective EAM on follow-up (a score of 0 for mNAPSI, LEI, or LDI). Observed values are reported, combined for pts receiving either CZP dose regimen. Results A total of 409 PsA pts were randomized; 273 received CZP from Wk0. Among CZP-randomized pts, 197 had nail psoriasis at BL (159 without, and 38 with, prior anti-TNF exposure), 172 had enthesitis (133 without, and 39 with, prior anti-TNF exposure), and 73 had dactylitis (56 without, and 17 with, prior anti-TNF exposure). Although relatively few pts were anti-TNF experienced, a large proportion of pts both with and without prior anti-TNF exposure with BL involvement went on to achieve total resolution of the respective EAM following 48 wks of CZP treatment (Table). Among pts completing the study, the proportions achieving total resolution were maintained or further increased from Wk48 to Wk216 (Table). Mean scores of all EAMs assessed showed improvements by Wk48 of CZP treatment in pts both with and without prior anti-TNF exposure, which were maintained to Wk216 in pts completing the study (Table). Conclusions PsA patients treated with CZP for up to 4 years, both with and without prior anti-TNF exposure, exhibited sustained improvements in the extra-articular manifestations of PsA. References Ritchlin C. Ann Rheum Dis 2009;68:1387–94. FitzGerald O. Ann Rheum Dis 2015;74(2):349. Acknowledgements This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. Editorial services were provided by Costello Medical Consulting. Disclosure of Interest O. FitzGerald Grant/research support from: AbbVie, Bristol Myers Squibb, Janssen, Novartis, Pfizer, Consultant for: AbbVie, Celgene, Janssen, Pfizer, Roche, UCB Pharma, Speakers bureau: AbbVie, Celgene, Janssen, Pfizer and UCB Pharma, R. Fleischmann Grant/research support from: Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, Janssen, MSD Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Eli Lilly, Pfizer, Sanofi-Aventis, UCB Pharma, A. Kavanaugh Grant/research support from: Abbott, Amgen, Bristol-Myers Squibb, Janssen, Pfizer, Roche, UCB Pharma, B. Hoepken Employee of: UCB Pharma, L. Peterson Employee of: UCB Pharma, D. Gladman Grant/research support from: Abbott, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD Pharmaceuticals, Novartis, Pfizer, and UCB Pharma, Consultant for: Abbott, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD Pharmaceuticals, Novartis, Pfizer, and UCB Pharma

Background The RAPID-PsA trial (NCT01087788) investigated the efficacy and safety of certolizumab pegol (CZP) in patients (pts) with psoriatic arthritis (PsA). It demonstrated that CZP treatment inhibits radiographic progression over 96 weeks (wks). 1 Objectives We report the long-term effect of CZP treatment on radiographic progression in pts with PsA over 4 years. Methods The RAPID-PsA phase 3 trial was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label (OL) to Wk216. Pts had active PsA and had failed ≥1 DMARD. Pts randomized to CZP (200mg Q2W or 400mg Q4W, following 400mg loading dose at Wks0, 2, 4) continued their assigned dose in the OL period. Radiographs taken at baseline (BL), and at Wks96, 168, 216, were read in a single reading campaign using the modified Total Sharp Score (mTSS) for PsA by 2 readers, blinded to patient information and time point sequence. The mean of the scores of the 2 readers was used. Outcomes reported are the least squares (LS) mean mTSS score, change from BL (CFB) in mTSS score, and the percentage of pts assessed for radiographic damage who achieved mTSS non-progression (defined either as CFB in mTSS score ≤0.5 or ≤0), for all Wk0 CZP-treated pts, irrespective of dose regimen. mTSS score and CFB were estimated using Mixed Model Repeated Measures (MMRM) estimates; proportions of pts with radiographic non-progression are presented as observed case. Results 409 PsA pts were randomized, of whom 273 received CZP from Wk0. The LS mean BL mTSS score was 16.0 and there was little increase from BL in mTSS score to Wk216 (Table). Amongst those who completed the study to Wk216, the majority of CZP-treated pts achieved radiographic non-progression to Wk216, both with non-progression defined as CFB in mTSS score ≤0.5 or ≤0 (Table). The change in LS mean mTSS score over time for Wk0 CZP-treated pts was consistently low throughout the trial: 0.14 (95% CI: 0.02–0.26) per 48 wks from BL to Wk96, and 0.18 (95% CI: 0.08–0.28) per 48 wks from Wk96 to Wk216. Conclusions There was little radiographic progression in CZP-treated PsA pts, as measured by mTSS, throughout the 4-year RAPID-PsA trial. References Mease P. RMD Open 2015;1:e000119;doi:10.1136/rmdopen-2015–000119. Acknowledgements This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. Editorial services were provided by Costello Medical Consulting. Disclosure of Interest D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB Pharma, Employee of: Director of Imaging Rheumatology B.V., R. Fleischmann Grant/research support from: Genentech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, Sanofi-Aventis, MSD Pharmaceuticals, Novartis, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol-Myers Squibb, Eli Lilly, Sanofi-Aventis, Novartis, AstraZeneca, Janssen, J. Wollenhaupt Grant/research support from: UCB Pharma, Consultant for: UCB Pharma, A. Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, Consultant for: Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, L. Bauer Employee of: UCB Pharma, B. Hoepken Employee of: UCB Pharma, L. Peterson Employee of: UCB Pharma, P. Mease Grant/research support from: (Abbott) AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Sun, UCB Pharma, Consultant for: (Abbott) AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Corrona, Dermira, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Sun, UCB Pharma, Zynerba, Speakers bureau: (Abbott) AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Genentech Inc, Janssen, Novartis, Pfizer, UCB Pharma

Background Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease that has a substantial impact on patients9 (pts) physical and emotional wellbeing. 1 Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-TNF that has been shown to improve patient-reported outcomes (PROs) in pts with PsA over 96 weeks (wks) of treatment in the RAPID-PsA study (NCT01087788). 2 Objectives To investigate whether initial improvements in PROs observed with CZP treatment were maintained over 4 years in the RAPID-PsA study. Methods RAPID-PsA was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label to Wk216. Pts were aged ≥18 years, with a diagnosis of active PsA, and had failed treatment with ≥1 DMARD. Pts originally randomized to CZP (400mg at Wks0,2,4 [loading dose] followed by either 200mg every 2 wks [Q2W] or 400mg every 4 wks [Q4W]) continued on their assigned dose during the open-label period. PROs assessed included Patient9s Global Assessment of Arthritis Pain (PtAAP; visual analog scale), fatigue (numeric rating scale), Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Physical and Mental Component Summary (SF-36 PCS/MCS), Psoriatic Arthritis Quality of Life (PsAQoL), and Dermatology Life Quality Index (DLQI; assessed in the subgroup of pts with ≥3% body surface area affected by psoriasis at baseline [BL]). Data are reported as the mean change from BL (CFB) for pts randomized to CZP at Wk0, with last observation carried forward (LOCF) imputation for Wk24, and LOCF imputation and observed case (OC) values for Wk216. Results Of 273 pts randomized to CZP at Wk0, 248 (91%) completed Wk24 and 183 (67%) completed Wk216. Improvements observed to Wk24 of treatment were generally maintained over 4 years (to Wk216) in all PROs assessed, regardless of prior anti-TNF exposure (Table). Similar improvements were observed in both CZP dose regimens for all PROs examined, including PtAAP (CFB at Wk216 in the 200mg Q2W group [with LOCF imputation]: -30.5, in the 400mg Q4W group: -33.8); fatigue (-2.3, -2.3); HAQ-DI (-0.50, -0.49); SF-36 PCS (8.73, 8.77); SF-36 MCS (3.91, 3.28); PsAQoL (-4.6, -4.4); and DLQI (-8.4, -6.8). Conclusions Early improvements with CZP treatment were maintained over 4 years in all PROs assessed in the RAPID-PsA study. Similar improvements were observed in pts with and without prior anti-TNF exposure, and in both CZP dose regimens. References Rosen C. Rheumatology 2012;51(3):571–6. Gladman D. Value in Health 2014;17(7):A386. Acknowledgements This study was funded by UCB Pharma. We thank the patients and their caregivers in addition to the investigators and their teams who contributed to this study. Editorial services were provided by Costello Medical Consulting. Disclosure of Interest D. Gladman Grant/research support from: Abbott, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, Consultant for: Abbott, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer, UCB Pharma, R. Fleischmann Grant/research support from: Genentech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol-Myers Squibb, Lilly, Sanofi-Aventis, MSD, Novartis, AstraZeneca, Janssen, Consultant for: Roche, Abbott, Amgen, UCB Pharma, Pfizer, Bristol-Myers Squibb, Lilly, Sanofi-Aventis, Novartis, AstraZeneca, Janssen, K. Harris Employee of: UCB Pharma, L. Peterson Employee of: UCB Pharma, P. Mease Grant/research support from: (Abbott) AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB Pharma, Consultant for: (Abbott) AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Corrona, Dermira, Janssen, Lilly, Merck, Novartis, Pfizer, Sun, UCB Pharma, Zynerba, Speakers bureau: (Abbott) AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Novartis, Pfizer, UCB Pharma